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)

• ClinicalTrials.gov Identifier: NCT01177384
• Recruitment Status: Completed
• First Posted: August 9, 2010
• Results First Posted: April 28, 2014
• Last Update Posted: August 16, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sitagliptin phosphate; Drug: Comparator: Placebo; Drug: Acarbose; Drug: Glimepiride	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 380 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 25, 2011
• Actual Primary Completion Date: March 25, 2013
• Actual Study Completion Date: March 25, 2013

Arms and Interventions

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 Name: 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 Name: 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: Comparator: Placebo; Placebo, to match sitagliptin tablet, once daily, orally for 24 weeks; 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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Hemoglobin A1c (A1C) at Week 24 [ Time Frame: Baseline and 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.
2. Number of Participants Who Experienced at Least One Adverse Event [ Time Frame: Up to Week 24 + 14 Day Post-Study Follow-up ]
3. Number of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 24 Weeks ]

Secondary Outcome Measures :

1. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline and 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Study Data/Documents: CSR Synopsis 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01177384
• Other Study ID Numbers: 0431-130; 2010_543 ( Other Identifier: Merck Registration Number ); CTRI/2011/10/002072 ( Registry Identifier: CTRI )
• First Posted: August 9, 2010
• Results First Posted: April 28, 2014
• Last Update Posted: August 16, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by Merck Sharp & Dohme Corp.:

Type 2 diabetes mellitus; T2DM

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Glimepiride; Acarbose; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Glycoside Hydrolase Inhibitors