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

Merck Sharp & Dohme LLC49 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Renal Insufficiency Type 2 Diabetes Mellitus

Interventions

OmarigliptinDRUG

Single oral dose of 3 mg (3 x 1-mg capsules)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin

AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.

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

Maximum Concentration (Cmax) of Omarigliptin

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

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

Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin

AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose.

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

Concentration at 168 Hours Post-dose (C168h) of Omarigliptin

C168h is a measure of the plasma drug concentration 168 hours post-dose.

Time frame: 168 hours post-dose

Apparent Volume of Distribution (Vd/F) of Omarigliptin

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.

Time frame: Up to 336 hours post-dose

Apparent Total Body Clearance (CL/F) of Omarigliptin

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).