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 August 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: August 1, 2014
Last verified: August 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

  Hide Study Locations
Locations
United States, Alabama
Call for Information (Investigational Site 0450) Recruiting
Birmingham, Alabama, United States, 35233-1711
United States, Arizona
Call for Information (Investigational Site 0735) Recruiting
Phoenix, Arizona, United States, 85016
United States, California
Call for Information (Investigational Site 0464) Recruiting
Los Angeles, California, United States, 90027
Call for Information (Investigational Site 0750) Recruiting
San Diego, California, United States, 92102
Call for Information (Investigational Site 0457) Recruiting
Ventura, California, United States, 93003
Call for Information (Investigational Site 0468) Recruiting
Ventura, California, United States, 93003
United States, Florida
Call for Information (Investigational Site 0463) Recruiting
Jacksonville, Florida, United States, 32207
Call for Information (Investigational Site 0452) Recruiting
Miami Lakes, Florida, United States, 33014
Call for Information (Investigational Site 0461) Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Call for Information (Investigational Site 0741) Recruiting
Atlanta, Georgia, United States, 30342
United States, Illinois
Call for Information (Investigational Site 0742) Recruiting
Chicago, Illinois, United States, 60643
United States, Kansas
Call for Information (Investigational Site 0737) Recruiting
Topeka, Kansas, United States, 66606
United States, Kentucky
Call for Information (Investigational Site 0465) Recruiting
Louisville, Kentucky, United States, 40202
United States, Louisiana
Call for Information (Investigational Site 0749) Recruiting
New Orleans, Louisiana, United States, 70115
United States, Massachusetts
Call for Information (Investigational Site 0466) Recruiting
Boston, Massachusetts, United States, 02115
United States, New Jersey
Call for Information (Investigational Site 0470) Recruiting
Neptune, New Jersey, United States, 07753
United States, New York
Call for Information (Investigational Site 0472) Recruiting
Lake Success, New York, United States, 11042
United States, Tennessee
Call for Information (Investigational Site 0473) Recruiting
Lebanon, Tennessee, United States, 37087
United States, Texas
Call for Information (Investigational Site 0740) Recruiting
Edinburg, Texas, United States, 78539
Call for Information (Investigational Site 0456) Recruiting
Fort Worth, Texas, United States, 76104
Australia
Merck Sharp & Dohme Recruiting
North Ryde, Australia
Contact: Gary Jankelowitz    61 2 8988 8246      
Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 3L1
Contact: Medical Information Centre / Centre de l'information medicale de Merck Canada    514-428-8600 / 1-800-567-2594      
Chile
Merck Sharp & Dohme (I.A.) Corp. Recruiting
Santiago, Chile
Contact: Maria Elena Azara Hernandez    56 2 6558958      
Colombia
MDS Colombia SAS Recruiting
Bogota, Colombia
Contact: Francesca Carvajal    57 1219109011090      
Czech Republic
Merck Sharp and Dohme s.r.o. Recruiting
Praha, Czech Republic
Contact: Simona Martinkova    420 233010213      
Denmark
Merck Sharp & Dohme Recruiting
Glostrup, Denmark
Contact: Gert Andersen    45 44824475      
Hungary
MSD Pharma Hungary Kft. Recruiting
Budapest, Hungary
Contact: Simona Martinkova    36 1 457 8522      
Israel
Merck Sharp & Dohme Co. Ltd. Recruiting
Hod Hasharon, Israel
Contact: Ofer Sharon    972 9 9539310      
Italy
MSD Italia S.r.l. Recruiting
Rome, Italy
Contact: Patrizia Nardini    39 06 361911      
Mexico
MSD Recruiting
Mexico City, Mexico
Contact: Juan Marques    52 55254819608      
New Zealand
Merck Sharp & Dohme (New Zealand) Ltd., Recruiting
Wellington, New Zealand
Contact: Gary Jankelowitz    61 2 8988 8246      
Panama
MSD CARD Recruiting
Panama, Panama
Contact: Soraya Cedraro    507-282-7200      
Philippines
Merck Sharp & Dohme (I.A.) Corporation Recruiting
Makati, Philippines
Contact: Cesar Recto    632 784 9500      
Russian Federation
Merck Sharp & Dohme IDEA, Inc. Recruiting
Moscow, Russian Federation
Contact: Maria Koroleva    7 0959410000      
South Africa
MSD (Pty) LTD South Africa Recruiting
Midrand, South Africa
Contact: Khanyi Mzolo    27 11 655 3140      
Taiwan
Merck Sharp & Dohme (I.A.) Corp. Recruiting
Taipei, Taiwan
Contact: Diana Zhang    886-2-66316030      
Ukraine
MSD Ukraine LLC Recruiting
Kiev, Ukraine
Contact: Eran Gefen    38 (044) 393 74 80      
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: August 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
Insulin, Globin Zinc
Glargine
Sitagliptin
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
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 August 28, 2014