Effects of Metformin Hydrochloride (HCl) in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, in Patients With Type 2 Diabetes Mellitus and the Effects of Colesevelam HCl on Lipids and Glucose on Pre-diabetic Patients.

Daiichi Sankyo502 enrolled

Overview

This is a 16-week double-blind, placebo-controlled (for colesevelam hydrochloride (HCl)) study in the type 2 diabetic subjects and pre-diabetic subjects. Diabetic participants will also be treated with open label, background,metformin HCl. Two-hundred sixty subjects with type 2 diabetes (T2DM) and 200 pre-diabetic subjects are planned to be be enrolled. Qualified subjects with T2DM will be randomized 1:1 to receive metformin HCl plus colesevelam HCl or metformin HCl plus placebo matching colesevelam HCl. Qualified pre-diabetic subjects will be randomized 1:1 to receive colesevelam HCl or matching placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

502

Conditions

Type 2 Diabetes Mellitus Hypercholesterolemia Pre-diabetes

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 79 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18 to 79 years, inclusive. * HbA1C in the range of greater than or equal to 6.5 percent to small than or equal to 10.0 percent, to be enrolled in the T2DM cohort. * 2-hour post 75 g OGTT glucose levels in the range of: * greater than or equal to 200 mg/dL to be enrolled in the T2DM cohort, or * greater than or equal to 140 to 200 mg/dL to be enrolled in the pre-diabetes cohort. * FPG levels in the range of: * greater than or equal to 126 mg/dL to be enrolled in the T2DM cohort, or * greater than or equal to 110 to smaller than or equal to 125 mg/dL to be enrolled in the pre-diabetes cohort. * LDL-C levels greater than or equal to 100 mg/dL. * Drug-naïve, defined as having never received treatment for T2DM or not having received antidiabetic drug therapy during the 3 months prior to screening visit. * Previous diagnosis of: * T2DM or prediabetes, to be enrolled in the respective cohorts, or * CHD, CVD, and/or primary hypercholesterolemia + BMI greater than or equal to 25 mg/kg2 to be screened for T2DM or pre-diabetes. * Understanding of the study procedures and agreement to participate in the study by giving written informed consent at screening visit. * Women may be enrolled if all 3 of the following criteria (in addition to the above criteria)are met: * They are not pregnant (women of childbearing potential must have a negative serum pregnancy test \[serum beta human chorionic gonadotropin )\] at screening visit); * They are not breast-feeding; and * They do not plan to become pregnant during the study. * In addition to all of the above criteria, women must also meet 1 of the following 3 criteria to be enrolled: * They have been post-menopausal for at least 1 year; or * They are of childbearing potential and will practice 1 of the following methods of birth control throughout the study: oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide; or female condom plus spermicide. Methods of contraception that are not acceptable are partner's use of condoms or partner's vasectomy. Exclusion Criteria: * History of type 1 diabetes and/or history of acute or chronic metabolic acidosis, including diabetic ketoacidosis. * History of chronic (requiring daily for greater than 2 months) use of insulin therapy, except for the treatment of gestational diabetes. * Current or prior (within the past 3 months) treatment with an oral antidiabetic drug. * Current or prior (within the past 3 months) treatment with colesevelam HCl (WelChol), colestipol, colestimide, or cholestyramine. * History of dysphagia, swallowing disorders, or intestinal motility disorder. * Any serious disorder, including pulmonary, hepatic, gastrointestinal (including clinically significant malabsorption), uncontrolled endocrine/metabolic, hematologic/oncologic (within the last 5 years), neurologic, and psychiatric diseases, that would interfere with the conduct of the study or interpretation of the data. * Acute coronary syndrome (eg, myocardial infarction or unstable angina), coronary intervention (coronary artery bypass graft or percutaneous transluminal coronary angioplasty or similar procedure), congestive heart failure (requiring pharmacological treatment), or transient ischemic attack within 3 months of screening visit. * History of pancreatitis. * History of acquired immune deficiency syndrome or human immunodeficiency virus. * History of drug or alcohol abuse within the past 2 years. * Hospitalization for any cause within 14 days prior to screening visit. * History of an allergic or toxic response to colesevelam HCl or any of its components. * Known hypersensitivity to metformin HCl. * Serum TG greater than or equal to 500 mg/dL. * Body mass index (BMI) greater than 40 kg/m2 .

Locations (31)

Unnamed facility

Birmingham, Alabama, United States

Unnamed facility

Los Gatos, California, United States

Unnamed facility

Tarzana, California, United States

Unnamed facility

Ocala, Florida, United States

Unnamed facility

Pocatello, Idaho, United States

Unnamed facility

Gary, Indiana, United States

Unnamed facility

New Orleans, Louisiana, United States

Unnamed facility

Olive Branch, Mississippi, United States

Unnamed facility

Dundee, New York, United States

Unnamed facility

West Seneca, New York, United States

...and 21 more locations

Outcomes

Primary Outcomes

Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects.

Time frame: Baseline to 16 weeks

Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Secondary Outcomes

Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks.

Time frame: Baseline to 4, 8, 12, and 16 weeks

Fasting Plasma Glucose When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks

Time frame: Baseline to 4, 8, 12, and 16 weeks

Fasting Insulin When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks

Time frame: Baseline to 4, 8, 12, and 16 weeks

Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

The Percent Change of Low Density Lipoprotein Cholesterol (LDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of Non-High Density Lipoprotein (Non-HDL) Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of High Density Lipoprotein Cholesterol(HDL-C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of Total Cholesterol (TC) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of Triglycerides (TG)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of Apolipoprotein A-1 (Apo A-1) When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of Apolipoprotein B (Apo B)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Percent Change of Apolipoprotein C3 (Apo C3)When Given to Drug-naïve, Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 weeks

Change in the Levels of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 weeks

Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change in the Calculated Very Low Density Lipoprotein Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.

Time frame: Baseline to 16 Weeks

Change in the Calculated High Density Lipoprotein Cholesterol When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.

Time frame: Baseline to 16 Weeks

Percent of Subjects Achieving HbA1c Goal of <7.0% at Weeks 4, 8, 12, and 16 if Baseline HbA1c Was > or = to 7.0% When Given to Drug-naïve, Diabetics

Time frame: Baseline to 4, 8, 12, and 16 Weeks

Percent of Subject Achieving HbA1c Goal of <6.5% at Weeks 4, 8, 12, and 16 When Given to Drug-naïve, Diabetic Subjects

Time frame: Baseline to 4, 8, 12 and 16 weeks

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 When Given to Drug-naïve, Diabetic Subjects

Time frame: Baseline to Weeks 8, and 16

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol Goal of <70 mg/dL at Weeks 8, 16 When Given as to Drug-naïve, Diabetics

Time frame: Baseline to Weeks 8, and 16

Change in Body Weight When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change in Waist-to-Hip Ratio When Given to Drug-Naive Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change in Plasma Glucose Area Under the Curve (0 to 120 Minutes) From the Baseline Glucose Tolerance Test (GTT) to the 16 Week GTT

Time frame: Baseline vs. 16 Weeks

Percent Change of Various Calculated Lipid Parameters When Given as Initial Therapy to Drug-naïve, Diabetic From Baseline to 16 Weeks Subjects

These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.

Time frame: Baseline to 16 Weeks

Percent of Subjects Achieving 2-Hr. Post Meal Glucose Goal of <180 mg/dL When Given to Drug-naïve, Diabetic Subjects From Baseline to Week 16

Time frame: Baseline to Week 16

Percent of Subjects Achieving Hs-C-Reactive Protein Goal of <2.0 mg/L When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Percent Change in Low Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Non-High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Total Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Apolipoprotein A-1 in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Apolipoprotein B in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Apolipoprotein CIII in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Triglycerides in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks

Time frame: Baseline to 8, and 16 Weeks

Percent Change in Hs-C-Reactive Protein in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline 16 Weeks

Level of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Particle Size of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change of Various Calculated Lipid Parameters in Pre-Diabetic Subjects From Baseline to 16 Weeks

These calculated values are reported as part of an NMR analysis. The calculations are done by LipoScience, Inc., and are proprietary.

Time frame: Baseline to 16 Weeks

Percent Change of HbA1c in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks

Time frame: Baseline to 4, 8, 12, and 16 Weeks

Percent Change of Fasting Plasma Glucose in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks

Time frame: Baseline to 4, 8, 12, and 16 weeks

Percent Change of Fasting Insulin in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks

Time frame: Baseline to 4, 8, 12, and 16 Weeks

Change of Fasting C-peptide Levels in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change of Glucose Levels 30 Minutes Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change of Glucose Levels 1 Hour Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change of Glucose Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change of Insulin Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change of C-Peptide Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects

Time frame: Baseline to 8, and 16 Weeks

Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <70 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects

Time frame: Baseline to 8, and 16 Weeks

Change in Body Weight in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Change in Waist-to-Hip Ratio in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Area Under the Curve for Plasma Glucose From 0 to 120 Minutes During the Oral Glucose Tolerance Tests in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Percent Achievement of <140 mg/dL Plasma Glucose 2 Hours Post the Oral Glucose Tolerance Test in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was >or= to 140 mg/dL From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Percent Achievement of <110 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 110 mg/dL From Baseline to 4, 8, 12, and 16 Weeks

Time frame: Baseline to 4, 8, 12, and 16 Weeks

Percent Achievement of <100 mg/dL Fasting Plasma Glucose in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 100 mg/dL From Baseline to 4, 8, 12 and 16 Weeks

Time frame: Baseline to 4, 8, 12 and 16 weeks

Percent Achievement of <140 mg/dL Plasma Glucose Post 2 Hour Glucose Tolerance Test and Fasting Plasma Glucose <110 mg/dL in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Percent Achievement of Hs-C-Reactive Protein <2.0 mg/L in Pre-Diabetic Subjects Whose Corresponding Baseline Value Was > or = to 2.0 mg/L From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks

Percent of Subjects Meeting Type 2 Diabetes Criteria (Fasting Plasma Glucose >or= to 126 mg/dL or Plasma Glucose >or= to 200 mg/dL Post 2 Hr Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks

Time frame: Baseline to 16 Weeks