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

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

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).

Study Overview

• Status: Completed
• Conditions: Type II Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin; Drug: Sitagliptin; Drug: Rescue; Drug: Placebo to sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 555
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: 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.; Drug: Placebo to sitagliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in HbA1C at Week 12	Baseline and Week 12
Number of Participants Who Experienced One or More Adverse Events (AE) up to Week 14	Up to Week 14
Number of Participants Who Experienced One or More AE up to Week 54	Up to Week 54
Number of Participants Who Experienced One or More AE up to Week 108	Up to Week 108
Number of Participants Who Experienced One or More AE up to Week 160	Up to Week 160
Number of participants Who Discontinued Study Treatment Due to An AE up to Week 12	Up to Week 12
Number of participants Who Discontinued Study Treatment Due to An AE up to Week 52	Up to Week 52
Number of participants Who Discontinued Study Treatment Due to An AE up to Week 106	Up to Week 106
Number of participants Who Discontinued Study Treatment Due to An AE up to Week 158	Up to Week 158

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in HbA1C at Week 52	Baseline and Week 52
Change from Baseline in HbA1C at Week 106	Baseline and Week 106
Change from Baseline in HbA1C at Week 158	Baseline and Week 158
Change from Baseline in Fasting Plasma Glucose (FPG) at Week 12	Baseline and Week 12
Change from Baseline in FPG at Week 52	Baseline and Week 52
Change from Baseline in FPG at Week 106	Baseline and Week 106
Change from Baseline in FPG at Week 158	Baseline and Week 158
Change from Baseline in Body Weight at Week 12	Baseline and Week 12
Change from Baseline in Body Weight at Week 52	Baseline and Week 52
Change from Baseline in Body Weight at Week 106	Baseline and Week 106
Change from Baseline in Body Weight at Week 158	Baseline and Week 158
Change From Baseline in Serum Fructosamine at Week 12	Baseline and Week 12
Change From Baseline in Daily Seven-Point Fingerstick Glucose Average at Week 12	Baseline and Week 12
Change From Baseline in Daily Seven-Point Fingerstick Glucose Average at Week 52	Baseline and Week 52

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Hanefeld M, Herman GA, Wu M, Mickel C, Sanchez M, Stein PP; Sitagliptin Study 014 Investigators. Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of patients with type 2 diabetes. Curr Med Res Opin. 2007 Jun;23(6):1329-39. doi: 10.1185/030079907X188152. Epub 2007 Apr 30.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2003
• Primary Completion (Actual): July 21, 2004
• Study Completion (Actual): May 14, 2006

Study Registration Dates

• First Submitted: June 1, 2007
• First Submitted That Met QC Criteria: June 1, 2007
• First Posted (Estimate): June 4, 2007

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-014; 2007_570

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis