| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02681094 | A Multi-Center, Randomized, Double-Blind, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Saxagliptin or Dapagliflozin All Given as add-on Therapy to Metformin in Subject With Type 2 Diabetes | PHASE3 | COMPLETED | 905 | — | — | Feb 26, 2016 | Jul 15, 2017 | Oct 10, 2018 | 110 | United States, Canada +4 |
| NCT02413398 | A Study to Evaluate the Effect of Dapagliflozin on Blood Glucose Level and Renal Safety in Patients With Type 2 Diabetes | PHASE3 | COMPLETED | 321 | — | — | Jun 15, 2015 | Nov 7, 2017 | Oct 31, 2018 | 87 | United States, Bulgaria +6 |
| NCT01392677 | Evaluation of Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Background Combination of Metformin and Sulfonylurea | PHASE3 | COMPLETED | 311 | — | — | Oct 1, 2011 | Aug 1, 2013 | Mar 12, 2014 | 42 | Canada, Czechia +4 |
| NCT01042977 | Efficacy and Safety in Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease | PHASE3 | COMPLETED | 964 | — | — | Mar 1, 2010 | Dec 1, 2012 | Feb 17, 2014 | 135 | United States, Argentina +8 |
| NCT01031680 | Efficacy and Safety in Patients With Type 2 Diabetes Mellitus, Cardiovascular Disease and Hypertension | PHASE3 | COMPLETED | 922 | — | — | Feb 1, 2010 | Dec 1, 2012 | Oct 29, 2013 | 140 | United States, Argentina +7 |
| NCT00859898 | Study of Dapagliflozin in Combination With Metformin XR to Initiate the Treatment of Type 2 Diabetes | PHASE3 | COMPLETED | 1,093 | — | — | Apr 1, 2009 | May 1, 2010 | Jul 7, 2016 | 123 | United States, India +4 |
| NCT00855166 | Evaluation of the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type 2 Diabetes | PHASE3 | COMPLETED | 182 | — | — | Feb 1, 2009 | Dec 1, 2011 | Oct 14, 2013 | 21 | Bulgaria, Czechia +3 |
| NCT00736879 | Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes | PHASE3 | COMPLETED | 497 | — | — | Sep 22, 2008 | Dec 29, 2009 | Apr 20, 2017 | 62 | United States, Canada +5 |
| NCT00976495 | Effects of Dapagliflozin on Kidney Function (Glomerular Filtration Rate) in Subjects With Type 2 Diabetes | PHASE2 | COMPLETED | 154 | — | — | Oct 1, 2009 | Nov 1, 2010 | Mar 8, 2017 | 12 | United States, Canada +1 |
| NCT00972244 | Trial to Evaluate the Efficacy and Safety of Dapagliflozin in Japanese Type 2 Diabetes Mellitus Patients | PHASE2 | COMPLETED | 417 | — | — | Aug 1, 2009 | May 1, 2010 | Oct 14, 2013 | 20 | Japan |
| NCT00831779 | Effects of Dapagliflozin on Insulin Resistance and Insulin Secretion in Subjects With Type 2 Diabetes | PHASE2 | COMPLETED | 116 | — | — | Apr 1, 2009 | Aug 1, 2010 | Apr 24, 2017 | 3 | United States |
| NCT03138356 | Bioequivalence Study of Combination Tablets of Saxagliptin / Dapagliflozin / Metformin XR (Extended-release) and Dapagliflozin / Metformin XR Relative to Individual Components in Healthy Subjects | PHASE1 | COMPLETED | 126 | — | — | May 25, 2017 | Nov 28, 2017 | Dec 7, 2017 | 1 | United Kingdom |
| NCT01535677 | To Compare the Similarity of a Combination Dapagliflozin/Metformin Tablet With the Two Drugs Administered Separately | PHASE1 | COMPLETED | 71 | — | — | Apr 1, 2013 | Jul 1, 2013 | Jul 9, 2015 | 1 | United Kingdom |
| NCT01525238 | PK Study of Dapagliflozin in Pediatric Subjects With T2DM | PHASE1 | COMPLETED | 53 | — | — | Jul 1, 2012 | Sep 1, 2014 | May 30, 2017 | 17 | United States, Mexico |
| NCT01165268 | Characterization of the Kinetics of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus (T2DM) | PHASE1 | COMPLETED | 24 | — | — | Aug 1, 2010 | Dec 1, 2010 | Nov 17, 2016 | 1 | United States |
| NCT01055652 | Drug-drug Interaction Study of Dapagliflozin With Voglibose in Japanese Type 2 Diabetes Mellitus Patients | PHASE1 | COMPLETED | 28 | — | — | Jan 1, 2010 | Apr 1, 2010 | Oct 17, 2011 | 2 | Japan |
| NCT00908271 | Study of the Absolute Oral Bioavailability of Dapagliflozin in Healthy Subjects | PHASE1 | COMPLETED | 7 | — | — | Jul 1, 2009 | Aug 1, 2009 | Oct 17, 2016 | 1 | United States |
| NCT00904176 | Study of the Effect of Dapagliflozin on the Pharmacokinetics of Warfarin or Digoxin in Healthy Subjects | PHASE1 | COMPLETED | 30 | — | — | Jun 1, 2009 | Aug 1, 2009 | Oct 17, 2016 | 1 | United States |
| NCT00842556 | Pharmacokinetic Drug Interaction Study of Dapagliflozin and Glimepiride or Sitagliptin in Healthy Subjects | PHASE1 | COMPLETED | 18 | — | — | Mar 1, 2009 | May 1, 2009 | Oct 17, 2016 | 1 | United States |
| NCT00839683 | Pharmacokinetic Drug Interaction Study of Dapagliflozin and Valsartan or Simvastatin in Healthy Subjects | PHASE1 | COMPLETED | 24 | — | — | Feb 1, 2009 | Mar 1, 2009 | Oct 17, 2016 | 1 | United States |
To demonstrate the superiority of the change from baseline HbA1c achieved with the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually after 24 weeks. Results were presented for the modified full analysis set. Note: Baseline was defined as the last assessment on or prior to the date of the first dose of the study medication.
To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes, CKD stage 3A, and moderate renal impairment (CKD 3A; eGFR 45-59 mL/min/1.73m\^2). The "number analyzed" (142 dapaglifozin, 134 placebo) represents the number with change from baseline available at Week 24.
To compare the change from baseline in HbA1c to week 24 between dapagliflozin 10 mg in combination with metformin and sulfonylurea and placebo in combination with metformin and sulfonylurea.
To compare the glycemic efficacy of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease, measured as the mean change in HbA1c from baseline to week 24.
To compare the clinical benefit of dapagliflozin 10 mg versus placebo when added to usual care in type 2 diabetes patients with cardiovascular disease at week 24, measured as the proportion of responders for a 3-item endpoint of clinical benefit, defined as an absolute drop of 0.5% or more from baseline HbA1c, and a relative drop of 3% or more from baseline for total body weight, and an absolute drop of 3 mmHg or more from baseline in seated systolic blood pressure.
Adjusted mean change in HbA1c from baseline at Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, ie, last observation carried forward (LOCF) was determined. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, 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 during the Qualification and Lead-In Periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the Double-Blind Period.
To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.
Adjusted mean change in HbA1c from baseline at Week 24, or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available was determined(LOCF). HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication (metformin) was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment, lead-in, and at Day 1, Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.
Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 12 measurement was available, the last available post-baseline measurement obtained on or after Day 23 was used regardless of rescue medication. Measurements were obtained during radomization visit, and Week 12 in the double-blind period by a central laboratory.
Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.
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.
No statistical analysis will be performed
No statistical analysis will be performed
No statistical analysis will be performed
Maximum observed plasma concentration (Cmax) was measured by plasma concentration of Dapagliflozin over time. The geometric means are reported in nanograms per milliliter (ng/mL).
Time of maximum observed plasma concentration (Tmax) for Dapagliflozin was derived from plasma concentrations versus time data. Medians were reported in hours (h).
Area under the plasma concentration-time curve from time zero extrapolated to infinite time was derived from concentration versus time data. Geometric means are reported in nanogram hours per milliliter (ng\*hr/mL).
Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of Dapagliflozin over time. The geometric means are reported in nanogram hours per milliliter (ng\*h/mL).
Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentrations versus time data. Means are reported in hours.
Apparent clearance after extravascular administration (CL/F) of Dapagliflozin was derived from plasma concentrations versus time data. Geometric means are reported in milliliters per minute (mL/min).
Geometric mean of apparent volume of distribution at terminal phase after extravascular administration of Dapagliflozin was derived from plasma concentration versus time data. Geometric means are reported in Liters (L)
| Arm | Type | Description |
|---|---|---|
| Saxagliptin+Dapagliflozin+Metformin | ACTIVE_COMPARATOR | 5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin |
| Dapagliflozin+Saxagliptin placebo+Metformin | ACTIVE_COMPARATOR | 5 mg Tablets, Oral, Once daily, 24 weeks for Dapagliflozin and Saxagliptin Placebo |
| Saxagliptin+Dapagliflozin placebo+metformin | ACTIVE_COMPARATOR | 5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin placebo |
| Dapagliflozin | EXPERIMENTAL | 10 mg Tablets, Oral, Once daily, 24 weeks |
| Placebo | PLACEBO_COMPARATOR | Matching placebo to Dapagliflozin 10 mg tablet. Oral, Once daily, 24 weeks |
| Dapagliflozin 10 mg tablet | EXPERIMENTAL | - |
| matching placebo tablet | PLACEBO_COMPARATOR | - |
| 1 | EXPERIMENTAL | dapagliflozin 10 mg tablet |
| 2 | PLACEBO_COMPARATOR | matching placebo tablet |
| Dapagliflozin + Metformin XR | EXPERIMENTAL | Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks |
| Dapagliflozin + Placebo | EXPERIMENTAL | Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks. Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks. |
| Metformin XR + Placebo | ACTIVE_COMPARATOR | Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks |
| A | EXPERIMENTAL | Dapagliflozin 10 mg plus Metformin |
| B | PLACEBO_COMPARATOR | Placebo plus Metformin |
| Dapagliflozin 1 mg | EXPERIMENTAL | Dapagliflozin: 1 mg |
| Dapagliflozin 2.5 mg | EXPERIMENTAL | Dapagliflozin: 2.5 mg |
| Dapagliflozin 5 mg | EXPERIMENTAL | Dapagliflozin: 5 mg |
| Hydrochlorothiazide | ACTIVE_COMPARATOR | - |
| 3 | EXPERIMENTAL | 5mg dapagliflozin |
| 4 | EXPERIMENTAL | 10mg dapagliflozin |
| 5 | PLACEBO_COMPARATOR | Placebo |
| 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). |
| Dapagliflozin 10 mg | EXPERIMENTAL | - |
| Dapagliflozin (T2DM) | ACTIVE_COMPARATOR | - |
| Dapagliflozin (Healthy Subjects) | ACTIVE_COMPARATOR | - |
| Dapagliflozin + Warfarin | ACTIVE_COMPARATOR | - |
| Warfarin | ACTIVE_COMPARATOR | - |
| Dapagliflozin + Digoxin | ACTIVE_COMPARATOR | - |
| Digoxin | ACTIVE_COMPARATOR | - |
| Glimepiride | ACTIVE_COMPARATOR | - |
| Dapagliflozin + Glimepiride | ACTIVE_COMPARATOR | - |
| Sitagliptin | ACTIVE_COMPARATOR | - |
| Dapagliflozin + Sitagliptin | ACTIVE_COMPARATOR | - |
| simvastatin | ACTIVE_COMPARATOR | - |
| Dapagliflozin + simvastatin | ACTIVE_COMPARATOR | - |
| valsartan | ACTIVE_COMPARATOR | - |
| Dapagliflozin + valsartan | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Dapagliflozin | DRUG | 5mg, orally, Green, plain, diamond-shaped, film-coated tablet |
| Placebo for Dapagliflozin | DRUG | Does not contain active ingredient, orally, Green, plain, diamond-shaped, film-coated tablet |
| Saxagliptin | DRUG | 5mg, orally, Plain, yellow, biconvex, round, film-coated tablet |
| Placebo for Saxagliptin | DRUG | Does not contain active ingredient, orally, Plain, yellow, biconvex, round, film-coated tablet |
| Dapagliflozin 10 mg | DRUG | Tablets administered orally once daily for 24 weeks. Randomization will be stratified by pre-enrolment anti-hyperglycemic therapy |
| Matching Placebo for Dapagliflozin | DRUG | Matching Placebo for Dapagliflozin tablets administered orally once daily for 24 weeks |
| placebo | DRUG | matching placebo tablet, oral, once daily, 24- week treatment and 28- week extension period |
| Metformin XR | DRUG | Tablets, Oral, up to 2000 mg, once daily, 24 weeks |
| dapagliflozin matching Placebo | DRUG | Tablets |
| metformin HCl Modified Release matching Placebo | DRUG | Tablets |
| Metformin | DRUG | Tablet oral 1500 - 2500 mg total daily dose 1-3 times a day104 weeks |
| Sitagliptin | DRUG | Tablet oral 100 mg total daily dose once daily rescue medication |
| Hydrochlorothiazide | DRUG | Tablets, Oral, 25 mg, once daily, 12 weeks |
| 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. |
| Dapagliflozin + Glucophage tablet fasted | DRUG | Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state |
| Dapagliflozin/metformin IR FDC tablet fasted | DRUG | single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state |
| Dapagliflozin + Glucophage tablet fed | DRUG | Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state |
| Dapagliflozin/metformin IR FDC tablet fed | DRUG | single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state |
| Warfarin | DRUG | Tablets, Oral, 25 mg, Single Dose |
| Digoxin | DRUG | Tablets, Oral, 0.25, Single Dose |
| Glimepiride | DRUG | Tablets, Oral, 4 mg, Single Dose |
| simvastatin | DRUG | Tablets, Oral, 20 mg, Single Dose |
| valsartan | DRUG | Tablets, Oral, 320 mg, Single Dose |
Inclusion Criteria: 1. Patients aged ≥18 years old at time of informed consent; 2. Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C≥7.5% to ≤10.0% at screening visit; 3. Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg per day; 4. BMI ≤45.0kg/m2 at...