Colesevelam Treatment for Impaired Fasting Glucose During Niacin Therapy

Study Overview
=================
Brief Summary
-----------------
The present study will assess the low-density lipoprotein cholesterol (LDL-C) lowering effect of colesevelam as an adjunct to niacin for the improvement of lipids and glycemic control in dyslipidemic subjects with impaired fasting glucose.

Official Title
-----------------
A 12-Week, Double-Blind, Randomized, Placebo-Controlled Study to Assess the LDL Cholesterol Lowering and Anti-Hyperglycemic Efficacy of Welchol® (Colesevelam) in Subjects With Impaired Fasting Glucose Who Are Taking Niaspan® (Niacin) for Dyslipidemia

Conditions
-----------------
Dyslipidemia, Hyperlipidemia, Hyperglycemia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women ≥ 18 years of age. Non-HDL-C ≥100 mg/dL and ≤220 mg/dL at Visits 1 and 2. FPG ≥90 mg/dL and ≤145 mg/dL, at Visits 1 and 2. HDL-C <60 mg/dL at Visits 1 and 2, regardless of gender. Untreated dyslipidemia, or statin treatment only with equipotency to atorvastatin ≤40 mg daily for at least 12 weeks prior to Screening Visit 1 and without change or initiation prior to randomization Exclusion Criteria: Known intolerance to niacin or bile acid-sequestering drugs or aspirin. Any contraindication to a study medication (niacin, aspirin or colesevelam). History of dysphagia, swallowing disorders or intestinal motility disorders. History of pancreatitis. Fasting TG >500 mg/dL at Visits 1 and 2 Currently taking medication for diabetes mellitus, Type 1 or 2,or currently taking glucose-lowering drugs (e.g. metformin) for any other indication. Currently taking drugs that may affect glycemic and/or lipid control (e.g., beta-blockers, etc.) if started within the 12 weeks prior to Visit 1, or prior to randomization. This does not apply to dietary supplements.). Body mass index (BMI) >40 kg/m2. History of acute myocardial infarction, unstable angina, transient ischemic attacks, stroke or revascularization procedure within the 3 months prior to Visit 1 or prior to randomization. Use of prescription strength niacin, bile acid sequestrants, fibrates or omega-3 fatty acids within 8 weeks prior to Visit 1 or prior to randomization. This does not apply to dietary supplements. Unwilling to abstain, during the study, from weight-loss drugs (including over-the-counter) or weight-loss programs during the study. Current use, or intended use during the study, of cyclic hormones (e.g., oral or vaginal contraceptives and estrogen replacement therapy). Females who are pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential not using an acceptable method of contraception. Acceptable methods include intrauterine device, cervical diaphragm plus spermicide, female condom plus spermicide, or partner's use of condoms plus spermicide. Partner's vasectomy only or use of condoms or spermicide only are not considered acceptable forms of birth control. Current use, or intended use during the study of cyclosporine. Recent history (past 12 months) of illicit drug use or excessive ethanol use. Excessive ethanol use will be defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz hard liquor). Exposure to any investigational agent within 30 days prior to Visit 1, and prior to randomization. Individual has a condition the Investigator believes would interfere with his ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 6 tablets daily, with up to 2000 mg niacin and 325 mg aspirin daily, for 12 weeks<br>|
| Experimental: Colesevelam<br> | Drug: Colesevelam<br>* 6 tablets (3750 mg total) daily, with up to 2000 mg niacin and 325 mg aspirin daily, for 12 weeks<br>* Other names: Welchol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low-density lipoprotein cholesterol (LDL-C) | The primary efficacy endpoint will be the mean percent change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in LDL-C. It will be measured as part of the fasting lipid panel at Visits 1, 2, 3, 7, and 8/ET (Weeks -6 to -2, -1, 1, 10 and 12/ET). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose (FPG) | The principal secondary efficacy endpoint is the mean change in FPG from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12). | 12 weeks | 
| NMR Lipid subfractions and lipoprotein-IR score | A secondary efficacy endpoint is the mean change from baseline (Week 1) to end-of-treatment(Week 12) in NMR Lipid subfractions and lipoprotein-IR score. | 12 weeks | 
| Hemoglobin A1C (HbA1C) | A secondary efficacy endpoint is the mean change from baseline (Week 1) to end-of-treatment(Week 12) in HbA1c. | 12 weeks | 
| Fructosamine | A secondary efficacy endpoint is the mean change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in fructosamine. | 12 weeks | 
| High sensitivity c-reactive protein (hs-CRP) | A secondary efficacy endpoint is the mean change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in hs-CRP. | 12 weeks | 
| Niacin-related flushing | Niacin-associated flushing will be measured using a visual analog scale (VAS)at Weeks 2,4,6,10 and 12. | 12 weeks | 
| Homeostasis model assessment of insulin resistance (HOMA-IR) score | A secondary efficacy endpoint is the mean change from baseline (Week 1) to end-of-treatment (Week 12) in HOMA-IR. | 12 weeks | 
| High-density lipoprotein cholesterol (HDL-C) | A secondary endpoint is the mean percent change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in HDL-C. | 12 weeks | 
| Non-high-density lipoprotein cholesterol (non-HDL-C) | A secondary endpoint is the mean percent change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in non-HDL-C. | 12 weeks | 
| Total Cholesterol (TC) | A secondary endpoint is the mean percent change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in TC. | 12 weeks | 
| Triglycerides (TG) | A secondary endpoint is the mean percent change from baseline (average of Weeks -1 and 1) to end-of-treatment (average of Weeks 10 and 12) in TG. | 12 weeks | 
| Fasting Insulin | A secondary efficacy endpoint is the mean change from baseline (Week 1) to end-of-treatment (Week 12) in fasting insulin. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dyslipidemia, hyperlipidemia, hyperglycemia, impaired fasting glucose