Clinical Trial to Evaluate the Safety and Efficacy of the Addition of Sitagliptin in Participants With Type 2 Diabetes Mellitus Receiving Acarbose Monotherapy (MK-0431-130)

A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial to Evaluate the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet/Exercise Therapy and Acarbose Monotherapy

This study will evaluate whether the addition of sitagliptin reduces hemoglobin A1C (A1C) more than the addition of placebo for participants with type 2 diabetes mellitus (T2DM) on a steady dose of acarbose. The primary hypothesis is that the addition of sitagliptin 100 mg once daily (q.d.) reduces A1C more than the addition of placebo in participants with T2DM with inadequate glycemic control on acarbose monotherapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin phosphate; Drug: Acarbose; Drug: Glimepiride; Drug: Comparator: Placebo

Detailed Description

The study includes an 8-week antihyperglycemic agent (AHA) wash-off period* (which includes a 2-week single-blind placebo run-in period) followed by a 24-week double-blind treatment period. All participants will receive open-label acarbose at a minimum dose of 50 mg three times daily (t.i.d.) during the run-in and treatment periods.

*: Wash-off only applicable to patients who were on acarbose and another AHA.

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• has T2DM and is on acarbose alone at a stable dose of at least 50 mg t.i.d.(three times a day) for at least 10 weeks or on acarbose at a stable dose of at least 50 mg t.i.d. (three times a day) for at least 10 weeks in combination with another antihyperglycemic agent (AHA)
• is at least 18 years of age (for participants in India: between 18 and 65 years of age)
• male or female who is unlikely to conceive (not of reproductive potential, or agrees to remain abstinent or use [or have partner use] acceptable birth control if of reproductive potential)

Exclusion Criteria:

• has a history of type 1 diabetes mellitus
• use of thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, or insulin
• has the following cardiovascular disorders: acute coronary syndrome; new or worsening symptoms of coronary heart disease; coronary artery intervention; stroke or transient ischemic neurological disorder
• has liver or kidney disease
• has cancer or any clinically significant disease or disorder as judged by the Investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin; Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])	Drug: Sitagliptin phosphate; Sitagliptin, 100 mg tablet once daily, orally for 24 weeks; Other Names: Januvia; Drug: Acarbose; Acarbose 50 mg or 100 mg tablet, 3 times daily, orally (continuing on the stable dose established prior to screening) for 24 weeks; Other Names: Precose; Drug: Glimepiride; Participants not meeting specific glycemic goals during the study will use glimepiride as rescue therapy. For countries where glimepiride is not available, participants will receive a sulfonylurea marketed in that country as rescue therapy.; Other Names: Amaryl®; Glimy
Placebo Comparator: Placebo; Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)	Drug: Acarbose; Acarbose 50 mg or 100 mg tablet, 3 times daily, orally (continuing on the stable dose established prior to screening) for 24 weeks; Other Names: Precose; Drug: Glimepiride; Participants not meeting specific glycemic goals during the study will use glimepiride as rescue therapy. For countries where glimepiride is not available, participants will receive a sulfonylurea marketed in that country as rescue therapy.; Other Names: Amaryl®; Glimy; Drug: Comparator: Placebo; Placebo, to match sitagliptin tablet, once daily, orally for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (A1C) at Week 24	A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. Efficacy analyses treated data as missing after the initiation of rescue therapy.	Baseline and Week 24
Number of Participants Who Experienced at Least One Adverse Event		Up to Week 24 + 14 Day Post-Study Follow-up
Number of Participants Who Discontinued Study Drug Due to an Adverse Event		Up to 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Change from baseline at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Efficacy analyses treated data as missing after the initiation of rescue therapy.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Wang W, Ning G, Ma J, Liu X, Zheng S, Wu F, Xu L, O'Neill EA, Fujita KP, Engel SS, Kaufman KD, Shankar RR. A randomized clinical trial of the safety and efficacy of sitagliptin in patients with type 2 diabetes mellitus inadequately controlled by acarbose alone. Curr Med Res Opin. 2017 Apr;33(4):693-699. doi: 10.1080/03007995.2016.1277200. Epub 2017 Jan 25.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2011
• Primary Completion (Actual): March 25, 2013
• Study Completion (Actual): March 25, 2013

Study Registration Dates

• First Submitted: June 30, 2010
• First Submitted That Met QC Criteria: August 6, 2010
• First Posted (Estimate): August 9, 2010

Study Record Updates

• Last Update Posted (Actual): August 16, 2018
• Last Update Submitted That Met QC Criteria: July 19, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; T2DM
• 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; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Glycoside Hydrolase Inhibitors; Sitagliptin Phosphate; Glimepiride; Acarbose
• Other Study ID Numbers: 0431-130; 2010_543 (Other Identifier: Merck Registration Number); CTRI/2011/10/002072 (Registry Identifier: CTRI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis