Type 2 Diabetes MellitusPhase 3NCT00570739

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.

A Phase 3 study testing Metformin HCl tablets and Colesevelam tablets and Colesevelam in people with Type 2 Diabetes Mellitus and Hypercholesterolemia, run by Daiichi Sankyo at 31 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 79 years
Conditions the study is for: Type 2 Diabetes Mellitus, Hypercholesterolemia, Pre-diabetes
What is being tested?: Metformin HCl tablets and Colesevelam tablets and Colesevelam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 502 participants
Where: 31 sitesin 4 countries
Study dates: Nov 2007to May 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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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.

Who cannot join

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.

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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 .

Trial locations and contacts

31 sites in 4 countries.

Country

City, postcode or hospital

31 sites in 4 countries

United States17 sites

Study site
Birmingham, Alabama
Study site
Corpus Christi, Texas
Study site
Dallas, Texas
Study site
Dundee, New York
Study site
Gary, Indiana
Study site
Kent, Ohio
Study site
Los Gatos, California
Study site
Marion, Ohio
Study site
New Orleans, Louisiana, 70112
Study site
Ocala, Florida
Study site
Olive Branch, Mississippi
Study site
Pocatello, Idaho
Study site
Portland, Oregon
Study site
San Antonio, Texas
Study site
Statesville, North Carolina
Study site
Tarzana, California
Study site
West Seneca, New York

Other trials in United States

Mexico6 sites

Study site
Delegacion, Cuauhtemoc
Study site
Guadalajara, Jalisco
Study site
Hermosillo, Sonora
Study site
Las Palmas, Chihuahua
Study site
Mérida, Yucatán
Study site
Monterrey, Nuevo León

Other trials in Mexico

India5 sites

Study site
Bangalore, Karnataka
Study site
Durgāpura, Jaipur
Study site
Kochi, Kerala
Study site
Mumbai, Dadar
Study site
Nashik, Maharashtra

Other trials in India

Colombia3 sites

Study site
Barranquilla, Atlántico
Study site
Bogota, Cundinamarca
Study site
Bucaramanga, Santander Department

Other trials in Colombia

About this study

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 (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.

Conditions: Type 2 Diabetes Mellitus, Hypercholesterolemia, Pre-diabetes
Being tested: Metformin HCl and Colesevelam Placebo, Metformin HCl tablets and Colesevelam tablets, Colesevelam placebo, Colesevelam
Keywords: Colesevelam, Type 2 Diabetes Mellitus, Pre-diabetes, Metformin
Medical subject headings: Diabetes Mellitus, Type 2, Hypercholesterolemia, Glucose Intolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Metformin HCl and Colesevelam PlaceboDrug
One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg placebo tablets once daily for 16 weeks
Metformin HCl tablets and Colesevelam tabletsDrug
One or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg tablets once daily for 16 weeks
Colesevelam placeboDrug
Six colesevelam 625 mg placebo tablets will be given once a day for 16 weeks
ColesevelamDrug
Six colesevelam 625 mg tablets will be given once a day for 16 weeks.

Study groups in NCT00570739
Study group	Role	What they receive
Diabetic Participants: Metformin HCl+Placebo for Colesevelam	Placebo comparator	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. Receives: Drug: Metformin HCl and Colesevelam Placebo
Diabetic participants: Metformin HCl + Colesevelam	Experimental	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. Receives: Drug: Metformin HCl tablets and Colesevelam tablets
Pre-diabetic Participants: Colesevelam Placebo	Placebo comparator	Participants will receive 6 placebo tablets matching colesevelam 625 mg. Study medication is to be administered once daily for 16 weeks. Receives: Drug: Colesevelam placebo
Pre-diabetes Participants: Colesevelam	Experimental	Participants will receive 6 colesevelam tablets, 625 mg. Study medication is to be administered once daily for 16 weeks. Receives: Drug: Colesevelam

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change of Hemoglobin A1C (HbA1C) From Baseline to 16 Weeks When Given as Initial Therapy to Drug-naïve, Diabetic Subjects.
Measured: Baseline to 16 weeks
Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks

Secondary outcomes (64)

Percent Change in Hemoglobin A1C (HbA1C) When Given to Drug-naïve, Diabetic Subjects From Baseline to 4, 8, 12 and 16 Weeks.
Measured: 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
Measured: 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
Measured: Baseline to 4, 8, 12, and 16 weeks
Fasting C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 weeks
30 Minute Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 weeks
1 Hour Post-Meal Glucose Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 weeks
2 Hour Post-Meal Glucose Levels to in Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 weeks
2 Hour Post-Meal Insulin Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 weeks
2 Hour Post-Meal C-Peptide Levels When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to 16 weeks
Change in the Size of Various Lipoprotein Particles When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change in the Calculated Total Triglycerides When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to Weeks 8, and 16
Change in Body Weight When Given to Drug-naïve, Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change in Waist-to-Hip Ratio When Given to Drug-Naive Diabetic Subjects From Baseline to 16 Weeks
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: Baseline to 16 Weeks
Percent Change in Low Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: 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
Measured: Baseline to 8, and 16 Weeks
Percent Change in High Density Lipoprotein-Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: Baseline to 8, and 16 Weeks
Percent Change in Total Cholesterol in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: Baseline to 8, and 16 Weeks
Percent Change in Apolipoprotein A-1 in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: Baseline to 8, and 16 Weeks
Percent Change in Apolipoprotein B in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: Baseline to 8, and 16 Weeks
Percent Change in Apolipoprotein CIII in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: Baseline to 8, and 16 Weeks
Percent Change in Triglycerides in Pre-Diabetic Subjects From Baseline to 8, and 16 Weeks
Measured: Baseline to 8, and 16 Weeks
Percent Change in Hs-C-Reactive Protein in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline 16 Weeks
Level of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Particle Size of Various Lipoprotein Particles in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: 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.
Measured: Baseline to 16 Weeks
Percent Change of HbA1c in Pre-Diabetic Subjects From Baseline to 4, 8, 12, and 16 Weeks
Measured: 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
Measured: 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
Measured: Baseline to 4, 8, 12, and 16 Weeks
Change of Fasting C-peptide Levels in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change of Glucose Levels 30 Minutes Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change of Glucose Levels 1 Hour Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change of Glucose Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change of Insulin Levels 2 Hours Post Oral Glucose Tolerance Test in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: 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
Measured: Baseline to 16 Weeks
Percent of Subjects Achieving Low Density Lipoprotein-Cholesterol of <100 mg/dL at Weeks 8, 16 in Pre-Diabetic Subjects
Measured: 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
Measured: Baseline to 8, and 16 Weeks
Change in Body Weight in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: Baseline to 16 Weeks
Change in Waist-to-Hip Ratio in Pre-Diabetic Subjects From Baseline to 16 Weeks
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to 16 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2007May 2009

First posted11 Dec 2007 (estimated)
Study startNov 2007
Primary completionApr 2009
Study completionMay 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Daiichi SankyoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 502 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00570739
Sponsor's protocol ID: WEL-411
Other IDs: IND 68,466
Status last verified: Jul 2010
First submitted: 10 Dec 2007
Last updated: 27 Jul 2010
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 22913890
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.
PubMed 22836068
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.
PubMed 20634176
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.
PubMed 20634175

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00570739
Acronym / sponsor ID: WEL-411
Conditions: Type 2 Diabetes Mellitus, Hypercholesterolemia, Pre-diabetes
Keywords: Colesevelam, Type 2 Diabetes Mellitus, Pre-diabetes, Metformin
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 502 participants (actual)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Study start: Nov 2007
Primary completion: Apr 2009 (actual)
Study completion: May 2009 (actual)
First posted: 11 Dec 2007 (estimated)
Results: Posted 13 Jul 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Diabetic Participants: Metformin HCl+Placebo for Colesevelam	Placebo comparator	Drug: Metformin HCl and Colesevelam PlaceboParticipants 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.
Diabetic participants: Metformin HCl + Colesevelam	Experimental	Drug: Metformin HCl tablets and Colesevelam tabletsParticipants 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.
Pre-diabetic Participants: Colesevelam Placebo	Placebo comparator	Drug: Colesevelam placeboParticipants will receive 6 placebo tablets matching colesevelam 625 mg. Study medication is to be administered once daily for 16 weeks.
Pre-diabetes Participants: Colesevelam	Experimental	Drug: ColesevelamParticipants will receive 6 colesevelam tablets, 625 mg. Study medication is to be administered once daily for 16 weeks.

Who may qualify

Ages: 18 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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:
FPG levels in the range of:
LDL-C levels greater than or equal to 100 mg/dL.

Key exclusion criteria (15 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Metformin HCl and Colesevelam PlaceboOne or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg placebo tablets once daily for 16 weeks	Drug	Diabetic Participants: Metformin HCl+Placebo for Colesevelam
Metformin HCl tablets and Colesevelam tabletsOne or two Metformin HCl tablets 850 mg (depending on tolerability) and 6 colesevelam 625 mg tablets once daily for 16 weeks	Drug	Diabetic participants: Metformin HCl + Colesevelam
Colesevelam placeboSix colesevelam 625 mg placebo tablets will be given once a day for 16 weeks	Drug	Pre-diabetic Participants: Colesevelam Placebo
ColesevelamSix colesevelam 625 mg tablets will be given once a day for 16 weeks.	Drug	Pre-diabetes Participants: Colesevelam

Primary outcome

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

64 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
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
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
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

Results and safety

Results posted to the registry on 13 Jul 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Type 2 Diabetes Group: Placebo + Metformin	141	120
Type 2 Diabetes Group: Colesevelam + Metformin	145	124
Pre-diabetic Group: Placebo	108	92
Pre-diabetic Group: Colesevelam	108	96

Primary outcome: 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. Least squares mean (Standard Error). Unit: Percentage of change of hemoglobin A1C

Measure	Type 2 Diabetes Group: Placebo + Metformin n = 137	Type 2 Diabetes Group: Colesevelam + Metformin n = 138
Value	-0.83 (0.064)	-1.09 (0.064)

Type 2 Diabetes Group: Placebo + Metformin vs Type 2 Diabetes Group: Colesevelam + Metformin: Mean Difference (Final Values): -0.26 (95% CI -0.44 to -0.09), p = 0.0035, ANCOVA

Population analysed: The number analyzed equals the full analysis set. The full analysis set included all randomized subjects who took at least 1 dose of randomized study medication, and had a baseline and at least 1 post-baseline efficacy variable measurement. This analysis set was used for the summary and analysis of all efficacy variables. LOCF was used.

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

Time frame: Baseline to 16 Weeks. Least squares mean (Standard Error). Unit: Percentage of change in LDL-C

Measure	Pre-Diabetes Group: Placebo n = 104	Pre-Diabetes Group: Colesevelam n = 103
Value	1.70 (2.054)	-13.89 (2.088)

Pre-Diabetes Group: Placebo vs Pre-Diabetes Group: Colesevelam: Mean Difference (Final Values): -15.59 (95% CI -21.07 to -10.11), p <0.0001, ANCOVA

Population analysed: The No. analyzed=the full analysis set (FAS). The FAS included randomized subjects who took at least 1 dose of randomized medication, had a baseline and at least 1 post-baseline efficacy variable measurement. The FAS was used for the summary and analysis of all efficacy variables. Last Observation Carried Forward was used for 16 week analyses.

64 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the signing of the informed consent form until the end of the study + a follow up period (until the AE resolved or stabilized). This period of time equals about 17.5 weeks.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Type 2 Diabetes Group: Placebo + Metformin	1 of 141 (0.7%)	97 of 141 (68.8%)	Not reported
Type 2 Diabetes Group: Colesevelam + Metformin	2 of 145 (1.4%)	97 of 141 (68.8%)	Not reported
Pre-diabetic Group: Placebo	2 of 108 (1.9%)	63 of 108 (58.3%)	Not reported
Pre-diabetic Group: Colesevelam	2 of 107 (1.9%)	57 of 107 (53.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2010.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22913890Rosenstock 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.
Derived from this study: PubMed 22836068Goldberg 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.
Derived from this study: PubMed 20634176Handelsman 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.
Derived from this study: PubMed 20634175Rosenstock 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael Jones study director

DSI

31 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Mexico, India, Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00570739, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2010.