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A 50-Week Extension Study on the Safety and Efficacy of Colesevelam in Adults with Primary Hypercholesterolemia

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American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

Colesevelam is a bile acid sequestrant that differs structurally from traditional bile acid sequestrants, allowing it to bind bile acids with greater affinity. Studies have shown that colesevelam significantly reduces low-density lipoprotein cholesterol (LDL-C) levels and, in some cases, significantly increases high-density lipoprotein cholesterol (HDL-C) levels in adults with primary hypercholesterolemia.

Objective

To investigate the safety and efficacy of colesevelam in adults with primary hypercholesterolemia.

Study Design

This multicenter, open-label, titration-based extension study enrolled subjects who completed one of three multicenter, randomized, double-blind, placebo-controlled phase II studies with colesevelam. This study consisted of a 4-week washout/dietary stabilization period, a 50-week open-label treatment period, and a 2-week follow-up period.

Setting

Ten clinical centers within the US.

Subjects

Males and females 18 years of age or older who had completed a previous short-term (4- or 6-week) phase II clinical study with colesevelam.

Intervention

At week 0 (following a 4-week washout of all lipid-lowering medication), subjects initiated treatment with colesevelam at a dosage of 1.5 g/day. Colesevelam was uptitrated to a maximum dosage of 3.75 g/day as necessary to achieve a 15–30% reduction from baseline in LDL-C level. At week 12, an HMG-CoA reductase inhibitor (statin) or niacin (nicotinic acid) could be added if colesevelam 3.75 g/day was not sufficient to result in a 15–30% reduction from baseline in LDL-C level.

Main Outcome Measure

The primary efficacy measure was the change in LDL-C level from baseline to week 50 across all treatment regimens. Secondary efficacy parameters included the change and percent change in total cholesterol, HDL-C, and triglyceride levels from baseline to week 50. There were three cohorts analyzed: (i) colesevelam monotherapy (included all subjects who received colesevelam monotherapy, regardless of dose); (ii) all treatment regimens (included all subjects who received colesevelam monotherapy or colesevelam plus low-dose statin or niacin therapy); and (iii) combination therapy (included only subjects who received colesevelam plus low-dose statin therapy). Two additional cohorts were also evaluated: (iv) maximum-dose colesevelam monotherapy (included only subjects who received colesevelam 3.75 g/day monotherapy); and (v) all maximum-dose colesevelam treatment regimens (included all subjects who received colesevelam 3.75 g/day, either as monotherapy or in combination with low-dose statin or niacin therapy).

Results

In total, 272 subjects were screened, 260 enrolled, and 186 completed the study. In total, 255 subjects were included in the intent-to-treat population. The maximum dosage of colesevelam (3.75 g/day) was taken by 50% of subjects (n = 94/188) at week 50; only 38 subjects received low-dose statin or niacin by study end. At week 50, LDL-C levels were significantly (p < 0.001) reduced from baseline across all treatment regimens (by 29.6 mg/dL [from 185.8 to 156.2 mg/dL; 15.0%]). Colesevelam also significantly reduced total cholesterol levels and significantly increased HDL-C and triglyceride levels across all treatment regimens (p <0.001 for all). Drug-related adverse events were reported by 36.2% of subjects across all treatment regimens (and by 47.4% of subjects who received colesevelam plus low-dose statin or niacin therapy).

Conclusion

In this study, colesevelam was found to be safe and effective for the management of LDL-C levels in adults with primary hypercholesterolemia.

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Acknowledgments

This study was sponsored by GelTex Pharmaceuticals, Inc. and was carried out between November 1996 and October 1998. In 2000, GelTex Pharmaceuticals, Inc. was acquired by Genzyme General, a division of Genzyme Corporation. Daiichi Sankyo, Inc. markets colesevelam hydrochloride (Welchol®). Medical writing services and editorial assistance provided by Karen Stauffer, PhD, of inScience Communications, a Wolters Kluwer business, were funded by Daiichi Sankyo, Inc. Although M.H. Davidson has received grant/research support and honorarium, and served as a consultant/speaker for several pharmaceutical companies, these have no influence or validity on the information provided in this study. J.M. Donovan is an employee of Genzyme Corporation, and S. Misir and M.R. Jones are employees of Daiichi Sankyo, Inc.

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Authors and Affiliations

  1. The University of Chicago Pritzker School of Medicine, 515 North State Street, Suite 2700, Chicago, IL, 60654, USA

    Michael H. Davidson (Director of Preventive Cardiology)

  2. Genzyme Corporation, Genzyme Center, Cambridge, Massachusetts, USA

    Joanne M. Donovan

  3. Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

    Soamnauth Misir & Michael R. Jones

Authors
  1. Michael H. Davidson
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  2. Joanne M. Donovan
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  3. Soamnauth Misir
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  4. Michael R. Jones
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Corresponding author

Correspondence to Michael H. Davidson.

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Davidson, M.H., Donovan, J.M., Misir, S. et al. A 50-Week Extension Study on the Safety and Efficacy of Colesevelam in Adults with Primary Hypercholesterolemia. Am J Cardiovasc Drugs 10, 305–314 (2010). https://doi.org/10.2165/11584310-000000000-00000

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  • DOI: https://doi.org/10.2165/11584310-000000000-00000

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