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 |
The purpose of this study is to assess:
1. the safety and tolerability of two sitagliptin 50 mg/metformin 1000 mg XR tablets in pediatric participants with type 2 diabetes mellitus (T2DM), aged 10 to 17 years
2. the ability of pediatric participants with T2DM, aged 10 to 17 years, to swallow two sitagliptin 50 mg/metformin 1000 mg XR tablets or two matching placebo tablets (excluding marking)
3. the pharmacokinetics of sitagliptin and metformin following the administration of two sitagliptin 50 mg/metformin 1000 mg XR tablets after the consumption of a low- to moderate-fat meal to pediatric participants with T2DM, aged 10 to 17 years.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject is a male or female, ≥10 and ≤ 17 years of age on day of signing informed consent with assignment to treatment to occur prior to 18th birthday
• Female participant of reproductive potential must not be pregnant and agrees to use (and/or have their partner use) two acceptable methods of birth control
• T2DM diagnosed by American Diabetes Association criteria
• No clinically significant abnormality on electrocardiogram
• No clinical or laboratory evidence to indicate a diagnosis of type 1 diabetes
• Nonsmoker
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E.4 | Principal exclusion criteria |
• Mental or legal incapacitation
• Estimated creatinine clearance of 80 mL/min or lower
• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of neoplastic disease
• Unable to refrain from or anticipates the use of any medication (with the exception of metformin and thyroid hormone) from approximately 2 weeks before the first dose of study drug through the poststudy visit
• Consumes alcohol or consumes excessive amounts of coffee, tea, cola, or other caffeinated beverages
• Had surgery, donated or lost 1 unit of blood, or participated in another investigational study within the past 4 weeks
• History of multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
• Currently a regular user (including illicit drugs) or has a history of drug (including alcohol) abuse
• Lactose intolerant
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Number of Participants Who Successfully Swallowed Study Medication (Med) on Day 2
2. Number of Participants Who Successfully Swallowed Study Med on Day 4
3. Number of Participants Who Successfully Swallowed Study Med on Day 6
4. Number of Participants Who Successfully Swallowed Study Med on Day 9
5. Area Under the Curve 0 to Last (AUC 0-last) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR
6. AUC 0-24 of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR
7. AUC 0-24 of Metformin Following Single Administration of Sitagliptin/Metformin XR
8. Area Under the Curve 0 to Infinity (AUC 0-∞) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR
9. Cmax of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR
10. Cmax of Metformin Following Single Dose Administration of Sitagliptin/Metformin XR
11. Tmax of Sitagliptin and Metformin Following Single Dose Administration of Sitagliptin/Metformin XR
12. Apparent Terminal Half Life (t1/2) of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR
13. Number of Participants Who Experienced an Adverse Event (AE)
14. Number of Participants Who Experienced an Abnormal Vital Sign Value
15. Number of Participants Who Discontinued Study Drug Due to an AE
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Day 2
2. Day 4
3. Day 6
4. Day 9
5. Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose
6. and 7. Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose
8. to 12. Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose
13. Up to 23 days (including approximately 10 to 14 days after the last dose of study drug)
14. Up to 23 days (including approximately 10 to 14 days after the last dose of study drug)
15. Up to 9 days
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability, swallowability |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety, pharmacokinetic, tolerability, swallowability |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
fixed-sequence, 2-period study |
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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 | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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 months | 18 |