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)

NCT01709305 | Completed Phase 4 Results

• 1 other identifier: 0431-313
• Study Type: interventional
• Target: 5,570
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)

  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.

  Phase 2 Baseline (Week 20) and Week 44

Secondary Outcomes (6)

• Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)

  Phase 2 Baseline (Week 20), Week 44

• Percentage of Participants With Hypoglycemia Events (Phase 2)

  From Week 20 through Week 44

• Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)

  From Week 20 through Week 44

• Percentage of Participants With a GI AE of Vomiting (Phase 2)

  From Week 20 through Week 44

• Percentage of Participants With a GI AE of Diarrhea (Phase 2)

  From Week 20 through Week 44

Study Arms (4)

Metformin + Sitagliptin + Glimepiride

ACTIVE COMPARATOR

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; Drug: Sitagliptin; Drug: Glimepiride

Metformin + Sitagliptin + Repaglinide

EXPERIMENTAL

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; Drug: Sitagliptin; Drug: Repaglinide

Metformin + Sitagliptin + Acarbose

EXPERIMENTAL

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; Drug: Sitagliptin; Drug: Acarbose

Metformin + Sitagliptin + Gliclazide

EXPERIMENTAL

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; Drug: Sitagliptin; Drug: Gliclazide

Interventions

Metformin 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.

Also known as: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

Metformin + Sitagliptin + Acarbose; Metformin + Sitagliptin + Gliclazide; Metformin + Sitagliptin + Glimepiride; Metformin + Sitagliptin + Repaglinide

Sitagliptin DRUG

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

Also known as: Januvia®, Tesavel®, Xelevia®, Ristaben®

Metformin + Sitagliptin + Acarbose; Metformin + Sitagliptin + Gliclazide; Metformin + Sitagliptin + Glimepiride; Metformin + Sitagliptin + Repaglinide

Acarbose DRUG

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

Also known as: Precose®, Glucobay™

Metformin + Sitagliptin + Acarbose

Repaglinide DRUG

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

Also known as: Prandin®, Fulaidi™

Metformin + Sitagliptin + Repaglinide

Glimepiride 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

Also known as: Amaryl®, Glimy

Metformin + Sitagliptin + Glimepiride

Gliclazide DRUG

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

Also known as: Diamicron MR™

Metformin + Sitagliptin + Gliclazide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 28271251 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Sitagliptin Phosphate; Acarbose; repaglinide; glimepiride; Gliclazide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Trisaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 18, 2012
• Study Start: November 8, 2012
• Primary Completion: April 17, 2015
• Study Completion: April 17, 2015
• Last Updated: August 21, 2018
• Results First Posted: May 11, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share