A Study of the Safety and Efficacy of MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus (MK-0431A-289 AM2)

This study is currently recruiting participants.
Verified April 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01760447
First received: January 2, 2013
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to assess the safety and efficacy of the addition of sitagliptin (administered as MK-0431A XR) compared with the addition of placebo to therapy with extended-release metformin (metformin XR) for the treatment of type 2 diabetes mellitus (T2DM) in pediatric participants with inadequate glycemic control on metformin monotherapy. The primary hypothesis is that the addition of sitagliptin reduces hemoglobin A1c (A1C) more than the addition of placebo after 20 weeks of treatment.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: MK-0431A XR
Drug: Placebo to MK-0431A XR
Drug: Metformin XR
Drug: Placebo to metformin XR
Drug: Insulin glargine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-0431A XR (a Fixed-dose Combination Tablet of Sitagliptin and Extended-release Metformin) in Pediatric Subjects With Type 2 Diabetes Mellitus With 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 20 ] [ Designated as safety issue: No ]
  • Number of participants who experienced at least one adverse event [ Time Frame: up to 54 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants who discontinued study drug due to an adverse event [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 240
Study Start Date: February 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-0431A XR
Phase A: two MK-0431A XR tablets orally daily (total daily dose: 100 mg sitagliptin and 1000, 1500 or 2000 mg metformin) plus two placebo to metformin XR tablets for 20 weeks. Insulin glargine may be administered as glycemic rescue therapy during Phase A of the study. Phase B: two MK-0431A XR tablets orally daily (total daily dose: 100 mg sitagliptin and 1000, 1500 or 2000 mg metformin) plus two placebo to metformin XR tablets for 34 weeks. Insulin glargine may be administered during Phase B of the study depending on the participants' glucose and A1C levels.
Drug: MK-0431A XR
MK-0431A XR fixed-dose combination tablet (sitagliptin/metformin: 50/500 mg, 50/1000 mg) administered prior to the morning meal
Drug: Placebo to metformin XR
Matching placebo to metformin XR tablet administered prior to the morning meal
Drug: Insulin glargine
The insulin regimen and dosing will be at the discretion of the investigator (based on locally accepted, national, or international guidelines for the indication and use of insulin glargine)
Other Name: Lantus
Active Comparator: Metformin XR
Phase A: two placebo to MK-0431A XR tablets orally daily plus two metformin XR tablets (total daily dose: 1000, 1500 or 2000 mg) for 20 weeks. Insulin glargine may be administered as glycemic rescue therapy during Phase A of the study. Phase B: two placebo to MK-0431A XR tablets orally daily plus two metformin XR tablets (total daily dose: 1000, 1500 or 2000 mg) for 34 weeks. Insulin glargine may be administered during Phase B of the study depending on the participants' glucose and A1C levels.
Drug: Placebo to MK-0431A XR
Matching placebo to MK-0431A XR fixed-dose combination tablet administered prior to the morning meal
Drug: Metformin XR
Metformin XR tablet (500 mg, 1000 mg) administered prior to the morning meal
Other Name: Glucophage® XR
Drug: Insulin glargine
The insulin regimen and dosing will be at the discretion of the investigator (based on locally accepted, national, or international guidelines for the indication and use of insulin glargine)
Other Name: Lantus

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has T2DM
  • Has not received treatment with insulin for at least 6 months prior to study participation
  • A1C greater than or equal to 7.0% and less than or equal to 10.0% on metformin immediate release (IR) or extended release (ER), greater than or equal to 1500 mg/day, for greater than or equal to 12 weeks. NOTE: Participants on a daily dose of metformin greater than or equal to 1000 mg/day, but less than 1500 mg/day for greater than or equal to 12 weeks may be eligible if there is documentation that higher doses are not tolerated.
  • Between 10 and 17 years of age (inclusive)
  • Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug

Exclusion Criteria:

  • Has type 1 diabetes mellitus
  • Has monogenic diabetes or secondary diabetes
  • Has previously taken a dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, saxagliptin, or linagliptin) or glucagon-like peptide-1 (GLP-1) receptor agonist (such as exenatide or liraglutide)
  • Is on or likely to require treatment for > or =2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
  • Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study
  • History of congenital heart disease or cardiovascular disease other than hypertension
  • History of active liver disease (other than non-alcoholic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
  • Active neuropathy (such as nephrotic syndrome or glomerulonephritis)
  • Chronic myopathy, mitochondrial disorder or a progressive neurological or neuromuscular disorder
  • Human immunodeficiency virus (HIV)
  • Hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndromes)
  • Is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
  • History of malignancy for < or =5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
  • History of idiopathic acute pancreatitis or chronic pancreatitis
  • History of recreational or illicit drug use, or of alcohol abuse or

dependence (within the past year)

  • Has donated blood products or has had phlebotomy of >10% of estimated

total blood volume within 8 weeks of study participation, or intends to donate

blood products or receive blood products within the projected duration of the study

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01760447

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 30 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01760447     History of Changes
Other Study ID Numbers: 0431A-289, 2012-004035-23
Study First Received: January 2, 2013
Last Updated: April 1, 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
Glargine
Sitagliptin
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014