Trial Outcomes & Findings for An 18 Week Efficacy and Safety Study of Saxagliptin and Metformin XR Combination in Subjects With Type 2 Diabetes (NCT NCT00960076)

Results Overview

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

282 participants

Primary outcome timeframe

Baseline to week 18

Results posted on

2011-09-27

Participant Flow

Of the 393 subjects who entered the lead-in period, 111 subjects did not enter the randomized, double-blind treatment period. Thus, a total of 282 subjects were randomized and treated.

Participant milestones

Participant milestones
Measure	Saxagliptin + Metformin Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Overall Study STARTED	138	144
Overall Study COMPLETED	130	119
Overall Study NOT COMPLETED	8	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Saxagliptin + Metformin Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Overall Study Adverse Event	1	7
Overall Study No longer met study criteria	1	5
Overall Study Withdrawal by Subject	1	2
Overall Study Lost to Follow-up	3	3
Overall Study Severe non-compliance to protocol	1	2
Overall Study Hyperglycemia	1	5
Overall Study Did not attend the termination visit	0	1

Baseline Characteristics

An 18 Week Efficacy and Safety Study of Saxagliptin and Metformin XR Combination in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saxagliptin + Metformin n=138 Participants Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=144 Participants Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)	Total n=282 Participants Total of all reporting groups
Age Continuous	55.22 years STANDARD_DEVIATION 9.41 • n=93 Participants	55.46 years STANDARD_DEVIATION 9.86 • n=4 Participants	55.34 years STANDARD_DEVIATION 9.64 • n=27 Participants
Sex: Female, Male Female	81 Participants n=93 Participants	71 Participants n=4 Participants	152 Participants n=27 Participants
Sex: Female, Male Male	57 Participants n=93 Participants	73 Participants n=4 Participants	130 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to week 18

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=137 Participants Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=142 Participants Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Change in HbA1c Level From Baseline to Week 18 (LOCF) Week 18	7.53 Percent Standard Error 0.093	7.93 Percent Standard Error 0.111
Change in HbA1c Level From Baseline to Week 18 (LOCF) Baseline	8.41 Percent Standard Error 0.076	8.28 Percent Standard Error 0.077
Change in HbA1c Level From Baseline to Week 18 (LOCF) Adjusted Change from Baseline to Week 18	-0.88 Percent Standard Error 0.077	-0.35 Percent Standard Error 0.076

SECONDARY outcome

Timeframe: Baseline to week 18

Adjusted mean change from baseline in 2-hour PPG (following MMTT) achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). PPG is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=121 Participants Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=117 Participants Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) Baseline	227.36 mg/dL Standard Error 6.022	223.68 mg/dL Standard Error 5.295
Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) Week 18	195.11 mg/dL Standard Error 5.876	216.24 mg/dL Standard Error 6.230
Change in 2-hour PPG Following Mixed Meal Tolerance Test (MMTT) From Baseline to Week 18 (LOCF) Adjusted Change from Baseline to Week 18	-31.52 mg/dL Standard Error 4.996	-8.20 mg/dL Standard Error 5.081

SECONDARY outcome

Timeframe: Baseline to week 18

Adjusted mean change from baseline in FPG achieved with saxagliptin added on to metformin versus metformin at Week 18 (Randomized Analysis Set). FPG is a continuous measure, the change from baseline for each participant is calculated as the Week 18 value minus the baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=137 Participants Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=142 Participants Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Change in FPG From Baseline to Week 18 (LOCF) Baseline	162.54 mg/dL Standard Error 4.146	163.35 mg/dL Standard Error 3.910
Change in FPG From Baseline to Week 18 (LOCF) Week 18	142.70 mg/dL Standard Error 3.633	156.32 mg/dL Standard Error 3.948
Change in FPG From Baseline to Week 18 (LOCF) Adjusted Change from Baseline to Week 18	-20.03 mg/dL Standard Error 3.146	-6.85 mg/dL Standard Error 3.090

SECONDARY outcome

Timeframe: Week 18 (LOCF)

Percent of subjects achieving therapeutic response (HbA1c \<7.0%) at Week 18 (LOCF) (Randomized analysis set)

Outcome measures

Outcome measures
Measure	Saxagliptin + Metformin n=137 Participants Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=142 Participants Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Percent of Subjects Reaching Goal (HbA1c <7%) at Week 18 (LOCF) - Percent of Subjects (1)	37.2 Percentage of Participants	26.1 Percentage of Participants

Adverse Events

Saxagliptin + Metformin

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Metformin (DB) + Metformin (OL)

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Saxagliptin + Metformin n=138 participants at risk Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=144 participants at risk Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/138	0.69% 1/144
Cardiac disorders Myocardial infarction	0.00% 0/138	0.69% 1/144
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/138	0.69% 1/144

Other adverse events

Other adverse events
Measure	Saxagliptin + Metformin n=138 participants at risk Saxagliptin 5 mg (DB) + Metformin XR 1500 mg (OL)	Metformin (DB) + Metformin (OL) n=144 participants at risk Metformin XR 500 mg (DB) + Metformin XR 1500 mg (OL)
Infections and infestations Urinary Tract Infection	5.1% 7/138	2.1% 3/144
Infections and infestations Nasopharyngitis	4.3% 6/138	5.6% 8/144
Gastrointestinal disorders Diarrhoea	5.8% 8/138	3.5% 5/144

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place