A Study of Different Doses of Sitagliptin (MK-0431) in Participants With Type 2 Diabetes Mellitus (MK-0431-014)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00481663
First received: June 1, 2007
Last updated: December 30, 2014
Last verified: December 2014
  Purpose

A study of different doses of MK-0431 in participants with type 2 diabetes mellitus. There have been 3 extensions to the base study (Extension 1: up to Week 52, Extension 2: up to Week 106, and Extension 3: up to Week 158). The primary hypothesis for the study is that In participants with type 2 diabetes who have inadequate glycemic control, after 12 weeks of treatment, a dose-response will be seen across once-daily doses of MK-0431 in lowering hemoglobin A1C (HbA1c).


Condition Intervention Phase
Type II Diabetes Mellitus
Drug: Sitagliptin
Drug: Placebo to sitagliptin
Drug: Metformin
Drug: Rescue
Phase 2

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 Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose-Ranging Finding Study of Once-Daily Dosing of Sitaglipin (MK-0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from Baseline in HbA1C at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Number of Participants Who Experienced One or More Adverse Events (AE) up to Week 14 [ Time Frame: Up to Week 14 ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Experienced One or More AE up to Week 54 [ Time Frame: Up to Week 54 ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Experienced One or More AE up to Week 108 [ Time Frame: Up to Week 108 ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Experienced One or More AE up to Week 160 [ Time Frame: Up to Week 160 ] [ Designated as safety issue: Yes ]
  • Number of participants Who Discontinued Study Treatment Due to An AE up to Week 12 [ Time Frame: Up to Week 12 ] [ Designated as safety issue: Yes ]
  • Number of participants Who Discontinued Study Treatment Due to An AE up to Week 52 [ Time Frame: Up to Week 52 ] [ Designated as safety issue: Yes ]
  • Number of participants Who Discontinued Study Treatment Due to An AE up to Week 106 [ Time Frame: Up to Week 106 ] [ Designated as safety issue: Yes ]
  • Number of participants Who Discontinued Study Treatment Due to An AE up to Week 158 [ Time Frame: Up to Week 158 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from Baseline in HbA1C at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Change from Baseline in HbA1C at Week 106 [ Time Frame: Baseline and Week 106 ] [ Designated as safety issue: No ]
  • Change from Baseline in HbA1C at Week 158 [ Time Frame: Baseline and Week 158 ] [ Designated as safety issue: No ]
  • Change from Baseline in Fasting Plasma Glucose (FPG) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in FPG at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Change from Baseline in FPG at Week 106 [ Time Frame: Baseline and Week 106 ] [ Designated as safety issue: No ]
  • Change from Baseline in FPG at Week 158 [ Time Frame: Baseline and Week 158 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at Week 106 [ Time Frame: Baseline and Week 106 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at Week 158 [ Time Frame: Baseline and Week 158 ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Fructosamine at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Daily Seven-Point Fingerstick Glucose Average at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Daily Seven-Point Fingerstick Glucose Average at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

Enrollment: 555
Study Start Date: August 2003
Study Completion Date: May 2006
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin 25 mg once daily
Sitaglipin (MK-0431), 25 mg, once daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods.
Drug: Sitagliptin Drug: Rescue
Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.
Experimental: Sitagliptin 50 mg once daily
Sitagliptin, 50 mg, once daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods.
Drug: Sitagliptin Drug: Rescue
Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.
Experimental: Sitaglipin 100 mg once daily
Sitagliptin, 100 mg, once daily for 158 weeks, orally
Drug: Sitagliptin Drug: Rescue
Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.
Experimental: Sitagliptin 50 mg twice daily
Sitagliptin 50 mg, twice daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods.
Drug: Sitagliptin Drug: Rescue
Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.
Placebo Comparator: Placebo to Sitagliptin → Metformin
Placebo to Sitagliptin, once daily, orally for 12 weeks. Participants randomized to the placebo treatment group during the base study were reallocated to treatment with metformin 850 mg twice daily (b.i.d., initiated with 850 mg q.d. for 4 weeks then force titrated to 850 mg b.i.d.) during either the first or initiation of the second extensions study periods.
Drug: Placebo to sitagliptin Drug: Metformin Drug: Rescue
Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and non-pregnant women
  • Fasting plasma glucose >= 130 mg/dL
  • HbA1c >=6.5% and >10.0%

Exclusion Criteria:

  • You have a history of type I diabetes
  • You are on a weight loss program with ongoing weight loss or taking weight loss medication
  • You have had surgery within 30 days
  • You hvae hepatitis B or C.
  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: NCT00481663

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

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00481663     History of Changes
Other Study ID Numbers: 0431-014, 2007_570
Study First Received: June 1, 2007
Last Updated: December 30, 2014
Health Authority: United States: Food and Drug Administration

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 August 02, 2015