A Study of the Effects of Co-Administration of Sitagliptin (MK-0431) and Metformin on Incretin Hormone Concentrations (MK-0431-110)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00830076
First received: January 26, 2009
Last updated: September 29, 2011
Last verified: September 2011
  Purpose

This study will assess the effects of sitagliptin and metformin alone and after co-administration on incretin hormone concentrations in patients with Type 2 diabetes.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: sitagliptin phosphate
Drug: metformin hydrochloride
Drug: Comparator: placebo sitagliptin
Drug: Comparator: placebo metformin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Study to Assess the Effects of Co-Administration of Sitagliptin and Metformin on Incretin Hormone Concentrations

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Incremental Post-prandial 4-hour Weighted Mean Active Glucagon-like Peptide-1 (GLP-1) Plasma Concentrations [ Time Frame: 6 hours postdose (4 hours postmeal) on Day 2 ] [ Designated as safety issue: No ]
    Meal was given 2 hours postdose. Blood samples for determination of active GLP-1 concentration were collected (4 hours postmeal) on Day 2 in each treatment period.


Secondary Outcome Measures:
  • β-cell Sensitivity [ Time Frame: 6 hour post-dose (4 hour postmeal) on Day 2 ] [ Designated as safety issue: No ]
    β-cell sensitivity was defined as the incremental post-prandial 4-hour area under the curve (AUC) for insulin secretion rate (ISR) normalized by the incremental post-prandial 4-hour plasma glucose AUC.

  • Incremental Post-prandial 4-hour Weighted Mean Plasma Glucose Concentrations [ Time Frame: 6 hours postdose (4 hours postmeal) on Day 2 ] [ Designated as safety issue: No ]
    Meal was given 2 hours postdose. Blood samples for determination of glucose concentration were collected (4 hours postmeal) on Day 2 in each treatment period.


Enrollment: 18
Study Start Date: December 2008
Study Completion Date: May 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin + placebo metformin Drug: sitagliptin phosphate
Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.
Other Name: Januvia
Drug: Comparator: placebo metformin
Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods.
Experimental: Metformin + placebo sitagliptin Drug: metformin hydrochloride
Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods.
Other Name: Glucophage
Drug: Comparator: placebo sitagliptin
Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.
Experimental: Sitagliptin + metformin
Co-administration of sitagliptin and metformin
Drug: sitagliptin phosphate
Sitagliptin 100 mg tablet on Day 1 and Day 2 in the morning. There will be a 7-day washout between treatment periods.
Other Name: Januvia
Drug: metformin hydrochloride
Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods.
Other Name: Glucophage
Placebo Comparator: Placebo sitagliptin + placebo metformin
Co-administration of placebo to sitagliptin and placebo to metformin
Drug: Comparator: placebo sitagliptin
Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods.
Drug: Comparator: placebo metformin
Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female subjects must have a negative pregnancy test
  • Subject has type 2 diabetes and is not currently receiving treatment with an oral AHA agent, has not received such treatment for 3 months prior to study, and/or has not received more than 4 total weeks treatment with an oral AHA agent for 12 to 18 months prior to the study
  • Subject is a nonsmoker or has not smoked and/or used nicotine for at least 6 months

Exclusion Criteria:

  • Subject has a history of stroke, seizures, or major neurological disorders
  • Female subject is breastfeeding
  • Subject cannot refrain from use of any prescription or non-prescription drugs beginning 2 weeks prior to first dose of study drug
  • Subject consumes more than 3 alcoholic beverages per day
  • Subject consumes more than 6 caffeinated beverages per day
  • Subject has had major surgery, or has donated or lost 1 unit of blood within 4 weeks of screening
  • Subject has a history of cancer, except certain skin or cervical cancer or other cancers treated more than 10 years prior to screening
  • Subject has a history of multiple and/or severe allergies or intolerance to drugs or food
  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: NCT00830076

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00830076     History of Changes
Other Study ID Numbers: MK-0431-110, 2009_521
Study First Received: January 26, 2009
Results First Received: September 29, 2011
Last Updated: September 29, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gastric Inhibitory Polypeptide
Incretins
Sitagliptin
Metformin
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Hypoglycemic Agents
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014