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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study of the Efficacy and Safety of WELCHOL as Add-on to Pioglitazone Therapy for Type 2 Diabetes Mellitus (T2DM)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Colesevelam
* Drug: Placebo
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colesevelam<br>Participants receive six colesevelam tablets (3.8 grams/day) in addition to pioglitazone-based therapy (30 mg or 45 mg) | Drug: Colesevelam<br>* Colesevelam 625 mg tablets<br>* Other names: Welchol;Drug: Pioglitazone<br>* 30 mg or 45 mg pioglitazone therapy<br>* Other names: Actos;|
| Placebo Comparator: Placebo<br>Participants receive six placebo tablets in addition to pioglitazone-based therapy (30 mg or 45 mg) | Drug: Placebo<br>* Placebo tablets appearing to be colesevelam<br>* Other names: No drug;Drug: Pioglitazone<br>* 30 mg or 45 mg pioglitazone therapy<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 |  | Baseline, Week 24 | 

Secondary Outcome Measures

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