Mechanisms of Glucose Lowering Effect of Colesevelam HCl

• Status: Completed
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The mechanism by which colesevelam HCl lowers glucose is not known. Knowledge of the potential mechanism of action is important for defining the role of the drug among oral antidiabetic agents available for use in subjects with diabetes. The objective of this study is to provide insight into the mechanisms of action of colesevelam HCl in T2DM. The mechanisms of interest include hepatic insulin sensitivity, rate of appearance of exogenous glucose and changes in incretin hormone concentrations.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Carine Beysen
• Treatments: Colesevelam Hydrochloride; Insulin

Criteria

Inclusion Criteria:

Subjects meeting the following criteria at the Screening Visit will be eligible to participate in the trial:

• Have given written informed consent

• Male or Female

1. Females of childbearing potential who are on approved birth control method:

oral, injectable, or implantable hormonal contraceptives; intrauterine device; diaphragm plus spermicide or female condom plus spermicide

2. Females of non-childbearing potential: hysterectomy, tubal ligation 6 months prior screening or post-menopausal for at least 1 year

• Previously diagnosed or newly diagnosed with T2DM

• Age 30 to 70 years, inclusive

• BMI ≥ 18.5 kg/m2 and ≤ 40 kg/m2

• HbA1C 7-10%, inclusive (exceptions between 6.7-7% may be enrolled with prior approval of SPONSOR)

• Fasting plasma glucose < 300 mg/dL

• Diet controlled or on stable dose of a sulfonylurea and/or meglitinides and/or metformin for ≥ 90 days before screening

• No history of liver, biliary or intestinal disease (AST/ALT < 2X upper limit of normal value)

• Normal TSH

• Agrees to maintain their regular diet and exercise routine

• Agrees to refrain from consumption of alcohol 48 hours prior to start of infusions (week 0 and week 12)

Exclusion Criteria:

Subjects are excluded from participation in the study if any of the following criteria apply:

• Type 1 diabetes mellitus or history of diabetic ketoacidosis

• Treatment with lipid lowering medication other than statins

• Treatment with statins that have not been stable for 3 months before screening

• Treatment with colesevelam HCl, cholestyramine or colestipol for hyperlipidemia within the last 3 months of screening

• Treatment with a thiazolidinedione (TZD) at any time

• Treatment with acarbose at any time

• Treatment with insulin in the past 6 months

• Treatment with antibiotics within the last 3 months

• Treatment with any medication affecting liver or intestinal function within the last 3 months

• Pregnant

• Breastfeeding

• Has had unstable weight within the last 3 months of screening (± 5 kg)

• History of an allergic or toxic reaction to colesevelam HCl

• History of dysphagia, swallowing disorders, or intestinal motility disorder

• Serum triglycerides ≥ 350 mg/dL at screening visit (exceptions up to 500 mg/dl may be enrolled with prior approval of SPONSOR)

• Serum LDL-C <60 mg/dL at screening visit

• Any condition or therapy which, in the opinion of the investigator, poses a risk to the subject or makes participation not in the subject's best interest

• Use of any investigational drug within 3 months of screening

• Chronic treatment with oral corticosteroids at any time or acute treatment within the last 3 months

• History of drug or alcohol abuse, is currently a user (including "recreational use") of any illicit drugs, or has a positive urine drug screen at screening

• Donated a unit of blood within 30 days before screening