A Study to Assess the Pharmacokinetics, Safety and Tolerability of Sitagliptin in Adolescents (0431-081)

Study Overview
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Brief Summary
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This study will assess the safety, tolerability and pharmacokinetics of sitagliptin in 10 to 17 year old diabetic patients.

Official Title
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A Single-Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Sitagliptin in Adolescents

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Sitagliptin phosphate
* Drug: Comparator: matching placebo


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin 50 mg<br>Participants were randomized to sitagliptin 50 mg | Drug: Sitagliptin phosphate<br>* Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of sitagliptin 50 mg tablet, sitagliptin 100 mg tablet, or sitagliptin 200 mg.<br>* Other names: Januvia;|
| Experimental: Sitagliptin 100 mg<br>Participants were randomized to sitagliptin 100 mg | Drug: Sitagliptin phosphate<br>* Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of sitagliptin 50 mg tablet, sitagliptin 100 mg tablet, or sitagliptin 200 mg.<br>* Other names: Januvia;|
| Experimental: Sitagliptin 200 mg<br>Participants were randomized to a single dose of sitagliptin 200 mg | Drug: Sitagliptin phosphate<br>* Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of sitagliptin 50 mg tablet, sitagliptin 100 mg tablet, or sitagliptin 200 mg.<br>* Other names: Januvia;|
| Placebo Comparator: Placebo to sitagliptin<br>Participants were randomized to matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg | Drug: Comparator: matching placebo<br>* Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Time 0 to Infinity Following a Single Dose of Sitagliptin | Serum samples were used to determine the AUC from time 0 to infinity for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. | Pre-dose through 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) Following a Single Dose of Sitagliptin | Serum samples were used to determine the Cmax for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. | Pre-dose through 72 hours post-dose | 
| Time of Occurence of Maximum Concentration (Tmax) Following a Single Dose of Sitagliptin | Serum samples were used to determine the Tmax for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. | Pre-dose through 72 hours post-dose | 
| Apparent Terminal Half-life (Apparent t1/2) Following a Single Dose of Sitagliptin | Serum samples were used to determine the apparent t1/2 for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups. | Pre-dose through 72 hours post-dose | 
| 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. | Pre-dose through 24 hours post-dose |