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

This study has been completed.

Sponsor:

Collaborator:

AstraZeneca

Information provided by:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00683657

First received: May 21, 2008

Last updated: November 30, 2010

Last verified: November 2010

History of Changes

Results First Received: February 19, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Type 2 Diabetes
Interventions:	Drug: Saxagliptin Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups

	Description
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.

Participant Flow: Overall Study

	Saxagliptin 5 mg + Metformin	Placebo + Metformin
STARTED	46	47
Randomized Subjects Data Set	46 ^[1]	47 ^[1]
COMPLETED	45	46
NOT COMPLETED	1	1
Adverse Event	0	1
Subject Withdrew Consent	1	0

[1]	Randomized subjects who took at least 1 dose of double-blind study medication.

Baseline Characteristics

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Reporting Groups

	Description
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.
Total	Total of all reporting groups

Baseline Measures

	Saxagliptin 5 mg + Metformin	Placebo + Metformin	Total
Number of Participants [units: participants]	46	47	93
Age, Customized [units: participants]
<65 years	40	38	78
>= 65 years to <75 years	6	8	14
>= 75 years	0	1	1
Age [units: years] Mean ± Standard Deviation	54.50 ± 9.20	55.77 ± 9.14	55.14 ± 9.14
Gender [units: participants]
Female	20	24	44
Male	26	23	49
Race/Ethnicity, Customized [units: Participants]
White	39	43	82
Black/African American	3	2	5
Asian	2	1	3
Other	2	1	3

Outcome Measures

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1. Primary:

Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4 [ Time Frame: Baseline, Week 4 ]

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2. Secondary:

Change From Baseline in 4-Hour Mean Weighted Postprandial Plasma Glucose at Week 4 [ Time Frame: Baseline, Week 4 ]

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3. Secondary:

Change From Baseline in 2-Hour Postprandial Plasma Glucose After the Evening Meal at Week 4 [ Time Frame: Baseline, Week 4 ]

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4. Secondary:

Change From Baseline in Mean Daily Glucose at Week 4 [ Time Frame: Baseline, Week 4 ]

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5. Secondary:

Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4 [ Time Frame: Baseline, Week 4 ]

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Measure Type	Secondary
Measure Title	Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4
Measure Description	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.
Time Frame	Baseline, Week 4
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.

Measured Values

	Saxagliptin 5 mg + Metformin	Placebo + Metformin
Number of Participants Analyzed [units: participants]	46	47
Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4 [units: mg/dL] Mean ± Standard Error
Baseline Mean	152.2 ± 4.14	158.9 ± 5.80
Week 4 Last Observation Carried Forward Mean	141.9 ± 3.99	162.9 ± 6.00
Adjusted Mean Change from Baseline	-10.8 ± 2.84	4.5 ± 2.81

Statistical Analysis 1 for Change From Baseline in 2-Day Average Fasting Plasma Glucose (FPG) at Week 4

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.0002
Mean Difference (Final Values) ^[4]	-15.3
Standard Error of the mean	± 4.00
95% Confidence Interval	( -23.3 to -7.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	With 39 subjects per treatment group, there was a 93% power for the primary endpoint to detect a difference in 24-hour mean weighted glucose of 16 mg/dL between saxagliptin and placebo, assuming a standard deviation of 20 mg/dL. Assuming a dropout rate of 15%, a total of 92 subjects (46 subjects per treatment arm) needed to be randomized.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	ANCOVA Model: post - pre = pretreatment
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Between-group comparisons significant at alpha = 0.05, significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[4]	Other relevant estimation information:
	Mean difference = adjusted mean change for saxagliptin 5 mg + Metformin - adjusted mean change for Placebo + Metformin

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00683657 History of Changes
Other Study ID Numbers:	CV181-066, Eudract-2008-000976-26
Study First Received:	May 21, 2008
Results First Received:	February 19, 2010
Last Updated:	November 30, 2010
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Italy: The Italian Medicines Agency United States: Food and Drug Administration Sweden: Medical Products Agency Sweden: Regional Ethical Review Board Finland: Finnish Medicines Agency Finland: Sub-Committee on Medical Research Ethics (TUKIJA) Israel: Ministry of Health Philippines: Bureau of Food and Drugs Philippines: National Ethics Committee Poland: Cental Evidence of Clinical Research

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