Comparison of Two Treatment Regimens (Sitagliptin Versus Liraglutide) on Participants Who Failed to Achieve Good Glucose Control on Metformin Alone (MK-0431-403)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01296412
First received: February 14, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

This study is being done to compare the effectiveness and safety of two treatment paradigms (oral sitagliptin with or without glimepiride versus liraglutide with or without increased dosing) for the treatment of participants with Type 2 Diabetes that is not adequately controlled with metformin alone. The primary hypothesis postulated that the mean change from baseline in hemoglobin A1c (A1C) in participants treated with a sitagliptin-based treatment is non-inferior to that of participants treated with a liraglutide-based

treatment.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: sitagliptin
Drug: liraglutide
Drug: glimepiride
Drug: metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Open-label Clinical Trial Comparing the Efficacy and Safety of a Sitagliptin-Based Treatment Paradigm to a Liraglutide-Based Treatment Paradigm in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Monotherapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in Hemoglobin A1c (A1C) [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    A1C is measured as percent. Thus, this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent.


Secondary Outcome Measures:
  • Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Change from baseline at Week 26 is defined as Week 26 minus Week 0.

  • Percentage of Participants Reaching A1C Goal of <7.0% [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  • Percentage of Participants Reaching A1C Goal of <6.5% [ Time Frame: Week 26 ] [ Designated as safety issue: No ]

Enrollment: 653
Study Start Date: March 2011
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin +/- glimepiride
Sitagliptin 100 mg tablet orally once daily for 26 weeks. Participants continued their stable dose of metformin >=1500 mg orally daily. Participants may have received glimepiride orally for glycemic control.
Drug: sitagliptin
100 mg tablet, orally, once daily.
Other Name: MK-0431, Januvia®, Tesavel®, Xelevia®, Ristaben®
Drug: glimepiride
starting dose of 1 mg tablet (up-titrated as needed), once daily, as needed, after Week 12.
Other Name: Amaryl®
Drug: metformin
metformin tablets at a dose of ≥1500 mg per day
Other Name: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Active Comparator: Liraglutide
Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin >=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Drug: liraglutide
0.6 mg by subcutaneous (pen) injection, once daily, on Days 1-7; up-titrated on Day 8 to 1.2 mg daily. At Week 12, dose may be increased to 1.8 mg once daily for participants who did not meet protocol-specified glycemic goals.
Other Name: Victoza®
Drug: metformin
metformin tablets at a dose of ≥1500 mg per day
Other Name: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • Type 2 diabetes mellitus.
  • On stable dose of metformin monotherapy at a dose of at least 1500 mg per day for at least 12 weeks and a hemoglobin A1C ≥7.0% and ≤11.0%.
  • Capable of using a liraglutide pen device.

Exclusion criteria

  • History of Type 1 Diabetes mellitus.
  • Use of any oral antihyperglycemic agent (AHA) besides metformin, within the prior 12 weeks of screening.
  • Cardiovascular disorders within the past 3 months including acute coronary syndrome or new or worsening symptoms of coronary heart disease, coronary artery intervention, stroke, or transient ischemic neurological disorder.
  • Impaired liver function.
  • Impaired kidney function.
  • History of malignancy or clinically important hematological disorder that requires disease-specific treatment (chemotherapy, radiation therapy, surgery) or, in the opinion of the investigator, is likely to recur during the duration of the study.
  • History of leukemia, lymphoma, aplastic anemia, myeloproliferative or myelodysplastic diseases, thrombocytopenia, or malignant melanoma, regardless of the time since treatment.
  • Pregnancy or breastfeeding, or intention to become pregnant or donate eggs within the projected duration of the study.
  • Participation in another study with an investigational drug or device within 12 weeks prior to screening.
  • History of hypersensitivity or any contraindication to sitagliptin, liraglutide, glimepiride, or metformin based upon the labels of the country of the investigational site.
  • Participation in a weight loss program and not yet in maintenance phase, or starting of a weight loss medication (such as orlistat or phentermine) within the prior 8 weeks.
  • Surgery within the prior 4 weeks or major surgery planned during the study.
  • Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
  • User of recreational or illicit drugs or recent history (within the last year) of drug abuse or increased alcohol consumption.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01296412     History of Changes
Other Study ID Numbers: 0431-403
Study First Received: February 14, 2011
Results First Received: February 5, 2013
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Sitagliptin
Metformin
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014