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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01557504
First received: March 16, 2012
Last updated: May 6, 2015
Last verified: May 2015

March 16, 2012
May 6, 2015
July 2012
April 2014   (final data collection date for primary outcome measure)
  • Number of Participants Who Successfully Swallowed Study Medication (Med) on Day 2 [ Time Frame: Day 2 ] [ Designated as safety issue: No ]
    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.
  • Number of Participants Who Successfully Swallowed Study Med on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    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 Med on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
    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.
  • Number of Participants Who Successfully Swallowed Study Med on Day 9 [ Time Frame: Day 9 ] [ Designated as safety issue: No ]
    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.
  • Area Under the Curve 0 to Last (AUC 0-last) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]
    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 outcome measure.
  • AUC 0-24 of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
    Due different units of measure for sitagliptin and metformin, metformin data are presented in another outcome measure.
  • AUC 0-24 of Metformin Following Single Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
    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 outcome measure.
  • Area Under the Curve 0 to Infinity (AUC 0-∞) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]
    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 outcome measure.
  • Cmax of Sitagliptin Following Single Dose Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]
    Due different units of measure for sitagliptin and metformin, metformin data are presented in another outcome measure.
  • Cmax of Metformin Following Single Dose Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]
    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 outcome measure.
  • Tmax of Sitagliptin and Metformin Following Single Dose Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]
    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 outcome measure.
  • Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 23 days (including approximately 10 to 14 days after the last dose of study drug) ] [ Designated as safety issue: Yes ]
    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 Experienced an Abnormal Vital Sign Value [ Time Frame: Up to 23 days (including approximately 10 to 14 days after the last dose of study drug) ] [ Designated as safety issue: Yes ]
    Vital sign measurements included blood pressure, heart rate, respiratory rate, and oral temperature.
  • Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 9 days ] [ Designated as safety issue: Yes ]
    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.
  • Pharmacokinetic analysis of sitagliptin and metformin: Area under the curve (AUC) 0 to infinity, AUC 0 to last, and AUC 0 to 24 hours [ Time Frame: From Baseline up to 72 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacokinetic analysis of sitagliptin and metformin: maximum concentration (Cmax) [ Time Frame: From Baseline up to 72 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacokinetic analysis of sitagliptin and metformin: time to maximum concentration (Tmax) [ Time Frame: From Baseline up to 72 hours post-dose ] [ Designated as safety issue: No ]
  • Number of participants who experienced at least one adverse event [ Time Frame: Through approximately 10 to 14 days following last dose ] [ Designated as safety issue: Yes ]
  • Number of participants who experienced at least one abnormal vital sign [ Time Frame: Through approximately 10 to 14 days following last dose ] [ Designated as safety issue: Yes ]
  • Number of participants who were able to swallow study drug [ Time Frame: Baseline through approximately 10 to 14 days following last dose ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01557504 on ClinicalTrials.gov Archive Site
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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)
A Study to Assess the Pharmacokinetics and the Ability for Pediatric Patients With Type 2 Diabetes to Swallow MK-0431A XR Tablets

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.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: Sitagliptin/metformin XR
    Fixed dose combination tablet of immediate-release sitagliptin 50 mg and extended-release (XR) metformin 1000 mg (total daily dose, sitagliptin 100 mg and metrformin XR 2000 mg).
    Other Names:
    • MK-0431A XR
    • Janumet XR
  • Drug: Placebo
    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.
  • Drug: Metformin
    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.
  • Drug: Thyroid hormone
    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.
  • Experimental: Sitagliptin/metformin XR followed by 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.
    Interventions:
    • Drug: Sitagliptin/metformin XR
    • Drug: Placebo
    • Drug: Metformin
    • Drug: Thyroid hormone
  • Placebo Comparator: Placebo only
    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.
    Interventions:
    • Drug: Placebo
    • Drug: Metformin
    • Drug: Thyroid hormone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
April 2014
April 2014   (final data collection date for primary outcome measure)

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
Both
10 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
United States
 
NCT01557504
0431A-296
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP