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Submitted by: Reina Kristine Marie Boter N/A Last Updated by: Reina Kristine Marie Boter 2019-07-01 10:44:54


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 Therapy (Alone or in Combination With Insulin)

PHRR140117-000162

MK0431A-289; CT.gov:NCT01760447

2013-CT0117

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 Therapy (Alone or in Combination With Insulin)

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 therapy (alone or in combination with insulin). The primary hypothesis is that the addition of sitagliptin reduces hemoglobin A1c (A1C) more than the addition of placebo after 20 weeks of treatment.

Start Date Duration in Months Target Completion Date Actual Completion Date
2014-05-07 73 2020-06-07 2019-06-10

Completed

Institution Classification Region LTO #
Merck Sharp & Dohme (I.A.) LLC Private Business NCR CDRR-NCR-S-16
Institution Region
Merck Sharp & Dohme (I.A.) LLC NCR
Name E-Mail Institution and Institution Address
Priscila Perez priscila.d.perez@merck.com 26/F Philamlife Tower Paseo De Roxas Makati City 1226
Name E-Mail Institution and Institution Address
Priscila Perez priscila.d.perez@merck.com 26/F Philamlife Tower Paseo De Roxas Makati City 1226
Name Expertise Affiliation
Benjamin P. Sablan, Jr., MD Pediatrics Philippine General Hospital
Chela Marie Romero, MD Internal Medicine Cebu Doctors' University Hospital
Grace P. Aquitania, MD Internal Med Davao Doctors Hospital
Lorna R. Abad, MD Pediatric endocrinologist Philippine Children's Medical Center
Project Location Institutional Ethics Review Board
Philippine General Hospital Philippine General Hospital Ethics Review Board
Cebu Doctors' University Hospital Cebu Doctors' University Hospital - Institutional Ethics Review Committee
Davao Doctors Hospital Davao Doctors Hospital Ethics Review Committee
Philippine Children's Medical Center Philippine Children's Medical Center IRB - Ethics Committee

Type 2 Diabetes Mellitus

Change from baseline in hemoglobin A1c (A1C)
[ Time Frame: Baseline and Week 20 ]
• Number of participants who experienced at least one
adverse event [ Time Frame: up to 54 weeks ]
• Number of participants who discontinued study drug due
to an adverse event [ Time Frame: Up to 54 weeks ]

Change from baseline in fasting plasma glucose (FPG) [ Time Frame: Baseline and Week 20 ]    Percentage of participants with A1C goals (<7%; <6.5%) [ Time Frame: Week 20 ]

Completed

  • Australia
  • Brazil
  • Bulgaria
  • Canada
  • Chile
  • Colombia
  • Costa Rica
  • Czech Republic
  • Denmark
  • Georgia
  • Greece
  • Guatemala
  • Honduras
  • Hungary
  • Israel
  • Italy
  • Mauritius
  • Mexico
  • Moldova
  • New Zealand
  • Panama
  • Philippines
  • Russia
  • Saudi Arabia
  • Serbia
  • South Africa
  • Sri Lanka
  • Taiwan
  • Ukraine
  • United States

Clinical Trial

MK0431A-289; CT.gov:NCT01760447

Unspecified

2013-09-25

0000-00-00

2

4

Philippines exceeded target sample size

07 May 2014

Inclusion Criteria:

•Has T2DM
•A1C greater than or equal to 6.5% and less than or equal to 10.0% on metformin (greater than or equal to 1500 mg/day) without insulin for greater than or equal to 12 weeks OR A1C greater than or equal to 7% and less than or equal to 10.0% on metformin (greater than or equal to 1500 mg/day) and insulin 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

Interventional

• 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 Sitagliptin + Metformin XR Matching placebo to Sitagliptin + Metformin XR fixeddose 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: 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). When thresholds for rescue are met, participants who are not on background insulin will initiate insulin glargine. Other Name: Lantus • Biological: Background insulinParticipants who enter the study on back ground insulin will continue on the same dose and formulation of insulin throughout the study. When thresholds for rescue are met, participants who have entered the study on background insulin will uptitrate their background insulin dose.

• 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 plus/minus
background insulin for 20 weeks. Insulin glargine may be administered, or background insulin may be uptitrated 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 plus/minus background insulin for 34 weeks. Insulin glargine may be administered, or background insulin may be uptitrated during Phase B of the study depending on the
participants' glucose and A1C levels.
Interventions:
◦ Drug: Sitagliptin + Metformin XR FDC
◦ Drug: Placebo to metformin XR
◦ Drug: Insulin glargine
◦ Biological: Background insulin

• 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) plus/minus background insulin for 20 weeks. Insulin glargine may be administered, or background insulin may be uptitrated 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) plus/minus background insulin for 34 weeks.
Insulin glargine may be administered, or background insulin may be up-titrated during Phase B of the study depending on the participants' glucose and A1C levels.
Interventions:
◦ Drug: Placebo to Sitagliptin + Metformin XR
◦ Drug: Metformin XR
◦ Drug: Insulin glargine
◦ Biological: Background insulin

Date Amendment Classification Reason
2014-09-22 Amendments related to the protocol admin
2018-07-13 Amendments related to the protocol Sample size is increased, Beginning and End of Study definition section was added, Provided clarification on analysis using the treatment effect estimand, Added analyses using the treatment policy estimand, including the
2015-05-28 Amendments related to the protocol Appropriate changes and clarifications have been made to accommodate the inclusion of patients on a background of insulin. Rationale for inclusion of insulin patients is that a higher number of pediatric patients are on baseline insulin, and since this has been studied in adults accordingly, inclusion in the pediatric study allows results to be generalizable to the broader population.
2016-02-17 Amendments related to the protocol Sample size is increased, Beginning and End of Study definition section was added, Provided clarification on analysis using the treatment effect estimand, Added analyses using the treatment policy estimand, including the

Randomized

Double Blind

(Patient, Investigator)

Parallel

Treatment

Phase III

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