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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Sitagliptin phosphate; Drug: Comparator: matching placebo

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sitagliptin 50 mg; Participants were randomized to sitagliptin 50 mg	Drug: Sitagliptin phosphate; 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.; Other Names: Januvia; MK-0431
EXPERIMENTAL: Sitagliptin 100 mg; Participants were randomized to sitagliptin 100 mg	Drug: Sitagliptin phosphate; 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.; Other Names: Januvia; MK-0431
EXPERIMENTAL: Sitagliptin 200 mg; Participants were randomized to a single dose of sitagliptin 200 mg	Drug: Sitagliptin phosphate; 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.; Other Names: Januvia; MK-0431
PLACEBO_COMPARATOR: Placebo to sitagliptin; Participants were randomized to matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg	Drug: Comparator: matching placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Fraser IP, Neufeld ND, Fox LA, Kipnes MS, Miller TL, Zeitler PS, Rodriguez H, Gilmartin JH, Lee SJ, Patterson JK, Li XS, Maganti L, Luo WL, Tatosian DA, Stoch SA. A randomized clinical trial to evaluate the single-dose pharmacokinetics, pharmacodynamics, and safety of sitagliptin in pediatric patients with type 2 diabetes. Pediatr Diabetes. 2019 Feb;20(1):48-56. doi: 10.1111/pedi.12790. Epub 2018 Nov 13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2008
• Primary Completion (ACTUAL): December 30, 2010
• Study Completion (ACTUAL): February 14, 2011

Study Registration Dates

• First Submitted: August 6, 2008
• First Submitted That Met QC Criteria: August 6, 2008
• First Posted (ESTIMATE): August 8, 2008

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-081; 2008_540

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php