Trial Outcomes & Findings for Safety and Efficacy Study of Subjects That Are Taking Saxagliptin Added Onto Metformin XR Compared to Subjects Taking Metformin XR Alone (NCT NCT00683657)

NCT ID: NCT00683657

Last Updated: 2015-06-01

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

93 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2015-06-01

Participant Flow

218 subjects were enrolled and 128 entered the 4-week dietary and exercise, and metformin extended release (XR) lead-in period. Thirty-five subjects did not enter treatment period (21 no longer met study criteria, 7 withdrew consent, 7 for poor protocol compliance).

Participant milestones

Participant milestones
Measure
Saxagliptin 5 mg + Metformin
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Overall Study
STARTED
46
47
Overall Study
Randomized Subjects Data Set
46
47
Overall Study
COMPLETED
45
46
Overall Study
NOT COMPLETED
1
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Saxagliptin 5 mg + Metformin
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Overall Study
Adverse Event
0
1
Overall Study
Subject Withdrew Consent
1
0

Baseline Characteristics

Safety and Efficacy Study of Subjects That Are Taking Saxagliptin Added Onto Metformin XR Compared to Subjects Taking Metformin XR Alone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Saxagliptin 5 mg + Metformin
n=46 Participants
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
n=47 Participants
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Total
n=93 Participants
Total of all reporting groups
Age, Continuous
54.50 years
STANDARD_DEVIATION 9.20 • n=5 Participants
55.77 years
STANDARD_DEVIATION 9.14 • n=7 Participants
55.14 years
STANDARD_DEVIATION 9.14 • n=5 Participants
Age, Customized
<65 years
40 participants
n=5 Participants
38 participants
n=7 Participants
78 participants
n=5 Participants
Age, Customized
>= 65 years to <75 years
6 participants
n=5 Participants
8 participants
n=7 Participants
14 participants
n=5 Participants
Age, Customized
>= 75 years
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
Sex: Female, Male
Female
20 Participants
n=5 Participants
24 Participants
n=7 Participants
44 Participants
n=5 Participants
Sex: Female, Male
Male
26 Participants
n=5 Participants
23 Participants
n=7 Participants
49 Participants
n=5 Participants
Race/Ethnicity, Customized
White
39 Participants
n=5 Participants
43 Participants
n=7 Participants
82 Participants
n=5 Participants
Race/Ethnicity, Customized
Black/African American
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in an analysis of change from baseline to Week 4 the subject must have had a baseline and a Week 4 measurement.

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.

Outcome measures

Outcome measures
Measure
Saxagliptin 5 mg + Metformin
n=41 Participants
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
n=44 Participants
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4
Baseline Mean
177.5 mg/dL
Standard Error 4.99
181.2 mg/dL
Standard Error 6.30
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4
Week 4 Mean
163.8 mg/dL
Standard Error 5.09
184.2 mg/dL
Standard Error 7.05
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4
Adjusted Mean Change from Baseline
-13.8 mg/dL
Standard Error 2.99
3.0 mg/dL
Standard Error 2.89

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in an analysis of change from baseline to Week 4 the subject must have had a baseline and a Week 4 measurement.

Adjusted mean change from baseline in 4-hour mean weighted postprandial (after mealtime) plasma glucose after 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
n=40 Participants
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
n=44 Participants
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Change From Baseline in 4-Hour Mean Weighted Postprandial Plasma Glucose at Week 4
Baseline Mean
212.1 mg/dL
Standard Error 6.80
211.1 mg/dL
Standard Error 6.60
Change From Baseline in 4-Hour Mean Weighted Postprandial Plasma Glucose at Week 4
Week 4 Mean
181.4 mg/dL
Standard Error 6.79
210.8 mg/dL
Standard Error 8.02
Change From Baseline in 4-Hour Mean Weighted Postprandial Plasma Glucose at Week 4
Adjusted Mean Change from Baseline
-30.7 mg/dL
Standard Error 5.14
-0.4 mg/dL
Standard Error 4.90

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in an analysis of change from baseline to Week 4 the subject must have had a baseline and a Week 4 measurement.

Adjusted mean change from baseline in 2-hour postprandial plasma glucose after 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
n=41 Participants
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
n=44 Participants
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Change From Baseline in 2-Hour Postprandial Plasma Glucose After the Evening Meal at Week 4
Baseline Mean
237.6 mg/dL
Standard Error 8.87
233.1 mg/dL
Standard Error 7.74
Change From Baseline in 2-Hour Postprandial Plasma Glucose After the Evening Meal at Week 4
Week 4 Mean
198.5 mg/dL
Standard Error 8.82
231.1 mg/dL
Standard Error 9.22
Change From Baseline in 2-Hour Postprandial Plasma Glucose After the Evening Meal at Week 4
Adjusted Change from Baseline
-38.2 mg/dL
Standard Error 7.49
-2.8 mg/dL
Standard Error 7.23

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in an analysis of change from baseline to Week 4 the subject must have had a baseline and a Week 4 measurement.

Adjusted mean change from baseline in daily glucose at Week 4. Mean daily glucose was calculated based on finger stick glucose measurements collected by the subjects at home in a 3-day period, prior to collection of the 24-hour blood samples at baseline and Week 4. Mean change from baseline was adjusted for baseline value.

Outcome measures

Outcome measures
Measure
Saxagliptin 5 mg + Metformin
n=38 Participants
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
n=44 Participants
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Change From Baseline in Mean Daily Glucose at Week 4
Baseline Mean
179.0 mg/dL
Standard Error 5.76
184.9 mg/dL
Standard Error 7.14
Change From Baseline in Mean Daily Glucose at Week 4
Week 4 Mean
167.5 mg/dL
Standard Error 4.87
191.8 mg/dL
Standard Error 8.41
Change From Baseline in Mean Daily Glucose at Week 4
Adjusted Change from Baseline
-11.7 mg/dL
Standard Error 3.02
7.0 mg/dL
Standard Error 2.94

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Randomized participants who took at least 1 dose of double-blind treatment. To be included in an analysis of change from baseline to Week 4 the subject must have had a baseline and a Week 4 measurement.

Adjusted mean change from baseline in 2-day average of FPG at baseline and Week 4. Baseline value=the average of the values at Day -2 and Day 1. Week 4 measurement=average of Day 26 and Day 28 value during the double blind period. At pre-randomization and Day 28 the FPG value was the plasma glucose value collected 30 minutes prior to the morning meal during domicile visits. Mean change from baseline was adjusted for baseline value.

Outcome measures

Outcome measures
Measure
Saxagliptin 5 mg + Metformin
n=46 Participants
Saxagliptin tablets, 5 mg, taken orally once daily for 4 weeks, plus metformin XR.
Placebo + Metformin
n=47 Participants
Placebo tablets, taken orally once daily for 4 weeks, plus metformin XR.
Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4
Baseline Mean
152.2 mg/dL
Standard Error 4.14
158.9 mg/dL
Standard Error 5.80
Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4
Week 4 Last Observation Carried Forward Mean
141.9 mg/dL
Standard Error 3.99
162.9 mg/dL
Standard Error 6.00
Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4
Adjusted Mean Change from Baseline
-10.8 mg/dL
Standard Error 2.84
4.5 mg/dL
Standard Error 2.81

Adverse Events

PLACEBO + MET

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

SAXA 5MG + MET

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
PLACEBO + MET
n=47 participants at risk
SAXA 5MG + MET
n=46 participants at risk
Nervous system disorders
HEADACHE
6.4%
3/47
2.2%
1/46
Gastrointestinal disorders
NAUSEA
6.4%
3/47
0.00%
0/46

Additional Information

Boaz Hirschberg

AstraZeneca Pharmaceuticals

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