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

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Sitagliptin/Metformin FDC Drug: Comparator: Glimepiride Drug: Matching placebo to Sitagliptin/Metformin FDC Drug: Matching placebo to glimepiride	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double Blind Study to Compare the Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (Janumet®) Compared to Glimepiride in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Glimepiride Sitagliptin Sitagliptin phosphate Janumet

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30 [ Time Frame: Baseline and Week 30 ] [ Designated as safety issue: No ]
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).
Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to 32 weeks ] [ Designated as safety issue: Yes ]
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.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 30 weeks ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 [ Time Frame: Baseline and Week 30 ] [ Designated as safety issue: No ]
Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at baseline).
Percentage of Participants With One or More Episodes of Hypoglycemia [ Time Frame: Up to Week 30 ] [ Designated as safety issue: Yes ]
Symptomatic episodes assessed as likely to be due to hypoglycemia were reported by investigators as adverse experiences of hypoglycemia. Adverse experiences of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required.
Change From Baseline in Body Weight at Week 30 [ Time Frame: Baseline and Week 30 ] [ Designated as safety issue: No ]
Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline)
Percentage of Participants With HbA1C < 7.0% at Week 30 [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%).


Enrollment:	292
Study Start Date:	May 2010
Study Completion Date:	October 2013
Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sitagliptin/Metformin FDC 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 Sitagliptin phosphate plus metformin hydrochloride combination tablet (MK-0431A) orally up to 50/1000 mg BID for 30 weeks Other Name: Janumet® Drug: Matching placebo to glimepiride Matching placebo to glimepiride tablet orally daily for 30 weeks
Active Comparator: Glimepiride 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 Glimepiride tablet orally up to 6 mg daily for 30 Weeks Other Name: Amaryl® Drug: Matching placebo to Sitagliptin/Metformin FDC Matching placebo to Sitagliptin/Metformin FDC 50/1000 mg orally BID for 30 weeks

Arms

Assigned Interventions

Experimental: Sitagliptin/Metformin FDC

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

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

Other Name: Janumet®

Drug: Matching placebo to glimepiride

Matching placebo to glimepiride tablet orally daily for 30 weeks

Active Comparator: Glimepiride

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

Glimepiride tablet orally up to 6 mg daily for 30 Weeks

Other Name: Amaryl®

Drug: Matching placebo to Sitagliptin/Metformin FDC

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

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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%

Exclusion Criteria:

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)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993187

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators


Study Director:	Medical Monitor	Merck Sharp & Dohme Corp.

More Information

No publications provided


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT00993187 History of Changes
Other Study ID Numbers:	0431A-202, 2009_672
Study First Received:	October 9, 2009
Results First Received:	September 8, 2014
Last Updated:	September 8, 2014
Health Authority:	South Korea: Korea Food and Drug Administration (KFDA)

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Glimepiride Metformin Sitagliptin Anti-Arrhythmia Agents Cardiovascular Agents Dipeptidyl-Peptidase IV Inhibitors Enzyme Inhibitors	Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Hypoglycemic Agents Immunologic Factors Immunosuppressive Agents Incretins Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protease Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015