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Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01485614
First received: December 1, 2011
Last updated: September 19, 2016
Last verified: September 2016
  Purpose
The purpose of the study is to assess the safety of the addition of sitagliptin, and its effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.

Condition Intervention Phase
Diabetes Mellitus
Type 2 Diabetes
Drug: Sitagliptin
Drug: Metformin
Drug: Placebo to sitagliptin
Drug: Placebo to metformin
Drug: Glycemic Rescue 1
Drug: Glycemic Rescue 2
Biological: Glycemic Rescue 3
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from baseline in A1C [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Number of participants with adverse events (AE) [ Time Frame: Up to 56 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants who discontinued study medication due to an AE [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in A1C at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Percentage of participants with an A1C target of <7.0%, <6.5% at Week 20 [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
  • Percentage of participants with an A1C target of <7.0%, <6.5% at Week 54 [ Time Frame: Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in FPG at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in insulin at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in insulin at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in proinsulin at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in proinsulin at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in proinsulin/insulin ratio at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in proinsulin/insulin ratio at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in Homeostatic Model Assessment of β-cell function (HOMA-β) at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in HOMA-β at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in Homeostatic Model Assessment of insulin resistance (HOMA-IR) at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in HOMA-IR at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in endpoints at 2 hours after the start of the meal for 2-hour PMG and 2-hour incremental PMG at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in endpoints at 2 hours after the start of the meal for 2-hour PMG and 2-hour incremental PMG at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Change from baseline in AUC endpoints (Total AUC and Excursion AUC) for glucose, insulin, C-peptide, proinsulin, proinsulin AUC/Insulin AUC, Insulin AUC/ Glucose AUC at Week 20 [ Time Frame: Baseline and Week 20 ] [ Designated as safety issue: No ]
  • Change from baseline in AUC endpoints (Total AUC and Excursion AUC) for glucose, insulin, C-peptide, proinsulin, proinsulin AUC/Insulin AUC, Insulin AUC/ Glucose AUC at Week 54 [ Time Frame: Baseline and Week 54 ] [ Designated as safety issue: No ]
  • Proportion of participants requiring glycemic rescue therapy at Week 20 [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
  • Proportion of participants requiring glycemic rescue therapy at Week 54 [ Time Frame: Week 54 ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: February 2012
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Phase A (20 weeks): Sitagliptin 100 mg oral tablet once daily prior to the morning meal and placebo to metformin oral tablet (500 mg), 2 tablets twice daily prior to morning and evening meals. Phase B (34 weeks): Participants who have not initiated glycemic rescue therapy will continue to receive Phase A treatments.
Drug: Sitagliptin
Other Name: Januvia
Drug: Placebo to metformin Drug: Glycemic Rescue 1
Participants in the sitagliptin arm who require glycemic rescue will receive metformin in both Phase A and Phase B. Participants in the placebo arm who require glycemic rescue will receive metformin in Phase A. Participants on background insulin will NOT have their insulin doses up-titrated, but will be rescued with metformin.
Biological: Glycemic Rescue 3
Participants who require glycemic rescue after Glycemic Rescue 1 or 2, will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated.
Experimental: Placebo
Phase A (20 weeks): Placebo to sitagliptin oral tablet once a day and placebo to metformin oral tablets (500 mg), 2 tablets twice daily prior to morning and evening meals. Phase B (34 weeks): Participants who have not initiated glycemic rescue therapy will receive 1 tablet of placebo to sitagliptin daily and 2 tablets of metformin (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily.
Drug: Metformin
Other Name: Glucophage
Drug: Placebo to sitagliptin Drug: Placebo to metformin Drug: Glycemic Rescue 2
Participants in the placebo arm who have switched to metformin in Phase B and require glycemic rescue will receive sitagliptin. Participants on background insulin will NOT have their insulin doses up-titrated, but will be rescued with sitagliptin.
Biological: Glycemic Rescue 3
Participants who require glycemic rescue after Glycemic Rescue 1 or 2, will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated.

Detailed Description:

This trial is of approximately 56 weeks in duration, including a screening period of up to 1 week, a 1-week single-blind placebo run-in period, a 20-week placebo-controlled, double blind treatment period [Phase A] and a 34-week double-blind active controlled treatment period [Phase B] during which participants randomized to the placebo arm who have not initiated glycemic rescue therapy with metformin during Phase A will receive metformin (in a blinded manner). A telephone contact will be performed 14 days after the last dose of study medication to assess for any serious adverse events (SAEs).

Two arms of the study were removed from the study by a protocol amendment.

  Eligibility

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

Inclusion Criteria:

  • Type 2 Diabetes Mellitus (T2DM)
  • Has not received treatment with an antihyperglycemic agent (AHA) for ≥12 weeks prior to the Screening Visit/Visit 1, or is on a stable dose of insulin (without any other AHA) for at least 12 weeks prior to the Screening Visit/Visit 1. At screening, participants on insulin doses that are not stable can have their insulin doses adjusted and be eligible to participate after their dose remains stable for ≥12 weeks, if they meet all other eligibility criteria. In India, only participants on stable doses of insulin will be eligible.
  • An A1C of ≥6.5% and ≤10.0% (For participants on insulin: an A1C ≥7.0% and ≤10.0%).

Exclusion Criteria:

  • History of type 1 diabetes mellitus, autoimmune diabetes mellitus or has a positive antibody screen for anti-GAD (Glutamic Acid Decarboxylase) or (Islet cell autoantigen) ICA-512.
  • Known monogenic diabetes, secondary diabetes, or a genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
  • Symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for ketonemia requiring immediate initiation of antihyperglycemic therapy.
  • Previously taken a DPP-4 (Dipeptidyl peptidase-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or (Glucagon-like peptide-1) GLP-1 receptor agonist (such as exenatide or liraglutide).
  • Hypersensitivity or contraindication (according to the product circular in the country of the investigational site) to metformin.
  • Chronic treatment with a medication known to cause weight gain within 30 days of study start or weight loss or increased blood glucose within 8 weeks of study start or treated with an anti-psychotic within the past 12 weeks.
  • On a weight loss program and not in the maintenance phase or have undergone bariatric surgery within 12 months prior to study start.
  • On or likely to require treatment with ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
  • Undergone a surgical procedure within the prior 4 weeks or has major surgery planned during the study.
  • History of congenital heart disease or cardiovascular disease other than hypertension.
  • Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
  • Active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).
  • Chronic myopathy, mitochondrial disorder, or a progressive neurological or neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).
  • Human immunodeficiency virus (HIV) as assessed by medical history.
  • Clinically significant hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndrome).
  • Under treatment for hyperthyroidism.
  • Exhibits abnormal growth patterns or is being treated with growth hormone.
  • History of malignancy or clinically important hematologic disorder.
  • History of idiopathic acute pancreatitis or chronic pancreatitis.
  • Known history of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year).
  • Donated blood products or has had phlebotomy of >10% of estimated total blood volume within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within the projected duration of the study.
  • Pregnant, has a positive urine pregnancy test at Screening Visit/Visit 1, is expecting to conceive within the projected duration of the study, or is breast-feeding.
  • Exclusionary laboratory values.
  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: NCT01485614

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

  Hide Study Locations
Locations
United States, Alabama
Call for Information (Investigational Site 0312) Recruiting
Birmingham, Alabama, United States, 35233-1711
Call for Information (Investigative Site 0312) Recruiting
Birmingham, Alabama, United States, 35233-1711
United States, Arizona
Call for Information (Investigational Site 0317) Recruiting
Phoenix, Arizona, United States, 85016
United States, California
Call for Information (Investigational Site 0013) Recruiting
Clovis, California, United States, 93612
Call for Information (Investigational Site 0302) Recruiting
Los Angeles, California, United States, 90027
Call for Information (Investigational Site 0018) Recruiting
Los Angeles, California, United States, 90048
Call for Information (Investigational Site 0020) Recruiting
Sacramento, California, United States, 95821
Call for Information (Investigational Site 0334) Recruiting
San Diego, California, United States, 92102
Call for Information (Investigational Site 0019) Recruiting
San Diego, California, United States, 92123
United States, Colorado
Call for Information (Investigational Site 0023) Recruiting
Aurora, Colorado, United States, 80045
United States, District of Columbia
Call for Information (Investigational Site 0330) Recruiting
Washington, District of Columbia, United States, 20010
Call for Information (Investigational Site 0337) Recruiting
Washington, District of Columbia, United States, 20020
United States, Florida
Call for Information (Investigational Site 0323) Recruiting
Jacksonville, Florida, United States, 32207
Call for Information (Investigational Site 0320) Recruiting
Miami, Florida, United States, 33136
United States, Georgia
Call for Information (Investigational Site 0325) Recruiting
Atlanta, Georgia, United States, 30342
Call for Information (Investigational Site 0326) Recruiting
Thomaston, Georgia, United States, 30286
United States, Louisiana
Call for Information (Investigational Site 0333) Recruiting
New Orleans, Louisiana, United States, 70115
United States, Mississippi
Call for Information (Investigational Site 0328) Recruiting
Jackson, Mississippi, United States, 39216
United States, Missouri
Call for Information (Investigational Site 0306) Recruiting
Kansas City, Missouri, United States, 64111
United States, Ohio
Call for Information (Investigational Site 0096) Recruiting
Toledo, Ohio, United States, 43606
United States, Oregon
Call for Information (Investigational Site 0336) Recruiting
Portland, Oregon, United States, 97239
United States, Texas
Call for Information (Investigational Site 0322) Recruiting
Edinburg, Texas, United States, 78539
Call for Information (Investigational Site 0017) Recruiting
Houston, Texas, United States, 77081
Call for Information (Investigational Site 0015) Recruiting
Lytle, Texas, United States, 78052
Argentina
Merck Sharp & Dohme (Argentina) Inc. Recruiting
Buenos Aires, Argentina
Contact: Alfredo Wilkinson    54 11 4796 8200      
Austria
MSD Osterreich GmbH Recruiting
Vienna, Austria
Contact: Karl Boegl    43 126044130      
Brazil
MSD Brasil Recruiting
Sao Paulo, Brazil
Contact: Ricardo Germano    55 11 51897942      
Bulgaria
Merck Sharp & Dohme Bulgaria EOOD Recruiting
Sofia, Bulgaria
Contact: Eran Gefen    38 (044) 393 74 80      
Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 3L1
Contact: Medical Information Centre Centre de IOinformation mZdicale 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      
Costa Rica
Merck Sharp & Dohme Recruiting
San Jose, Costa Rica
Contact: Soraya Cedraro    507-282-7200      
Denmark
Merck Sharp & Dohme Recruiting
Glostrup, Denmark
Contact: Gert Andersen    45 44824475      
Dominican Republic
Merck Sharp & Dohme Recruiting
Santo Domingo, Dominican Republic
Contact: Felipe Arbelaez    (787) 474-8200      
Georgia
Merck Sharp & Dohme IDEA, Inc. Recruiting
Tbilisi, Georgia
Contact: Eran Gefen    38 (044) 393 74 80      
Germany
MSD Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Greece
Vianex, S.A. / MSD Recruiting
Alimos, Greece
Contact: Lazaros Poughias    30 2109897322      
Guatemala
MSD CARD Recruiting
Guatemala, Guatemala
Contact: Soraya Cedraro    507-282-7200      
Honduras
MSD CARD Recruiting
Tegucigalpa, Honduras
Contact: Soraya Cedraro    507-282-7200      
Hungary
MSD Pharma Hungary Kft. Recruiting
Budapest, Hungary
Contact: Szabolcs Barýtfi    36 1 888 5300      
Israel
Merck Sharp & Dohme Co. Ltd. Recruiting
Hod Hasharon, Israel
Contact: Gally Teper    972-9-9533310      
Italy
MSD Italia S.r.l. Recruiting
Rome, Italy
Contact: Patrizia Nardini    39 06 361911      
Latvia
Merck Sharp & Dohme Latvija SIA Recruiting
Riga, Latvia
Contact: Katrin Moeschlin    +46 (0) 8E578E135 00      
Lithuania
UAB "Merck Sharp & Dohme" Recruiting
Vilnius, Lithuania
Contact: Katrin Moeschlin    +46 (0) 8E578E135 00      
Malaysia
MSD Recruiting
Petaling Jaya, Malaysia
Contact: Boon Hock Yeoh    60 377181723      
Mauritius
Merck Sharp & Dohme Ilaclari Ltd. Sti Recruiting
Port Louis, Mauritius
Contact: Cem Ozesen    90 212 3361260      
Mexico
MSD Recruiting
Mexico City, Mexico
Contact: Juan Marques    52 55254819608      
Moldova, Republic of
Merck Sharp & Dohme IDEA, Inc. Recruiting
Chisinau, Moldova, Republic of
Contact: Tatyana Gots    38 044 393-7480      
New Zealand
Merck Sharp & Dohme (New Zealand) Ltd., Recruiting
Wellington, New Zealand
Contact: Australian Medical Information Centre    61 2 8988 8428      
Philippines
Merck Sharp & Dohme (I.A.) Corporation Recruiting
Makati, Philippines
Contact: Cesar Recto    632 784 9500      
Poland
MSD Polska Sp. Z o.o. Recruiting
Warsaw, Poland
Contact: Adam Czernik    48 22 4784324      
Romania
Merck Sharp & Dohme Romania SRL Recruiting
Bucharest, Romania
Contact: Simona Olaru    38 (044) 393 74 80      
Russian Federation
Merck Sharp & Dohme IDEA, Inc. Recruiting
Moscow, Russian Federation
Contact: Tatiana Serebriakova    74959167100, EXT.366      
Saudi Arabia
MSD (IA) Corp - SA Branch Recruiting
Riyadh, Saudi Arabia
Contact: Samer El-Ali    04 4269100      
Serbia
Merck Sharp & Dohme Recruiting
Belgrade, Serbia
Contact: Eran Gefen    38 (044) 393 74 80      
Slovakia
Merck Sharp Dohme S.R.O. Recruiting
Bratislava, Slovakia
Contact: Eva Kaszasova    420 233010213      
South Africa
MSD (Pty) LTD South Africa Recruiting
Midrand, South Africa
Contact: Khanyi Mzolo    27 11 655 3140      
Spain
Merck Sharp and Dohme de Espana S.A. Recruiting
Madrid, Spain
Contact: Joaquin Mateos Chacon    (0034) 913210600      
Sweden
MSD Sweden Recruiting
Stockholm, Sweden
Contact: Tryggve Ljung    46 (0)70 545 28 66      
Thailand
MSD (Thailand) Ltd. Recruiting
Bangkok, Thailand
Contact: Thanu Komolsai    66 2262 5746      
United Arab Emirates
Merck Sharp & Dohme Recruiting
Dubai, United Arab Emirates
Contact: Samer El-Ali    04 4269100      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01485614     History of Changes
Other Study ID Numbers: 0431-083 
Study First Received: December 1, 2011
Last Updated: September 19, 2016
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
Metformin
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
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 September 28, 2016