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
  Purpose

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.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin/metformin XR
Drug: Placebo
Drug: Metformin
Drug: Thyroid hormone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Assess the Pharmacokinetics and the Ability for Pediatric Patients With Type 2 Diabetes to Swallow MK-0431A XR Tablets

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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.


Enrollment: 25
Study Start Date: July 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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.

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557504

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01557504     History of Changes
Other Study ID Numbers: 0431A-296
Study First Received: March 16, 2012
Results First Received: April 6, 2015
Last Updated: May 6, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Hormones
Metformin
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on May 21, 2015