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

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:
NCT01485614
First received: December 1, 2011
Last updated: August 19, 2014
Last verified: August 2014

December 1, 2011
August 19, 2014
February 2012
November 2017   (final data collection date for primary outcome measure)
  • 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 ]
  • Change from baseline in A1C [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: 54 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01485614 on ClinicalTrials.gov Archive Site
  • 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 patients requiring glycemic rescue therapy at Week 20 [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
  • Proportion of patients requiring glycemic rescue therapy at Week 54 [ Time Frame: Week 54 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Study to Assess Safety & Efficacy of Sitagliptin as Initial Monotherapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants (MK-0431-083)
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Diabetes Mellitus
  • Type 2 Diabetes
  • Drug: Sitagliptin
    100 mg oral tablet of sitagliptin prior to the morning meal in Phase A and Phase B.
    Other Name: Januvia
  • Drug: Metformin
    Metformin (500 mg), 2 tablets twice daily prior to morning and evening meals
    Other Name: Glucophage
  • Drug: Placebo to sitagliptin
    After randomization: Participants randomized to the Placebo Phase A/Metformin Phase B arm will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. Phase B: Participants in the Placebo Phase A/Metformin Phase B arm will continue to receive 1 oral tablet of placebo to sitagliptin prior to the morning meal. For 1 week, participants will receive 1 oral tablet of placebo to sitagliptin prior to the morning meal.
  • Drug: Placebo to metformin
    After randomization: Participants randomized to the Sitagliptin Arm and those randomized to the Placebo Phase A/Metformin Phase B arm will receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. Phase B: Participants in the Sitagliptin Arm will continue to receive 2 oral tablets of placebo to metformin prior to the morning and evening meals. For 1 week participants will receive oral tablets of placebo to metformin (500 mg), 2 tablets prior to the morning and evening meals.
  • Drug: Metformin Rescue
    Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 1 (blinded), eligible participants receiving sitagliptin or placebo (in Phase A), or sitagliptin (in Phase B) will initiate metformin.
  • Drug: Sitagliptin Rescue
    Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 1 (blinded), eligible participants receiving metformin (in Phase B) will initiate sitagliptin.
  • Biological: Insulin Rescue
    Mandatory glycemic rescue will be initiated in both Phase A and Phase B for participants meeting defined glycemic thresholds. For Rescue Step 2 (open-label), participants receiving sitagliptin, placebo or metformin will receive insulin according to routine clinical practice.
  • Experimental: Sitagliptin
    Sitagliptin 100 mg oral tablet once a day and placebo to metformin oral tablet (500 mg), 2 tablets twice daily prior to morning and evening meals for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will continue to receive Phase A treatment during Phase B (34 weeks).
    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo to sitagliptin
    • Drug: Placebo to metformin
    • Drug: Metformin Rescue
    • Drug: Sitagliptin Rescue
    • Biological: Insulin Rescue
  • Active Comparator: Metformin
    Metformin (500 mg) oral tablets, 2 tablets twice daily prior to morning and evening meals and placebo to sitagliptin (100 mg), oral tablet once daily for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will continue to receive Phase A treatment for 34 weeks (Phase B). This arm of the study was removed by a protocol amendment.
    Interventions:
    • Drug: Metformin
    • Drug: Placebo to sitagliptin
    • Drug: Placebo to metformin
    • Drug: Metformin Rescue
    • Drug: Sitagliptin Rescue
    • Biological: Insulin Rescue
  • Experimental: Placebo Phase A/Sitagliptin B
    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 for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will receive 1 tablet of sitagliptin daily and 2 tablets of metformin placebo twice daily prior to morning and evening meals (Phase B). This arm of the study was removed by a protocol amendment.
    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo to sitagliptin
    • Drug: Placebo to metformin
  • Experimental: Placebo Phase A / Metformin Phase B
    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 for 20 weeks (Phase A). Participants who have not initiated glycemic rescue therapy will receive 1 tablet of sitagliptin-placebo daily and metformin oral tablets (500 mg), 2 tablets twice daily prior to morning and evening meals during Phase B (34 weeks).
    Interventions:
    • Drug: Metformin
    • Drug: Placebo to sitagliptin
    • Drug: Placebo to metformin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
170
November 2017
November 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Type 2 Diabetes Mellitus (T2DM)
  • Has not received treatment with an oral antihyperglycemic agent (AHA) or insulin for ≥12 weeks prior to the Screening Visit/Visit 1.
  • An A1C of ≥6.5% 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.
  • History of idiopathic acute pancreatitis or chronic pancreatitis.
Both
10 Years to 17 Years
No
Contact: Toll Free Number 1-888-577-8839
United States,   Argentina,   Australia,   Austria,   Bulgaria,   Canada,   Chile,   Colombia,   Denmark,   Dominican Republic,   France,   Germany,   Guatemala,   Hungary,   Israel,   Italy,   Latvia,   Lithuania,   Malaysia,   Mexico,   New Zealand,   Panama,   Philippines,   Poland,   Romania,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Thailand
 
NCT01485614
0431-083
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP