Trial Outcomes & Findings for Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes (NCT NCT01646320)
NCT ID: NCT01646320
Last Updated: 2016-06-22
Results Overview
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 6, 12, 18, and 24 in the double-blind period.
COMPLETED
PHASE3
320 participants
From Baseline to Week 24
2016-06-22
Participant Flow
Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial with Dapagliflozin added to Saxagliptin in Combination with Metformin compared to placebo added to Saxagliptin in combination with Metformin in Subjects with Type 2 Diabetes who have Inadequate Glycemic Control on Metformin and Saxagliptin
Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IR Arm 2: Placebo + Saxagliptin + Metformin IR
Participant milestones
| Measure |
Dapa+Saxa+Met
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Short-term Period (Day 1 to Week 24)
STARTED
|
160
|
160
|
|
Short-term Period (Day 1 to Week 24)
COMPLETED
|
148
|
153
|
|
Short-term Period (Day 1 to Week 24)
NOT COMPLETED
|
12
|
7
|
|
Long-term Period (Weeks 24 to 52)
STARTED
|
147
|
147
|
|
Long-term Period (Weeks 24 to 52)
COMPLETED
|
141
|
140
|
|
Long-term Period (Weeks 24 to 52)
NOT COMPLETED
|
6
|
7
|
Reasons for withdrawal
| Measure |
Dapa+Saxa+Met
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Short-term Period (Day 1 to Week 24)
Adverse Event
|
3
|
0
|
|
Short-term Period (Day 1 to Week 24)
No longer meets study criteria
|
0
|
1
|
|
Short-term Period (Day 1 to Week 24)
Not reported
|
2
|
2
|
|
Short-term Period (Day 1 to Week 24)
Other
|
1
|
0
|
|
Short-term Period (Day 1 to Week 24)
Lost to Follow-up
|
4
|
4
|
|
Short-term Period (Day 1 to Week 24)
Withdrawal by Subject
|
2
|
0
|
|
Long-term Period (Weeks 24 to 52)
Subject no longer meets study criteria
|
2
|
0
|
|
Long-term Period (Weeks 24 to 52)
Withdrawal by Subject
|
0
|
2
|
|
Long-term Period (Weeks 24 to 52)
Adverse Event
|
4
|
2
|
|
Long-term Period (Weeks 24 to 52)
Lack of Efficacy
|
0
|
1
|
|
Long-term Period (Weeks 24 to 52)
Lost to Follow-up
|
0
|
2
|
Baseline Characteristics
Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Dapa+Saxa+Met
n=160 Participants
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
n=160 Participants
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Total
n=320 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.2 YEARS
STANDARD_DEVIATION 8.61 • n=5 Participants
|
55.0 YEARS
STANDARD_DEVIATION 9.60 • n=7 Participants
|
55.1 YEARS
STANDARD_DEVIATION 9.10 • n=5 Participants
|
|
Age, Customized
< 65 years
|
137 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
269 Participants
n=5 Participants
|
|
Age, Customized
>= 65 years
|
23 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
90 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
174 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
70 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
146 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
ASIAN
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
BLACK/AFRICAN AMERICAN
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
OTHER
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
WHITE
|
150 Participants
n=5 Participants
|
147 Participants
n=7 Participants
|
297 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
AMERICAN INDIAN/ALASKA NATIVE
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
NATIVE HAWAIIAN/OTHER PACIFIC ISLANDER
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline to Week 24Population: The Randomized Subjects Data Set consists of all randomized subjects who received at least one dose of double-blind study medication during the double-blind treatment period.
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 6, 12, 18, and 24 in the double-blind period.
Outcome measures
| Measure |
Dapa+Saxa+Met
n=158 Participants
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
n=158 Participants
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24
|
-0.82 Percentage of glycosylated hemoglobin
Standard Error 0.0686
|
-0.1 Percentage of glycosylated hemoglobin
Standard Error 0.0704
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: The Randomized Subjects Data Set consists of all randomized subjects who received at least one dose of double-blind study medication during the double-blind treatment period. Number of participants analyzed corresponds to the number of randomized subjects with non-missing baseline value and at least one post-baseline value.
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. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 6, 12, 18, and 24 in the double-blind period
Outcome measures
| Measure |
Dapa+Saxa+Met
n=158 Participants
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
n=157 Participants
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24
|
-32.7 mg/dL
Standard Error 2.821
|
-5.3 mg/dL
Standard Error 2.968
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: The Randomized Subjects Data Set consists of all randomized subjects who received at least one dose of double-blind study medication during the double-blind treatment period. Number of participants analyzed is the number of randomized subjects with non-missing baseline and Week 24 (LOCF) values.
2-hour postprandial glucose (PPG) from a liquid meal tolerance test (2-h MTT) Subject must be fasted for at least 8 hrs prior to the MTT.
Outcome measures
| Measure |
Dapa+Saxa+Met
n=134 Participants
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
n=132 Participants
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in 120-minute Postprandial Glucose (PPG) at Week 24
|
-73.5 mg/dL
Standard Error 4.055
|
-38.0 mg/dL
Standard Error 4.104
|
SECONDARY outcome
Timeframe: From baseline to Week 24Population: The Randomized Subjects Data Set consists of all randomized subjects who received at least one dose of double-blind study medication during the double-blind treatment period
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. Body weights were measured during the qualification and lead-in periods and on Day 1 and Weeks 6, 12, 18, and 24 in the double-blind period.
Outcome measures
| Measure |
Dapa+Saxa+Met
n=158 Participants
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
n=158 Participants
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Body Weight at Week 24
|
-1.91 kg
Standard Error 0.2191
|
-0.41 kg
Standard Error 0.2270
|
SECONDARY outcome
Timeframe: From baseline to week 24Population: The Randomized Subjects Data Set consists of all randomized subjects who received at least one dose of double-blind study medication during the double-blind treatment period
Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis.
Outcome measures
| Measure |
Dapa+Saxa+Met
n=158 Participants
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
Pla+Saxa+Met
n=158 Participants
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Percentage of Subjects Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
|
36.7 Percentage of subjects
|
13.3 Percentage of subjects
|
Adverse Events
DAPA + SAXA + MET
PLA + SAXA + MET
Serious adverse events
| Measure |
DAPA + SAXA + MET
n=160 participants at risk
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
PLA + SAXA + MET
n=160 participants at risk
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
CARDIAC FAILURE ACUTE
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Cardiac disorders
VENTRICULAR TACHYCARDIA
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Gastrointestinal disorders
GASTRIC ULCER
|
0.00%
0/160
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
ABSCESS LIMB
|
0.00%
0/160
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
APPENDICITIS
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Infections and infestations
GANGRENE
|
0.00%
0/160
|
0.62%
1/160 • Number of events 1
|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Injury, poisoning and procedural complications
ANKLE FRACTURE
|
0.00%
0/160
|
0.62%
1/160 • Number of events 1
|
|
Investigations
LIVER FUNCTION TEST ABNORMAL
|
0.00%
0/160
|
0.62%
1/160 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INVASIVE DUCTAL BREAST CARCINOMA
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.62%
1/160 • Number of events 1
|
0.00%
0/160
|
Other adverse events
| Measure |
DAPA + SAXA + MET
n=160 participants at risk
Participants received dapagliflozin, 10 mg, and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
PLA + SAXA + MET
n=160 participants at risk
Participants received dapagliflozin matching placebo and open-label saxagliptin 5 mg and metformin ≥1500 mg per day for up to 52 weeks
|
|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
2.5%
4/160 • Number of events 4
|
1.9%
3/160 • Number of events 3
|
|
Gastrointestinal disorders
DIARRHOEA
|
4.4%
7/160 • Number of events 7
|
5.6%
9/160 • Number of events 11
|
|
Gastrointestinal disorders
DYSPEPSIA
|
1.2%
2/160 • Number of events 2
|
2.5%
4/160 • Number of events 4
|
|
Gastrointestinal disorders
NAUSEA
|
2.5%
4/160 • Number of events 4
|
5.0%
8/160 • Number of events 9
|
|
General disorders
CHEST PAIN
|
0.62%
1/160 • Number of events 1
|
2.5%
4/160 • Number of events 5
|
|
Hepatobiliary disorders
HEPATIC STEATOSIS
|
0.62%
1/160 • Number of events 1
|
2.5%
4/160 • Number of events 4
|
|
Infections and infestations
INFLUENZA
|
7.5%
12/160 • Number of events 14
|
7.5%
12/160 • Number of events 14
|
|
Infections and infestations
NASOPHARYNGITIS
|
3.1%
5/160 • Number of events 5
|
5.0%
8/160 • Number of events 9
|
|
Infections and infestations
PHARYNGITIS
|
3.8%
6/160 • Number of events 6
|
1.9%
3/160 • Number of events 3
|
|
Infections and infestations
URINARY TRACT INFECTION
|
9.4%
15/160 • Number of events 19
|
10.0%
16/160 • Number of events 19
|
|
Infections and infestations
VULVOVAGINAL MYCOTIC INFECTION
|
4.4%
7/160 • Number of events 9
|
0.62%
1/160 • Number of events 1
|
|
Injury, poisoning and procedural complications
CONTUSION
|
0.62%
1/160 • Number of events 1
|
2.5%
4/160 • Number of events 4
|
|
Metabolism and nutrition disorders
DYSLIPIDAEMIA
|
4.4%
7/160 • Number of events 7
|
1.9%
3/160 • Number of events 3
|
|
Metabolism and nutrition disorders
HYPERTRIGLYCERIDAEMIA
|
3.1%
5/160 • Number of events 5
|
5.6%
9/160 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
2.5%
4/160 • Number of events 4
|
1.2%
2/160 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
3.1%
5/160 • Number of events 5
|
6.2%
10/160 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
1.2%
2/160 • Number of events 2
|
3.8%
6/160 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
1.9%
3/160 • Number of events 4
|
2.5%
4/160 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
1.9%
3/160 • Number of events 3
|
3.8%
6/160 • Number of events 6
|
|
Nervous system disorders
DIZZINESS
|
3.8%
6/160 • Number of events 6
|
0.00%
0/160
|
|
Nervous system disorders
HEADACHE
|
6.9%
11/160 • Number of events 16
|
8.1%
13/160 • Number of events 15
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/160
|
3.1%
5/160 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
3.1%
5/160 • Number of events 5
|
1.9%
3/160 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.00%
0/160
|
2.5%
4/160 • Number of events 4
|
Additional Information
Eva Johnsson, Clinical Science Lead
AstraZeneca Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place