Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (FDC) Compared to Glimepiride in Participants With Type 2 Diabetes Mellitus (MK-0431A-202)

NCT00993187 | Completed Phase 4 Results

• 2 other identifiers: 0431A-2022009_672
• Study Type: interventional
• Target: 292
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the effect of sitagliptin/metformin FDC 50/1000 mg (Janumet®), MK-0431A) compared with the effect of glimepiride on hemoglobin A1c (HbA1c). The primary hypothesis is that after 30 weeks, sitagliptin/metformin FDC 50/1000 mg provides superior reduction in HbA1c (mean change from baseline) compared to glimepiride.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30

  HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline).

  Baseline and Week 30

• Number of Participants Who Experienced at Least One Adverse Event (AE)

  An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

  Up to 32 weeks

• Number of Participants Who Discontinued Study Drug Due to an Adverse Event

  An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

  Up to 30 weeks

Secondary Outcomes (4)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30

  Baseline and Week 30

• Percentage of Participants With One or More Episodes of Hypoglycemia

  Up to Week 30

• Change From Baseline in Body Weight at Week 30

  Baseline and Week 30

• Percentage of Participants With HbA1C < 7.0% at Week 30

  Week 30

Study Arms (2)

Sitagliptin/Metformin FDC

EXPERIMENTAL

Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks.

Drug: Sitagliptin/Metformin FDC; Drug: Matching placebo to glimepiride

Glimepiride

ACTIVE COMPARATOR

Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day.

Drug: Comparator: Glimepiride; Drug: Matching placebo to Sitagliptin/Metformin FDC

Interventions

Sitagliptin/Metformin FDC DRUG

Sitagliptin phosphate plus metformin hydrochloride combination tablet (MK-0431A) orally up to 50/1000 mg BID for 30 weeks

Also known as: Janumet®

Sitagliptin/Metformin FDC

Comparator: Glimepiride DRUG

Glimepiride tablet orally up to 6 mg daily for 30 Weeks

Also known as: Amaryl®

Glimepiride

Matching placebo to Sitagliptin/Metformin FDC DRUG

Matching placebo to Sitagliptin/Metformin FDC 50/1000 mg orally BID for 30 weeks

Glimepiride

Matching placebo to glimepiride DRUG

Matching placebo to glimepiride tablet orally daily for 30 weeks

Sitagliptin/Metformin FDC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has type 2 diabetes mellitus
• Is currently not on an anti-hypoglycemic agent (AHA) (off for at least 12 weeks) and has a Visit 1/Screening Visit HbA1c greater than or equal to 7.0% and less than or equal to 9.5%; or is currently on AHA monotherapy or low-dose oral combination therapy (i.e., less than or equal to 50% maximum labeled dose of each agent) and has a Visit 1/Screening Visit HbA1c greater than or equal to 6.5% and less than or equal to 9.0%

You may not qualify if:

• Has a history of type 1 diabetes mellitus or a history of ketoacidosis
• Has been on any investigational or approved glucagon-like peptide-1 (GLP-1) analogue (such as exenatide, liraglutide, etc.), any investigational or approved dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, etc.) or a peroxisome proliferator-activated receptor (PPAR) gamma agonist agent (such as rosiglitazone, pioglitazone, etc.) within 12 weeks of Visit 1
• Required insulin within the prior 12 weeks
• Has a hypersensitivity or contraindication to any sulfonylurea medication (such as glimepiride, glipizide, etc.), DPP-4 inhibitor (such as sitagliptin, vildagliptin, alogliptin, etc.), or biguanide medication (such as metformin, etc.)
• Has inadequately controlled hypertension
• Has cirrhosis or active liver disease
• Has severe cardiac conditions
• Is obese
• Has human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Kim SS, Kim IJ, Lee KJ, Park JH, Kim YI, Lee YS, Chung SC, Lee SJ. Efficacy and safety of sitagliptin/metformin fixed-dose combination compared with glimepiride in patients with type 2 diabetes: A multicenter randomized double-blind study. J Diabetes. 2017 Apr;9(4):412-422. doi: 10.1111/1753-0407.12432. Epub 2016 Aug 8.

  PMID: 27229178 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Metformin; Biguanides; Guanidines; Amidines; Organic Chemicals; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: May 4, 2010
• Primary Completion: October 29, 2013
• Study Completion: October 29, 2013
• Last Updated: August 22, 2018
• Results First Posted: September 15, 2014

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share