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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
First Primary Objective- Safety and Tolerability: To assess the safety and tolerability of single doses of sitagliptin in 10 to 17 year old subjects with type 2 diabetes.
Second Primary Objective- Pharmacokinetic Estimation of AUC0-¥ : To obtain preliminary plasma pharmacokinetic data (AUC0-∞), following single dose administration of sitagliptin in 10- to 17-year-old subjects with type 2diabetes.
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E.2.2 | Secondary objectives of the trial |
First Secondary Objective: To obtain preliminary plasma pharmacokinetic data (e.g., AUC(0-24 hr), Cmax, Tmax, apparent t1/2) following single dose administration of MK-0431 in 10 to 17 year old subjects with type 2 diabetes.
Second Secondary Objective: To assess the effects over time of single doses of MK-0431 on plasma dipeptidyl peptidase IV (DPP-4) activity in 10 to 17 year old subjects with type 2 diabetes.
Exploratory Objective: To explore the relationship between pharmacokinetic parameters (e.g., AUC(0-¥), Cmax, Tmax, apparent t1/2) and pharmacodynamic parameters (insulin, C-peptide, plasma DPP-IV activity, active GLP 1 levels).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Males or females who are 10 - 17 years of age
•History of type 2 diabetes
•Nonsmoker
•No clinical or laboratory evidence to indicate a diagnosis of type 1 diabetes
•See protocol for complete list of inclusion criteria.
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E.4 | Principal exclusion criteria |
•History of diabetic ketoacidosis
•History of stroke, chronic seizures or major neurological disorder
•Consumes alcohol
•Consume more than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola or other beverages containing caffeine per day
•Unable to swallow tablets
•Has had surgery, donated or lost 1 unit of blood, or participated in another investigational study within a minimum of 4 weeks prior to starting the study
•History of multiple and/or severe allergies or has had an allergic reaction to or significant intolerability to prescription or non-prescription drugs or food
•Currently a regular user of any illicit drugs or has a history of drug or alcohol abuse
•History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
•Has an estimated creatinine clearance of less than or equal to 80 mL/min
•Refer to protocol for complete list.
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E.5 End points |
E.5.1 | Primary end point(s) |
•Number of participants who experienced at least one adverse event pre-study through 10 to 14 days following administration of study drug.
•Area Under the Concentration-time Curve (AUC) from 0 to infinity following a single dose of sitagliptin pre-dose through 72 hours post-dose.
Serum samples were used to determine the AUC from time 0 to infinity for sitagliptin.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood samples for plasma sitagliptin and DPP-IV activity were collected predose and at specified time points postdose through 72 hours postdose. |
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E.5.2 | Secondary end point(s) |
Maximum Concentration (Cmax), Time of occurrence of Maximum Concentration (Tmax), Apparent Terminal Half-life (Apparent t1/2) following a single dose of sitagliptin.
Plasma Dipeptidyl Peptidase-4 (DPP-4) activity following a single dose of sitagliptin or Placebo. Plasma DPP-4 activity was analyzed using the 24-hour weighted average inhibition (WAI) and percent inhibition at 24 hours post-dose. WAI was defined as the AUC of inhibition divided by the length of the post-dose time interval. Positive values of WAI represent a decrease in DPP-4 activity.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Blood samples for plasma sitagliptin were collected predose and at specified time points postdose through 72 hours postdose.
Blood samples for plasma DPP-IV activity were collected predose and at specified time points postdose through 24 hours postdose.
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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 | Yes |
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 |
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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 |
Pharmacokinetics in adolescent patients |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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 | 3 |
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 years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |