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Michael R. Jones - One of the best experts on this subject based on the ideXlab platform.

  • Safety and efficacy of Colesevelam HCl in the treatment of elderly patients.
    Drugs & Aging, 2014
    Co-Authors: James R. Gavin, Michael R. Jones, Ford Dm, Kenneth E Truitt
    Abstract:

    Background and objectives Colesevelam significantly lowers cholesterol in patients with hypercholesterolemia, and both cholesterol and hemoglobin A1C (A1C) in patients with type 2 diabetes mellitus (T2DM). The purpose of this post hoc analysis was to evaluate the efficacy and safety/tolerability of Colesevelam in older (≥65 years) and younger (

  • effect of Colesevelam hcl monotherapy on lipid particles in type 2 diabetes mellitus
    Cardiovascular Drugs and Therapy, 2014
    Co-Authors: Robert S Rosenson, Michael R. Jones, S P Rigby, Hubert S. Chou
    Abstract:

    Purpose In addition to lowering hemoglobin A1C, Colesevelam has been shown to improve the atherogenic lipoprotein profile of subjects with type 2 diabetes mellitus (T2DM) when used in combination with metformin and/or sulfonylureas. A recent study evaluated the effects of Colesevelam as antidiabetes monotherapy in adults with T2DM who had inadequate glycemic control (hemoglobin A1C ≥7.5 to ≤9.5 %) with diet and exercise alone; we report here the effects on lipoprotein particle subclasses.

  • atypical mechanism of glucose modulation by Colesevelam in patients with type 2 diabetes
    Clinical medicine insights. Endocrinology and diabetes, 2013
    Co-Authors: O M Nwose, Michael R. Jones
    Abstract:

    Colesevelam’s glucose-lowering mechanism of action is not completely understood. Clinical trials of Colesevelam suggest that its mechanism, and often adverse effects, differ from those of other oral antidiabetes drugs. Colesevelam does not affect insulin sensitivity (unlike thiazolidinediones), insulin secretion (unlike sulfonylureas and meglitinides), or early insulin response or glucagon (unlike dipeptidyl peptidase-4 inhibitors). Colesevelam may have some effect on glucose absorption, but likely via a different mechanism than α-glucosidase inhibitors. Colesevelam and metformin have similarities regarding hepatic glucose production, but divergent effects on gluconeogenesis versus glycogenolysis, suggesting differing mechanisms of drug action for improving glycemic control. Colesevelam is thought to be a portal glucagon-like peptide-1 (GLP-1) secretagogue with primarily hepatic effects. Bile acid binding by Colesevelam leads to TGR5 activation, increased secretion of GLP-1 or other incretins, and inhibition of hepatic glycogenolysis. Colesevelam’s mechanism of action appears to be atypical of other antidiabetes medications, making it a potentially suitable component of many combination regimens in the treatment of type 2 diabetes.

  • Role of Colesevelam in Combination Lipid-Lowering Therapy
    American Journal of Cardiovascular Drugs, 2013
    Co-Authors: Michael R. Jones, Oliseyenum M. Nwose
    Abstract:

    Hyperlipidemia is associated with an increased risk of cardiovascular events; reducing low-density lipoprotein cholesterol (LDL-C), the primary target for cholesterol-lowering therapy, lowers the risk for such events. Although bile acid sequestrants were the first class of drugs to show a mortality benefit related to LDL-C lowering, statins are now considered first-line pharmacological therapy for reducing LDL-C levels because of their potency and their remarkable record of successful outcomes studies. Nevertheless, a substantial proportion of patients do not achieve LDL-C goals with statin monotherapy. In addition, because of adverse effects (primarily myopathy), some patients may be unwilling to use or unable to tolerate statin therapy at all or may not tolerate a full therapeutic statin dose. Also, statins may increase risk of new-onset diabetes in patients at high risk for diabetes. Thus, there remains a need for other lipid-lowering drugs to be used in combination with or in place of statins. The purpose of this article is to review available data from the literature on the use of Colesevelam, a second-generation bile acid sequestrant, in combination with other lipid-lowering agents. Colesevelam has been studied in combination with statins, niacin, fibrates, and ezetimibe (including some three-drug combinations). An additive reduction in LDL-C was seen with all combinations. Other observed effects of Colesevelam in combination with other lipid-lowering drugs include reductions in apolipoprotein (apo) B (with statins, fibrates, ezetimibe, statin plus niacin, or statin plus ezetimibe) and high-sensitivity C-reactive protein (with statins), and increases in apo A-I (with statins, ezetimibe, or statins plus niacin). Triglyceride levels remained relatively unchanged when Colesevelam was combined with statins, fibrates, ezetimibe, or statin plus ezetimibe, and decreased with the triple combination of Colesevelam, statin, and niacin. Colesevelam offset the negative glycemic effects of statins and niacin in subjects with insulin resistance or impaired glucose tolerance. Colesevelam was generally well tolerated when added to other lipid-lowering therapies in clinical trials, with gastrointestinal effects such as constipation being the predominant adverse events. Since Colesevelam is not absorbed and works primarily in the intestine, it has a low potential for systemic metabolic drug–drug interactions with other drugs. Colesevelam has been shown to not interact with the lipid-lowering drugs lovastatin and fenofibrate; where interaction may be anticipated, separating dosing times by 4 h reduces the impact of any interaction. Available data confirms that Colesevelam has additive cholesterol-lowering effects when used in combination with other lipid-lowering therapies. Furthermore, in some patient populations, the additional glucose-lowering effect of Colesevelam may be beneficial in offsetting hyperglycemic effects of other lipid-lowering drugs.

  • Colesevelam improved lipoprotein particle subclasses in patients with prediabetes and primary hyperlipidaemia
    Diabetes and Vascular Disease Research, 2013
    Co-Authors: Ronald B Goldberg, Soamnauth Misir, Robert S Rosenson, Eric Hernandeztriana, Michael R. Jones
    Abstract:

    Background: A randomised, double-blind, placebo-controlled study evaluated lipid- and glucose-lowering effects of Colesevelam in patients with prediabetes and primary hyperlipidaemia. We report the effect of Colesevelam on lipoprotein particle concentration and particle size (determined by nuclear magnetic resonance spectroscopy) in these patients. Methods: Adults with prediabetes (World Health Organization criteria), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥2.6 mmol/L) and triglycerides < 500 mg/dL (<5.6 mmol/L) were randomised to Colesevelam 3.75 g/day or placebo for 16 weeks. The intent-to-treat population comprised 103 Colesevelam and 106 placebo recipients. Results: At the end of the study, mean reduction from baseline in total LDL particle concentration was significantly greater with Colesevelam versus placebo (mean treatment difference: −113 nmol/L; p = 0.02). Increases in total very low-density lipoprotein particle concentration (VLDL-P) and high-density lipoprotein particle concentration (HDL-P) did not differ significantly between the groups; however, with Colesevelam versus placebo, there were significantly (p < 0.05) greater increases in large and medium VLDL-P and large HDL-P and reductions in small VLDL-P. Mean size increases were significantly greater with Colesevelam for VLDL (mean treatment difference: 5.3 nm; p < 0.0001) and HDL (0.1 nm; p = 0.002). Conclusions: Colesevelam improved the overall atherogenic lipoprotein profile in adults with prediabetes and primary hyperlipidaemia, despite potentially less favourable changes in VLDL particles.

Michael H Davidson - One of the best experts on this subject based on the ideXlab platform.

  • effect of Colesevelam and niacin on low density lipoprotein cholesterol and glycemic control in subjects with dyslipidemia and impaired fasting glucose
    Journal of Clinical Lipidology, 2013
    Co-Authors: Michael H Davidson, Michael W Rooney, Elisabeth Pollock, Joan Drucker, Young Choy
    Abstract:

    Background Niacin monotherapy in patients with dyslipidemia and impaired fasting glucose (IFG) may result in hyperglycemia. Colesevelam has the unique dual approvals to lower low-density lipoprotein cholesterol (LDL-C) and to improve glycemic control in type 2 diabetes mellitus. Objectives The aim of our study was to evaluate the effect of combined Colesevelam and niacin treatment on LDL-C–lowering and glycemic control in subjects with IFG and dyslipidemia. Methods Men or women ≥ 18 years of age, with dyslipidemia (non–high-density lipoprotein cholesterol ≥ 100 mg/dL and ≤ 220 mg/dL; high-density lipoprotein cholesterol Results Adjunct Colesevelam had significantly greater LDL-C–lowering effect than niacin alone (placebo); –20.67% vs −12.86%, respectively ( P  = .0088). Niacin-mediated increases in FPG were significantly less with adjunct Colesevelam (1.8 mg/dL vs 6.7 mg/dL; P  = .0046), and fewer Colesevelam subjects had increases of ≥10 mg/dL in FPG (8 vs 17, respectively). Adjunct Colesevelam resulted in significantly smaller increases in hemoglobin A 1c than placebo (0.06% vs 0.18%, respectively; P  = .005). Consistent with hemoglobin A 1c and FPG changes, fructosamine levels significantly decreased with Colesevelam treatment (−5.0 μmol/L) but increased with placebo (3.0 μmol/L; P  =.0255). Conclusions Colesevelam as an adjunct to niacin therapy further lowers LDL-C while obviating the adverse effects of niacin on glucose metabolism in patients with dyslipidemia and IFG.

  • the efficacy of Colesevelam hcl in the treatment of heterozygous familial hypercholesterolemia in pediatric and adult patients
    Clinical Therapeutics, 2013
    Co-Authors: Michael H Davidson
    Abstract:

    Abstract Background Familial hypercholesterolemia (FH) is a common autosomal co-dominant genetic disorder that results in severely increased levels of LDL-C. Patients with FH are at an increased risk for premature coronary artery disease. Expert panels therefore recommend initiation of lipid-lowering therapy in childhood to reduce the very high lifetime risk of coronary artery disease. The bile acid sequestrant Colesevelam is indicated to reduce elevated LDL-C levels in adults with primary hyperlipidemia and in boys and postmenarchal girls (aged 10–17 years) with heterozygous FH. Objective The purpose of this article was to review currently available data on the use of Colesevelam in the treatment of heterozygous FH. Methods PubMed and Google Scholar were searched to identify clinical trials evaluating Colesevelam in patients with heterozygous FH. Results The search returned 2 results (both multicenter, multinational studies): 1 study conducted in adults and the other in pediatric patients. In the study in adults with refractory FH, the addition of Colesevelam to a maximally tolerated regimen of a statin plus ezetimibe provided a significantly greater reduction from baseline in LDL-C levels compared with placebo. Significantly greater reductions from baseline in LDL-C were also seen in pediatric patients with heterozygous FH receiving Colesevelam (alone or in combination with statins) compared with placebo. Colesevelam was generally well tolerated in studies in patients with FH; consistent with other Colesevelam studies, gastrointestinal disorders were the most common drug-related adverse events, but these events rarely led to study withdrawal. Conclusions Currently available data demonstrate that Colesevelam, alone or in combination therapy, is efficacious and well tolerated in the treatment of heterozygous FH in adults and pediatric patients, supporting its use as a treatment option in both of these patient populations.

  • A 50-week extension study on the safety and efficacy of Colesevelam in adults with primary hypercholesterolemia.
    American Journal of Cardiovascular Drugs, 2012
    Co-Authors: Michael H Davidson, Joanne M Donovan, Soamnauth Misir, Michael R. Jones
    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 

  • A 50-Week Extension Study on the Safety and Efficacy of Colesevelam in Adults with Primary Hypercholesterolemia
    American Journal of Cardiovascular Drugs, 2010
    Co-Authors: Michael H Davidson, Joanne M Donovan, Soamnauth Misir, Michael R. Jones
    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

  • a 50 week extension study on the safety and efficacy of Colesevelam in adults with primary hypercholesterolemia
    American Journal of Cardiovascular Drugs, 2010
    Co-Authors: Michael H Davidson, Joanne M Donovan, Soamnauth Misir, Michael R. Jones
    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.

Steven K Burke - One of the best experts on this subject based on the ideXlab platform.

  • effects of Colesevelam hcl on sterol and bile acid excretion in patients with type iia hypercholesterolemia
    Digestive Diseases and Sciences, 2005
    Co-Authors: Joanne M Donovan, Jonathan L Isaacsohn, K Von Bergmann, K D R Setchell, A S Pappu, D R Illingworth, T Olson, Steven K Burke
    Abstract:

    Colesevelam HCl is a potent bile acid–binding polymer. This study's aim was to determine effects of Colesevelam HCl on sterol and bile acid excretion in patients with type IIa hypercholesterolemia. Twenty-four patients (low-density lipoprotein cholesterol, 130 to 220 mg/dL) enrolled in an open-label, parallel-design study, entered an American Heart Association/National Cholesterol Education Program diet for 6 weeks and were randomized to Colesevelam HCl, 2.3 or 3.8 g/day for 4 weeks. In an apparent dose-related manner, respective mean serum concentrations of low-density lipoprotein cholesterol decreased by 10% (P < 0.01) and 13% (P = 0.05), mean total cholesterol levels decreased by 4.9% (P = 0.05) and 6.1% (P = 0.09), and total fecal bile acid excretion showed median changes of +324% (P < 0.05) and +316% (P < 0.05). Colesevelam HCl did not affect fecal neutral sterol or fecal fatty acid excretion; however, 24-hr urinary mevalonic acid levels significantly increased in both treatment groups (P < 0.05). The cholesterol-lowering action of Colesevelam HCl appears to be mediated through increased bile acid excretion.

  • absorption of Colesevelam hydrochloride in healthy volunteers
    Annals of Pharmacotherapy, 2002
    Co-Authors: Dennis P Heller, Steven K Burke, David M Davidson, Joanne M Donovan
    Abstract:

    OBJECTIVE:To assess whether Colesevelam hydrochloride is absorbed in healthy volunteers.METHODS:A single-center, open-label, radiolabeled study was performed with 16 healthy volunteers. Subjects were administered non-radiolabeled Colesevelam hydrochloride 1.9 g twice daily for 4 weeks, followed by a single dose of [14C]-Colesevelam 2.4 g (480 μCi). These subjects continued to receive non-radioactive Colesevelam 1.9 g twice daily for 4 days after administration of the radiolabeled dose. Blood, urine, and feces were collected immediately prior to administration of [14C]-Colesevelam and at specified intervals after administration. The whole-blood equivalent concentration of Colesevelam was calculated using data collected throughout the 96 hours following radiolabeled drug administration. The proportion of [14C]-Colesevelam excreted through urine or feces was calculated based on the amount of radioactivity recovered up to 216 hours after the radiolabeled dose.RESULTS:The mean cumulative total recovery of [14C...

  • effect of Colesevelam on lovastatin pharmacokinetics
    Annals of Pharmacotherapy, 2002
    Co-Authors: Joanne M Donovan, James C Kisicki, Mark R Stiles, William G Tracewell, Steven K Burke
    Abstract:

    OBJECTIVE:To assess potential interactions of Colesevelam hydrochloride and lovastatin in healthy volunteers when lovastatin alone was administered with dinner, both lovastatin and Colesevelam were administered with dinner, and Colesevelam was administered with dinner and lovastatin was administered 4 hours later with a snack.METHODS:A single-center, open-label, 3-period, crossover drug interaction study was performed with 22 healthy volunteers. Blood samples were collected at specified intervals before and after dosing, and plasma concentrations of lovastatin and lovastatin hydroxyacid were measured using a liquid chromatography/mass spectroscopy/mass spectroscopy method.RESULTS:Maximal concentration (Cmax), AUC from time 0 to the last time point measured (AUC0-t), and AUC0-∞ values for lovastatin were 102%, 94%, and 104%, and for lovastatin hydroxyacid were 102%, 91%, and 92%, respectively, of control values when Colesevelam and lovastatin were coadministered with dinner. Administration of Colesevelam w...

  • coadministration of Colesevelam hydrochloride with atorvastatin lowers ldl cholesterol additively
    Atherosclerosis, 2001
    Co-Authors: Donald B Hunninghake, Phillip Toth, Joanne M Donovan, David M Davidson, William Insull, Steven K Burke
    Abstract:

    Colesevelam hydrochloride is a novel, potent, non-absorbed lipid-lowering agent previously shown to reduce low density lipoprotein (LDL) cholesterol. To examine the efficacy and safety of coadministration of Colesevelam and atorvastatin, administration of these agents alone or in combination was examined in a double-blind study of 94 hypercholesterolemic men and women (baseline LDL cholesterol ≥160 mg/dl). After 4 weeks on the American Heart Association Step I diet, patients were randomized among five groups: placebo; Colesevelam 3.8 g/day; atorvastatin 10 mg/day; coadminstered Colesevelam 3.8 g/day plus atorvastatin 10 mg/day; or atorvastatin 80 mg/day. Fasting lipids were measured at screening, baseline and 2 and 4 weeks of treatment. LDL cholesterol decreased by 12–53% in all active treatment groups (P<0.01). LDL cholesterol reductions with combination therapy (48%) were statistically superior to Colesevelam (12%) or low-dose atorvastatin (38%) alone (P<0.01), but similar to those achieved with atorvastatin 80 mg/day (53%). Total cholesterol decreased 6–39% in all active treatment groups (P<0.05). High density lipoprotein cholesterol increased significantly for all groups including placebo (P<0.05). Triglycerides decreased in patients taking atorvastatin alone (P<0.05), but were unaffected by Colesevelam alone or in combination. The frequency of side effects did not differ among groups. At recommended starting doses of each agent, coadministration of Colesevelam and atorvastatin was well tolerated, efficacious and produced additive LDL cholesterol reductions comparable to those observed with the maximum atorvastatin dose.

  • Coadministration of Colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively.
    Atherosclerosis, 2001
    Co-Authors: Donald B Hunninghake, Joanne M Donovan, David M Davidson, Phillip D Toth, William Insull, Steven K Burke
    Abstract:

    Colesevelam hydrochloride is a novel, potent, non-absorbed lipid-lowering agent previously shown to reduce low density lipoprotein (LDL) cholesterol. To examine the efficacy and safety of coadministration of Colesevelam and atorvastatin, administration of these agents alone or in combination was examined in a double-blind study of 94 hypercholesterolemic men and women (baseline LDL cholesterol ≥160 mg/dl). After 4 weeks on the American Heart Association Step I diet, patients were randomized among five groups: placebo; Colesevelam 3.8 g/day; atorvastatin 10 mg/day; coadminstered Colesevelam 3.8 g/day plus atorvastatin 10 mg/day; or atorvastatin 80 mg/day. Fasting lipids were measured at screening, baseline and 2 and 4 weeks of treatment. LDL cholesterol decreased by 12–53% in all active treatment groups (P

Joanne M Donovan - One of the best experts on this subject based on the ideXlab platform.

  • A 50-week extension study on the safety and efficacy of Colesevelam in adults with primary hypercholesterolemia.
    American Journal of Cardiovascular Drugs, 2012
    Co-Authors: Michael H Davidson, Joanne M Donovan, Soamnauth Misir, Michael R. Jones
    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 

  • A 50-Week Extension Study on the Safety and Efficacy of Colesevelam in Adults with Primary Hypercholesterolemia
    American Journal of Cardiovascular Drugs, 2010
    Co-Authors: Michael H Davidson, Joanne M Donovan, Soamnauth Misir, Michael R. Jones
    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

  • a 50 week extension study on the safety and efficacy of Colesevelam in adults with primary hypercholesterolemia
    American Journal of Cardiovascular Drugs, 2010
    Co-Authors: Michael H Davidson, Joanne M Donovan, Soamnauth Misir, Michael R. Jones
    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.

  • Colesevelam hcl improves fasting plasma glucose and lipid levels in patients with prediabetes
    Postgraduate Medicine, 2009
    Co-Authors: Yehuda Handelsman, Joanne M Donovan, Stacey L Abby, Michael R. Jones
    Abstract:

    AbstractAlthough Colesevelam hydrochloride (HCl) is indicated to reduce low-density lipoprotein cholesterol (LDL-C) in patients with hyperlipidemia and improve glycemic control in patients with type 2 diabetes, its effects on glucose and lipids in patients with prediabetes have not been previously studied. To evaluate the effects of Colesevelam HCl in patients with prediabetes, a post-hoc analysis was conducted on data from a 24-week lipid-lowering study. Using baseline laboratory safety data for fasting plasma glucose (FPG), 88 patients were identified as having prediabetes according to American Diabetes Association criteria. Fasting plasma glucose was reduced by 4.0 mg/dL with Colesevelam HCl 3.8 g/day and by 6.1 mg/dL with Colesevelam HCl 4.5 g/day compared with placebo. Additionally, LDL-C was reduced by 13.2% and 12.0% with Colesevelam HCl 3.8 and 4.5 g/day, respectively, versus placebo. Colesevelam HCl 3.8 g/day also significantly reduced total cholesterol and apolipoprotein (apo)B levels, whereas n...

  • effects of Colesevelam hcl on sterol and bile acid excretion in patients with type iia hypercholesterolemia
    Digestive Diseases and Sciences, 2005
    Co-Authors: Joanne M Donovan, Jonathan L Isaacsohn, K Von Bergmann, K D R Setchell, A S Pappu, D R Illingworth, T Olson, Steven K Burke
    Abstract:

    Colesevelam HCl is a potent bile acid–binding polymer. This study's aim was to determine effects of Colesevelam HCl on sterol and bile acid excretion in patients with type IIa hypercholesterolemia. Twenty-four patients (low-density lipoprotein cholesterol, 130 to 220 mg/dL) enrolled in an open-label, parallel-design study, entered an American Heart Association/National Cholesterol Education Program diet for 6 weeks and were randomized to Colesevelam HCl, 2.3 or 3.8 g/day for 4 weeks. In an apparent dose-related manner, respective mean serum concentrations of low-density lipoprotein cholesterol decreased by 10% (P < 0.01) and 13% (P = 0.05), mean total cholesterol levels decreased by 4.9% (P = 0.05) and 6.1% (P = 0.09), and total fecal bile acid excretion showed median changes of +324% (P < 0.05) and +316% (P < 0.05). Colesevelam HCl did not affect fecal neutral sterol or fecal fatty acid excretion; however, 24-hr urinary mevalonic acid levels significantly increased in both treatment groups (P < 0.05). The cholesterol-lowering action of Colesevelam HCl appears to be mediated through increased bile acid excretion.

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  • Long-term (52–78 weeks) treatment with Colesevelam HCl added to metformin therapy in type 2 diabetes mellitus patients
    Diabetes Metabolic Syndrome and Obesity: Targets and Therapy, 2012
    Co-Authors: Harold E Bays
    Abstract:

    OBJECTIVE: To evaluate the long-term safety, tolerability, and efficacy of Colesevelam HCl (Colesevelam) in type 2 diabetes mellitus patients receiving metformin monotherapy or metformin combination therapy. METHODS: This post-hoc subgroup analysis examined data from type 2 diabetes mellitus patients aged 18 to 75 years with a hemoglobin A(1c) of 7.5% to 9.5%, who received metformin as part of their treatment via their participation in one of three randomized, double-blind base studies wherein Colesevelam (3.75 g/day) or a placebo was added to existing metformin-, insulin-, or sulfonylurea-based treatment. After completing the base studies, the subjects who initially received blinded Colesevelam (n = 196) or the placebo (n = 166) entered a 52-week extension study wherein they received open-label Colesevelam (3.75 g/day). RESULTS: This analysis describes the 362 patients receiving background metformin therapy who also received open-label Colesevelam (3.75 g/day) during a 1-year extension study. From a safety perspective, hypoglycemia was reported by 11 patients (3.0%; none severe). Drug-related adverse events (AEs) occurred in 38 patients (10.5%). At least one serious AE occurred in 35 patients (9.7%), with only one being assessed by investigators as drug related (exacerbation of diverticulitis). Twenty-four patients (6.6%) discontinued open-label treatment because of an AE (10 due to a drug-related AE). Compared with baseline values obtained prior to the start of both the base and extension studies, Colesevelam improved and maintained improvement in hemoglobin A(1c) and various lipid parameters. CONCLUSION: This analysis found Colesevelam to be generally safe and effective for long-term therapy in type 2 diabetes mellitus patients with inadequately controlled glucose while treated with metformin monotherapy or metformin combination therapy.

  • Colesevelam hydrochloride added to background metformin therapy in patients with type 2 diabetes mellitus a pooled analysis from 3 clinical studies
    Endocrine Practice, 2011
    Co-Authors: Harold E Bays
    Abstract:

    OBJECTIVE: To evaluate the glucose- and lipid-altering efficacy of Colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM). METHODS: This post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo-controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive Colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin. RESULTS: In this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive Colesevelam HCl and 341 to receive placebo. In comparison with placebo, Colesevelam HCl significantly reduced hemoglobin A1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P<.001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P<.0001 for all). Median triglyceride levels were increased with Colesevelam HCl (median treatment difference: +12.8%; P<.0001). In comparison with placebo, Colesevelam HCl significantly increased apo A-I (mean treatment difference: +3.3%; P<.0001), whereas the mean increase in HDL-C with Colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated. CONCLUSION: When added to metformin-including therapy, Colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non-HDL-C, and apo B in patients with inadequately controlled T2DM.

  • Colesevelam hydrochloride added to background metformin therapy in patients with type 2 diabetes mellitus: a pooled analysis from 3 clinical studies.
    Endocrine Practice, 2011
    Co-Authors: Harold E Bays
    Abstract:

    OBJECTIVE: To evaluate the glucose- and lipid-altering efficacy of Colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM). METHODS: This post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo-controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive Colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin. RESULTS: In this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive Colesevelam HCl and 341 to receive placebo. In comparison with placebo, Colesevelam HCl significantly reduced hemoglobin A1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P

  • Colesevelam hydrochloride powder for oral suspension versus cholestyramine powder for oral suspension: comparison of acceptability and tolerability.
    Endocrine Practice, 2011
    Co-Authors: Harold E Bays, Kevin C Maki, Kathy Schmitz
    Abstract:

    OBJECTIVE: To compare tolerability of Colesevelam hydrochloride powder versus a cholesterol-lowering equivalent dose of generic cholestyramine powder, each mixed in water, by means of the validated Bile Acid Sequestrant Acceptability (BASA) Scale. METHODS: We conducted a randomized, single-blind, single-visit, single-site study, comparing doses of 2 different bile acid sequestrant powders for oral suspension that produce similar cholesterol lowering: Colesevelam hydrochloride (3.75 g) and generic cholestyramine (12 g), each mixed in a transparent cup with tap water. RESULTS: The study sample consisted of 42 participants-12 men and 30 women. The study subjects were non-Hispanic white (64%) or black (36%), with a mean age of 50 years and a mean body mass index of 32.2 kg/m2. The components of the BASA Scale included taste, texture, appearance, and mixability. Colesevelam hydrochloride and cholestyramine did not differ significantly when assessed by both the unweighted and the weighted global BASA Scale. Although study participants indicated that the colorless or whitish Colesevelam hydrochloride powder tasted better (P

  • Colesevelam hydrochloride powder for oral suspension versus cholestyramine powder for oral suspension comparison of acceptability and tolerability
    Endocrine Practice, 2011
    Co-Authors: Harold E Bays, Kevin C Maki, Kathy Schmitz
    Abstract:

    OBJECTIVE: To compare tolerability of Colesevelam hydrochloride powder versus a cholesterol-lowering equivalent dose of generic cholestyramine powder, each mixed in water, by means of the validated Bile Acid Sequestrant Acceptability (BASA) Scale. METHODS: We conducted a randomized, single-blind, single-visit, single-site study, comparing doses of 2 different bile acid sequestrant powders for oral suspension that produce similar cholesterol lowering: Colesevelam hydrochloride (3.75 g) and generic cholestyramine (12 g), each mixed in a transparent cup with tap water. RESULTS: The study sample consisted of 42 participants-12 men and 30 women. The study subjects were non-Hispanic white (64%) or black (36%), with a mean age of 50 years and a mean body mass index of 32.2 kg/m2. The components of the BASA Scale included taste, texture, appearance, and mixability. Colesevelam hydrochloride and cholestyramine did not differ significantly when assessed by both the unweighted and the weighted global BASA Scale. Although study participants indicated that the colorless or whitish Colesevelam hydrochloride powder tasted better (P<.0001), they thought that the orange-colored cholestyramine had a more appealing appearance (P<.0001). Regarding the potential for taking the drug "for the rest of your life," 71.4% of study participants rated taste as "very important," and 11.9% rated appearance as "very important. CONCLUSION: Although study participants thought that the orange-colored generic cholestyramine powder had a better appearance, they also reported that Colesevelam hydrochloride for oral suspension tasted better. A minority of study participants thought appearance was "very important"; a substantial majority thought taste was "very important" for potential long-term compliance.