Dose Response Finding Study of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance (MK-0431-105)

A Phase II, Randomized, Placebo-Controlled, Parallel-group, Double-Blind, Dose Response Finding Clinical Trial to Study the Efficacy and Safety of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance Who Have Inadequate Glycemic Control on Diet/Exercise Therapy

This study is being done to evaluate the safety, efficacy, and dose level of sitagliptin (MK-0431/ONO-5435) used once daily (qd) in Japanese participants with impaired glucose tolerance who have inadequate glycemic control using diet and exercise therapy.

Study Overview

• Status: Completed
• Conditions: Glucose Intolerance
• Intervention / Treatment: Drug: Placebo for Sitagliptin 25 mg; Drug: Placebo for Sitagliptin 50 mg; Drug: Sitagliptin 25 mg; Drug: Sitagliptin 50 mg

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Impaired glucose tolerance
• On diet/exercise therapy
• Unlikely to conceive
• Meets all of the following glycemic parameters: Hemoglobin A1c (Japan Diabetes Society value) <6.1%, Fasting Plasma Glucose <126 mg/dL, and 2-hr plasma glucose level in 75g oral glucose tolerance test ≥140 mg/dL and <200 mg/dL

Exclusion Criteria:

• History of diabetes mellitus
• Disease or condition of clear or likely glucose tolerance disorder
• Previously treated with a drug to prevent diabetes and/or any antihyperglycemic drug

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will take one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Drug: Placebo for Sitagliptin 25 mg; 1 tablet orally once daily before breakfast for 8 weeks; Drug: Placebo for Sitagliptin 50 mg; 1 tablet orally once daily before breakfast for 8 weeks
Experimental: Sitagliptin 25 mg; Participants will take one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks.	Drug: Placebo for Sitagliptin 50 mg; 1 tablet orally once daily before breakfast for 8 weeks; Drug: Sitagliptin 25 mg; 1 tablet orally once daily before breakfast for 8 weeks; Other Names: MK-0431/ONO-5435
Experimental: Sitagliptin 50 mg; Participants will take one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks.	Drug: Placebo for Sitagliptin 25 mg; 1 tablet orally once daily before breakfast for 8 weeks; Drug: Sitagliptin 50 mg; 1 tablet orally once daily before breakfast for 8 weeks; Other Names: MK-0431/ONO-5435

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8	Glucose total AUC 0-2 hours for MTT was measured at Baseline (Week 0) and at Week 8. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at standard meal loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 8, participants received study drug or placebo 30 minutes prior to consuming a standard meal.	Baseline (Week 0) and Week 8
Percentage of Participants Who Experienced One or More Adverse Events (AEs)	An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	Up to 10 weeks
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7	Glucose total AUC 0-2 hours for 75 g OGTT was measured at Baseline (Week -1) and at Week 7. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at 75 g glucose loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 7, participants received study drug or placebo 30 minutes prior to loading 75 g glucose solution.	Baseline (Week -1) and Week 7

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Kaku K, Kadowaki T, Terauchi Y, Okamoto T, Sato A, Okuyama K, Arjona Ferreira JC, Goldstein BJ. Sitagliptin improves glycaemic excursion after a meal or after an oral glucose load in Japanese subjects with impaired glucose tolerance. Diabetes Obes Metab. 2015 Nov;17(11):1033-41. doi: 10.1111/dom.12507. Epub 2015 Jul 17.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2011
• Primary Completion (Actual): April 9, 2012
• Study Completion (Actual): April 9, 2012

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 3, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; 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; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-105; MK-0431-105 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf