A Study to Assess the Pharmacokinetics and the Ability for Pediatric Participants With Type 2 Diabetes to Swallow MK-0431A XR Tablets (MK-0431A-296)

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Sitagliptin/metformin XR; Drug: Placebo; Drug: Metformin; Drug: Thyroid hormone

• Registration Number: NCT01557504
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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 to pediatric participants with T2DM, aged 10 to 17 years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-03-16
• Study First Submitted QC: 2012-03-16
• Study First Posted: 2012-03-19
• Study Start: 2012-07-18
• Primary Completion: 2014-04-29
• Study Completion: 2014-04-29
• Results First Submitted: 2015-04-06
• Results First Submitted QC: 2015-05-06
• Results First Posted: 2015-05-22
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-06
• Last Update Posted: 2020-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• 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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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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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sitagliptin/metformin XR followed by placebo	Sitagliptin/metformin XR	Day 1 (Period 1): participants will receive a single dose of two sitagliptin/metformin XR tablets with a low- to moderate-fat meal (breakfast). Days 2-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.
Sitagliptin/metformin XR followed by placebo	Placebo	Day 1 (Period 1): participants will receive a single dose of two sitagliptin/metformin XR tablets with a low- to moderate-fat meal (breakfast). Days 2-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.
Sitagliptin/metformin XR followed by placebo	Thyroid hormone	Day 1 (Period 1): participants will receive a single dose of two sitagliptin/metformin XR tablets with a low- to moderate-fat meal (breakfast). Days 2-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.
Placebo only	Placebo	Days 1-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.
Placebo only	Thyroid hormone	Days 1-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.
Sitagliptin/metformin XR followed by placebo	Metformin	Day 1 (Period 1): participants will receive a single dose of two sitagliptin/metformin XR tablets with a low- to moderate-fat meal (breakfast). Days 2-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.
Placebo only	Metformin	Days 1-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Successfully Swallowed Study Med on Day 4	Day 4	The Swallowing Ability Questionnaire was completed on Day 4 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
Number of Participants Who Successfully Swallowed Study Medication (Med) on Day 2	Day 2	The Swallowing Ability Questionnaire was completed on Day 2 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
Tmax of Sitagliptin and Metformin Following Single Dose Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose	In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration.
Apparent Terminal Half Life (t1/2) of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose	In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Owing to resumption of therapeutic metformin administration 24 hours after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to Cmax, Tmax and AUC0-24hr. Therefore, metformin arm is not included in this endpoint.
Number of Participants Who Experienced an Adverse Event (AE)	Up to 23 days (including approximately 10 to 14 days after the last dose of study drug)	An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Number of Participants Who Successfully Swallowed Study Med on Day 6	Day 6	The Swallowing Ability Questionnaire was completed on Day 6 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
Area Under the Curve 0 to Last (AUC 0-last) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose	In this study, metformin products were withheld 24 hours (hrs) prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hrs post study drug administration. Owing to resumption of therapeutic metformin administration 24 hrs after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and area under the curve 0 to 24 hrs (AUC0-24hr). Therefore, metformin arm is not included in this endpoint.
AUC 0-24 of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose	Due different units of measure for sitagliptin and metformin, metformin data are presented in another endpoint.
Area Under the Curve 0 to Infinity (AUC 0-∞) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose	In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Owing to resumption of therapeutic metformin administration 24 hours after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to Cmax, Tmax and AUC0-24hr. Therefore, metformin arm is not included in this endpoint.
Cmax of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose	Due different units of measure for sitagliptin and metformin, metformin data are presented in another endpoint.
Number of Participants Who Successfully Swallowed Study Med on Day 9	Day 9	The Swallowing Ability Questionnaire was completed on Day 9 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
AUC 0-24 of Metformin Following Single Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose	In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Due different units of measure for sitagliptin and metformin, sitagliptin data are presented in another endpoint.
Cmax of Metformin Following Single Dose Administration of Sitagliptin/Metformin XR	Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose	In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Due different units of measure for sitagliptin and metformin, sitagliptin data are presented in another endpoint.
Number of Participants Who Experienced an Abnormal Vital Sign Value	Up to 23 days (including approximately 10 to 14 days after the last dose of study drug)	Vital sign measurements included blood pressure, heart rate, respiratory rate, and oral temperature.
Number of Participants Who Discontinued Study Drug Due to an AE	Up to 9 days	An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.