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Trial record 84 of 1009 for:    Area Under Curve AND insulin

Effects of Colesevelam on How the Body Responds to Insulin in Patients With Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00147745
Recruitment Status : Completed
First Posted : September 7, 2005
Results First Posted : December 4, 2009
Last Update Posted : April 2, 2014
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: Colesevelam
Drug: Colesevelam matching placebo
Drug: Insulin glargine (Lantus)
Enrollment 36
Recruitment Details Subjects were recruited from 21 June 2005 to 22 January 2008 at 3 clinical research sites in the United States of America.
Pre-assignment Details Subjects were taken off any non-sulfonylurea oral anti-diabetic agents for a period of time appropriate to the drug. Qualified subjects were randomized to colesevelam hydrochloride, placebo, or open-label insulin glargine for 12 weeks. Difficulties enrolling into the insulin group caused the size of this group to decrease from 15 to 6 subjects.
Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Hide Arm/Group Description colesevelam 3.8g administered daily for 12 weeks Colesevelam matching placebo for 12 weeks open-label Insulin Glargine for 12 weeks
Period Title: Overall Study
Started 16 14 6
Completed 15 14 6
Not Completed 1 0 0
Reason Not Completed
Withdrawal by Subject             1             0             0
Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine Total
Hide Arm/Group Description colesevelam 3.8g administered daily for 12 weeks Colesevelam matching placebo for 12 weeks open-label Insulin Glargine for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 16 14 6 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants 14 participants 6 participants 36 participants
55.7
(30 to 71)
54.0
(38 to 66)
52.8
(34 to 71)
54.6
(30 to 71)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 6 participants 36 participants
Female
4
  25.0%
6
  42.9%
1
  16.7%
11
  30.6%
Male
12
  75.0%
8
  57.1%
5
  83.3%
25
  69.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 6 participants 36 participants
Hispanic 1 2 2 5
Black or African American 5 3 1 9
White 8 9 3 20
Unknown or Not Reported 2 0 0 2
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants 14 participants 6 participants 36 participants
16 14 6 36
Body Mass  
Mean (Full Range)
Unit of measure:  Kg/m2
Number Analyzed 16 participants 14 participants 6 participants 36 participants
33.7
(24.6 to 46.1)
33.7
(27.7 to 44.8)
35.2
(29.9 to 46.7)
34.0
(24.6 to 46.7)
Fasting Plasma Glucose  
Mean (Full Range)
Unit of measure:  mg/dL
Number Analyzed 16 participants 14 participants 6 participants 36 participants
162.6
(81 to 208)
207.9
(135 to 418)
199.0
(129 to 314)
186.3
(81 to 418)
HbA1c  
Mean (Full Range)
Unit of measure:  Percent
Number Analyzed 16 participants 14 participants 6 participants 36 participants
8.2
(7.1 to 9.8)
8.5
(7.3 to 10.0)
9.3
(8.2 to 10.9)
8.5
(7.1 to 10.9)
Height  
Mean (Full Range)
Unit of measure:  Cm
Number Analyzed 16 participants 14 participants 6 participants 36 participants
171.7
(159 to 190)
168.6
(162 to 187)
170.8
(157 to 179)
170.4
(157 to 190)
Weight  
Mean (Full Range)
Unit of measure:  Kg
Number Analyzed 16 participants 14 participants 6 participants 36 participants
98.6
(73.2 to 128.5)
95.8
(72.8 to 130.5)
103.4
(75.8 to 144.8)
98.3
(72.8 to 144.8)
1.Primary Outcome
Title Difference in Endogenous (Hepatic) Glucose Output During a High-dose Insulin Infusion From Baseline to After 12 Weeks of Treatment.
Hide Description The parameter measured is the endogenous (hepatic) glucose output during a high-dose insulin infusion. A decrease after treatment with colesevelam is indicative of greater sensitivity of the liver to insulin.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed was all randomized subjects who received medication and had a baseline and at least 1 post-randomization assessment of an efficacy variable. One placebo participant did not have a valid post-randomization insulin clamp study. Therefore, the number included in the placebo group for this analysis was 13.
Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Hide Arm/Group Description:
colesevelam 3.8g administered daily for 12 weeks
Colesevelam matching placebo for 12 weeks
open-label Insulin Glargine for 12 weeks
Overall Number of Participants Analyzed 15 13 6
Least Squares Mean (Standard Error)
Unit of Measure: mg/kg/min
-0.06  (0.048) -0.011  (0.051) -0.01  (0.076)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Colesevelam Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5499
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval 95%
-0.10 to 0.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.070
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5723
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.05
Confidence Interval 95%
-0.23 to 0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.090
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Colesevelam Matching Placebo, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3138
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.09
Confidence Interval 95%
-0.09 to 0.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.091
Estimation Comments [Not Specified]
2.Primary Outcome
Title Difference in Endogenous (Hepatic) Glucose Output During a Low-dose Insulin Infusion From Baseline to Week 12.
Hide Description The parameter measured is the endogenous (hepatic) glucose output during a low-dose insulin infusion. A decrease is indicative of greater senstitivity of the liver to insulin.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed was all randomized subjects who received medication and had a baseline and at least 1 post-randomization assessment of an efficacy variable. One placebo participant did not have a valid post-randomization insulin clamp study. Therefore, the number included in the placebo group for this analysis was 13.
Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Hide Arm/Group Description:
colesevelam 3.8g administered daily for 12 weeks
Colesevelam matching placebo for 12 weeks
open-label Insulin Glargine for 12 weeks
Overall Number of Participants Analyzed 15 13 6
Least Squares Mean (Standard Error)
Unit of Measure: mg/kg/min
-0.08  (0.044) -0.16  (0.048) -0.04  (0.070)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Colesevelam Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2042
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.08
Confidence Interval 95%
-0.05 to 0.22
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.065
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6855
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval 95%
-0.20 to 0.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.083
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Colesevelam Matching Placebo, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1727
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval 95%
-0.05 to 0.29
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.085
Estimation Comments [Not Specified]
3.Primary Outcome
Title Acute Effect of a Single Dose of Colesevelam on Oral Glucose Absorption From Baseline to First Dose
Hide Description Change in area under the curve for glucose (AUCg) after a glucose tolerance test. A decrease in AUCg is indicative of a drug effect.
Time Frame Baseline (Day -4) to first dose (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The entire study population was included in this analysis
Arm/Group Title Colesevelam 3.8g
Hide Arm/Group Description:
colesevelam 3.8g administered daily for 12 weeks
Overall Number of Participants Analyzed 36
Mean (Standard Deviation)
Unit of Measure: mg*hr/dL
-38.4  (105.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0362
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title The Acute Effect of Colesevelam (Multiple Doses) on Oral Glucose Absorption From Baseline to 12 Weeks
Hide Description The parameter measured is the change in area under the curve for glucose(AUCg) after an oral glucose tolerance test. A decrease in AUCg indicative of drug effect on glucose absorption.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
One participant in the colesevelam 3.8g group discontinued. Therefore, 15 participants were included in this analysis.
Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Hide Arm/Group Description:
colesevelam 3.8g administered daily for 12 weeks
Colesevelam matching placebo for 12 weeks
open-label Insulin Glargine for 12 weeks
Overall Number of Participants Analyzed 15 14 6
Least Squares Mean (Standard Error)
Unit of Measure: mg*hr/dL
-49.1  (36.75) -4.7  (36.93) -59.3  (57.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Colesevelam Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4104
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -44.4
Confidence Interval 95%
-152.8 to 64.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 53.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8857
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.1
Confidence Interval 95%
-132.6 to 152.9
Parameter Dispersion
Type: Standard Error of the mean
Value: 69.98
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Colesevelam Matching Placebo, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4226
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -54.5
Confidence Interval 95%
-191.3 to 82.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 67.08
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Hemoglobin A1C Due to Effect of Colesevelam From Baseline to 12 Weeks
Hide Description The parameter measured is the percent of hemoglobin A that is glycosylated. A decrease in this parameter is indicative of improved glucose control.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

One participant in the colesevelam 3.8g group discontinued. Therefore, 15 participants were included in this analysis.

The least squares mean is adjusted for baseline values. This corrects for differences in baseline values between treatment groups.

Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Hide Arm/Group Description:
colesevelam 3.8g administered daily for 12 weeks
Colesevelam matching placebo for 12 weeks
open-label Insulin Glargine for 12 weeks
Overall Number of Participants Analyzed 15 14 6
Least Squares Mean (Standard Error)
Unit of Measure: percent
-0.29  (0.258) 0.16  (0.260) -0.81  (0.426)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Colesevelam Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2286
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.45
Confidence Interval 95%
-1.20 to 0.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.366
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Colesevelam 3.8g, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3184
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.52
Confidence Interval 95%
-0.53 to 1.57
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.515
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Colesevelam Matching Placebo, Open-label Insulin Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0613
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.97
Confidence Interval 95%
-1.99 to 0.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.500
Estimation Comments [Not Specified]
Time Frame 12 week treatment period plus 30 days after the last dose of study medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Hide Arm/Group Description colesevelam 3.8g administered daily for 12 weeks Colesevelam matching placebo for 12 weeks open-label Insulin Glargine for 12 weeks
All-Cause Mortality
Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/14 (0.00%)      0/6 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Colesevelam 3.8g Colesevelam Matching Placebo Open-label Insulin Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/16 (87.50%)      10/14 (71.43%)      4/6 (66.67%)    
Cardiac disorders       
ventricular extrasystoles  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
Gastrointestinal disorders       
Abdominal Pain Upper  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
Constipation  1  6/16 (37.50%)  1/14 (7.14%)  0/6 (0.00%)  0
Diarrhea NOS  1  1/16 (6.25%)  1/14 (7.14%)  0/6 (0.00%)  0
Flatulence  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
Gastroesophageal Reflux disease  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Vomiting NOS  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
General disorders       
Infusion site pain  1  0/16 (0.00%)  0 2/14 (14.29%)  0/6 (0.00%)  0
Oedema  1  1/16 (6.25%)  1/14 (7.14%)  0/6 (0.00%)  0
Immune system disorders       
Seasonal allergy  1  0/16 (0.00%)  0 0/14 (0.00%)  0 1/6 (16.67%) 
Infections and infestations       
Ear Infection NOS  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Nasopharyngitis  1  1/16 (6.25%)  2/14 (14.29%)  0/6 (0.00%)  0
Sinusitis  1  0/16 (0.00%)  0 0/14 (0.00%)  0 1/6 (16.67%) 
Tooth Abcess  1  1/16 (6.25%)  0/14 (0.00%)  0 1/6 (16.67%) 
Vaginosis Fungal NOS  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
Viral Infection NOS  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Injury, poisoning and procedural complications       
Heat exhaustion  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Investigations       
Electrocardiogram QT prolonged  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Elecrtocariogram ST Segment Depression  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Electrocardiogram T Wave Abnormal  1  2/16 (12.50%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Electrocardiogram T Wave Inversion  1  0/16 (0.00%)  0 2/14 (14.29%)  0/6 (0.00%)  0
Heart Rate Increased  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back Pain  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Pain in Extremity  1  0/16 (0.00%)  0 1/14 (7.14%)  1/6 (16.67%) 
Nervous system disorders       
Headache  1  2/16 (12.50%)  5/14 (35.71%)  1/6 (16.67%) 
Migraine NOS  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
Reproductive system and breast disorders       
Dysmenorrhea  1  0/16 (0.00%)  0 1/14 (7.14%)  0/6 (0.00%)  0
Erectile Dysfunction NOS  1  0/16 (0.00%)  0 0/14 (0.00%)  0 1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/16 (6.25%)  0/14 (0.00%)  0 0/6 (0.00%)  0
Pharyngolaryngeal Pain  1  1/16 (6.25%)  2/14 (14.29%)  1/6 (16.67%) 
Sinus Pain  1  0/16 (0.00%)  0 0/14 (0.00%)  0 1/6 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
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.
If identified by Daiichi Sankyo, Inc. (DSI), any of DSI's confidential information as defined herein shall be deleted…Nothing in this publication section shall be taken as giving DSI any right of editorial control over any publication prepared by Study Site.
Results Point of Contact
Name/Title: John Raia, Senior Director, Professional Affairs
Organization: Daiichi Sankyo, Inc
Phone: (973) 944-2683
EMail: jraia@dsi.com
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00147745     History of Changes
Other Study ID Numbers: WEL-201
First Submitted: September 2, 2005
First Posted: September 7, 2005
Results First Submitted: July 15, 2009
Results First Posted: December 4, 2009
Last Update Posted: April 2, 2014