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Effects of Metformin Hydrochloride (HCl) in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, in Patients With Type 2 Diabetes Mellitus and the Effects of Colesevelam HCl on Lipids and Glucose on Pre-diabetic Patients.

This study has been completed.
Sponsor:
Information provided by:
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00570739
First received: December 10, 2007
Last updated: July 19, 2010
Last verified: July 2010
Results First Received: April 6, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Type 2 Diabetes Mellitus
Hypercholesterolemia
Pre-diabetes
Interventions: Drug: Metformin HCl and Colesevelam Placebo
Drug: Metformin HCl tablets and Colesevelam tablets
Drug: Colesevelam placebo
Drug: Colesevelam

  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
Two cohorts of participants, type 2 diabetics (T2DM) and pre-diabetics, were recruited from 07 Jan 2008 to 15 Dec 2008. The sites were located in Colombia, India, Mexico, and the USA. The sites included private physician offices, group practices, clinics, hospitals, institutes, and university centers.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Due to the different metabolic nature of the two groups the "Total" column under Baseline Characteristics is populated with data for the diabetic group, except where the total could be obtained by just adding the number of participants. Please note: in the outcomes section, LOCF=Last Observation carried forward

Reporting Groups
  Description
Type 2 Diabetes Group: Placebo + Metformin This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks.
Type 2 Diabetes Group: Colesevelam + Metformin This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks.
Pre-diabetic Group: Placebo This group was given 6 placebo tablets once a day. They matched the colesevelam tablets. This treatment duration was 16 weeks.
Pre-diabetic Group: Colesevelam This group was given 6 colesevelam tablets, 625mg, once a day. This treatment duration was 16 weeks.

Participant Flow:   Overall Study
    Type 2 Diabetes Group: Placebo + Metformin     Type 2 Diabetes Group: Colesevelam + Metformin     Pre-diabetic Group: Placebo     Pre-diabetic Group: Colesevelam  
STARTED     141     145     108     108  
COMPLETED     120     124     92     96  
NOT COMPLETED     21     21     16     12  
Adverse Event                 8                 6                 2                 2  
Lost to Follow-up                 4                 5                 4                 1  
Physician Decision                 1                 1                 0                 0  
Withdrawal by Subject                 7                 7                 3                 5  
Required restricted medication                 0                 0                 1                 0  
Met discontinuation criteria                 1                 0                 1                 1  
Not specified                 0                 2                 5                 3  



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Type 2 Diabetes Group: Placebo + Metformin This group received 6 matching colesevalm placebo tablets/day + open-label metformin. The dose of metformin depended on the participant's tolerability. This treatment duration was 16 weeks.
Type 2 Diabetes Group: Colesevelam + Metformin This group received 6 colevevelam tablets 625 mg once daily + open-label metformin once a day. The dose of metformin depended on the participant's tolerance for the drug. This treatment duration was 16 weeks.
Pre-diabetic Group: Placebo This group received 6 colesevelam matching placebo tablets once per day for 16 weeks
Pre-diabetic Group: Colesevelam This group received 6 colesevelam tablets, 625mg, once per day for 16 weeks.
Total Total of all reporting groups

Baseline Measures
    Type 2 Diabetes Group: Placebo + Metformin     Type 2 Diabetes Group: Colesevelam + Metformin     Pre-diabetic Group: Placebo     Pre-diabetic Group: Colesevelam     Total  
Number of Participants  
[units: participants]
  141     145     108     108     502  
Age  
[units: years]
Mean ± Standard Deviation
  53.9  ± 10.11     52.7  ± 11.46     55.7  ± 11.14     53.3  ± 12.27     53.3  ± 10.81  
Gender  
[units: participants]
         
Female     85     76     81     68     310  
Male     56     69     27     40     192  
Race/Ethnicity, Customized  
[units: Participants]
         
Asian     30     32     15     14     91  
Black/African American     1     3     1     1     6  
White     20     21     14     11     66  
Hispanic     90     89     78     82     339  
Region of Enrollment  
[units: participants]
         
United States     30     30     17     16     93  
Mexico     56     58     40     41     195  
Colombia     25     26     36     37     124  
India     30     31     15     14     90  
Previously diagnosed with neither diabetes nor pre-diabetes  
[units: Participant]
  14     15     26     22     77  
Previously diagnosed with pre-diabetes  
[units: Participant]
  17     21     81     85     204  
Previously diagnosed with type 2 diabetes  
[units: Participant]
  110     109     1     1     221  
Body Mass Index  
[units: kg/m squared]
Mean ± Standard Deviation
  29.78  ± 4.44     30.58  ± 4.669     30.82  ± 4.18     30.93  ± 4.89     30.19  ± 4.57  
Fasting glucose  
[units: mg/dL]
Mean ± Standard Deviation
  145.7  ± 37.54     153.4  ± 39.04     106.8  ± 14.80     104.1  ± 11.33     149.6  ± 38.43  
Fasting insulin  
[units: uIU/mL]
Mean ± Standard Deviation
  12.82  ± 8.44     13.86  ± 15.75     11.03  ± 5.55     13.12  ± 8.75     13.34  ± 12.66  
Glucose 2 hours after meal  
[units: mg/dL]
Mean ± Standard Deviation
  220.3  ± 58.68     234.7  ± 71.36     153.7  ± 39.81     153.7  ± 37.90     227.7  ± 65.74  
Height  
[units: cm]
Mean ± Standard Deviation
  160.6  ± 10.64     162.3  ± 9.67     159.1  ± 9.95     160.8  ± 9.96     161.5  ± 10.18  
Hemoglobin A1c  
[units: Percent]
Mean ± Standard Deviation
  7.53  ± 0.94     7.76  ± 1.04     6.07  ± 0.45     6.02  ± 0.46     7.65  ± 1.0  
Low Density Lipoprotein Cholesterol  
[units: mg/dL]
Mean ± Standard Deviation
  135.5  ± 26.66     129.1  ± 23.08     136.8  ± 28.48     132.8  ± 23.88     132.2  ± 25.07  
Weight  
[units: kg]
Mean ± Standard Deviation
  77.26  ± 16.17     80.84  ± 15.53     78.18  ± 13.76     80.63  ± 18.02     79.08  ± 15.92  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects.   [ Time Frame: Baseline to 16 weeks ]

2.  Primary:   Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

3.  Secondary:   Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks.   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

4.  Secondary:   Fasting Plasma Glucose When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

5.  Secondary:   Fasting Insulin When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

6.  Secondary:   Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

7.  Secondary:   30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

8.  Secondary:   1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

9.  Secondary:   2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

10.  Secondary:   2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

11.  Secondary:   2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

12.  Secondary:   The Percent Change of Low Density Lipoprotein Cholesterol (LDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

13.  Secondary:   Percent Change of Non-High Density Lipoprotein (Non-HDL) Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

14.  Secondary:   Percent Change of High Density Lipoprotein Cholesterol(HDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

15.  Secondary:   Percent Change of Total Cholesterol (TC) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

16.  Secondary:   Percent Change of Triglycerides (TG)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

17.  Secondary:   Percent Change of Apolipoprotein A-1 (Apo A-1) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

18.  Secondary:   Percent Change of Apolipoprotein B (Apo B)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

19.  Secondary:   Percent Change of Apolipoprotein C3 (Apo C3)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 weeks ]

20.  Secondary:   Change in the Levels of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 weeks ]

21.  Secondary:   Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

22.  Secondary:   Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

23.  Secondary:   Change in the Calculated Very Low Density Lipoprotein Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

24.  Secondary:   Change in the Calculated High Density Lipoprotein Cholesterol When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

25.  Secondary:   Percent of Subjects Achieving HbA1c Goal of <7.0% at Weeks 4, 8, 12, and 16 if Baseline HbA1c Was > or = to 7.0% When Given to Drug-naïve, Diabetics   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

26.  Secondary:   Percent of Subject Achieving HbA1c Goal of <6.5% at Weeks 4, 8, 12, and 16 When Given to Drug-naïve, Diabetic Subjects   [ Time Frame: Baseline to 4, 8, 12 and 16 weeks ]

27.  Secondary:   Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 When Given to Drug-naïve, Diabetic Subjects   [ Time Frame: Baseline to Weeks 8, and 16 ]

28.  Secondary:   Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol Goal of <70 mg/dL at Weeks 8, 16 When Given as to Drug-naïve, Diabetics   [ Time Frame: Baseline to Weeks 8, and 16 ]

29.  Secondary:   Change in Body Weight When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

30.  Secondary:   Change in Waist-to-Hip Ratio When Given to Drug-Naive Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

31.  Secondary:   Change in Plasma Glucose Area Under the Curve (0 to 120 Minutes) From the Baseline Glucose Tolerance Test (GTT) to the 16 Week GTT   [ Time Frame: Baseline vs. 16 Weeks ]

32.  Secondary:   Percent Change of Various Calculated Lipid Parameters When Given as Initial Therapy to Drug-naïve, Diabetic From Baseline to 16 Weeks Subjects   [ Time Frame: Baseline to 16 Weeks ]

33.  Secondary:   Percent of Subjects Achieving 2-Hr. Post Meal Glucose Goal of <180 mg/dL When Given to Drug-naïve, Diabetic Subjects From Baseline to Week 16   [ Time Frame: Baseline to Week 16 ]

34.  Secondary:   Percent of Subjects Achieving Hs-C-Reactive Protein Goal of <2.0 mg/L When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

35.  Secondary:   Percent Change in Low Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

36.  Secondary:   Percent Change in Non-High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

37.  Secondary:   Percent Change in High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

38.  Secondary:   Percent Change in Total Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

39.  Secondary:   Percent Change in Apolipoprotein A-1 in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

40.  Secondary:   Percent Change in Apolipoprotein B in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

41.  Secondary:   Percent Change in Apolipoprotein CIII in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

42.  Secondary:   Percent Change in Triglycerides in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks   [ Time Frame: Baseline to 8, and 16 Weeks ]

43.  Secondary:   Percent Change in Hs-C-Reactive Protein in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline 16 Weeks ]

44.  Secondary:   Level of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

45.  Secondary:   Particle Size of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

46.  Secondary:   Change of Various Calculated Lipid Parameters in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

47.  Secondary:   Percent Change of HbA1c in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

48.  Secondary:   Percent Change of Fasting Plasma Glucose in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 weeks ]

49.  Secondary:   Percent Change of Fasting Insulin in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

50.  Secondary:   Change of Fasting C-peptide Levels in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

51.  Secondary:   Change of Glucose Levels 30 Minutes Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

52.  Secondary:   Change of Glucose Levels 1 Hour Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

53.  Secondary:   Change of Glucose Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

54.  Secondary:   Change of Insulin Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

55.  Secondary:   Change of C-Peptide Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

56.  Secondary:   Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects   [ Time Frame: Baseline to 8, and 16 Weeks ]

57.  Secondary:   Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <70 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects   [ Time Frame: Baseline to 8, and 16 Weeks ]

58.  Secondary:   Change in Body Weight in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

59.  Secondary:   Change in Waist-to-Hip Ratio in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

60.  Secondary:   Area Under the Curve for Plasma Glucose From 0 to 120 Minutes During the Oral Glucose Tolerance Tests in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

61.  Secondary:   Percent Achievement of <140 mg/dL Plasma Glucose 2 Hours Post the Oral Glucose Tolerance Test in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was >or= to 140 mg/dL From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

62.  Secondary:   Percent Achievement of <110 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 110 mg/dL From Baseline to 4, 8, 12, and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12, and 16 Weeks ]

63.  Secondary:   Percent Achievement of <100 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 100 mg/dL From Baseline to 4, 8, 12 and 16 Weeks   [ Time Frame: Baseline to 4, 8, 12 and 16 weeks ]

64.  Secondary:   Percent Achievement of <140 mg/dL Plasma Glucose Post 2 Hour Glucose Tolerance Test and Fasting Plasma Glucose <110 mg/dL in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

65.  Secondary:   Percent Achievement of Hs-C-Reactive Protein <2.0 mg/L in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 2.0 mg/L From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]

66.  Secondary:   Percent of Subjects Meeting Type 2 Diabetes Criteria (Fasting Plasma Glucose >or= to 126 mg/dL or Plasma Glucose >or= to 200 mg/dL Post 2 Hr Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks   [ Time Frame: Baseline to 16 Weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: John Raia, Senior Director Professional Affairs
Organization: Daiichi Sankyo, Inc.
phone: (973) 944-2683
e-mail: jraia@dsi.com


No publications provided by Daiichi Sankyo Inc.

Publications automatically indexed to this study:

Responsible Party: Michael Jones, Sr. Director, Medical Affairs, Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00570739     History of Changes
Other Study ID Numbers: WEL-411, IND 68,466
Study First Received: December 10, 2007
Results First Received: April 6, 2010
Last Updated: July 19, 2010
Health Authority: United States: Food and Drug Administration