Trial Outcomes & Findings for Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes (NCT NCT01606007)
NCT ID: NCT01606007
Last Updated: 2017-05-15
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1282 participants
Primary outcome timeframe
Baseline (Week 0) and at Week 24
Results posted on
2017-05-15
Participant Flow
Of 1282 participants enrolled subjects, 534 eligible subjects entered the randomized, double-blind treatment period. Of 534 randomized and treated subjects, 490 subjects completed the study.
Participant milestones
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Overall Study
STARTED
|
176
|
179
|
179
|
|
Overall Study
COMPLETED
|
161
|
160
|
169
|
|
Overall Study
NOT COMPLETED
|
15
|
19
|
10
|
Reasons for withdrawal
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Overall Study
Reason 'Other' in the protocol
|
0
|
1
|
1
|
|
Overall Study
Pregnancy
|
0
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
6
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
1
|
|
Overall Study
discontinue study treatment
|
0
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
6
|
8
|
5
|
|
Overall Study
Poor/Non-compliance
|
1
|
0
|
0
|
Baseline Characteristics
Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
n=176 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
n=179 Participants
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
n=179 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
Total
n=534 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.6 Years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
53.5 Years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
53.4 Years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
53.8 Years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
|
Age, Customized
<65 years
|
148 participants
n=5 Participants
|
158 participants
n=7 Participants
|
160 participants
n=5 Participants
|
466 participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
28 participants
n=5 Participants
|
21 participants
n=7 Participants
|
19 participants
n=5 Participants
|
68 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
82 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
266 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
94 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
268 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
121 participants
n=5 Participants
|
131 participants
n=7 Participants
|
120 participants
n=5 Participants
|
372 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black african/american
|
22 participants
n=5 Participants
|
16 participants
n=7 Participants
|
22 participants
n=5 Participants
|
60 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
12 participants
n=5 Participants
|
33 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
22 participants
n=5 Participants
|
22 participants
n=7 Participants
|
25 participants
n=5 Participants
|
69 participants
n=4 Participants
|
|
Body Mass Index (BMI)
|
31.8 kg/m^2
STANDARD_DEVIATION 5.142 • n=5 Participants
|
31.46 kg/m^2
STANDARD_DEVIATION 5.321 • n=7 Participants
|
31.76 kg/m^2
STANDARD_DEVIATION 4.787 • n=5 Participants
|
31.67 kg/m^2
STANDARD_DEVIATION 5.080 • n=4 Participants
|
|
T2DM duration
|
8.2 years
STANDARD_DEVIATION 5.52 • n=5 Participants
|
7.4 years
STANDARD_DEVIATION 5.40 • n=7 Participants
|
7.1 years
STANDARD_DEVIATION 5.04 • n=5 Participants
|
7.6 years
STANDARD_DEVIATION 5.33 • n=4 Participants
|
|
HbA1c
|
9.03 %
STANDARD_DEVIATION 1.05 • n=5 Participants
|
8.87 %
STANDARD_DEVIATION 1.16 • n=7 Participants
|
8.92 %
STANDARD_DEVIATION 1.18 • n=5 Participants
|
8.94 %
STANDARD_DEVIATION 1.13 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 0) and at Week 24Population: All randomized participants who received study medication and had nonmissing HbA1c values at baseline and 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.
Outcome measures
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
n=143 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
n=151 Participants
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
n=158 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24
|
-0.88 % HbA1c
Interval -1.03 to -0.72
|
-1.20 % HbA1c
Interval -1.35 to -1.04
|
-1.47 % HbA1c
Interval -1.62 to -1.31
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and at Week 24Population: All randomized participants who received study medication and had nonmissing PPG values at baseline and Week 24 (LOCF)
Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at week 24 in the doubleblind period, including observations prior to rescue.
Outcome measures
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
n=147 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
n=144 Participants
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
n=154 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24 (Last Observation Carried Forward [LOCF])
|
-35.6 MG/DL PPG
95% Confidence Interval 3.510 • Interval -42.5 to -28.7
|
-70.4 MG/DL PPG
95% Confidence Interval 3.538 • Interval -77.4 to -63.5
|
-79.6 MG/DL PPG
95% Confidence Interval 3.426 • Interval -86.3 to -72.8
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and at Week 24Population: All randomized participants who received study medication and had nonmissing PPG values at baseline and Week 24
Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue.
Outcome measures
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
n=142 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
n=148 Participants
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
n=155 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
|
-14.0 mg/dL
Interval -19.6 to -8.4
|
-31.7 mg/dL
Interval -37.3 to -26.2
|
-37.8 mg/dL
Interval -43.2 to -32.3
|
SECONDARY outcome
Timeframe: At Week 24Population: All randomized participants who received study medication and were not missing baseline and Week 24 (LOCF) values
Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.
Outcome measures
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
n=175 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
n=173 Participants
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
n=177 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
|
18.3 % of Participants
Interval 13.0 to 23.5
|
22.2 % of Participants
Interval 16.1 to 28.3
|
41.4 % of Participants
Interval 34.5 to 48.2
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and at Week 24Population: All randomized participants who received study medication and had nonmissing body weight values at baseline and Week 24
Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained at Week 24 in the doubleblind period, including observations prior to rescue.
Outcome measures
| Measure |
Arm 1: Saxagliptin+Metformin XR+Placebo
n=145 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 2: Dapagliflozin+Metformin XR+Placebo
n=152 Participants
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
Arm 3: Saxagliptin+Dapagliflozin+Metformin XR
n=159 Participants
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Body Weight at Week 24
|
0.00 Body weight Kg
Interval -0.48 to 0.49
|
-2.39 Body weight Kg
Interval -2.87 to -1.91
|
-2.05 Body weight Kg
Interval -2.52 to -1.58
|
Adverse Events
SAXA + MET
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
DAPA + MET
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
SAXA + DAPA + MET
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SAXA + MET
n=176 participants at risk
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Placebo matching with Dapagliflozin Tablets, Oral, 0mg, Once daily, 24 weeks
|
DAPA + MET
n=179 participants at risk
Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148 Drug: Placebo matching with Saxagliptin Tablets, Oral, 0mg, Once daily, 24 weeks
|
SAXA + DAPA + MET
n=179 participants at risk
Drug: Saxagliptin Tablets, Oral, 5mg , Once daily, 24 weeks Other Names: Onglyza Drug: Metformin XR Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks Other Names: Glucophage XR Drug: Dapagliflozin Tablets, Oral, 10mg , Once daily, 24 weeks Other Names: BMS512148
|
|---|---|---|---|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.00%
0/176 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.56%
1/179 • Number of events 1 • 24 weeks
|
|
Gastrointestinal disorders
PANCREATITIS CHRONIC
|
0.00%
0/176 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.56%
1/179 • Number of events 1 • 24 weeks
|
|
Gastrointestinal disorders
UMBILICAL HERNIA
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
General disorders
CHEST PAIN
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Infections and infestations
TOOTH INFECTION
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Injury, poisoning and procedural complications
PATELLA FRACTURE
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
GASTRIC NEOPLASM
|
0.00%
0/176 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.56%
1/179 • Number of events 1 • 24 weeks
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.00%
0/176 • 24 weeks
|
0.56%
1/179 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA
|
0.00%
0/176 • 24 weeks
|
0.56%
1/179 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
0.57%
1/176 • Number of events 1 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
0.00%
0/179 • 24 weeks
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60