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Saxagliptin

Phase 3

Diabetes Mellitus, Type 2 | Small molecule | Metabolic |AstraZeneca PLC|Last Updated: Dec 11, 2018

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials4
Total Enrollment3,094

FDA Designations

No designations recorded

Clinical trial landscape

Saxagliptin · 37 trials · 5 indications

Phase 3 23Phase 2 1Phase 1 13
NCT02551874A 24-week Open-Label, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects withType 2 Diabetes Who Have Glycemic Control on MetforminType 2 Diabetes Mellitus
COMPLETED650 Analytics
NCT02273050Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Drug Naive Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic ControlType 2 Diabetes Mellitus
COMPLETED1,136 Analytics
NCT02284893Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy AloneType 2 Diabetes
COMPLETED461 Analytics
NCT02104804Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin Combined With Metformin in Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic ControlType 2 Diabetes Mellitus
COMPLETED953 Analytics
NCT01606007Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 DiabetesType 2 Diabetes
COMPLETED1,282 Analytics
NCT01619059Safety and Efficacy of Saxagliptin in Triple Therapy to Treat Subjects With Type 2 DiabetesType 2 Diabetes
COMPLETED315 Analytics
NCT01434186A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Saxagliptin (BMS-477118) in Combination With Metformin IR or Metformin XR in Pediatric Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin AloneDiabetes Mellitus, Type 2
COMPLETED32 Analytics
NCT01204775Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Saxagliptin as Monotherapy in Pediatric Patients With Type 2 DiabetesType 2 Diabetes
COMPLETED26 Analytics
NCT01128153Saxagliptin Triple Oral TherapyType 2 Diabetes
COMPLETED257 Analytics
NCT00960076An 18 Week Efficacy and Safety Study of Saxagliptin and Metformin XR Combination in Subjects With Type 2 DiabetesType 2 Diabetes
COMPLETED282 Analytics
PHASE3COMPLETED
A 24-week Open-Label, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects withType 2 Diabetes Who Have Glycemic Control on Metformin
Type 2 Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Drug Naive Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control
Type 2 Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin Combined With Metformin in Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control
Type 2 Diabetes MellitusUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy of Saxagliptin in Triple Therapy to Treat Subjects With Type 2 Diabetes
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Saxagliptin (BMS-477118) in Combination With Metformin IR or Metformin XR in Pediatric Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Saxagliptin as Monotherapy in Pediatric Patients With Type 2 Diabetes
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
Saxagliptin Triple Oral Therapy
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
An 18 Week Efficacy and Safety Study of Saxagliptin and Metformin XR Combination in Subjects With Type 2 Diabetes
Type 2 DiabetesUnlock trial analytics

Study Endpoints

Primary Endpoints

Mean Change From Baseline in HbA1c at Week 24
Baseline and Week 24

To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 0.3%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue
Baseline to Week 24 (prior to rescue)

To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to reduction in HbA1c (%) at the end of 24 weeks of double-blinded treatment.

Mean Change in HbA1c
Baseline (randomization) to Week 26
Change in HbA1c From Baseline to Week 24
Baseline to 24 weeks
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24
Baseline (Week 0) and at Week 24

HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue.

Mean Change in HbA1c From Baseline to Week 16
16 week short term treatment period
Change in HbA1c From Baseline to Week 24, Last Observation Carried Forward (LOCF)
From Baseline to Week 24 weeks

Adjusted Mean Change in HbA1c from baseline to Week 24 using analysis of covariance model

Change in HbA1c Level From Baseline to Week 18 (LOCF)
Baseline to week 18

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.

Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4
Baseline, Week 4

Adjusted mean change from baseline in MWG achieved with saxagliptin 5 mg plus metformin XR versus placebo plus metformin XR at Week 24. MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed as average mg/dL. Glucose measurements were collected 30 minutes before and just prior to each meal (0 minutes) and 30, 60, 120, and 180 minutes after each meal (with 1 additional measurement at 240 minutes after the evening meal), midnight, 3 AM, and at end-of-domicile visit 24 hours after the first measurement. Mean change from baseline was adjusted for baseline value.

Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c)
Baseline , Week 24

Adjusted\* mean change from baseline in glycosylated haemoglobin A1c (HbA1c) achieved with saxagliptin 5 mg versus placebo at Week 24 (LOCF, Full Analysis set). HbA1c is a continuous measure, the change from baseline for each subject is calculated as the Week 24 values minus the baseline value. HbA1c data were excluded on and after rescue medication.

Mean Hemoglobin A1C (A1c) and Change From Baseline to Week 12
Baseline, Week 12

Mean change was adjusted for baseline.

Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])
Baseline to Week 24

Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use

Hemoglobin A1c (HbA1c) Change From Baseline to Week 18
Baseline, Week 18

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus sitagliptin added on to metformin at Week 18 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.

Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF)
Baseline , Week 12 (LOCF)

Adjusted\* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.

Insulin Secretion Rate Area Under the Curve (AUC) During Intravenous (IV)-Oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12
Baseline, Week 12

Adjusted percent change in the insulin secretion rate AUC during a hyperglycemic clamp with an enteral glucose load \[intravenous-oral hyperglycemic clamp (180-480 minutes)\] at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.

Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Baseline, Week 24

Mean change from baseline in A1C at Week 24, adjusted for baseline value.

Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Baseline, Week 24

Mean change from baseline is adjusted for baseline value.

Hemoglobin A1c (A1C) Changes From Baseline at Week 24
Baseline, Week 24

To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C ≥7.0% and ≤10.0%.

A1C Changes From Baseline at Week 24 - Open Label Cohort
Baseline, Week 24

To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C ≥7.0% and ≤10.0%.

Analysis of Test for Positive Efficacy Trend in Change From Baseline in Hemoglobin A1c (A1C) at Week 12 in the 0-40 mg Cohort
Baseline, Week 12

Positive efficacy trend among doses of saxagliptin by assessing the adjusted mean change from baseline in A1C in the 0-40 mg cohort. The unit of measurement for A1C is percent.

Change From Baseline in A1C at Week 12 in the 0-40 mg Cohort
Baseline, Week 12

Adjusted mean change from baseline in A1C achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

Area under plasma concentration-time curve from time zero to infinity (AUC)
Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)

To assess pharmacokinetics (PK) in terms of AUC in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.

Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)

To assess PK in terms of AUC0-t in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.

Maximum observed plasma concentration (Cmax)
Day 1 to Day 4 (At pre-dose and post-dose at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 hours)

To assess PK in terms of Cmax in Cohort 1 after administration of Treatment A, B (under fed condition), C (under fasted condition) and Cohort 2 after administration of Treatment D, E (under fed condition) and F (under fasted condition) in healthy volunteers.

Saxagliptin Maximum Observed Concentrations (Cmax)
Day 1-3 (Period 1) and Day 8-10 (Period 2)

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Dapagliflozin Maximum Observed Concentrations (Cmax)
Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2)

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
Day 1-3 (Period 1) and Day 8-10 (Period 2)

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])
Day 1-3 (Period 1) and Day 8-10 (Period 2)

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
Day 1-3 (Period 1) and Day 8-10 (Period 2)

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
Day 1-3 (Period 1) and Day 8-10 (Period 2)

5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

Maximum observed plasma concentration (Cmax) for Saxagliptin and Dapagliflozin
54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [(AUC(0-T)] for Saxagliptin and Dapagliflozin
54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days
Area under the concentration-time curve from time zero extrapolated to infinite time [(AUC(INF)] for Saxagliptin and Dapagliflozin
54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days
Maximum plasma concentration (Cmax) for saxagliptin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets
Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose
Maximum plasma concentration (Cmax) for metformin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets
Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose
Area under plasma concentration time curve (AUC) for saxagliptin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets
Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose
Area under plasma concentration time curve (AUC) for metformin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets
Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin From a Single Dose of Dapagliflozin Versus Cmax of Dapagliflozin From Co-administered Saxagliptin Plus Dapagliflozin - Pharmacokinetic Evaluable Population
Day 1 (0 h to 60 h post dose) in each period

The geometric mean of the maximum observed plasma concentration (Cmax) is presented below; serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h,and 60 h postdose, relative to dosing on Day 1 in each cross over period and these data are summarized in the Pharmacokinetic (PK) parameter of Cmax presented here. Plasma samples were analyzed for dapagliflozin by High Performance Liquid chromatography-Mass Spectrometry (HPLC-MS/MS) using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Dapagliflozin Cmax was derived from plasma concentration versus time data using a non-compartmental method, using a validated PK analysis program ™. Actual sampling times were used for PK calculations. Cmax was reported in ng/mL.

Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity [AUC(INF)] of Dapagliflozin From a Single Dose of Dapagliflozin Versus AUC (INF) of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population
Day 1 (0h to 60h post dose) in each period

AUC(INF) is area under the plasma concentration-time curve from time 0 extrapolated to infinity. Serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(INF) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus AUC(0-T) for Dapagliflozin When Co-administered With 5 mg Saxagliptin
Day 1 (0h to 60h post dose) in each period

AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method). Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(0-T) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

Maximum Observed Concentration (Cmax) of a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population
Day 1 (0h to 60h post dose) in each period

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). Cmax for Saxagliptin was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in nanograms per milliliter (ng/mL).

AUC(0-T) of Saxagliptin From Single Dose 5 mg Saxagliptin Versus AUC(0-T) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population
Day 1 (0h to 60h post dose) in each period

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(0-T), the area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

AUC(INF) of Saxagliptin From a Single Dose of 5 mg Saxagliptin Versus AUC(INF) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population
Day 1 (0h to 60h post dose) in each period

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(INF) was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

Maximum Observed Concentrations (Cmax) of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets
Days 1, 2, and 3 of Periods 1 and 2
AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T])of Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets
Days 1, 2, and 3 of Periods 1 and 2

AUC=Area under the concentration-time curve

AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) for Metformin, Saxagliptin, and 5-Hydroxy (5-OH) Saxagliptin as a Fixed-dose Combination (FDC) and as Individual Tablets
Days 1, 2, and 3 of Periods 1 and 2

AUC=Area Under the Concentration-time Curve

Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax)
Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.

Metformin PK Parameter AUC(0-inf)
Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.

Metformin PK Parameter Cmax
Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing

PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
Periods 1 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing.
Saxagliptin Observed Maximum Plasma Concentration (Cmax)
Periods 1 & 2: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 & 48 hrs post-dosing. Period 3: predosing on Days 2 & 3; predosing, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hrs postdosing on Day 4
Metformin AUC(0-inf)
Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
Metformin Cmax
Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.
Evidence of steady-state pharmacokinetics (PK) of 2.5 mg saxagliptin administered twice daily with meals to healthy subjects
Within the first 24 hours of dosing
Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

Cmax of single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max)
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

T-half and T-max for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg) or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Metformin Mean Cmax
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

Cmax of single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Metformin Mean AUC (0-T)
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

AUC (0-T for single-dose metformin (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Metformin Mean AUC(0-INF)
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

AUC (0-INF) for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Metformin T-half and T-max
Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr

T-half and T-max for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg), or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.

Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF])
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T])
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax)
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF)
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax)
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.

Metformin PK Parameter AUC(INF)
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

Metformin PK Parameter AUC(0-T)
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

Metformin PK Parameter T-HALF
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

Metformin PK Parameter Tmax
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period

Single-dose PK parameters of metformin were derived from plasma concentration versus time data.

Pharmacokinetic variables for saxagliptin after single and multiple oral doses of 5 mg saxagliptin
Multiple timepoints during 9 days

Secondary Endpoints

Mean Change From Baseline in Total Body Weight at Week 24
Baseline and Week 24
Percentage of Subjects With Confirmed Hypoglycaemia at Week 24
Baseline and Week 24
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 24
Baseline and Week 24
Unlock Study Endpoints

Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Saxagliptin/Dapagliflozin/MetforminEXPERIMENTALOral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin
Insulin Glargine, Lantos/MetforminACTIVE_COMPARATORInsulin glargine administered once a day with starting dose of 0.2 Unit per kg or 10 units.
Saxagliptin 5 mg + Metformin (500 mg with titration)EXPERIMENTALSaxagliptin 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
Saxagliptin 5 mg + PlaceboACTIVE_COMPARATORSaxagliptin 5 mg once daily and Placebo 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
Metformin (500 mg with titration) + PlaceboACTIVE_COMPARATORPlacebo 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
A1:Saxagliptin / Placebo + Dapagliflozin / PlaceboEXPERIMENTALSaxagliptin 5 mg and matching placebo 0 mg (once daily) plus Dapagliflozin 10 mg and matching placebo 0 mg (once daily)
A2: Sitagliptin / placeboEXPERIMENTALSitagliptin 100 mg and matching placebo 0 mg (once daily)
Saxagliptin 5mgEXPERIMENTALSaxagliptin 5mg, administered to subjects with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
PlaceboPLACEBO_COMPARATORPlacebo administered to subjects with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Arm 1: Saxagliptin+Metformin XR+PlaceboACTIVE_COMPARATOR -
Arm 2: Dapagliflozin+Metformin XR+PlaceboACTIVE_COMPARATOR -
Arm 3: Saxagliptin+Dapagliflozin+Metformin XREXPERIMENTAL -
Arm 1: Saxagliptin+Dapagliflozin+Metformin IREXPERIMENTAL -
Arm 2: Placebo+Dapagliflozin+Metformin IREXPERIMENTAL -
Arm 1: Saxagliptin +Metformin XR/IREXPERIMENTALSaxagliptin Tablet, 2.5 mg, or Saxagliptin Tablet, 5 mg, (based on subject's weight) Metformin XR/IR 1000 mg-2000 mg
Arm 2: Placebo +Metformin XR/IRPLACEBO_COMPARATORPlacebo matching saxagliptin 0 mg Metformin XR/IR 1000 mg - 2000 mg
SaxagliptinEXPERIMENTALSaxagliptin Tablet, 2.5 mg, or Saxagliptin Tablet, 5 mg, (based on subject's weight)
Saxagliptin 5 mg once dailyEXPERIMENTAL -
Placebo once dailyPLACEBO_COMPARATOR -
1EXPERIMENTALSaxagliptin
2ACTIVE_COMPARATORMetformin Extended Release
Saxagliptin + Metformin XR + matching Metformin XR placeboEXPERIMENTAL(Saxagliptin 5 mg plus Metformin XR 1500 plus matching Metformin XR 500 mg placebo)
Metformin XR + Metformin XR + matching Saxagliptin placeboACTIVE_COMPARATOR(Metformin XR 500 mg plus Metformin XR 1500 mg plus matching Saxagliptin 5 mg placebo)
Saxagliptin plus metformin IRACTIVE_COMPARATOR -
Placebo plus metformin IRPLACEBO_COMPARATOR -
Saxagliptin, 5 mg + insulinEXPERIMENTALSaxagliptin, 5 mg, plus insulin, administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Placebo + insulinPLACEBO_COMPARATORPlacebo administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Saxagliptin 5 mg + MetforminEXPERIMENTAL -
Placebo + MetforminPLACEBO_COMPARATOR -
SaxaEXPERIMENTALSaxagliptin
Saxagliptin (A)EXPERIMENTALMetformin 500-1500 mg (open-label, as needed for rescue in LT)
Placebo (ST) / Metformin (LT) (B)PLACEBO_COMPARATORMetformin 500-1500 mg (open-label, as needed for rescue in LT)
Saxagliptin plus open-label TZD (A)EXPERIMENTALSaxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)
Saxagliptin plus open-label TZD (B)EXPERIMENTALSaxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)
Placebo plus open-label TZD (C)PLACEBO_COMPARATORPlacebo PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)
Saxagliptin + Metformin (A)EXPERIMENTALPioglitazone 15-45 mg (as needed for rescue)
Saxagliptin + Metformin (B)EXPERIMENTALPioglitazone 15-45 mg (as needed for rescue)
Saxagliptin + Metformin (C)EXPERIMENTALPioglitazone 15-45 mg (as needed for rescue)
Placebo+ Metformin (D)PLACEBO_COMPARATORPioglitazone 15-45 mg (as needed for rescue)
Saxagliptin 2.5 mg (A)EXPERIMENTALMetformin 500-2000 mg (as needed for rescue)
Saxagliptin 5 mg (B)EXPERIMENTALMetformin 500-2000 mg (as needed for rescue)
Saxagliptin 10 mg (C)EXPERIMENTALMetformin 500-2000 mg (as needed for rescue)
Placebo (D)PLACEBO_COMPARATORMetformin 500-2000 mg (as needed for rescue)
Open-Label Treatment Cohort (Direct Enrollees) (E)EXPERIMENTALSaxagliptin 10 mg Metformin 500-2000 mg (as needed for rescue)
Saxagliptin (2.5 mg)EXPERIMENTAL -
Saxagliptin (5 mg)EXPERIMENTAL -
Saxagliptin (10 mg)EXPERIMENTAL -
Saxagliptin (20 mg)EXPERIMENTAL -
Saxagliptin (40 mg)EXPERIMENTAL -
Saxagliptin (100 mg)EXPERIMENTAL -
Cohort 1: Sequence 1 (ABC)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 1: Sequence 2 (ACB)EXPERIMENTALSubjects were randomized to treatment sequence 1 ACB: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 1: Sequence 3 (BAC)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 1: Sequence 4 (BCA)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 1: Sequence 5 (CAB)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 1: Sequence 6 (CBA)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. A= Reference product - 2.5mg ONGLYZA (2.5mg saxagliptin) and 5/1000mg XIGDUO XR (5 mg dapagliflozin / 1000mg Metformin XR) after food. B = Test product - Triple FCDP consisting of 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR after food. C = Test product - Triple FCDP tablet consisting of 2.5mg saxagliptin / 5mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 2: Sequence 1 (DEF)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 2: Sequence 2 (DFE)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 2: Sequence 3 (EDF)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 2: Sequence 4 (EFD)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food.
Cohort 2: Sequence 5 (FDE)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food.
COhort 2: Sequence 6 (FED)EXPERIMENTALSubjects were randomized to treatment sequence 1 ABC: On Day 1, each subjects will receive orally single-dose of the treatment assigned to that treatment period. D= Reference product - 5mg ONGLYZA (5mg saxagliptin) and 10/1000mg XIGDUO XR (10 mg dapagliflozin / 1000mg Metformin XR) after food. E = Test product - Triple FCDP consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR after food. F = Test product - Triple FCDP tablet consisting of 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR without food.
Treatment AEXPERIMENTALSingle oral dose of saxagliptin tablet coadministered with dapagliflozin tablet
Treatment BEXPERIMENTALSingle oral dose of FDC (fixed-dose combination) tablet
Treatment A: Saxagliptin 2.5mg+Dapagliflozin 5mg; FastingOTHERSaxagliptin 2.5 mg tablet and Dapagliflozin 5 mg tablet single dose orally on Day 1 in one of 3 periods
Treatment B: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; FastingOTHERSaxagliptin 2.5 mg/Dapagliflozin 5 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment C: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; FedOTHERSaxagliptin 2.5 mg/Dapagliflozin 5 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment D: Saxagliptin 5mg+Dapagliflozin 10mg; FastingOTHERSaxagliptin 5 mg tablet and Dapagliflozin 10 mg tablet single dose orally for on Day 1 in one of 3 periods
Treatment E: Saxagliptin 5mg/Dapagliflozin 10mg FDC; FastingOTHERSaxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment F: Saxagliptin 5mg/Dapagliflozin 10mg FDC; FedOTHERSaxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Lower doseEXPERIMENTALco-administration of a single oral dose of a 5 mg saxagliptin tablet and a 500 mg metformin XR (Glucophage XR®) tablet vs. single FDC tablet consisting of 5 mg saxagliptin and 500 mg metformin XR (Kombiglyze XR)
Higher doseEXPERIMENTALco-administration of a single oral dose of a 5 mg saxagliptin tablet and two (2) 500 mg metformin XR (Glucophage XR®) tablets vs. Single FDC tablet consisting of 5 mg saxagliptin and 1000 mg metformin XR (Kombiglyze XR)
A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin)EXPERIMENTALTreatment A: Saxagliptin 5mg, Tablet, Oral; Single dose Treatment B: Dapagliflozin 10mg, Tablet, Oral; single dose Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; single dose
A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-DapagliflozinEXPERIMENTALTreatment A: Saxagliptin 5mg, Tablet, Oral, single dose; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment B: Dapagliflozin 10mg, Tablet, Oral, single dose
B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin)EXPERIMENTALTreatment B: Dapagliflozin 10mg, Tablet, Oral, single dose. Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose
B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-SaxagliptinEXPERIMENTALTreatment B: Dapagliflozin 10mg, Tablet, Oral, single dose; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose
C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-DapagliflozinEXPERIMENTALTreatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose; Treatment B: Dapagliflozin 10mg, Tablet, Oral, single dose
C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-SaxagliptinEXPERIMENTALTreatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, single dose; Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, single dose; Treatment A: Saxagliptin 5mg, Tablet, Oral, single dose
Arm 1: Treatments A,B/B,AEXPERIMENTALPeriod 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg fixed-dose combination (FDC) in the fasted state (Treatment A), followed by a washout period of at least 7 days. Then, participants received single oral doses of saxagliptin, 5-mg, and metformin extended-release (XR), 500-mg, tablets together in the fasted state (Treatment B). Followed by a washout period of at least 4 days. Period 2: Participants received single oral doses of saxagliptin, 5-mg and metformin XR, 500-mg tablets together in the fasted state (Treatment B), followed by a washout period of at least 7 days. Then, participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg FDC, in the fasted state (Treatment A).
Arm 2: Treatments C,D/D,CEXPERIMENTALPeriod 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg fixed-dose combination (FDC), in the fed state (Treatment C), followed by a washout period of at least 7 days. Then, participants received a single oral dose of saxagliptin, 5-mg, and metformin extended-release (XR), 500-mg tablets together in the fed state (Treatment D). Followed by a washout period of at least 4 days. Period 2: Participants received a single oral dose of saxagliptin, 5-mg and metforminXR, 500-mg tablets together in the fed state (Treatment D), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 500 mg FDC, in the fed state (Treatment C).
Arm 3: Treatments E, F/F,EEXPERIMENTALPeriod 1: Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg fixed-dose combination (FDC), in the fasted state (Treatment E), followed by a washout period of at least 7 days. Participants received single oral doses of saxagliptin, 5-mg and metformin extended-release (XR), 1000-mg tablets together in the fasted state (Treatment F). Followed by a washout period of at least 4 days. Period 2: Participants received single oral doses of saxagliptin, 5- mg and metformin XR, 1000-mg tablets together in the fasted state (Treatment F), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg FDC, in the fasted state (Treatment E).
Arm 4: Treatments G,H/H,GEXPERIMENTALPeriod 1: Participants received a single oral dose of saxagliptin , 5 mg/metformin, 1000 mg fixed-dose combination (FDC), in the fed state (Treatment G), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5-mg and metformin extended-release (XR), 1000-mg tablets together in the fed state (Treatment H). Followed by a washout period of at least 4 days. Period 2: Participants received a single oral dose of saxagliptin, 5-mg and metformin XR, 1000-mg tablets together in the fed state (Treatment H), followed by a washout period of at least 7 days. Participants received a single oral dose of saxagliptin, 5 mg/metformin, 1000 mg FDC, in the fed state (Treatment G).
Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting)OTHERA single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fasted condition.
Arm B (saxagliptin 2.5 mg + metformin 850 mg FDC; Fasting)OTHERA single oral dose of 2.5-mg saxagliptin/850-mg metformin fixed dose combination (FDC) administered in the fasted condition.
Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)OTHERA single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fed condition.
Arm D (saxagliptin 2.5 mg + metformin 850 mg FDC; Fed)OTHERA single oral dose of 2.5-mg saxagliptin/850-mg metformin FDC administered in the fed condition.
5 mg saxagliptin + 2 Glucophage XR 500 mg tabletEXPERIMENTAL -
FDC tablet (5 mg saxa + 1000 mg metformin XR) (single dose)EXPERIMENTALunder fed state, single dose
FDC tablet (5 mg saxa + 1000 mg metformin XR) (4 days)EXPERIMENTALunder fed state, 4 days
5 mg saxagliptin + a single 500 mg metformin XR tabletEXPERIMENTAL -
FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)EXPERIMENTALunder fed state
FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting)EXPERIMENTALunder fasted state
S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)EXPERIMENTALParticipants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\])
S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)EXPERIMENTALParticipants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)
S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)EXPERIMENTALParticipants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)
S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)EXPERIMENTALParticipants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)
Arm AOTHERCo-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
Arm BOTHERSingle oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
Arm COTHERCo-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
Arm DOTHERSingle oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Interventions

NameTypeDescription
Saxagliptin, OnglyzaDRUGTablets, Oral, 5mg , Once daily, 24 weeks
Dapagliflozin, FarxigaDRUGTablets, Oral, 10mg , Once daily, 24 weeks
Glargine insulinDRUG100 Units/ml solution for injection in a prefilled SoloStar pen
MetforminDRUGTablets, Oral, ≥ 1500mg/≤ 2500mg, Once daily, 24 weeks
Saxagliptin 5 mgDRUGTablet, Oral, 5 mg, Once daily in the morning
Placebo 5 mg for SaxagliptinDRUGTablet, Oral, 5 mg, Once daily in the morning
Placebo 500 mg for metformin (with titration)DRUGTablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.
Metformin 500 mg with titrationDRUGTablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.
SaxagliptinDRUGadministered orally once daily
DapagliflozinDRUGadministered orally once daily
SitagliptinDRUGadministered orally once daily
Placebo matching with SaxagliptinDRUGadministered orally once daily
Placebo matching with DapagliflozinDRUGadministered orally once daily
Placebo matching with SitagliptinDRUGadministered orally once daily
Saxagliptin 5mgDRUGSaxagliptin 5mg (plus stable insulin dose), given orally once daily (24 weeks); subjects stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue).
Placebo for SaxagliptinDRUGPlacebo tablets (plus stable insulin dose), given orally once daily (24 weeks); subjects stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue).
Metformin XRDRUGTablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks
Metformin IRDRUGTablets, Oral, ≥ 1500mg, Twice daily, Up to 52 weeks
Placebo (Saxagliptin)DRUGTablets, Oral, Once daily, 1-16 weeks
Placebo (Metformin)DRUGTablets, Oral, Once daily, 1-16 weeks
Metformin (Active Rescue)DRUGTablets, Oral, 500 mg, Titrated as needed, 2-52 weeks
PlaceboDRUGtablet once daily for 24 weeks to be taken orally
Placebo matching Metformin XRDRUGTablets, Oral, 0 mg, once daily, 4 weeks
Placebo matching SaxagliptinDRUGTablets, Oral, 0 mg, once daily, 4 weeks
Saxagliptin plus metformin IRDRUGTablets, Oral, 2.5 mg, Twice daily, 12 weeks
Placebo plus metformin IRDRUGTablets, Oral, Placebo, Twice daily, 12 weeks
Saxagliptin, 5 mg + insulinDRUGSaxagliptin, 5-mg tablets (plus stable insulin dose), given orally once daily (24 weeks short-term, 28 weeks long-term); participants stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue)
Placebo + insulinDRUGPlacebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin
Metformin (blinded)DRUGTablet, Oral, 500 mg titrated to 1000 mg, Once daily (up to 104 weeks LT, starting at Week 12)
Metformin (open-label)DRUGTablets, Oral, 500-1500 mg, as needed (starting in LT)
pioglitazoneDRUGTablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT)
rosiglitazoneDRUGTablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT)
Saxagliptin + MetforminDRUGTablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
Placebo + MetforminDRUGTablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT)
Placebo matching MetforminDRUGTablets, Oral, 0 mg, daily (42 months LT)
2.5 mg Saxagliptin tabletDRUGA competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with Type 2 diabetes mellitus (T2DM).
5 mg dapagliflozin / 1000 mg metformin XR tabletDRUGDapagliflozin - An inhibitor of sodium-glucose co-transporter 2 (SGLT-2), reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Triple FCDP - 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XRDRUGSaxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM. Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
5 mg saxagliptinDRUGA competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM.
10 mg dapagliflozin / 1000 mg metformin XR tabletDRUGDapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XRDRUGSaxagliptin - A competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, slows the inactivation of the incretin hormones, thereby increases their bloodstream concentrations and reduces fasting and post-prandial glucose concentrations in a glucose-dependent manner in subjects with T2DM. Dapagliflozin - An inhibitor of SGLT-2, reduces re-absorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin - Lowers both basal and post-prandial plasma glucose by decreasing hepatic glucose production and intestinal absorption of glucose; improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Saxagliptin/Dapagliflozin FDCDRUG -
Metformin XR 500 mgDRUGMetformin XR oral tablet 500 mg, single dose
Mertformin XR 2 x 500 mgDRUGMetformin XR oral tablet 2 x 500 mg, single dose
Komboglyze XR 5/500 mgDRUGoral FDC tablet (saxagliptin 5 mg and metformin 500 mg), single dose
Komboglyze XR 5/1000 mgDRUGoral FDC tablet (saxagliptin 5 mg and metformin 1000 mg), single dose
Saxagliptin/metformin fixed-dose combination (FDC)DRUGTablet, oral, 5 mg/500 mg FDC, once on Day 1 only, 1 day
Metformin extended-release (XR)DRUGTablet, oral, 500 mg, once on Day 1 only, 1 day
Saxagliptin/Metformin FDCDRUGTablet, Oral, 5 mg/1000 mg FDC, once on Day 1 only, 1 day
saxagliptin + metformin (FDC tablet)DRUGTablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose
Glucophage XRDRUGTablets, Oral, 500 mg, once daily, Single dose
saxagliptin + metformin XR (FDC tablet)DRUGTablet, Oral, (saxagliptin 5 mg)(metformin XR 1000 mg), once daily, 4 days
Co-administration of Saxagliptin and Metformin IR, FastedDRUGParticipants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin, FastingDRUGParticipants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Co-administration of Saxagliptin and Metformin IR, FedDRUGParticipants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions
Saxagliptin/Metformin, FedDRUGParticipants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
Metformin IR (glucophage)DRUGTablets, Oral, 1000 mg, Once Daily, 1 week
Saxagliptin + Metformin IR (FDC)DRUGTablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week
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Eligibility Criteria

Age Range18 Years to 120 Years
SexALL
Healthy VolunteersNo
Study Sites40

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * At least 18 years of age at screening * HbA1c ≥ 8% and ≤ 12% at screening * Fasting plasma glucose (FPG) ≤ 270 mg/dL (15mmol/L) * Stable dose metformin ≥ 1500 mg per day with...

Countries:United StatesCzechiaDenmarkHungaryMexicoPolandRomaniaSouth AfricaSpainSwedenChinaCanadaPuerto RicoSouth KoreaRussiaBelgiumIndiaTaiwanUnited KingdomAustraliaThailandColombiaCosta RicaPeruArgentinaIsraelGermanyFranceItalyPhilippinesNorwayBelarusBulgariaCroatiaEstoniaLatviaLithuaniaUkraineBrazilChile
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Frequently asked questions about Saxagliptin

What is Saxagliptin used for?

Saxagliptin is used for the treatment of Type 2 Diabetes Mellitus (T2DM). It is being studied in patients with Type 2 Diabetes who are not controlled with diet and exercise, as an add-on to metformin, and in triple therapy regimens. It is an investigational small molecule in Phase 3 clinical development.

How does Saxagliptin work?

Saxagliptin is a small molecule that targets DPP-4 (dipeptidyl peptidase-4), an enzyme that degrades incretin hormones. By inhibiting DPP-4, Saxagliptin increases levels of active incretins, which help regulate blood glucose by enhancing insulin secretion and reducing glucagon release, thereby improving glycemic control in Type 2 Diabetes.

Who makes Saxagliptin?

Saxagliptin is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. AstraZeneca is conducting clinical trials to evaluate the safety and efficacy of Saxagliptin in patients with Type 2 Diabetes Mellitus.

What phase is Saxagliptin in?

Saxagliptin is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The Phase 3 trials are evaluating its use in Type 2 Diabetes, including as monotherapy, add-on to metformin, and in triple therapy combinations.

What clinical trials is Saxagliptin in?

Saxagliptin has been studied in several clinical trials, including NCT00374907 (a Phase 3 study in subjects with Type 2 Diabetes not controlled with diet and exercise), NCT00666458 (a Phase 3 add-on to metformin comparison with sitagliptin), and NCT01619059 (a Phase 3 triple therapy study). All trials are completed.

Is Saxagliptin the same as Onglyza?

Saxagliptin is also known as Onglyza. It is a DPP-4 inhibitor being developed by AstraZeneca for the treatment of Type 2 Diabetes Mellitus. The drug is currently in Phase 3 clinical trials and is not yet approved.