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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01709305
First received: October 16, 2012
Last updated: April 6, 2016
Last verified: April 2016
  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. The study would be declared successful if at least one of the three primary hypotheses was met.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Metformin
Drug: Sitagliptin
Drug: Acarbose
Drug: Repaglinide
Drug: Glimepiride
Drug: Gliclazide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

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) and Week 44 ] [ Designated as safety issue: No ]
    HbA1c is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change from baseline reflects the Week 44 A1C minus baseline A1C. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used. Change from baseline was based on the constrained longitudinal data analysis (cLDA) model including all available measurements from baseline through the last visit. The terms in the cLDA model include treatment, time in weeks (categorical), regions, and treatment-by-time interaction.


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 ]
    Change from baseline in body weight in Phase 2 was reported. Change from baseline reflects the Week 44 body weight minus baseline body weight. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used.

  • Percentage of Participants With Hypoglycemia Events (Phase 2) [ Time Frame: From Week 20 through Week 44 ] [ Designated as safety issue: Yes ]
    Hypoglycemia events represent epidsodes symptomatic of hypoglycemia (e.g., weakness, dizziness, shakiness, increased sweating, palpitations, or confusion) and/or finger stick glucose values of ≤70 mg/dL (3.9 mmol/L). The percentage of participants with hypoglycemia events was reported.

  • Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2) [ Time Frame: From Week 20 through Week 44 ] [ Designated as safety issue: Yes ]
    The percentage of participants with a GI AE of "nausea" was reported.

  • Percentage of Participants With a GI AE of Vomiting (Phase 2) [ Time Frame: From Week 20 through Week 44 ] [ Designated as safety issue: Yes ]
    The percentage of participants with a GI AE of "vomiting" was reported.

  • Percentage of Participants With a GI AE of Diarrhea (Phase 2) [ Time Frame: From Week 20 through Week 44 ] [ Designated as safety issue: Yes ]
    The percentage of participants with a GI AE of "diarrhea" was reported.

  • Percentage of Participants With a GI AE of Abdominal Pain (Phase 2) [ Time Frame: From Week 20 through Week 44 ] [ Designated as safety issue: Yes ]
    The percentage of participants with a GI AE of "abdominal pain" was reported.


Enrollment: 5570
Study Start Date: November 2012
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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; administered with food.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Sitagliptin
Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food
Other Names:
  • Januvia®
  • Tesavel®
  • Xelevia®
  • Ristaben®
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
Other Names:
  • Amaryl®
  • Glimy
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).
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; administered with food.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Sitagliptin
Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food
Other Names:
  • Januvia®
  • Tesavel®
  • Xelevia®
  • Ristaben®
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.
Other Names:
  • Prandin®
  • Fulaidi™
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).
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; administered with food.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Sitagliptin
Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food
Other Names:
  • Januvia®
  • Tesavel®
  • Xelevia®
  • Ristaben®
Drug: Acarbose
Acarbose, 50 mg oral tablets, TID (150 mg total daily dose); administered with the first bite of each main meal.
Other Names:
  • Precose®
  • Glucobay™
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).
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; administered with food.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Sitagliptin
Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food
Other Names:
  • Januvia®
  • Tesavel®
  • Xelevia®
  • Ristaben®
Drug: Gliclazide
Gliclazide, 30 mg oral tablets, QD or BID (30 mg to 120 mg total daily dose); administered with meal.
Other Name: Diamicron MR™

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  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: NCT01709305

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01709305     History of Changes
Other Study ID Numbers: 0431-313 
Study First Received: October 16, 2012
Results First Received: April 6, 2016
Last Updated: April 6, 2016
Health Authority: China: Ministry of Health

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Repaglinide
Glimepiride
Metformin
Sitagliptin Phosphate
Gliclazide
Acarbose
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycoside Hydrolase Inhibitors
Anti-Arrhythmia Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 30, 2016