Clinical trial NCT01709305: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-10-18
Enrollment: 5570
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)
timeFrame: Phase 2 Baseline (Week 20) and Week 44
Secondary outcomes:
measure: Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)
timeFrame: Phase 2 Baseline (Week 20), Week 44
measure: Percentage of Participants With Hypoglycemia Events (Phase 2)
timeFrame: From Week 20 through Week 44
measure: Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)
timeFrame: From Week 20 through Week 44
measure: Percentage of Participants With a GI AE of Vomiting (Phase 2)
timeFrame: From Week 20 through Week 44
measure: Percentage of Participants With a GI AE of Diarrhea (Phase 2)
timeFrame: From Week 20 through Week 44
measure: Percentage of Participants With a GI AE of Abdominal Pain (Phase 2)
timeFrame: From Week 20 through Week 44
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.