A Study to Evaluate the Efficacy and Safety of Sitagliptin and MK0431A in Comparison to a Commonly Used Medication in Patients With Type 2 Diabetes (0431-068)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00541450
First received: October 5, 2007
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of sitagliptin and MK0431A in comparison to a commonly used medication in patients with type 2 diabetes.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Comparator: sitagliptin phosphate (sitagliptin)
Drug: sitagliptin phosphate (+) metformin hydrochloride
Drug: Comparator: pioglitazone
Drug: Matching placebo to pioglitazone
Drug: Matching placebo to sitagliptin
Drug: Matching Placebo to Sita/Met FDC
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, Active-Comparator (Pioglitazone) Controlled Clinical Trial to Study the Efficacy and Safety of Sitagliptin and MK0431A (A Fixed-Dose Combination Tablet of Sitagliptin and Metformin) in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks [ Time Frame: Baseline to 40 weeks ] [ Designated as safety issue: No ]
    The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin.

  • Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    The change in A1C compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. A1c represents percentage of glycosylated hemoglobin.


Secondary Outcome Measures:
  • Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks [ Time Frame: Baseline and 40 weeks ] [ Designated as safety issue: No ]
    The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the Sita/Met FDC and the pioglitazone groups at Week 40.

  • Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the participants treated with Sitagliptin or Pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate.

  • Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks [ Time Frame: Baseline and 40 weeks ] [ Designated as safety issue: No ]
    The change in FPG compared to baseline was measured for the Sita/Met FDC and the pioglitazone groups at Week 40.

  • Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    The change in FPG compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate.


Enrollment: 492
Study Start Date: January 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sita/Met FDC

In Phase A (Treatment Day 1 to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to 15 mg pioglitazone q.d. for 6 weeks followed by matching placebo to 30 mg pioglitazone for the next 6 weeks.

In Phase B (Treatment Week 12-Week 40), participants were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks; as well as matching placebo to 45 mg pioglitazone.

Drug: Comparator: sitagliptin phosphate (sitagliptin)
sitagliptin 100 mg tablet q.d. orally for a 12-wk treatment period
Other Name: MK0431, Januvia™
Drug: sitagliptin phosphate (+) metformin hydrochloride
sitagliptin/metformin HCl (Sita/Met) 50/500 mg b.i.d. orally and then 50/1000 mg b.i.d. orally for a 28-wk treatment period
Other Name: MK-0431A, Janumet™
Drug: Matching placebo to pioglitazone

matching placebo to pioglitazone tablet q.d. orally, for a 40-wk treatment period.

Participants were administered matching placebo the 15 mg pioglitazone q.d. orally for 6 weeks, followed by matching placebo to 30 mg pioglitazone q.d orally for 6 weeks, followed by matching placebo to 45 mg pioglitazone q.d. orally, up to 40 weeks.

Active Comparator: Pioglitazone

In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone and matching placebo to sitagliptin. At Week 6, participants were up-titrated to 30 mg pioglitazone q.d.

In Phase B (Treatment Week 12 to Week 40), participants were administered 45 mg pioglitazone q.d.; as well as matching placebo to Sita/Met FDC (50/500 increased to 50/1000 b.i.d. after 4 weeks).

Drug: Comparator: pioglitazone
pioglitazone 15 mg tablet q.d. orally for 6 weeks, followed by 30 mg q.d orally for 6 weeks, followed by 45 mg q.d. orally, up to 40 weeks.
Other Name: Actos®
Drug: Matching placebo to sitagliptin
matching placebo to sitagliptin q.d., orally for a 12-wk treatment period.
Drug: Matching Placebo to Sita/Met FDC
matching placebo to Sita/Met FDC - 50/500 mg b.i.d. for 4 weeks and then 50/1000 mg b.i.d. orally for a 28-wk treatment period (Week 12 to Week 40).

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients between the ages of 18 and 78 with type 2 diabetes mellitus
  • Patient has not been on any antihyperglycemic agent (Insulin or oral) in the last 3 months

Exclusion Criteria:

  • Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis
  • Patient has previously been treated with sitagliptin or has previously been in a study using a DPP-4 inhibitor
  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: NCT00541450

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

Additional Information:
Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00541450     History of Changes
Other Study ID Numbers: 0431-068, 2007_501
Study First Received: October 5, 2007
Results First Received: January 13, 2011
Last Updated: March 24, 2014
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
Pioglitazone
Sitagliptin
Metformin
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

ClinicalTrials.gov processed this record on August 28, 2014