Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Saxagliptin, saxagliptin, Saxagliptin, insulin, Saxagliptin 5mg, Saxagliptin, Onglyza
Saxagliptin, Metformin · 44 trials · 6 indications
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.
To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.
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.
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.
Adjusted Mean Change in HbA1c from baseline to Week 24 using analysis of covariance model
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.
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.
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 change was adjusted for baseline.
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
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.
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.
Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 52 value minus the baseline value.
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.
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Mean change from baseline is adjusted for baseline value.
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%.
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%.
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.
Adjusted mean change from baseline in A1C achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.
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.
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.
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.
To measure the PK exposure for saxagliptin, 5-hydroxy saxagliptin (where applicable), dapagliflozin and metformin using plasma concentrations in subjects following IMP administration.
To measure the PK exposure for saxagliptin, 5-hydroxy saxagliptin (where applicable), dapagliflozin and metformin using plasma concentrations in subjects following IMP administration.
To measure the PK exposure for saxagliptin, 5-hydroxy saxagliptin (where applicable), dapagliflozin and metformin using plasma concentrations in subjects following IMP administration.
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state
Cmax=Maximum observed plasma concentration CI=Confidence interval FDC=Fixed dosed combination XR=Extended release
AUC(0-T)=Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
AUC(INF)=Area under the plasma concentration-time curve from time zero extrapolated to infinity
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.
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).
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).
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).
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).
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).
AUC=Area under the concentration-time curve
AUC=Area Under the Concentration-time Curve
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.
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.
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.
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.
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t \[calculated using the linear trapezoidal rule\] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t \[calculated using the linear trapezoidal rule\] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
| Arm | Type | Description |
|---|---|---|
| Saxagliptin/Dapagliflozin/Metformin | EXPERIMENTAL | Oral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin |
| Insulin Glargine, Lantos/Metformin | ACTIVE_COMPARATOR | Insulin glargine administered once a day with starting dose of 0.2 Unit per kg or 10 units. |
| Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo | EXPERIMENTAL | Saxagliptin 5 mg /dapagliflozin 10 mg Placebo once a day orally |
| Glimepiride or Placebo | EXPERIMENTAL | Glimepiride or placebo 1mg or 2mg or 3mg or 4mg or 6mg once a day orally |
| Saxagliptin 5 mg + Metformin (500 mg with titration) | EXPERIMENTAL | Saxagliptin 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed. |
| Saxagliptin 5 mg + Placebo | ACTIVE_COMPARATOR | Saxagliptin 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) + Placebo | ACTIVE_COMPARATOR | Placebo 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 / Placebo | EXPERIMENTAL | Saxagliptin 5 mg and matching placebo 0 mg (once daily) plus Dapagliflozin 10 mg and matching placebo 0 mg (once daily) |
| A2: Sitagliptin / placebo | EXPERIMENTAL | Sitagliptin 100 mg and matching placebo 0 mg (once daily) |
| Saxagliptin 5mg | EXPERIMENTAL | Saxagliptin 5mg, administered to subjects with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin |
| Placebo | PLACEBO_COMPARATOR | Placebo administered to subjects with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin |
| Arm 1: Saxagliptin+Metformin XR+Placebo | ACTIVE_COMPARATOR | - |
| Arm 2: Dapagliflozin+Metformin XR+Placebo | ACTIVE_COMPARATOR | - |
| Arm 3: Saxagliptin+Dapagliflozin+Metformin XR | EXPERIMENTAL | - |
| Arm 1: Saxagliptin+Dapagliflozin+Metformin IR | EXPERIMENTAL | - |
| Arm 2: Placebo+Dapagliflozin+Metformin IR | EXPERIMENTAL | - |
| Arm 1: Saxagliptin +Metformin XR/IR | EXPERIMENTAL | Saxagliptin 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/IR | PLACEBO_COMPARATOR | Placebo matching saxagliptin 0 mg Metformin XR/IR 1000 mg - 2000 mg |
| Saxagliptin | EXPERIMENTAL | Saxagliptin Tablet, 2.5 mg, or Saxagliptin Tablet, 5 mg, (based on subject's weight) |
| Saxagliptin 5 mg once daily | EXPERIMENTAL | - |
| Placebo once daily | PLACEBO_COMPARATOR | - |
| 1 | EXPERIMENTAL | Saxagliptin |
| 2 | ACTIVE_COMPARATOR | Metformin Extended Release |
| Saxagliptin + Metformin XR + matching Metformin XR placebo | EXPERIMENTAL | (Saxagliptin 5 mg plus Metformin XR 1500 plus matching Metformin XR 500 mg placebo) |
| Metformin XR + Metformin XR + matching Saxagliptin placebo | ACTIVE_COMPARATOR | (Metformin XR 500 mg plus Metformin XR 1500 mg plus matching Saxagliptin 5 mg placebo) |
| Saxagliptin plus metformin IR | ACTIVE_COMPARATOR | - |
| Placebo plus metformin IR | PLACEBO_COMPARATOR | - |
| Saxagliptin, 5 mg + insulin | EXPERIMENTAL | Saxagliptin, 5 mg, plus insulin, administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin |
| Placebo + insulin | PLACEBO_COMPARATOR | Placebo administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin |
| Saxagliptin 5 mg + Metformin | EXPERIMENTAL | - |
| Placebo + Metformin | PLACEBO_COMPARATOR | - |
| Saxa | EXPERIMENTAL | Saxagliptin |
| Glipizide | EXPERIMENTAL | - |
| Saxagliptin (A) | EXPERIMENTAL | Metformin 500-1500 mg (open-label, as needed for rescue in LT) |
| Placebo (ST) / Metformin (LT) (B) | PLACEBO_COMPARATOR | Metformin 500-1500 mg (open-label, as needed for rescue in LT) |
| Saxagliptin 2.5 mg QAM (A) | EXPERIMENTAL | PLUS open-label metformin (as needed as rescue medication) |
| Saxagliptin 2.5 mg titrated to 5 mg QAM (B) | EXPERIMENTAL | PLUS open-label metformin (as needed as rescue medication) |
| Saxagliptin 5 mg QAM (C) | EXPERIMENTAL | PLUS open-label metformin (as needed as rescue medication) |
| Saxagliptin 5 mg QPM (D) | EXPERIMENTAL | PLUS open-label metformin (as needed as rescue medication) |
| Placebo (E) | PLACEBO_COMPARATOR | PLUS open-label metformin (as needed as rescue medication) |
| Saxagliptin and Metformin (A) | EXPERIMENTAL | PLUS open-label pioglitazone (as needed as rescue medication) |
| Saxagliptin and Metformin (B) | EXPERIMENTAL | PLUS open-label pioglitazone (as needed as rescue medication) |
| Saxagliptin and Placebo (C) | EXPERIMENTAL | PLUS open-label pioglitazone (as needed as rescue medication) |
| Metformin and Placebo (D) | ACTIVE_COMPARATOR | PLUS open-label pioglitazone (as needed as rescue medication) |
| Saxagliptin 2.5 mg + Glyburide 7.5 mg (A) | EXPERIMENTAL | Metformin 500-2500 mg (as needed) |
| Saxagliptin 5 mg + Glyburide 7.5 mg (B) | EXPERIMENTAL | Metformin 500-2500 mg (as needed) |
| Placebo + Glyburide 7.5 mg (C) | PLACEBO_COMPARATOR | Metformin 500-2500 mg (as needed) |
| Saxagliptin plus open-label TZD (A) | EXPERIMENTAL | Saxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication) |
| Saxagliptin plus open-label TZD (B) | EXPERIMENTAL | Saxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication) |
| Placebo plus open-label TZD (C) | PLACEBO_COMPARATOR | Placebo PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication) |
| Saxagliptin + Metformin (A) | EXPERIMENTAL | Pioglitazone 15-45 mg (as needed for rescue) |
| Saxagliptin + Metformin (B) | EXPERIMENTAL | Pioglitazone 15-45 mg (as needed for rescue) |
| Saxagliptin + Metformin (C) | EXPERIMENTAL | Pioglitazone 15-45 mg (as needed for rescue) |
| Placebo+ Metformin (D) | PLACEBO_COMPARATOR | Pioglitazone 15-45 mg (as needed for rescue) |
| Saxagliptin 2.5 mg (A) | EXPERIMENTAL | Metformin 500-2000 mg (as needed for rescue) |
| Saxagliptin 5 mg (B) | EXPERIMENTAL | Metformin 500-2000 mg (as needed for rescue) |
| Saxagliptin 10 mg (C) | EXPERIMENTAL | Metformin 500-2000 mg (as needed for rescue) |
| Placebo (D) | PLACEBO_COMPARATOR | Metformin 500-2000 mg (as needed for rescue) |
| Open-Label Treatment Cohort (Direct Enrollees) (E) | EXPERIMENTAL | Saxagliptin 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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) | EXPERIMENTAL | Subjects 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 1 Treatment A | EXPERIMENTAL | Single-dose of saxagliptin (2.5 mg), dapagliflozin (5 mg), metformin (1000 mg) XR (Extended-release) FDC (Fixed-dose combination) tablet administered orally under fasted condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (ABC), (ACB), (BAC), (BCA), (CAB) or (CBA). |
| Cohort 1 Treatment B | EXPERIMENTAL | Single-dose of saxagliptin (2.5 mg), dapagliflozin (5 mg), metformin (850 mg) XR FDC tablet, administered orally under fasted condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (ABC), (ACB), (BAC), (BCA), (CAB) or (CBA). |
| Cohort 1 Treatment C (Reference product) | ACTIVE_COMPARATOR | Single-dose of Onglyza® (2.5 mg saxagliptin), Forxiga® (5 mg dapagliflozin) and Glucophage XR® (2 x 500 mg metformin XR) co-administered under fasted condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (ABC), (ACB), (BAC), (BCA), (CAB) or (CBA). |
| Cohort 2 Treatment D | EXPERIMENTAL | Single-dose of saxagliptin (2.5 mg), dapagliflozin (5 mg), metformin (1000 mg) XR FDC tablet administered orally under fed condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state The treatment sequences are (DEF), (DFE), (EDF), (EFD), (FDE) or (FED). |
| Cohort 2 Treatment E | EXPERIMENTAL | Single-dose of saxagliptin (2.5 mg), dapagliflozin (5 mg), metformin (850 mg) XR FDC tablet, administered orally under fed condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (DEF), (DFE), (EDF), (EFD), (FDE) or (FED). |
| Cohort 2 Treatment F (Reference Product) | ACTIVE_COMPARATOR | Single-dose of Onglyza® (2.5 mg saxagliptin), Forxiga® (5 mg dapagliflozin) and Glucophage XR® (2 x 500 mg metformin) co-administered under fed condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (DEF), (DFE), (EDF), (EFD), (FDE) or (FED). |
| Cohort 3 Treatment G | EXPERIMENTAL | Single-dose dapagliflozin (5 mg) / metformin (1000 mg) XR FDC tablet administered orally under fed condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (GHI), (GIH), (HGI), (HIG), (IHG) or (IGH). |
| Cohort 3 Treatment H | EXPERIMENTAL | Single-dose dapagliflozin (5 mg) / metformin (850 mg) XR FDC tablet administered orally under fed condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (GHI), (GIH), (HGI), (HIG), (IHG) or (IGH). |
| Cohort 3 Treatment I (Reference Product) | ACTIVE_COMPARATOR | Single-dose Forxiga® (5 mg dapagliflozin) and Glucophage XR® (2 x 500 mg metformin) co-administered under fed condition. Within each cohort, subjects will be randomized to 1 of 6 treatment sequences, each subject will receive 3 single-dose treatments in either a fasted or fed-state. The treatment sequences are (GHI), (GIH), (HGI), (HIG), (IHG) or (IGH). |
| Treatment A | EXPERIMENTAL | Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet |
| Treatment B | EXPERIMENTAL | Single oral dose of FDC (fixed-dose combination) tablet |
| Treatment A: Saxagliptin 2.5mg+Dapagliflozin 5mg; Fasting | OTHER | Saxagliptin 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; Fasting | OTHER | Saxagliptin 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; Fed | OTHER | Saxagliptin 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; Fasting | OTHER | Saxagliptin 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; Fasting | OTHER | Saxagliptin 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; Fed | OTHER | Saxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods |
| Arm A: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao) | EXPERIMENTAL | Saxagliptin 5 mg /Metformin 1000 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day 1 of Periods 1 and 2 |
| Arm B: Saxagliptin/Metformin XR FDC (Mt. Vernon) | EXPERIMENTAL | Saxagliptin 5 mg/Metformin 1000 mg (Mt. Vernon) tablet by mouth once daily on Day 1 of Periods 1 and 2 |
| Arm C: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao) | EXPERIMENTAL | Saxagliptin 5 mg/Metformin 500 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day1 of Periods 1 and 2 |
| Arm D: Saxagliptin/Metformin XR FDC (Mt. Vernon) | EXPERIMENTAL | Saxagliptin 5 mg/Metformin 500 mg (Mt. Vernon) tablet by mouth once daily Day 1 of Periods 1 and 2 |
| Lower dose | EXPERIMENTAL | co-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 dose | EXPERIMENTAL | co-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) | EXPERIMENTAL | Treatment 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)-Dapagliflozin | EXPERIMENTAL | Treatment 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) | EXPERIMENTAL | Treatment 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)-Saxagliptin | EXPERIMENTAL | Treatment 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-Dapagliflozin | EXPERIMENTAL | Treatment 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-Saxagliptin | EXPERIMENTAL | Treatment 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,A | EXPERIMENTAL | Period 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,C | EXPERIMENTAL | Period 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,E | EXPERIMENTAL | Period 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,G | EXPERIMENTAL | Period 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). |
| Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state) | OTHER | Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fasted state |
| Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fasted state) | OTHER | Single oral dose of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet administered in the fasted state |
| Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state) | OTHER | Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fed state |
| Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fed state) | OTHER | Single oral dose of saxagliptin, 2.5 mg/metformin, 500 mg, FDC tablet administered in the fed state |
| Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting) | OTHER | A 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) | OTHER | A 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) | OTHER | A 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) | OTHER | A single oral dose of 2.5-mg saxagliptin/850-mg metformin FDC administered in the fed condition. |
| 5 mg saxagliptin + a single 500 mg metformin XR tablet | EXPERIMENTAL | - |
| FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed) | EXPERIMENTAL | under fed state |
| FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting) | EXPERIMENTAL | under fasted state |
| 5 mg saxagliptin + 2 Glucophage XR 500 mg tablet | EXPERIMENTAL | - |
| FDC tablet (5 mg saxa + 1000 mg metformin XR) (single dose) | EXPERIMENTAL | under fed state, single dose |
| FDC tablet (5 mg saxa + 1000 mg metformin XR) (4 days) | EXPERIMENTAL | under fed state, 4 days |
| Arm A | OTHER | Co-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 B | OTHER | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions |
| Arm C | OTHER | Co-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 D | OTHER | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal |
| Name | Type | Description |
|---|---|---|
| Saxagliptin, Onglyza | DRUG | Tablets, Oral, 5mg , Once daily, 24 weeks |
| Dapagliflozin, Farxiga | DRUG | Tablets, Oral, 10mg , Once daily, 24 weeks |
| Glargine insulin | DRUG | 100 Units/ml solution for injection in a prefilled SoloStar pen |
| Metformin | DRUG | Tablets, Oral, ≥ 1500mg/≤ 2500mg, Once daily, 24 weeks |
| Saxagliptin | DRUG | - |
| Dapagliflozin | DRUG | - |
| Glimepiride | DRUG | - |
| Placebo | OTHER | - |
| Saxagliptin 5 mg | DRUG | Tablet, Oral, 5 mg, Once daily in the morning |
| Placebo 5 mg for Saxagliptin | DRUG | Tablet, Oral, 5 mg, Once daily in the morning |
| Placebo 500 mg for metformin (with titration) | DRUG | Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration. |
| Metformin 500 mg with titration | DRUG | Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration. |
| Sitagliptin | DRUG | administered orally once daily |
| Placebo matching with Saxagliptin | DRUG | administered orally once daily |
| Placebo matching with Dapagliflozin | DRUG | administered orally once daily |
| Placebo matching with Sitagliptin | DRUG | administered orally once daily |
| Saxagliptin 5mg | DRUG | Saxagliptin 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 Saxagliptin | DRUG | Placebo 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 XR | DRUG | Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks |
| Metformin IR | DRUG | Tablets, Oral, ≥ 1500mg, Twice daily, Up to 52 weeks |
| Placebo (Saxagliptin) | DRUG | Tablets, Oral, Once daily, 1-16 weeks |
| Placebo (Metformin) | DRUG | Tablets, Oral, Once daily, 1-16 weeks |
| Metformin (Active Rescue) | DRUG | Tablets, Oral, 500 mg, Titrated as needed, 2-52 weeks |
| Placebo matching Metformin XR | DRUG | Tablets, Oral, 0 mg, once daily, 4 weeks |
| Placebo matching Saxagliptin | DRUG | Tablets, Oral, 0 mg, once daily, 4 weeks |
| Saxagliptin plus metformin IR | DRUG | Tablets, Oral, 2.5 mg, Twice daily, 12 weeks |
| Placebo plus metformin IR | DRUG | Tablets, Oral, Placebo, Twice daily, 12 weeks |
| Saxagliptin, 5 mg + insulin | DRUG | Saxagliptin, 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 + insulin | DRUG | Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin |
| Sulphonylurea | DRUG | Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks) |
| Metformin (blinded) | DRUG | Tablet, Oral, 500 mg titrated to 1000 mg, Once daily (up to 104 weeks LT, starting at Week 12) |
| Metformin (open-label) | DRUG | Tablets, Oral, 500-1500 mg, as needed (starting in LT) |
| pioglitazone | DRUG | Tablets, Oral, 15-45 mg, as needed (12 months LT) |
| Glyburide | DRUG | Capsules, Oral, OL, 7.5 mg, Daily, AM (24 weeks ST, 12 months LT) |
| rosiglitazone | DRUG | Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT) |
| Saxagliptin + Metformin | DRUG | Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT) |
| Placebo + Metformin | DRUG | Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT) |
| Placebo matching Metformin | DRUG | Tablets, Oral, 0 mg, daily (42 months LT) |
| 2.5 mg Saxagliptin tablet | DRUG | 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 Type 2 diabetes mellitus (T2DM). |
| 5 mg dapagliflozin / 1000 mg metformin XR tablet | DRUG | Dapagliflozin - 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 XR | DRUG | Saxagliptin - 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 saxagliptin | DRUG | 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. |
| 10 mg dapagliflozin / 1000 mg metformin XR tablet | DRUG | 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. |
| Triple FCDP - 5 mg saxagliptin / 10 mg dapagliflozin / 1000 mg metformin XR | DRUG | Saxagliptin - 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. |
| 2.5 mg saxagliptin / 5 mg dapagliflozin / 850 mg metformin XR FDC tablet | DRUG | Used in Treatment B and Treatment E. |
| 2.5 mg saxagliptin / 5 mg dapagliflozin / 1000 mg metformin XR FDC tablet | DRUG | Used in Treatment A and Treatment D. |
| 5 mg dapagliflozin / 850 mg metformin XR FDC | DRUG | Used in Treatment H. |
| 5 mg dapagliflozin / 1000 mg metformin XR FDC | DRUG | Used in Treatment G. |
| 2.5 mg ONGLYZA® (saxagliptin) tablet | DRUG | Used in treatments C and F. |
| 5 mg Forxiga® (dapagliflozin) tablet | DRUG | Used in treatments C, F and I. |
| 500 mg Glucophage XR® | DRUG | Used in treatments C, F and I. |
| Saxagliptin/Dapagliflozin FDC | DRUG | - |
| Saxagliptin/Metformin | DRUG | - |
| Metformin XR 500 mg | DRUG | Metformin XR oral tablet 500 mg, single dose |
| Mertformin XR 2 x 500 mg | DRUG | Metformin XR oral tablet 2 x 500 mg, single dose |
| Komboglyze XR 5/500 mg | DRUG | oral FDC tablet (saxagliptin 5 mg and metformin 500 mg), single dose |
| Komboglyze XR 5/1000 mg | DRUG | oral FDC tablet (saxagliptin 5 mg and metformin 1000 mg), single dose |
| Saxagliptin/metformin fixed-dose combination (FDC) | DRUG | Tablet, oral, 5 mg/500 mg FDC, once on Day 1 only, 1 day |
| Metformin extended-release (XR) | DRUG | Tablet, oral, 500 mg, once on Day 1 only, 1 day |
| Saxagliptin/Metformin FDC | DRUG | Tablet, Oral, 5 mg/1000 mg FDC, once on Day 1 only, 1 day |
| Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state) | DRUG | Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week |
| Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state) | DRUG | Tablets, oral, 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC), once daily, 1 week |
| Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state) | DRUG | Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week |
| Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state) | DRUG | Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin FDC, once daily, 1 week |
| saxagliptin + metformin (FDC tablet) | DRUG | Tablet, oral, (saxagliptin 2.5 mg) (metformin 850 mg), once daily, single dose |
| saxagliptin + metformin XR (FDC tablet) | DRUG | Tablet, Oral, (saxagliptin 5 mg)(metformin XR 500 mg), once daily, Single dose |
| Glucophage XR | DRUG | Tablets, Oral, 500 mg, once daily, Single dose |
| Metformin IR (glucophage) | DRUG | Tablets, Oral, 1000 mg, Once Daily, 1 week |
| Saxagliptin + Metformin IR (FDC) | DRUG | Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week |
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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| FibroBiologics, Inc. | FBLG | 1 | PHASE1 | Undisclosed |
| MiMedx Group, Inc. | MDXG | 2 | N/A | Undisclosed |
| Integra LifeSciences Holdings Corporation | IART | 1 | N/A | Undisclosed |
| Organogenesis Holdings, Inc. Class A | ORGO | 1 | N/A | Undisclosed |
| Healthcare Services Group, Inc. | HCSG | 1 | N/A | Undisclosed |
Saxagliptin is an investigational small molecule in Phase 3 clinical development for the treatment of Type 2 Diabetes Mellitus. It is being studied in patients whose blood sugar is not adequately controlled with diet and exercise, as well as in combination with other diabetes therapies such as metformin.
Saxagliptin is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The company is conducting clinical trials to evaluate the safety and efficacy of this drug in patients with Type 2 Diabetes Mellitus.
Saxagliptin is in Phase 3 clinical development. It is an investigational drug and has not yet been approved by regulatory authorities. The Phase 3 trials are designed to assess its efficacy and safety in treating Type 2 Diabetes Mellitus, including studies where it is added to metformin therapy.
Saxagliptin has been studied in several clinical trials, including NCT00374907, a Phase 3 study in patients with Type 2 Diabetes not controlled with diet and exercise, and NCT00666458, an 18-week add-on to metformin study comparing Saxagliptin to sitagliptin. NCT01619059 is a Phase 3 trial evaluating Saxagliptin in triple therapy.
Saxagliptin is a small molecule that targets dipeptidyl peptidase-4 (DPP-4), an enzyme involved in glucose metabolism. By inhibiting DPP-4, Saxagliptin helps to increase the levels of incretin hormones, which stimulate insulin release and lower blood sugar levels in patients with Type 2 Diabetes Mellitus.