Trial Outcomes & Findings for Safety and Efficacy of Saxagliptin in Triple Therapy to Treat Subjects With Type 2 Diabetes (NCT NCT01619059)
NCT ID: NCT01619059
Last Updated: 2016-04-22
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
315 participants
Primary outcome timeframe
From Baseline to Week 24
Results posted on
2016-04-22
Participant Flow
Of 315 participants randomized, 298 completed Short-Term (ST) treatment period. Of 297 participants entered Long-Term (LT) treatment period, 280 completed.
Participant milestones
| Measure |
Placebo + Dapagliflozin 10mg + Metformin
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Short-Term (ST) Treatment Period
STARTED
|
162
|
153
|
|
Short-Term (ST) Treatment Period
COMPLETED
|
156
|
142
|
|
Short-Term (ST) Treatment Period
NOT COMPLETED
|
6
|
11
|
|
Long-Term (LT) Treatment Period
STARTED
|
155
|
142
|
|
Long-Term (LT) Treatment Period
COMPLETED
|
147
|
133
|
|
Long-Term (LT) Treatment Period
NOT COMPLETED
|
8
|
9
|
Reasons for withdrawal
| Measure |
Placebo + Dapagliflozin 10mg + Metformin
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Short-Term (ST) Treatment Period
Adverse Event
|
1
|
0
|
|
Short-Term (ST) Treatment Period
Withdrawal by Subject
|
2
|
5
|
|
Short-Term (ST) Treatment Period
Lost to Follow-up
|
2
|
4
|
|
Short-Term (ST) Treatment Period
Non-compliance, not Met Study Criteria
|
1
|
2
|
|
Long-Term (LT) Treatment Period
Lack of Efficacy
|
0
|
1
|
|
Long-Term (LT) Treatment Period
Adverse Event
|
2
|
3
|
|
Long-Term (LT) Treatment Period
Withdrawal by Subject
|
3
|
2
|
|
Long-Term (LT) Treatment Period
Death
|
1
|
0
|
|
Long-Term (LT) Treatment Period
Lost to Follow-up
|
2
|
2
|
|
Long-Term (LT) Treatment Period
Not Met Study Criteria
|
0
|
1
|
Baseline Characteristics
Safety and Efficacy of Saxagliptin in Triple Therapy to Treat Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Placebo + Dapagliflozin 10mg + Metformin
n=162 Participants
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=153 Participants
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Total
n=315 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.5 YEARS
STANDARD_DEVIATION 9.32 • n=5 Participants
|
54.7 YEARS
STANDARD_DEVIATION 9.83 • n=7 Participants
|
54.6 YEARS
STANDARD_DEVIATION 9.56 • n=5 Participants
|
|
Age, Customized
< 65
|
140 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
272 Participants
n=5 Participants
|
|
Age, Customized
>= 65
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
86 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
166 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
149 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
AMERICAN INDIAN/ALASKA NATIVE
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
ASIAN
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
BLACK/AFRICAN AMERICAN
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
OTHER
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
WHITE
|
141 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
277 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline to 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 |
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=139 Participants
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Placebo + Dapagliflozin 10mg + Metformin
n=149 Participants
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24
|
-0.51 Percent of glycosylated haemoglobin
Standard Error 0.0624
|
-0.16 Percent of glycosylated haemoglobin
Standard Error 0.0605
|
SECONDARY outcome
Timeframe: From Baseline to 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. PPG measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue.
Outcome measures
| Measure |
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=135 Participants
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Placebo + Dapagliflozin 10mg + Metformin
n=144 Participants
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24
|
-37.1 mg/dL
Standard Error 3.286
|
-31.3 mg/dL
Standard Error 3.182
|
SECONDARY outcome
Timeframe: From Baseline to Week 24Population: All randomized participants who received study medication and had nonmissing FPG 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 double-blind period, including observations prior to rescue.
Outcome measures
| Measure |
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=139 Participants
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Placebo + Dapagliflozin 10mg + Metformin
n=146 Participants
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24
|
-9.1 mg/dL
Standard Error 2.644
|
-5.3 mg/dL
Standard Error 2.590
|
SECONDARY outcome
Timeframe: From Baseline to 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 |
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=139 Participants
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Placebo + Dapagliflozin 10mg + Metformin
n=146 Participants
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
|
35.3 Percent of participants
95% Confidence Interval 2.644 • Interval 28.2 to 42.4
|
23.1 Percent of participants
95% Confidence Interval 2.590 • Interval 16.9 to 29.3
|
Adverse Events
Placebo + Dapagliflozin 10mg + Metformin
Serious events: 11 serious events
Other events: 37 other events
Deaths: 0 deaths
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
Serious events: 7 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo + Dapagliflozin 10mg + Metformin
n=162 participants at risk
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=153 participants at risk
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Cardiac disorders
ANGINA PECTORIS
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Eye disorders
RETINAL DETACHMENT
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Gastrointestinal disorders
COLITIS
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Gastrointestinal disorders
GASTRITIS
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
General disorders
CHEST PAIN
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
General disorders
HERNIA
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Infections and infestations
PYELONEPHRITIS
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Injury, poisoning and procedural complications
FALL
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Investigations
STAPHYLOCOCCUS TEST POSITIVE
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Musculoskeletal and connective tissue disorders
RHABDOMYOLYSIS
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC CANCER
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Nervous system disorders
SYNCOPE
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.62%
1/162 • Number of events 1
|
0.00%
0/153
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
DIABETIC FOOT
|
0.00%
0/162
|
0.65%
1/153 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Vascular disorders
PERIPHERAL ARTERY THROMBOSIS
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
|
Vascular disorders
PERIPHERAL VASCULAR DISORDER
|
0.00%
0/162
|
0.65%
1/153 • Number of events 1
|
Other adverse events
| Measure |
Placebo + Dapagliflozin 10mg + Metformin
n=162 participants at risk
Participants received Saxagliptin-matching placebo, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
Saxagliptin 5mg + Dapagliflozin 10mg + Metformin
n=153 participants at risk
Participants received Saxagliptin 5mg, dapagliflozin 10mg once daily plus open-label metformin for up to 52 weeks
|
|---|---|---|
|
Gastrointestinal disorders
DIARRHOEA
|
3.7%
6/162 • Number of events 6
|
5.2%
8/153 • Number of events 8
|
|
Infections and infestations
NASOPHARYNGITIS
|
4.9%
8/162 • Number of events 8
|
5.9%
9/153 • Number of events 10
|
|
Infections and infestations
URINARY TRACT INFECTION
|
6.8%
11/162 • Number of events 13
|
7.2%
11/153 • Number of events 16
|
|
Nervous system disorders
HEADACHE
|
7.4%
12/162 • Number of events 13
|
5.9%
9/153 • Number of events 12
|
Additional Information
Eva Johnsson, Clinical Science Lead
AstraZeneca Pharmaceuticals
Phone: +46 31 7762484
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place