Metformin Add-on Regimen Comparison Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431A-136)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01545388
First received: March 1, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

This study will evaluate the effect of the addition of metformin once daily (q.d.) or twice daily (b.i.d.) to sitagliptin monotherapy in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control with diet/exercise therapy and sitagliptin monotherapy. The primary hypotheses are that the addition of metformin 250 mg b.i.d. or metformin 500 mg q.d. is superior to the addition of placebo on the change from baseline in hemoglobin A1c (HbA1c) at 24 weeks and that the addition of metformin 500 mg q.d. is non-inferior to the addition of metformin 250 mg b.i.d. on the change from baseline in HbA1c at 24 weeks.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Metformin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Placebo and Active-Controlled, Double-Blind Clinical Trial to Study the Efficacy and Safety of the Addition of Metformin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet/Exercise Therapy and Sitagliptin Monotherapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.

  • Percentage of Participants Who Experienced at Least One Adverse Event [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Based on a cLDA model with terms for treatment, other prior AHA therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.


Enrollment: 337
Study Start Date: February 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin 500 mg q.d.
Participants will receive sitagliptin daily (continuing their pre-study dose), 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
Drug: Sitagliptin
Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)
Other Name: MK-0431/ONO-5435
Drug: Metformin
Metformin, orally, 500 mg daily (single dose; two 250 mg tablets) for 24 weeks
Drug: Placebo
Placebo to match metformin 250 mg tablets, orally, for 24 weeks
Experimental: Metformin 250 mg b.i.d.
Participants will receive sitagliptin daily (continuing their pre-study dose), 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
Drug: Sitagliptin
Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)
Other Name: MK-0431/ONO-5435
Drug: Metformin
Metformin, orally, 500 mg daily (divided dose; 250 mg tablet b.i.d.) for 24 weeks
Drug: Placebo
Placebo to match metformin 250 mg tablets, orally, for 24 weeks
Placebo Comparator: Placebo
Participants will receive sitagliptin daily (continuing their pre-study dose), 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
Drug: Sitagliptin
Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)
Other Name: MK-0431/ONO-5435
Drug: Placebo
Placebo to match metformin 250 mg tablets, orally, for 24 weeks

  Eligibility

Ages Eligible for Study:   20 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 Diabetes Mellitus (T2DM)
  • Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 4 weeks, on any additional oral hypoglycemic agent (AHA) in the prior 8 weeks, and HbA1c ≥ 6.0% and ≤ 9.0%; or
  • Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 10 weeks, not on any additional oral AHA in the prior 8 weeks, and HbA1c ≥ 6.5% and < 10.0%

Exclusion Criteria:

  • Type 1 diabetes mellitus,
  • Secondary diabetes mellitus, or
  • Gestational diabetes mellitus
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01545388     History of Changes
Other Study ID Numbers: 0431A-136, ONO-5435A
Study First Received: March 1, 2012
Results First Received: February 10, 2014
Last Updated: August 11, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

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

ClinicalTrials.gov processed this record on October 21, 2014