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A Study of Omarigliptin (MK-3102) in Participants With Impaired Renal Function (MK-3102-009)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01407276
First received: July 29, 2011
Last updated: October 30, 2015
Last verified: October 2015
  Purpose
This is a 2-part study in participants with renal impairment and matched healthy participants to investigate the effect of impaired renal function on the plasma and urine levels of omarigliptin (MK-3102) after taking a single 3 mg dose by mouth.

Condition Intervention Phase
Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Drug: Omarigliptin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Two-Part, Single-Dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of MK-3102 in Patients With Impaired Renal Function

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose ] [ Designated as safety issue: No ]
    AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.

  • Maximum Concentration (Cmax) of Omarigliptin [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose ] [ Designated as safety issue: No ]
    Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

  • Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose ] [ Designated as safety issue: No ]
    AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose.

  • Concentration at 168 Hours Post-dose (C168h) of Omarigliptin [ Time Frame: 168 hours post-dose ] [ Designated as safety issue: No ]
    C168h is a measure of the plasma drug concentration 168 hours post-dose.

  • Apparent Volume of Distribution (Vd/F) of Omarigliptin [ Time Frame: Up to 336 hours post-dose ] [ Designated as safety issue: No ]
    Vd/F is defined as the distribution of a medication between the plasma and the rest of the body after the dose. It is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of the drug.

  • Apparent Total Body Clearance (CL/F) of Omarigliptin [ Time Frame: Up to 336 hours post-dose ] [ Designated as safety issue: No ]
    CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic, and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes).

  • Renal Clearance (CLr) of Omarigliptin [ Time Frame: Up to 336 hours post-dose ] [ Designated as safety issue: No ]
    CLr is a calculation of the rate at which a drug is removed from the body via renal clearance pathways, expressed as volume (milliliters) per unit of time (minutes). CLr was only determined for Panels A-F.

  • Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin [ Time Frame: Up to 48 hours post-dose ] [ Designated as safety issue: No ]
    fe48h is expressed as percentage of omarigliptin not metabolized and excreted in urine. fe48h was only determined for Panels A-F.

  • Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin [ Time Frame: Up to 48 hours post-dose ] [ Designated as safety issue: No ]
    Ae0-48h is a measure of the cumulative amount of drug excreted in the urine for 48 hours post-dose. Ae0-48h was only determined for Panels A-F.

  • Time to Maximum Concentration (Tmax) of Omarigliptin [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose ] [ Designated as safety issue: No ]
    Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose.

  • Apparent Terminal Half-life (t1/2) of Omarigliptin [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, 168, 240, and 336 hours post-dose ] [ Designated as safety issue: No ]
    T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%.


Secondary Outcome Measures:
  • Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: From pre-dose to 14 days post-dose (Up to Day 15) ] [ Designated as safety issue: Yes ]
    An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product.

  • Number of Participants Withdrawn From Study [ Time Frame: Up to Day 15 ] [ Designated as safety issue: Yes ]

Enrollment: 49
Study Start Date: August 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Mild Renal Impairment (Panel A) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 1: Control to Match Panel A (Panel B) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 1: Moderate Renal Impairment (Panel C) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 1: Control to Match Panel C (Panel D) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 1: Severe Renal Impairment (Panel E) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 1: Control to Match Panel E (Panel F) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 2: End-stage Renal Disease needing hemodialysis (Panel G) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102
Experimental: Part 2: Control to Match Panel G (Panel H) Drug: Omarigliptin
Single oral dose of 3 mg (3 x 1-mg capsules)
Other Name: MK-3102

Detailed Description:
In Part I, three panels of 6 participants each will be enrolled with varying degrees of renal disease (mild, moderate, or severe renal impairment) based on their estimated glomerular filtration rate (eGFR). Each of these panels will be matched with a corresponding panel of equal number of healthy, age-, race-, BMI- and gender-matched control participants. All panels will receive a single oral dose of 3-mg omarigliptin, followed by plasma sampling and urine collection. In Part II, 6 participants with end stage renal disease (ESRD) requiring hemodialysis will receive a single 3-mg oral dose of omarigliptin immediately following hemodialysis (HD) (Period 1) and 2 hours prior to HD (Period 2).There will be approximately 1 month between Period 1 and Period 2. A corresponding panel of equal number, healthy matched control subjects (age, race, BMI, gender) will also receive a single 3 mg dose by mouth. Omarigliptin dose administration will be followed by plasma sampling for both panels.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Impaired Renal Function Subjects:

  • Females of reproductive potential must have a negative pregnancy test and agree to use 2 methods of birth control
  • Diagnosis of renal insufficiency based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation

Healthy Subjects:

  • Females of reproductive potential must have a negative pregnancy test and agree to use 2 methods of birth control;
  • In general good health

Exclusion Criteria:

Impaired Renal Function Subjects:

  • Is mentally or legally incapacitated
  • Has rapidly fluctuating renal function or has demonstrated or suspected renal artery stenosis
  • History of significant endocrine (other than Type 2 diabetes), gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
  • History of stroke, chronic seizures or major neurological disease
  • Uncontrolled Type 2 diabetes or history of Type 1 diabetes or ketoacidosis
  • History of cancer (Some exceptions apply)
  • Regular user of barbiturates or sleep aides
  • Consumes excessive amounts of alcohol (more than 2 drinks/day)
  • Consumes excessive amounts of caffeinated beverages (more than 6/day)
  • Has had major surgery or has lost or donated 1 unit of blood within 4 weeks
  • Has a history of significant multiple and/or severe allergies
  • Current or history of illicit drug abuse
  • Nursing mothers

Healthy Subjects:

  • Is mentally or legally incapacitated;
  • Has a history of stroke, chronic seizures, or major neurological disorder
  • Renal impairment
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
  • Hypoglycemia, glucose intolerance, Type 1 or Type 2 diabetes, or ketoacidosis
  • History of cancer (Some exceptions apply)
  • Regular user of barbiturates or sleep aides
  • Consumes excessive amounts of alcohol (more than 2 drinks/day)
  • Consumes excessive amounts of caffeinated beverages (more than 6/day)
  • Has had major surgery or has lost or donated 1 unit of blood within 4 weeks
  • Has a history of significant multiple and/or severe allergies
  • Current or history of illicit drug abuse
  • Nursing mothers
  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: NCT01407276

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

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01407276     History of Changes
Other Study ID Numbers: 3102-009 
Study First Received: July 29, 2011
Results First Received: September 29, 2015
Last Updated: October 30, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Renal Insufficiency
Renal Insufficiency, Chronic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on December 06, 2016