Official Title: “Effects of Metformin HCl in Combination With Colesevelam HCl, Compared to Metformin HCl Alone, as Initial Therapy in Drug naïve Subjects With Type 2 Diabetes Mellitus, and the Effects of Colesevelam HCl on the Lipid Profile in Subjects With Pre Diabetes”

This is a 16-week double-blind, placebo-controlled study (for colesevelam HCl); in the type 2 diabetes group, subjects will also be treated with open label background,metformin HCl.

Two-hundred sixty subjects with type 2 DM and 200 subjects with pre-diabetes will 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 subjects with pre diabetes will be randomized 1:1 to receive colesevelam HCl or matching placebo.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: April 2009

This is a 16-week, double-blinded, placebo-controlled, randomized, parallel-group, multi-center study in pre-diabetic subjects and drug-naive subjects with T2DM.

Intervention(s) in this Clinical Trial

• Drug: Colesevelam HCl
  • 3.75 g/day as 6 unbranded tablets, 16 weeks
• Drug: Metformin HCl
  • currently marketed tablets. 850mg qd for 1 week, increased to 850 mg bid (1700 mg/day) on the second week. The latter dosage would then be maintained for an additional 14 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• Placebo Comparator: 2
• Experimental: 3
• Active Comparator: 4

Primary Measures

• To evaluate the effects of metformin HCl plus colesevelam HCl combination therapy compared to metformin HCl alone on hemoglobin A1C (HbA1C) when given as initial therapy in drug-naïve subjects
  • Time Frame: 16 weeks
    Safety Issue?: No

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 .

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 79 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Daiichi Sankyo Inc.

Overall Clinical Trial Officials and Contacts

Michael Jones Study Director DSI  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00570739

Study ID Number: WEL-411

ClinicalTrials.gov Identifier: NCT00570739

Health Authority: United States: Food and Drug Administration