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.

NCT ID: NCT00570739

Last Updated: 2010-07-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

502 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-11-30

Study Completion Date

2009-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Type 2 Diabetes Mellitus Hypercholesterolemia Pre-diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Diabetic Participants: Metformin HCl+Placebo for Colesevelam

Participants will receive either 850 mg or 1700 mg of metformin HCl, depending on tolerability + 6 placebo tablets matching colesevelam 625 mg. Study medication is to be administered once daily for 16 weeks.

Group Type PLACEBO_COMPARATOR

Metformin HCl and Colesevelam Placebo

Intervention Type DRUG

One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg placebo tablets once daily for 16 weeks

Diabetic participants: Metformin HCl + Colesevelam

Participants will receive either 850 mg or 1700 mg of metformin HCl, depending on tolerability + 6 colesevelam tablets, 625 mg. Study medication is to be administered once daily for 16 weeks.

Group Type EXPERIMENTAL

Metformin HCl tablets and Colesevelam tablets

Intervention Type DRUG

One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg tablets once daily for 16 weeks

Pre-diabetic Participants: Colesevelam Placebo

Participants will receive 6 placebo tablets matching colesevelam 625 mg. Study medication is to be administered once daily for 16 weeks.

Group Type PLACEBO_COMPARATOR

Colesevelam placebo

Intervention Type DRUG

Six colesevelam 625 mg placebo tablets will be given once a day for 16 weeks

Pre-diabetes Participants: Colesevelam

Participants will receive 6 colesevelam tablets, 625 mg. Study medication is to be administered once daily for 16 weeks.

Group Type EXPERIMENTAL

Colesevelam

Intervention Type DRUG

Six colesevelam 625 mg tablets will be given once a day for 16 weeks.

Interventions

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Metformin HCl and Colesevelam Placebo

One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg placebo tablets once daily for 16 weeks

Intervention Type DRUG

Metformin HCl tablets and Colesevelam tablets

One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg tablets once daily for 16 weeks

Intervention Type DRUG

Colesevelam placebo

Six colesevelam 625 mg placebo tablets will be given once a day for 16 weeks

Intervention Type DRUG

Colesevelam

Six colesevelam 625 mg tablets will be given once a day for 16 weeks.

Intervention Type DRUG

Eligibility Criteria

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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 .
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Daiichi Sankyo, Inc.

Principal Investigators

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Michael Jones

Role: STUDY_DIRECTOR

DSI

Locations

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Birmingham, Alabama, United States

Site Status

Los Gatos, California, United States

Site Status

Tarzana, California, United States

Site Status

Ocala, Florida, United States

Site Status

Pocatello, Idaho, United States

Site Status

Gary, Indiana, United States

Site Status

New Orleans, Louisiana, United States

Site Status

Olive Branch, Mississippi, United States

Site Status

Dundee, New York, United States

Site Status

West Seneca, New York, United States

Site Status

Statesville, North Carolina, United States

Site Status

Kent, Ohio, United States

Site Status

Marion, Ohio, United States

Site Status

Portland, Oregon, United States

Site Status

Corpus Christi, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

San Antonio, Texas, United States

Site Status

Barranquilla, Atlántico, Colombia

Site Status

Bogota, Cundinamarca, Colombia

Site Status

Bucaramanga, Santander Department, Colombia

Site Status

Mumbai, Dadar, India

Site Status

Durgāpura, Jaipur, India

Site Status

Bangalore, Karnataka, India

Site Status

Kochi, Kerala, India

Site Status

Nashik, Maharashtra, India

Site Status

Las Palmas, Chihuahua, Mexico

Site Status

Delegacion, Cuauhtemoc, Mexico

Site Status

Guadalajara, Jalisco, Mexico

Site Status

Monterrey, Nuevo León, Mexico

Site Status

Hermosillo, Sonora, Mexico

Site Status

Mérida, Yucatán, Mexico

Site Status

Countries

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United States Colombia India Mexico

References

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Rosenstock J, Hernandez-Triana E, Handelsman Y, Misir S, Jones MR. Clinical effects of colesevelam in Hispanic subjects with primary hyperlipidemia and prediabetes. Postgrad Med. 2012 Jul;124(4):14-20. doi: 10.3810/pgm.2012.07.2564.

Reference Type DERIVED
PMID: 22913890 (View on PubMed)

Goldberg RB, Rosenson RS, Hernandez-Triana E, Misir S, Jones MR. Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus. J Clin Lipidol. 2012 Jul-Aug;6(4):318-24. doi: 10.1016/j.jacl.2012.05.005. Epub 2012 May 29.

Reference Type DERIVED
PMID: 22836068 (View on PubMed)

Handelsman Y, Goldberg RB, Garvey WT, Fonseca VA, Rosenstock J, Jones MR, Lai YL, Jin X, Misir S, Nagendran S, Abby SL. Colesevelam hydrochloride to treat hypercholesterolemia and improve glycemia in prediabetes: a randomized, prospective study. Endocr Pract. 2010 Jul-Aug;16(4):617-28. doi: 10.4158/EP10129.OR.

Reference Type DERIVED
PMID: 20634176 (View on PubMed)

Rosenstock J, Fonseca VA, Garvey WT, Goldberg RB, Handelsman Y, Abby SL, Lai YL, Jin X, Misir S, Nagendran S, Jones MR. Initial combination therapy with metformin and colesevelam for achievement of glycemic and lipid goals in early type 2 diabetes. Endocr Pract. 2010 Jul-Aug;16(4):629-40. doi: 10.4158/EP10130.OR.

Reference Type DERIVED
PMID: 20634175 (View on PubMed)

Other Identifiers

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IND 68,466

Identifier Type: -

Identifier Source: secondary_id

WEL-411

Identifier Type: -

Identifier Source: org_study_id

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