Trial Outcomes & Findings for Effects of Colesevelam on How the Body Responds to Insulin in Patients With Type 2 Diabetes (NCT NCT00147745)

Last Updated: 2014-04-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Baseline to 12 weeks

Results posted on

2014-04-02

Participant Flow

Subjects were recruited from 21 June 2005 to 22 January 2008 at 3 clinical research sites in the United States of America.

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.

Participant milestones

Participant milestones
Measure	Colesevelam 3.8g colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine open-label Insulin Glargine for 12 weeks
Overall Study STARTED	16	14	6
Overall Study COMPLETED	15	14	6
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Colesevelam 3.8g colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine open-label Insulin Glargine for 12 weeks
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Colesevelam 3.8g n=16 Participants colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo n=14 Participants Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine n=6 Participants open-label Insulin Glargine for 12 weeks	Total n=36 Participants Total of all reporting groups
Age, Continuous	55.7 years n=5 Participants	54.0 years n=7 Participants	52.8 years n=5 Participants	54.6 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized White	8 Participants n=5 Participants	9 Participants n=7 Participants	3 Participants n=5 Participants	20 Participants n=4 Participants
Race/Ethnicity, Customized Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	16 participants n=5 Participants	14 participants n=7 Participants	6 participants n=5 Participants	36 participants n=4 Participants
Body Mass	33.7 kg/m2 n=5 Participants	33.7 kg/m2 n=7 Participants	35.2 kg/m2 n=5 Participants	34.0 kg/m2 n=4 Participants
Fasting Plasma Glucose	162.6 mg/dL n=5 Participants	207.9 mg/dL n=7 Participants	199.0 mg/dL n=5 Participants	186.3 mg/dL n=4 Participants
HbA1c	8.2 percent n=5 Participants	8.5 percent n=7 Participants	9.3 percent n=5 Participants	8.5 percent n=4 Participants
Height	171.7 cm n=5 Participants	168.6 cm n=7 Participants	170.8 cm n=5 Participants	170.4 cm n=4 Participants
Weight	98.6 kg n=5 Participants	95.8 kg n=7 Participants	103.4 kg n=5 Participants	98.3 kg n=4 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Colesevelam 3.8g n=15 Participants colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo n=13 Participants Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine n=6 Participants open-label Insulin Glargine for 12 weeks
Difference in Endogenous (Hepatic) Glucose Output During a High-dose Insulin Infusion From Baseline to After 12 Weeks of Treatment.	-0.06 mg/kg/min Standard Error 0.048	-0.011 mg/kg/min Standard Error 0.051	-0.01 mg/kg/min Standard Error 0.076

PRIMARY outcome

Timeframe: Baseline to 12 weeks

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.

Outcome measures

Outcome measures
Measure	Colesevelam 3.8g n=15 Participants colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo n=13 Participants Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine n=6 Participants open-label Insulin Glargine for 12 weeks
Difference in Endogenous (Hepatic) Glucose Output During a Low-dose Insulin Infusion From Baseline to Week 12.	-0.08 mg/kg/min Standard Error 0.044	-0.16 mg/kg/min Standard Error 0.048	-0.04 mg/kg/min Standard Error 0.070

PRIMARY outcome

Timeframe: Baseline (Day -4) to first dose (Day 1)

Population: The entire study population was included in this analysis

Change in area under the curve for glucose (AUCg) after a glucose tolerance test. A decrease in AUCg is indicative of a drug effect.

Outcome measures

Outcome measures
Measure	Colesevelam 3.8g n=36 Participants colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine open-label Insulin Glargine for 12 weeks
Acute Effect of a Single Dose of Colesevelam on Oral Glucose Absorption From Baseline to First Dose	-38.4 mg*hr/dL Standard Deviation 105.75	—	—

SECONDARY outcome

Timeframe: Baseline to 12 weeks

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

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.

Outcome measures

Outcome measures
Measure	Colesevelam 3.8g n=15 Participants colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo n=14 Participants Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine n=6 Participants open-label Insulin Glargine for 12 weeks
The Acute Effect of Colesevelam (Multiple Doses) on Oral Glucose Absorption From Baseline to 12 Weeks	-49.1 mg*hr/dL Standard Error 36.75	-4.7 mg*hr/dL Standard Error 36.93	-59.3 mg*hr/dL Standard Error 57.27

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: 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.

The parameter measured is the percent of hemoglobin A that is glycosylated. A decrease in this parameter is indicative of improved glucose control.

Outcome measures

Outcome measures
Measure	Colesevelam 3.8g n=15 Participants colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo n=14 Participants Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine n=6 Participants open-label Insulin Glargine for 12 weeks
Change in Hemoglobin A1C Due to Effect of Colesevelam From Baseline to 12 Weeks	-0.29 percent Standard Error 0.258	0.16 percent Standard Error 0.260	-0.81 percent Standard Error 0.426

Adverse Events

Colesevelam 3.8g

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Colesevelam Matching Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Open-label Insulin Glargine

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

John Raia, Senior Director, Professional Affairs

Daiichi Sankyo, Inc

Phone: (973) 944-2683

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Colesevelam 3.8g n=16 participants at risk colesevelam 3.8g administered daily for 12 weeks	Colesevelam Matching Placebo n=14 participants at risk Colesevelam matching placebo for 12 weeks	Open-label Insulin Glargine n=6 participants at risk open-label Insulin Glargine for 12 weeks
Cardiac disorders ventricular extrasystoles	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Gastrointestinal disorders Constipation	37.5% 6/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Gastrointestinal disorders Diarrhea NOS	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Gastrointestinal disorders Flatulence	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Gastrointestinal disorders Gastroesophageal Reflux disease	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Gastrointestinal disorders Vomiting NOS	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
General disorders Infusion site pain	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	14.3% 2/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
General disorders Oedema	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Immune system disorders Seasonal allergy	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Infections and infestations Ear Infection NOS	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Infections and infestations Nasopharyngitis	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	14.3% 2/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Infections and infestations Sinusitis	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Infections and infestations Tooth Abcess	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Infections and infestations Vaginosis Fungal NOS	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Infections and infestations Viral Infection NOS	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Heat exhaustion	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Investigations Electrocardiogram QT prolonged	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Investigations Elecrtocariogram ST Segment Depression	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Investigations Electrocardiogram T Wave Abnormal	12.5% 2/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Investigations Electrocardiogram T Wave Inversion	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	14.3% 2/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Investigations Heart Rate Increased	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Back Pain	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Nervous system disorders Headache	12.5% 2/16 • 12 week treatment period plus 30 days after the last dose of study medication.	35.7% 5/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Nervous system disorders Migraine NOS	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	7.1% 1/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Reproductive system and breast disorders Erectile Dysfunction NOS	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal Pain	6.2% 1/16 • 12 week treatment period plus 30 days after the last dose of study medication.	14.3% 2/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Sinus Pain	0.00% 0/16 • 12 week treatment period plus 30 days after the last dose of study medication.	0.00% 0/14 • 12 week treatment period plus 30 days after the last dose of study medication.	16.7% 1/6 • 12 week treatment period plus 30 days after the last dose of study medication.