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)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess: 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 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) 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.

Official Title
-----------------
A Study to Assess the Pharmacokinetics and the Ability for Pediatric Patients With Type 2 Diabetes to Swallow MK-0431A XR Tablets

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Sitagliptin/metformin XR
* Drug: Placebo
* Drug: Metformin
* Drug: Thyroid hormone


Participation Criteria
=================
Eligibility Criteria
-----------------
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 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

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin/metformin XR followed by placebo<br>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. | Drug: Sitagliptin/metformin XR<br>* Fixed dose combination tablet of immediate-release sitagliptin 50 mg and extended-release (XR) metformin 1000 mg (total daily dose, sitagliptin 100 mg and metformin XR 2000 mg).<br>* Other names: Janumet XR;Drug: Placebo<br>* Matching placebo to fixed dose combination tablet of sitagliptin and metformin. Matching placebo tablets are same size, shape and color as the active product, but do not contain any markings.<br>Drug: Metformin<br>* Concomitant use of metformin is permitted during the study provided the participant has been receiving a stable metformin dose for at least 12 weeks prior to the dose of study drug. Administration of metformin will be withheld for 24 hours prior to study drug administration and for 24 hours postdose.<br>Drug: Thyroid hormone<br>* Concomitant use of thyroid hormone (eg, levothyroxine) is permitted during the study provided the participant has been receiving a stable dose for at least 12 weeks prior to study drug administration and is euthyroid as documented by thyroid stimulating hormone testing at prestudy. Administration of thyroid hormone will be withheld for 24 hours prior to study drug administration and for 24 hours postdose.<br>|
| Placebo Comparator: Placebo only<br>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. | Drug: Placebo<br>* Matching placebo to fixed dose combination tablet of sitagliptin and metformin. Matching placebo tablets are same size, shape and color as the active product, but do not contain any markings.<br>Drug: Metformin<br>* Concomitant use of metformin is permitted during the study provided the participant has been receiving a stable metformin dose for at least 12 weeks prior to the dose of study drug. Administration of metformin will be withheld for 24 hours prior to study drug administration and for 24 hours postdose.<br>Drug: Thyroid hormone<br>* Concomitant use of thyroid hormone (eg, levothyroxine) is permitted during the study provided the participant has been receiving a stable dose for at least 12 weeks prior to study drug administration and is euthyroid as documented by thyroid stimulating hormone testing at prestudy. Administration of thyroid hormone will be withheld for 24 hours prior to study drug administration and for 24 hours postdose.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Successfully Swallowed Study Med on 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. | Day 9 | 
| Area Under the Curve 0 to Last (AUC 0-last) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR | 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. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose | 
| AUC 0-24 of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR | Due different units of measure for sitagliptin and metformin, metformin data are presented in another endpoint. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose | 
| AUC 0-24 of Metformin Following Single Administration of Sitagliptin/Metformin XR | 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. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose | 
| Area Under the Curve 0 to Infinity (AUC 0-∞) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR | 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. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose | 
| Cmax of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR | Due different units of measure for sitagliptin and metformin, metformin data are presented in another endpoint. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose | 
| Cmax of Metformin Following Single Dose Administration of Sitagliptin/Metformin XR | 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. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose | 
| Tmax of Sitagliptin and Metformin Following Single Dose Administration of Sitagliptin/Metformin XR | 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. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose | 
| Apparent Terminal Half Life (t1/2) of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR | 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. | Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose | 
| Number of Participants Who Experienced an Adverse Event (AE) | 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. | Up to 23 days (including approximately 10 to 14 days after the last dose of study drug) | 
| Number of Participants Who Experienced an Abnormal Vital Sign Value | Vital sign measurements included blood pressure, heart rate, respiratory rate, and oral temperature. | Up to 23 days (including approximately 10 to 14 days after the last dose of study drug) | 
| Number of Participants Who Discontinued Study Drug Due to an AE | 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. | Up to 9 days | 
| Number of Participants Who Successfully Swallowed Study Medication (Med) on 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. | Day 2 | 
| Number of Participants Who Successfully Swallowed Study Med on 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. | Day 4 | 
| Number of Participants Who Successfully Swallowed Study Med on 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. | Day 6 |