Clinical trial NCT01407276: A Study of Omarigliptin (MK-3102) in Participants With Impaired Renal Function (MK-3102-009)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-08-02
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin
timeFrame: 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
measure: Maximum Concentration (Cmax) of Omarigliptin
timeFrame: 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
measure: Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose
measure: Concentration at 168 Hours Post-dose (C168h) of Omarigliptin
timeFrame: 168 hours post-dose
measure: Apparent Volume of Distribution (Vd/F) of Omarigliptin
timeFrame: Up to 336 hours post-dose
measure: Apparent Total Body Clearance (CL/F) of Omarigliptin
timeFrame: Up to 336 hours post-dose
measure: Renal Clearance (CLr) of Omarigliptin
timeFrame: Up to 336 hours post-dose
measure: Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin
timeFrame: Up to 48 hours post-dose
measure: Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin
timeFrame: Up to 48 hours post-dose
measure: Time to Maximum Concentration (Tmax) of Omarigliptin
timeFrame: 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
measure: Apparent Terminal Half-life (t1/2) of Omarigliptin
timeFrame: 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
Secondary outcomes:
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: From pre-dose to 14 days post-dose (Up to Day 15)
measure: Number of Participants Withdrawn From Study
timeFrame: Up to Day 15
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: