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

NCT01092663 | Completed Results DMC

• 1 other identifier: KM-29
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Keywords

Colesevelam; type 2 diabetes; sitagliptin; glucose metabolism

Outcome Measures

Primary Outcomes (11)

• Hemoglobin A1C

  Change from baseline in hemoglobin A1C after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments

  Baseline and 12 weeks

• Fasting Plasma Glucose

  Change from baseline in fasting plasma glucose concentrations after 12 weeks of colesevelam or colesevelam plus sitagliptin treatments.

  Baseline and 12 weeks

• Fasting Endogenous Glucose Production

  Change from baseline in fasting endogenous glucose production after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment

  baseline and 12 weeks

• Fasting Gluconeogenesis

  Change from baseline in fasting gluconeogenesis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment

  baseline and 12 weeks

• Fasting Glycogenolysis

  Change from baseline in fasting glycogenolysis after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatment

  baseline and 12 weeks

• Fasting Plasma Glucose Clearance

  Change from baseline in fasting plasma glucose clearance after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments.

  baseline and 12 weeks

• Appearance Rate of Oral Glucose

  Change from baseline in appearance rate of oral glucose after 12 weeks of colesevelam alone or colesevelam plus sitagliptin treatments

  baseline and 12 weeks

• Postprandial Endogenous Glucose Production

  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.

  baseline and 12 weeks

• Postprandial Rate of Total Glucose Disposal Area Under the Curve (AUC)

  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.

  baseline and 12 weeks

• Whole-body Glycolytic Disposal of Oral Glucose

  Change in baseline in whole-body glycolytic disposal of oral glucose after 12 weeks of colesevelam alone or colesevelam plus glucose treatments

  baseline and 12 weeks

• Postprandial Glucose (AUC)

  Comparison between baseline and 12 weeks values of postrandial glucose (AUC).

  Baseline and 12 weeks

Secondary Outcomes (10)

• Fasting Plasma C-peptide

  Baseline and 12 weeks

• Fasting Plamsa Glucagon

  Baseline and 12 weeks

• Fasting Active Plasma Glucagon Like-Peptide 1 (GLP-1)

  Baseline and 12 weeks

• Fasting Plasma Total Glucose-dependent Insulinotropic Peptide (GIP)

  Baseline and 12 weeks

• Fasting Insulin

  Baseline and 12 weeks

Study Arms (2)

Colesevelam HCl: 3 tablets, 2x/day

ACTIVE COMPARATOR

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

Colesevelam plus Sitagliptin

ACTIVE COMPARATOR

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; Drug: Sitagliptin

Interventions

Colesevelam HCl DRUG

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.

Also known as: Welchol

Colesevelam HCl: 3 tablets, 2x/day; Colesevelam plus Sitagliptin

Sitagliptin DRUG

Subjects will be given 100mg/day. Subjects will be given 1 tablet (100mg) with breakfast for 12 weeks.

Also known as: Januvia

Colesevelam plus Sitagliptin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• KineMed: lead

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94110, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Healthcare Discoveries, LLC d/b/a ICON Development Solutions

San Antonio, Texas, 78209, United States

Location

Related Publications (7)

• 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. doi: 10.1016/j.clinthera.2007.01.003.

  PMID: 17379048 BACKGROUND

• 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. doi: 10.1001/archinte.168.18.1975.

  PMID: 18852398 BACKGROUND

• 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. doi: 10.2337/dc08-0283. Epub 2008 May 5.

  PMID: 18458145 BACKGROUND

• 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. doi: 10.1001/archinte.168.14.1531.

  PMID: 18663165 BACKGROUND

• 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. doi: 10.2337/dc06-0703.

  PMID: 17130196 BACKGROUND

• 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. doi: 10.1111/j.1463-1326.2006.00704.x.

  PMID: 17300595 BACKGROUND

• Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; Sitagliptin 036 Study Group. 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 Aug;30(8):1979-87. doi: 10.2337/dc07-0627. Epub 2007 May 7.

  PMID: 17485570 BACKGROUND

Related Links

• Ethics and Compliance

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Colesevelam Hydrochloride; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Carine Beysen, PhD
• Organization: KineMed, Inc.

cbeysen@kinemed.com

510-655-6525

Study Officials

• Carine Beysen, DPhil

  KineMed, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2010
• First Posted: March 25, 2010
• Study Start: March 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: January 17, 2013
• Results First Posted: January 17, 2013

Record last verified: 2013-01

Locations

US (3)