Trial Outcomes & Findings for Study To Evaluate 24 Hour Blood Sugar Control (24-hour Mean Weighted Glucose) In Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared To Subjects Taking Metformin XR 1500 mg Up-titrated To Metformin XR 2000 mg (NCT NCT00918138)

Last Updated: 2015-05-21

Results Overview

Adjusted mean change from baseline in MWG achieved with saxagliptin 5 mg plus metformin XR versus placebo plus metformin XR at Week 24. MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed as average mg/dL. Glucose measurements were collected 30 minutes before and just prior to each meal (0 minutes) and 30, 60, 120, and 180 minutes after each meal (with 1 additional measurement at 240 minutes after the evening meal), midnight, 3 AM, and at end-of-domicile visit 24 hours after the first measurement. Mean change from baseline was adjusted for baseline value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

219 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2015-05-21

Participant Flow

219 participants were enrolled; 126 entered single-blind dietary/exercise/metformin extended release (XR) lead-in period (either 4- or 8-weeks long, based on pre-enrollment metformin dose). 33 participants did not enter treatment period (22 no longer met study criteria, 7 withdrew consent, 2 lost to follow-up, 1 adverse event, and 1 other reason).

Participant milestones

Participant milestones
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Overall Study STARTED	46	47
Overall Study COMPLETED	44	46
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Overall Study Subject withdrew consent	1	1
Overall Study Death	1	0

Baseline Characteristics

Study To Evaluate 24 Hour Blood Sugar Control (24-hour Mean Weighted Glucose) In Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared To Subjects Taking Metformin XR 1500 mg Up-titrated To Metformin XR 2000 mg

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg n=46 Participants saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg n=47 Participants metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo	Total n=93 Participants Total of all reporting groups
Age, Continuous	53.89 years STANDARD_DEVIATION 9.41 • n=5 Participants	50.64 years STANDARD_DEVIATION 9.74 • n=7 Participants	52.25 years STANDARD_DEVIATION 9.66 • n=5 Participants
Age, Customized <65 years	40 participants n=5 Participants	45 participants n=7 Participants	85 participants n=5 Participants
Age, Customized >=65 years	6 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	25 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized White	43 Participant n=5 Participants	45 Participant n=7 Participants	88 Participant n=5 Participants
Race/Ethnicity, Customized Black/African American	3 Participant n=5 Participants	2 Participant n=7 Participants	5 Participant n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	16 Participant n=5 Participants	17 Participant n=7 Participants	33 Participant n=5 Participants
Race/Ethnicity, Customized Not Hispanic/ Not Latino	8 Participant n=5 Participants	8 Participant n=7 Participants	16 Participant n=5 Participants
Race/Ethnicity, Customized Not Reported	22 Participant n=5 Participants	22 Participant n=7 Participants	44 Participant n=5 Participants
Age categorization Females Only <= 50 years	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Age categorization Females Only > 50 years	16 participants n=5 Participants	16 participants n=7 Participants	32 participants n=5 Participants
Weight	91.27 kg STANDARD_DEVIATION 18.43 • n=5 Participants	86.94 kg STANDARD_DEVIATION 15.24 • n=7 Participants	89.09 kg STANDARD_DEVIATION 16.94 • n=5 Participants
Body Mass Index (BMI)	32.45 kg/m^2 STANDARD_DEVIATION 5.08 • n=5 Participants	31.06 kg/m^2 STANDARD_DEVIATION 4.28 • n=7 Participants	31.75 kg/m^2 STANDARD_DEVIATION 4.72 • n=5 Participants
BMI Categorization < 30 kg/m^2	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
BMI Categorization >= 30 kg/m^2	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants
Glycosylated Hemoglobin (A1C)	8.6 percentage STANDARD_DEVIATION 0.9 • n=5 Participants	8.4 percentage STANDARD_DEVIATION 0.9 • n=7 Participants	8.5 percentage STANDARD_DEVIATION 0.9 • n=5 Participants
Fasting Plasma Glucose (FPG)	163.5 mg/dL STANDARD_DEVIATION 32.32 • n=5 Participants	164.2 mg/dL STANDARD_DEVIATION 36.21 • n=7 Participants	163.8 mg/dL STANDARD_DEVIATION 34.16 • n=5 Participants
FPG Categorization < 126 mg/dL	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
FPG Categorization >= 126 mg/dL to < 150 mg/dL	11 participants n=5 Participants	14 participants n=7 Participants	25 participants n=5 Participants
FPG Categorization >= 150 mg/dL to < 220 mg/dL	28 participants n=5 Participants	23 participants n=7 Participants	51 participants n=5 Participants
FPG Categorization >= 220 mg/dL to < 300 mg/dL	2 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants
120-minute postprandial glucose (PPG)	281.3 mg/dL STANDARD_DEVIATION 51.59 • n=5 Participants	283.3 mg/dL STANDARD_DEVIATION 66.14 • n=7 Participants	282.3 mg/dL STANDARD_DEVIATION 59.08 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who had both baseline and Week 4 assessments.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg n=43 Participants saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg n=44 Participants metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4 Baseline Mean	191.3 mg/dL Standard Error 6.26	192.0 mg/dL Standard Error 6.14
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4 Week 4 Mean	173.2 mg/dL Standard Error 5.85	184.2 mg/dL Standard Error 6.52
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4 Adjusted Change from Baseline	-19.0 mg/dL Standard Error 5.69	-8.2 mg/dL Standard Error 5.96

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who had both baseline and Week 4 assessments.

Adjusted mean change from baseline in 2-hour postprandial (after mealtime) plasma glucose two hours after start of the evening meal during 24-hour domicile visits evaluated both at pre-randomization (baseline) and at Week 4. Mean change from baseline was adjusted for baseline value.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg n=44 Participants saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg n=46 Participants metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal) Baseline mean	229.7 mg/dL Standard Error 9.07	234.0 mg/dL Standard Error 10.32
Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal) Week 4 mean	195.3 mg/dL Standard Error 7.99	228.1 mg/dL Standard Error 11.30
Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal) Adjusted mean change from baseline	-31.4 mg/dL Standard Error 9.69	-0.2 mg/dL Standard Error 10.09

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who had both baseline and Week 4 assessments. Last Observation Carried Forward (LOCF).

FPG measurements were done at baseline, day 14 and 28. At baseline and day 28, the FPG value=plasma glucose value collected 30 minutes prior to the morning meal during the domicile visit.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg n=45 Participants saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg n=47 Participants metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal Baseline mean	162.9 mg/dL Standard Error 4.84	164.2 mg/dL Standard Error 5.28
Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal Week 4 LOCF mean	155.2 mg/dL Standard Error 6.49	161.8 mg/dL Standard Error 5.23
Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal Adjusted mean change from baseline	-9.3 mg/dL Standard Error 5.93	-3.6 mg/dL Standard Error 6.17

OTHER_PRE_SPECIFIED outcome

Timeframe: AEs: up to last treatment day (LTD) +1 day or last visit day (LVD), whichever came last ; SAEs: up to LTD +30 days or LVD + 30 days, whichever came last. Mean duration of exposure=27.7 days for Saxa 5 mg + Met XR 1500 mg, and 28.3 days for Met 2000 mg.

Population: Treated participants

'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick for glucose \<= 50 mg/dL and associated symptoms.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg n=46 Participants saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg n=47 Participants metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Participants With Confirmed Hypoglycemia Events During the Treatment Period	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Hypoglycemic events are based upon the Saxagliptin Predefined List of Events, which includes hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness. The Hypoglycemic events occurred in less than 5% of the participants and hence do not appear in the adverse events module.

Outcome measures

Outcome measures
Measure	Saxagliptin 5 mg + Metformin XR 1500 mg n=46 Participants saxagliptin 5 mg plus metformin XR 1500 plus matching metformin XR 500 mg placebo	Metformin 2000 mg n=47 Participants metformin XR 500 mg plus metformin XR 1500 mg plus matching saxagliptin 5 mg placebo
Participants With Reported Hypoglycemic Adverse Events During Treatment Period	1 participants	2 participants

Adverse Events

Metformin 2000 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Saxagliptin 5 mg + Metformin XR 1500 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Metformin 2000 mg n=47 participants at risk Metformin XR 500 mg plus Metformin XR 1500 mg plus matching Saxagliptin 5 mg placebo	Saxagliptin 5 mg + Metformin XR 1500 mg n=46 participants at risk Saxagliptin 5 mg plus Metformin XR 1500 plus matching Metformin XR 500 mg placebo
General disorders DEATH	0.00% 0/47	2.2% 1/46

Other adverse events

Other adverse events
Measure	Metformin 2000 mg n=47 participants at risk Metformin XR 500 mg plus Metformin XR 1500 mg plus matching Saxagliptin 5 mg placebo	Saxagliptin 5 mg + Metformin XR 1500 mg n=46 participants at risk Saxagliptin 5 mg plus Metformin XR 1500 plus matching Metformin XR 500 mg placebo
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 0/47	6.5% 3/46

Additional Information

Boaz Hirschberg

AstraZeneca Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER