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

This study is currently recruiting participants.
Verified March 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01709305
First received: October 16, 2012
Last updated: March 12, 2014
Last verified: March 2014

October 16, 2012
March 12, 2014
November 2012
May 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01709305 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313 AM1)
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)

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.

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).

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • 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 Name: Diamicron MR™
  • 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).
    Interventions:
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Glimepiride
  • 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).
    Interventions:
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Repaglinide
  • 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).
    Interventions:
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Acarbose
  • 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).
    Interventions:
    • Drug: Metformin
    • Drug: Sitagliptin
    • Drug: Gliclazide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
5500
May 2015
May 2015   (final data collection date for primary outcome measure)

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)

Both
18 Years to 75 Years
No
Contact: Toll Free Number 1-888-577-8839
China
 
NCT01709305
0431-313
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP