The Effects of Co-admin of Colesevelam and Sitagliptin on Glucose Metabolism in Subjects With Type 2 Diabetes Mellitus - Full Text View

Purpose

This study will assess the effects of colesevelam, alone or in combination with sitagliptin, on glucose metabolism in subjects with T2DM inadequately controlled by diet and exercise

Condition	Intervention
Diabetes Mellitus, Type 2	Drug: Colesevelam HCl Drug: Sitagliptin

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Effects of Co-administration of Colesevelam and Sitagliptin on Glucose Metabolism in Patients With Type 2 Diabetes

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Dextrose Colesevelam Colesevelam hydrochloride Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by KineMed:

Primary Outcome Measures:

Hemoglobin A1C [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in hemoglobin A1C after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments
Fasting Plasma Glucose [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline in fasting plasma glucose concentrations after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments.
Fasting Endogenous Glucose Production [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in fasting endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment
Fasting Gluconeogenesis [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in fasting gluconeogenesis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment
Fasting Glycogenolysis [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in fasting glycogenolysis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment
Fasting Plasma Glucose Clearance [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in fasting plasma glucose clearance after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments.
Appearance Rate of Oral Glucose [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in appearance rate of oral glucose after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments
Postprandial Endogenous Glucose Production [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in postprandial endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments

Mean value was calculated using all results measured between 10 and 300 min post meal.
Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC) [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change from baseline in postprandial rate of total glucose disposal (AUC) after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments

AUC was calculated by the trapezoid method using all results measured between 0 and 300 min during the meal tolerance test.
Whole-body Glycolytic Disposal of Oral Glucose [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
Change in baseline in whole-body glycolytic disposal of oral glucose after 12 weeks of colesevelam alone or colesevelam plus glucose treatments
Postprandial Glucose (AUC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
Comparison between baseline and 12 weeks values of postrandial glucose (AUC).

Secondary Outcome Measures:

Fasting Plasma C-peptide [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on plamsa C-peptide concentrations.
Fasting Plamsa Glucagon [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on plasma glucagon concentrations.
Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on plasma GLP-1 concentrations.
Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on plasma Glucose-dependent Insulinotropic Peptide (GIP) concentrations.
Fasting Insulin [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on fasting insulin concentrations
Postprandial Insulin (AUC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on postprandial insulin (AUC)
Postprandial C-peptide (AUC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effect of treatments on postprandial C-peptide (AUC)
Postprandial Active GLP-1 (AUC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effects of treatments on postprandial active GLP-1 (AUC)
Postprandial Total GIP (AUC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effects of treatment on postprandial total GIP (AUC)
Postprandial Glucagon (AUC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
To evaluate the effects of treatment on postprandial glucagon (AUC)

Enrollment:	61
Study Start Date:	March 2010
Study Completion Date:	July 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Colesevelam HCl: 3 tablets, 2x/day Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks.	Drug: Colesevelam HCl Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. Other Name: Welchol
Active Comparator: Colesevelam plus Sitagliptin Colesevelam: Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. Sitagliptin: Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks.	Drug: Colesevelam HCl Subjects will be given 3.75 g/day. Subjects will be given 3 tablets (625mg each) with breakfast and 3 tablets (625mg) with dinner for 12 weeks. Other Name: Welchol Drug: Sitagliptin Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks. Other Name: Januvia

Detailed Description:

The hypothesis is that co-administrationof colesevelam plus sitagliptin results in a greater reduction in HbA1c compared to colesevelam HCl treatment by

improving the effects of colesevelam on fasting glucose metabolism
improving the effects of colsevelam on postprandial glucose metabolism

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or Female
Females of childbearing potential are on approved birth control method
Negative pregnancy testing for females of childbearing potential
Previously diagnosed or newly diagnosed with T2DM drug naïve subjects
HbA1c: 6.7-10%
Age 18 - 80 years
BMI ≥ 18.5 kg/m2 and ≤ 40 kg/m2
Fasting serum glucose < 300 mg/dL
Normal liver function, normal thyroid function, no history of liver, biliary or intestinal disease
Normal TSH
On stable diet and exercise routine for at least 4 weeks prior to screening
Has had a stable weight (+/-5%) for ≥3 months before screening

Exclusion Criteria:

A history of type 1 diabetes mellitus or history of diabetic ketoacidosis
History of chronic (required daily for > 2 months) use of insulin therapy
Treatment with blood pressure lowering therapy that has not been stable for three months before screening
Treatment with lipid lowering medication other than statins
Treatment with statins that has not been stable for three months before screening
Treatment with a DPP-4 inhibitor or and GLP1 agonists at any time
Treatment with a thiazolidinedione (TZD) within the last 6 months of screening
History of an allergic or toxic reaction to sitagliptin or colesevelam
History of dysphagia, swallowing disorders, bowel obstruction, intestinal motility disorder, and gastrointestinal disorders
History of major gastrointestinal surgery
History of kidney problems
Fasting plasma triglycerides > 300 mg/dL
Serum LDL-C <60 mg/dL
Positive toxicology test
Known hypersensitivity to colesevelam HCl or sitagliptin.
Any contraindications to a study medication (colesevelam HCl or sitagliptin).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092663

Locations

United States, California
University of California, San Francisco
San Francisco, California, United States, 94110
United States, Florida
Clinical Pharmacology of Miami
Miami, Florida, United States, 33014
United States, Texas
Healthcare Discoveries, LLC d/b/a ICON Development Solutions
San Antonio, Texas, United States, 78209

Sponsors and Collaborators

KineMed

Investigators

Principal Investigator:

Carine Beysen, DPhil

KineMed, Inc.

More Information

Additional Information:

link to completed trials This link exits the ClinicalTrials.gov site

Ethics and Compliance This link exits the ClinicalTrials.gov site

Publications:

Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clin Ther. 2007 Jan;29(1):74-83.

Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008 Oct 13;168(18):1975-83.

Fonseca VA, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care. 2008 Aug;31(8):1479-84. Epub 2008 May 5.

Goldberg RB, Fonseca VA, Truitt KE, Jones MR. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control receiving insulin-based therapy. Arch Intern Med. 2008 Jul 28;168(14):1531-40.

Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7.

Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP; Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007 Mar;9(2):194-205.

Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE. Effect of Initial Combination Therapy with Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, and Metformin on Glycemic Control in Patients with Type 2 Diabetes. Diabetes Care. 2007 May 7; [Epub ahead of print]

Responsible Party:	KineMed
ClinicalTrials.gov Identifier:	NCT01092663 History of Changes
Other Study ID Numbers:	KM-29
Study First Received:	March 23, 2010
Results First Received:	November 12, 2012
Last Updated:	January 15, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by KineMed:

Colesevelam
type 2 diabetes
sitagliptin
glucose metabolism

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Colesevelam
Sitagliptin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2013