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

NCT ID: NCT01709305

Last Updated: 2018-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5570 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-08
• Study Completion Date: 2015-04-17

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. The study would be declared successful if at least one of the three primary hypotheses was met.

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 has already been 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).

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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; administered with food.

Sitagliptin

Intervention Type: DRUG

Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food

Glimepiride

Intervention Type: DRUG

Glimepiride, 1 mg and/or 2 mg oral tablets, QD (up to 6 mg daily); administered before the first main meal of the day

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).

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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; administered with food.

Sitagliptin

Intervention Type: DRUG

Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food

Repaglinide

Intervention Type: DRUG

Repaglinide, 0.5 mg and/or 1 mg oral tablets, TID (up to 16 mg daily); administered within 30 minutes of each meal.

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).

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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; administered with food.

Sitagliptin

Intervention Type: DRUG

Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food

Acarbose

Intervention Type: DRUG

Acarbose, 50 mg oral tablets, TID (150 mg total daily dose); administered with the first bite of each main meal.

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).

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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; administered with food.

Sitagliptin

Intervention Type: DRUG

Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food

Gliclazide

Intervention Type: DRUG

Gliclazide, 30 mg oral tablets, QD or BID (30 mg to 120 mg total daily dose); administered with meal.

Interventions

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; administered with food.

Intervention Type: DRUG

Sitagliptin

Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food

Intervention Type: DRUG

Acarbose

Acarbose, 50 mg oral tablets, TID (150 mg total daily dose); administered with the first bite of each main meal.

Intervention Type: DRUG

Repaglinide

Repaglinide, 0.5 mg and/or 1 mg oral tablets, TID (up to 16 mg daily); administered within 30 minutes of each meal.

Intervention Type: DRUG

Glimepiride

Glimepiride, 1 mg and/or 2 mg oral tablets, QD (up to 6 mg daily); administered before the first main meal of the day

Intervention Type: DRUG

Gliclazide

Gliclazide, 30 mg oral tablets, QD or BID (30 mg to 120 mg total daily dose); administered with meal.

Intervention Type: DRUG

Other Intervention Names

Fortamet®; Glucophage®; Glucophage® XR; Glumetza®; Riomet®; Metgluco®; Glycoran®; Januvia®; Tesavel®; Xelevia®; Ristaben®; Precose®; Glucobay™; Prandin®; Fulaidi™; Amaryl®; Glimy; Diamicron MR™

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Xu W, Mu Y, Zhao J, Zhu D, Ji Q, Zhou Z, Yao B, Mao A, Engel SS, Zhao B, Bi Y, Zeng L, Ran X, Lu J, Ji L, Yang W, Jia W, Weng J. Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial. Sci China Life Sci. 2017 Mar;60(3):225-238. doi: 10.1007/s11427-016-0409-7. Epub 2017 Feb 7.

Reference Type: RESULT

PMID: 28271251 (View on PubMed)

Other Identifiers

0431-313

Identifier Type: -

Identifier Source: org_study_id