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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
KineMed
ClinicalTrials.gov Identifier:
NCT01092663
First received: March 23, 2010
Last updated: January 15, 2013
Last verified: January 2013
  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:


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

  1. improving the effects of colesevelam on fasting glucose metabolism
  2. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Publications:

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
Sitagliptin
Colesevelam
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014