Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313 AM1) | RxWiki

Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313 AM1)

Overview[ - collapse ][ - ]

Purpose	To assess the effect of adding acarbose or repaglinide or gliclazide to sitagliptin plus metformin, compared to adding glimepiride, on glycemic improvements in Type 2 Diabetes Mellitus (T2DM) participants who require the addition of a third oral anti-hyperglycemic agent (OAHA) according to China Guideline for Type 2 Diabetes. The three co-primary hypotheses are that after 24 weeks of treatment in phase 2, the mean change from baseline in hemoglobin A1c (A1c) in participants receiving either (1)acarbose or (2)repaglinide or (3)gliclazide added to sitagliptin and metformin combination is non-inferior to that of participants receiving glimepiride added to sitagliptin and metformin combination.
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Metformin Drug: Sitagliptin Drug: Acarbose Drug: Repaglinide Drug: Glimepiride Drug: Gliclazide
Phase	Phase 4
Sponsor	Merck Sharp & Dohme Corp.
Responsible Party	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier	NCT01709305
First Received	October 16, 2012
Last Updated	April 17, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	October 16, 2012
Last Updated Date	April 17, 2014
Start Date	November 2012
Estimated Primary Completion Date	May 2015
Current Primary Outcome Measures	Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2) [Time Frame: Phase 2 Baseline (Week 20), Week 44] [Designated as safety issue: No]
Current Secondary Outcome Measures	Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2) [Time Frame: Phase 2 Baseline (Week 20), Week 44] [Designated as safety issue: Yes] Number of Participants With Hypoglycemia Events (Phase 2) [Time Frame: From Week 20 through Week 44] [Designated as safety issue: Yes] Number of Participants With Gastrointestinal Adverse Events (Phase 2) [Time Frame: From Week 20 through Week 44] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief Title	Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313 AM1)
Official Title	A Multicenter, Randomized, Active-Controlled, Open-label Clinical Trial to Evaluate the Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose as a Third OAHA on Top of Sitagliptin+Metformin Combination Therapy in Chinese Patients With Type 2 Diabetes Mellitus (Phase IV; Protocol No. MK-0431-313-01)
Brief Summary	To assess the effect of adding acarbose or repaglinide or gliclazide to sitagliptin plus metformin, compared to adding glimepiride, on glycemic improvements in Type 2 Diabetes Mellitus (T2DM) participants who require the addition of a third oral anti-hyperglycemic agent (OAHA) according to China Guideline for Type 2 Diabetes. The three co-primary hypotheses are that after 24 weeks of treatment in phase 2, the mean change from baseline in hemoglobin A1c (A1c) in participants receiving either (1)acarbose or (2)repaglinide or (3)gliclazide added to sitagliptin and metformin combination is non-inferior to that of participants receiving glimepiride added to sitagliptin and metformin combination.
Detailed Description	Participants coming on study will be stabilized to a standardized metformin dose: this may take about 10 weeks, and then combination therapy with metformin + sitagliptin will begin during Phase 1 (Week 0 through Week 20). If a participant is already on a stabilized metformin dose, they will start immediately on combination therapy with metformin + sitagliptin for 20 weeks (Phase 1). In Phase 2, participants who have failed to achieve adequate glycemic control (A1c ≥ 7% and ≤ 10% at Week 16 and fasting finger stick glucose ≥130 mg/dL and ≤280 mg/dL at Week 20) will be randomized to receive add-on therapy with glimepiride, repaglinide, acarbose, or gliclazide for 24 weeks (Week 20 through Week 44).
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Type 2 Diabetes Mellitus
Intervention	Drug: Metformin Metformin, 500 mg or 850 mg oral tablets, twice or three times a day (BID or TID) for a total dose of at least 1500 mg daily Other Names: Fortamet® Glucophage® Glucophage® XR Glumetza® Riomet® Metgluco® Glycoran® Drug: Sitagliptin Sitagliptin, 100 mg oral tablet, once daily (QD) Other Names: Januvia® Tesavel® Xelevia® Ristaben® Drug: Acarbose Acarbose, 50 mg oral tablets, TID (150 mg total daily dose) Other Names: Precose® Glucobay™ Drug: Repaglinide Repaglinide, 0.5 mg and/or 1 mg oral tablets, TID (up to 16 mg daily) Other Names: Prandin® Fulaidi™ Drug: Glimepiride Glimepiride, 1 mg and/or 2 mg oral tablets, QD (up to 6 mg daily) Other Names: Amaryl® Glimy Drug: Gliclazide Gliclazide, 30 mg oral tablets, QD or BID (30 mg to 120 mg total daily dose) Other Names: Diamicron MR™
Study Arm (s)	Active Comparator: Metformin + Sitagliptin + Glimepiride During Phase 2, participants receive up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). Experimental: Metformin + Sitagliptin + Repaglinide During Phase 2, participants receive up to 16 mg repaglinide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). Experimental: Metformin + Sitagliptin + Acarbose During Phase 2, participants receive 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). Experimental: Metformin + Sitagliptin + Gliclazide During Phase 2, participants receive 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	5500
Estimated Completion Date	May 2015
Estimated Primary Completion Date	May 2015
Eligibility Criteria	Inclusion Criteria: - Has Type 2 Diabetes Mellitus - Agrees to use an effective method of contraception or must not otherwise be at risk of becoming pregnant (female participants) Exclusion Criteria: - Has a history of type 1 diabetes mellitus or a history of ketoacidosis - Has been treated with insulin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, a Glucagon-like peptide-1 (GLP-1) mimetic or analogue before - Is on a weight loss program (not in maintenance phase), has started a weight loss medication, or has undergone bariatric surgery within 12 months - Has undergone a surgical procedure within 4 weeks - Has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder - Has a medical history of active liver disease, including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease - Has poorly controlled hypertension - Has severe peripheral vascular disease - Has human immunodeficiency virus (HIV) - Has had a clinically important hematological disorder - Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking. - Has a history of intolerance or hypersensitivity or any contraindication to study medications (including sitagliptin, metformin, glimepiride, repaglinide, acarbose or gliclazide) based upon the Chinese label - Is on or likely to require treatment with ≥2 consecutive weeks or repeated courses of pharmacologic doses of corticosteroids (other than inhaled, nasal, or topical corticosteroids) - Is pregnant or breast feeding or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug (female participants)
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Toll Free Number 1-888-577-8839
Location Countries	China

Administrative Information[ + expand ][ + ]

NCT Number	NCT01709305
Other Study ID Numbers	0431-313
Has Data Monitoring Committee	No
Information Provided By	Merck Sharp & Dohme Corp.
Study Sponsor	Merck Sharp & Dohme Corp.
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	April 2014

Locations[ + expand ][ + ]