Trial Outcomes & Findings for Evaluate Efficacy and Safety of Saxagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes (NCT NCT00661362)

NCT ID: NCT00661362

Last Updated: 2012-03-08

Results Overview

Adjusted\* mean change from baseline in HbA1c achieved with saxagliptin 5 mg + metformin versus placebo + metformin 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. \*Adjusted for baseline HbA1c.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 570 participants
• Primary outcome timeframe: Baseline , Week 24
• Results posted on: 2012-03-08

Participant Flow

Participant milestones

Measure	Saxagliptin 5 mg + Metformin Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin Placebo tablet, OD, added on to stable Metformin for 24 weeks
Overall Study STARTED	283	287
Overall Study COMPLETED	254	247
Overall Study NOT COMPLETED	29	40

Reasons for withdrawal

Measure	Saxagliptin 5 mg + Metformin Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin Placebo tablet, OD, added on to stable Metformin for 24 weeks
Overall Study Adverse Event	5	4
Overall Study Incorrect enrollment	2	0
Overall Study Study specific discontinuation criteria	4	11
Overall Study Withdrawal by Subject	13	23
Overall Study Lost to Follow-up	3	1
Overall Study Severe non-compliance to protocol	0	1
Overall Study Safety reasons	1	0
Overall Study Metformin dose haven't decreasd to 2.5 g	1	0

Baseline Characteristics

Evaluate Efficacy and Safety of Saxagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Saxagliptin 5 mg + Metformin n=283 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=287 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks	Total n=570 Participants Total of all reporting groups
Age Continuous	53.75 Years STANDARD_DEVIATION 10.42 • n=5 Participants	54.36 Years STANDARD_DEVIATION 10.06 • n=7 Participants	54.05 Years STANDARD_DEVIATION 10.24 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	148 Participants n=7 Participants	295 Participants n=5 Participants
Sex: Female, Male Male	136 Participants n=5 Participants	139 Participants n=7 Participants	275 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline , Week 24

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post baseline efficacy measurement.

Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 5 mg + metformin versus placebo + metformin 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. *Adjusted for baseline HbA1c.

Outcome measures

Measure	Saxagliptin 5 mg + Metformin n=275 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=279 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks
Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) Baseline	7.90 percent Standard Error 0.049	7.94 percent Standard Error 0.050
Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) Week 24	7.10 percent Standard Error 0.056	7.55 percent Standard Error 0.062
Absolute Change From Baseline to Week 24 in Glycosylated Haemoglobin A1c (HbA1c) adjusted baseline HbA1c	-0.78 percent Standard Error 0.051	-0.37 percent Standard Error 0.050

SECONDARY outcome

Timeframe: Baseline , Week 24

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post baseline efficacy measurement

Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 5 mg + metformin versus placebo + metformin at week 24 (Last Observation Carried Out (LOCF), Full Analysis set). FPG is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. *Adjusted for baseline FPG.

Outcome measures

Measure	Saxagliptin 5 mg + Metformin n=278 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=281 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks
Absolute Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) mmol/L Baseline	8.57 mmol/L Standard Error 0.117	8.87 mmol/L Standard Error 0.137
Absolute Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) mmol/L Week 24	7.61 mmol/L Standard Error 0.117	8.30 mmol/L Standard Error 0.127
Absolute Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) mmol/L Adjusted Change from Baseline	-1.14 mmol/L Standard Error 0.114	-0.58 mmol/L Standard Error 0.111

SECONDARY outcome

Timeframe: Baseline , Week 24

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24 LOCF for efficacy, subjects must have had a baseline and at least 1 post baseline efficacy measurement

Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 5 mg + metformin versus placebo + metformin at week 24 (LOCF, Full Analysis set). FPG is a continuous measure, the change from baseline for each subject is calculated as the week 24 values minus the baseline value. *Adjusted for baseline FPG.

Outcome measures

Measure	Saxagliptin 5 mg + Metformin n=278 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=281 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks
Absolute Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) mg/dL Baseline	154.54 mg/dL Standard Error 2.103	159.73 mg/dL Standard Error 2.467
Absolute Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) mg/dL Week 24	137.15 mg/dL Standard Error 2.116	149.54 mg/dL Standard Error 2.286
Absolute Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) mg/dL Adjusted Change from Baseline	-20.52 mg/dL Standard Error 2.051	-10.42 mg/dL Standard Error 2.004

SECONDARY outcome

Timeframe: Baseline , Week 24

Population: MMTT was measured on a subset of patients in China cohort only at baseline and Wk 24. Randomized participants who took at least 1 dose of double-blind treatment to be included in analysis: change from baseline to Wk 24 (LOCF), must have had a baseline and a post baseline data.

Adjusted* mean change from baseline in PPG AUC achieved with saxagliptin 5 mg + metformin versus placebo + metformin at week 24 (LOCF, Full Analysis set). Trapezoidal method was used to compute AUC under the 3 hour PPG curve. The change from baseline for each subject is calculated as the week 24 value minus the baseline value. *Adjusted for baseline PPG AUC.

Outcome measures

Measure	Saxagliptin 5 mg + Metformin n=113 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=111 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks
Change From Baseline in the Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During a Mixed Meal Tolerance Test (MMTT) in a Subgroup Baseline	2355 mmol*min/L Standard Error 45.6	2427 mmol*min/L Standard Error 51.5
Change From Baseline in the Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During a Mixed Meal Tolerance Test (MMTT) in a Subgroup Week 24	2058 mmol*min/L Standard Error 44.4	2249 mmol*min/L Standard Error 46.9
Change From Baseline in the Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During a Mixed Meal Tolerance Test (MMTT) in a Subgroup Adjusted Change from Baseline	-315 mmol*min/L Standard Error 38.6	-160 mmol*min/L Standard Error 39.0

SECONDARY outcome

Timeframe: Baseline , Week 24

Population: MMTT was measured on a subset of patients in China cohort only at baseline and Wk 24. Randomized participants who took at least 1 dose of double-blind treatment to be included in analysis: change from baseline to Wk 24 (LOCF), must have had a baseline and a post baseline data.

Adjusted* mean change from baseline in PPG AUC achieved with saxagliptin 5 mg + metformin versus placebo+metformin at week 24 (LOCF, Full Analysis set). Trapezoidal method was used to compute AUC under the 3 hour PPG curve. The change from baseline for each subject is calculated as the week 24 value minus the baseline value. *Adjusted for baseline PPG AUC.

Outcome measures

Measure	Saxagliptin 5 mg + Metformin n=113 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=111 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks
Change From Baseline in the Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During a Mixed Meal Tolerance Test (MMTT) in a Subgroup Baseline	42423 mg*min/dL Standard Error 821.9	43719 mg*min/dL Standard Error 927.3
Change From Baseline in the Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During a Mixed Meal Tolerance Test (MMTT) in a Subgroup Week 24	37071 mg*min/dL Standard Error 799.4	40521 mg*min/dL Standard Error 845.7
Change From Baseline in the Area Under the Curve (AUC) From 0 to 180 Minutes for Postprandial Glucose (PPG) During a Mixed Meal Tolerance Test (MMTT) in a Subgroup Adjusted Change from Baseline	-5673 mg*min/dL Standard Error 695.9	-2871 mg*min/dL Standard Error 702.1

SECONDARY outcome

Timeframe: Baseline , Week 24

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Wk 24(LOCF) for efficacy, subjects must have had a baseline and at least 1 post baseline efficacy measurement.

Proportion of participants achieving a therapeutic glycemic response, defined as having HbA1c < 7.0% for saxagliptin + metformin versus placebo + metformin at week 24

Outcome measures

Measure	Saxagliptin 5 mg + Metformin n=275 Participants Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=279 Participants Placebo tablet, OD, added on to stable Metformin for 24 weeks
Proportion of Patients Achieving a Therapeutic Glycemic Response	46.5 Percentage of participants	30.5 Percentage of participants

Adverse Events

Saxagliptin 5 mg + Metformin

Serious events: 8 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo + Metformin

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Saxagliptin 5 mg + Metformin n=283 participants at risk Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=287 participants at risk Placebo tablet, OD, added on to stable Metformin for 24 weeks
Infections and infestations Anal Abscess	0.35% 1/283	0.00% 0/287
Infections and infestations Appendicitis	0.35% 1/283	0.00% 0/287
Infections and infestations Hepatitis B	0.35% 1/283	0.00% 0/287
Infections and infestations Pulmonary Tuberculosis	0.35% 1/283	0.00% 0/287
Infections and infestations Urinary Tract Infection	0.00% 0/283	0.35% 1/287
Injury, poisoning and procedural complications Ankle Fracture	0.35% 1/283	0.00% 0/287
Injury, poisoning and procedural complications Clavicle Fracture	0.35% 1/283	0.00% 0/287
Injury, poisoning and procedural complications Rib Fracture	0.35% 1/283	0.00% 0/287
Hepatobiliary disorders Cholecystitis Acute	0.35% 1/283	0.00% 0/287
Nervous system disorders Cerebral Infarction	0.35% 1/283	0.35% 1/287
Metabolism and nutrition disorders Diabetic Foot	0.00% 0/283	0.35% 1/287

Other adverse events

Measure	Saxagliptin 5 mg + Metformin n=283 participants at risk Saxagliptin 5 mg tablet, once daily (OD), added on to stable Metformin for 24 weeks	Placebo + Metformin n=287 participants at risk Placebo tablet, OD, added on to stable Metformin for 24 weeks
Infections and infestations Upper Respiratory Tract Infection	6.7% 19/283	4.5% 13/287

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Principal Investigator will provide AstraZeneca as soon as possible with preliminary data and drafts of proposed publications and disclosures, whether oral or in writing, with the proposed final manuscript. AZ shall have a period of 30 days from receipt of the proposed final manuscript for any publication or other disclosure to review it and may within such time require that submission for publication or disclosure of the manuscript be delayed.
• Publication restrictions are in place

Restriction type: OTHER