Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 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: November 18, 2014
Last verified: November 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: Sitagliptin + Metformin XR FDC
Drug: Placebo to Sitagliptin + Metformin 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: 90
Study Start Date: February 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin + Metformin XR FDC
Phase A: two sitagliptin + extended-release (XR) metformin fixed-dose combination (FDC) tablets (MK-0431A XR) orally daily (total daily dose: 100 mg sitagliptin and 1000, 1500 or 2000 mg metformin XR) 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 sitagliptin + metformin XR FDC tablets orally daily (total daily dose: 100 mg sitagliptin and 1000, 1500 or 2000 mg metformin XR) 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: Sitagliptin + Metformin XR FDC
Sitagliptin + Metformin XR fixed-dose combination tablet (sitagliptin/metformin: 50/500 mg, 50/1000 mg) administered with a meal, preferably in the evening
Drug: Placebo to metformin XR
Matching placebo to metformin XR tablet administered with a meal, preferably in the evening
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
Placebo Comparator: Placebo to Sitagliptin + Metformin XR FDC
Phase A: two placebo to sitagliptin + metformin XR FDC 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 sitagliptin + metformin XR FDC 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 Sitagliptin + Metformin XR
Matching placebo to Sitagliptin + Metformin XR fixed-dose combination tablet administered with a meal, preferably in the evening
Drug: Metformin XR
Metformin XR tablet (500 mg, 1000 mg) administered with a meal, preferably in the evening
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 12 weeks prior to study participation
  • A1C greater than or equal to 6.5% and less than or equal to 10.0% on metformin immediate release (IR) or extended release (XR), 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
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: NCT01760447

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

  Show 40 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: November 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Insulin
Insulin, Long-Acting
Metformin
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014