E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- MK-0431A-289: 1.Over 54 weeks, to assess the safety and tolerability of the addition of sitagliptin (administered as MK-0431A XR) in pediatric patients (ages 10-17 years) with T2DM with inadequate glycemic control on metformin therapy (alone or in combination with insulin). - MK-0431A-P289 Phase A and MK-0431A-170 base study: 2. After 20 weeks, to assess the effect of the addition of sitagliptin (administered as MK-0431A or MK-0431A XR) relative to the addition of placebo on A1C in pediatric patients (ages 10-17 years) with T2DM with inadequate glycemic control on metformin therapy (alone or in combination with insulin). - MK-0431A-P289 Phase A+B and MK-0431A-170 base and extension study: 3. Over 54 weeks, to assess the safety and tolerability of the addition of sitagliptin (administered as MK-0431A or MK-0431A XR) in pediatric patients (ages 10-17 years) with T2DM with inadequate glycemic control on metformin therapy (alone or in combination with insulin). |
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E.2.2 | Secondary objectives of the trial |
- MK-0431A XR P289 Phase A and MK-0431A P170 base study 1. After 20 weeks, to assess the effect of the addition of sitagliptin (MK-0431A or MK-0431A XR) relative to placebo on fasting plasma glucose (FPG) in pediatric patients (ages 10-17 years) with T2DM with inadequate glycemic control on metformin therapy (alone or in combination with insulin). 2. After 20 weeks, to assess the effect of the addition of sitagliptin (MK-0431A or MK-0431A XR) relative to placebo on the proportion of patients initiating glycemic rescue therapy in pediatric patients (ages 10-17 years) with T2DM with inadequate glycemic control on metformin therapy (alone or in combination with insulin). 3. After 20 weeks, to assess the effect of the addition of sitagliptin (MK-0431A or MK-0431A XR) relative to placebo on the proportion of patients with A1C at goal (<7.0%) in pediatric patients (ages 10-17 years) with T2DM with inadequate glycemic control on metformin therapy (alone or in combination with insulin). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood, serum and plasma) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal 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
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline in hemoglobin A1c (A1C) 2. Number of participants who experienced at least one adverse event 3. Number of participants who discontinued study drug due to an adverse event
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: Baseline and Week 20 2. Time Frame: up to 54 weeks 3. Time Frame: Up to 54 weeks
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E.5.2 | Secondary end point(s) |
1. Change from baseline in fasting plasma glucose (FPG) 2. Percentage of participants with A1C goals (<7%; <6.5%) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline and Week 20 2. Time Frame: Week 20 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Colombia |
Costa Rica |
Georgia |
Guatemala |
Honduras |
India |
Israel |
Mauritius |
Mexico |
Moldova, Republic of |
New Zealand |
Panama |
Philippines |
Russian Federation |
Saudi Arabia |
Serbia |
South Africa |
Sri Lanka |
Taiwan |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |