Colesevelam as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus

Phase 3

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Colesevelam; Drug: Pioglitazone

• Registration Number: NCT00789750
• Lead Sponsor: Daiichi Sankyo

Brief Summary

The current study investigates colesevelam as add-on therapy to pioglitazone to improve glycemic control in subjects with type 2 diabetes mellitus not adequately controlled with pioglitazone monotherapy or pioglitazone in combination with either metformin or a sulfonylurea. The study will evaluate if colesevelam add-on to pioglitazone therapy for type 2 diabetes mellitus will be safe, well tolerated, and efficacious.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-11-10
• Study First Submitted QC: 2008-11-10
• Study First Posted: 2008-11-13
• Study Start: 2009-04
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Disposition First Submitted: 2013-08-06
• Disposition First Submitted QC: 2013-08-06
• Disposition First Posted: 2013-08-12
• Results First Submitted: 2017-05-24
• Status Verified: 2017-06
• Results First Submitted QC: 2017-06-23
• Last Update Submitted: 2017-06-23
• Results First Posted: 2017-06-26
• Last Update Posted: 2017-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 562

Inclusion Criteria

• Diagnosis of Type 2 diabetes mellitus
• Inadequate glycemic control on a stable dose (at least 2 months prior to screening) of pioglitazone at 30 or 45 mg/day, with or without one or two other oral antidiabetic medications [metformin or a sulfonylurea, or dipeptidyl peptidase (DPP-IV) inhibitor]
• Hemoglobin A1c (HbA1c) >= 7.5% and =< 9.5% at screening
• Fasting plasma glucose =<240 mg/dL at randomization (Week 0/Day 1).
• Male or female >= 18 years of age.
• Women of childbearing potential must be using an adequate method of contraception as detailed per-protocol
• Fasting C-peptide level >0.5 ng/mL at screening
• Clinically stable in regards to medical conditions other than type 2 diabetes
• Concomitant medications are at stable doses for at least 30 days prior to enrollment, and are not anticipated to need adjustment during the study period

Exclusion Criteria

• History of Type 1 diabetes and/or history of ketoacidosis
• History of bowel obstruction
• History of hypertriglyceridemia-induced pancreatitis
• Fasting serum triglyceride concentration >500 mg/dL
• History of dysphagia, swallowing disorders, gastroparesis, other gastrointestinal motility disorders, major gastrointestinal surgery
• History of insulin use >= 2 weeks duration during the previous 3 months or a total of >2 months insulin therapy at any time prior to screening
• Treatment with bile acid sequestrants, including colesevelam within 3 months prior to screening
• Female subject who is pregnant or breastfeeding
• History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, or any revascularization within 6 months prior to screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants receive six placebo tablets in addition to pioglitazone-based therapy (30 mg or 45 mg)
Colesevelam	Pioglitazone	Participants receive six colesevelam tablets (3.8 grams/day) in addition to pioglitazone-based therapy (30 mg or 45 mg)
Colesevelam	Colesevelam	Participants receive six colesevelam tablets (3.8 grams/day) in addition to pioglitazone-based therapy (30 mg or 45 mg)
Placebo	Pioglitazone	Participants receive six placebo tablets in addition to pioglitazone-based therapy (30 mg or 45 mg)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24	Baseline, Week 24

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c at Week 16	Baseline, Week 16
Change From Baseline in HbA1c at Week 4	Baseline, Week 4
Number of Participants Achieving an HbA1c Goal of <7.0%	Week 24
Change From Baseline in HbA1c at Week 8	Baseline, Week 8
Number of Participants With a Decrease of >= 0.7 Percent in HbA1c	Week 24
Number of Participants With a Reduction in FPG of >= 30 mg/dL	Week 24
Percent Change From Baseline in Total Cholesterol (TC)	Baseline, Week 24	TC is measured in milligrams per deciliter (mg/dL)
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	Baseline, Week 24	LDL-C is measured in mg/dL
Percent Change From Baseline in Apolipoprotein A-1 (Apo A-I)	Baseline, Week 24	Apo A-1 is measured in mg/dL
Percent Change From Baseline in Apolipoprotein B (Apo B)	Baseline, Week 24	Apo B is measured in mg/dL
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	Baseline, Week 24	HOMA-IR is a calculation of fasting insulin and fasting glucose that shows the level of insulin resistance. Lower numbers are better.
Change From Baseline in Fasting C-peptide	Baseline, Week 24
Change From Baseline in Fasting Plasma Glucose (FPG)	Baseline, Week 24	In this study a reduction in FPG of at least 30 mg/dL is considered glycemic response.
Percent Change From Baseline in Non-HDL-C	Baseline, Week 24	Non-HDL-C is measured in mg/dL
Change From Baseline in Fasting Insulin Levels	Baseline, Week 24
Number of Participants With a Decrease of >= 0.5 Percent in HbA1c	Week 24
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	Baseline, Week 24	HDL-C is measured in mg/dL
Percent Change From Baseline in Triglycerides (TG)	Baseline, Week 24	TG are measured in mg/dL