A Study of Omarigliptin (MK-3102) in Participants With Impaired Renal Function (MK-3102-009)
- Conditions
- Chronic Renal InsufficiencyType 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT01407276
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Mild Renal Impairment (Panel A) Omarigliptin - Part 1: Control to Match Panel A (Panel B) Omarigliptin - Part 1: Moderate Renal Impairment (Panel C) Omarigliptin - Part 1: Control to Match Panel E (Panel F) Omarigliptin - Part 2: End-stage Renal Disease needing hemodialysis (Panel G) Omarigliptin - Part 2: Control to Match Panel G (Panel H) Omarigliptin - Part 1: Severe Renal Impairment (Panel E) Omarigliptin - Part 1: Control to Match Panel C (Panel D) Omarigliptin -
- Primary Outcome Measures
Name Time Method Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Omarigliptin 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 AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose.
Maximum Concentration (Cmax) of Omarigliptin 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 Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Concentration at 168 Hours Post-dose (C168h) of Omarigliptin 168 hours post-dose C168h is a measure of the plasma drug concentration 168 hours post-dose.
Apparent Volume of Distribution (Vd/F) of Omarigliptin Up to 336 hours post-dose 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.
Area Under the Concentration-time Curve From Time 0 to 168 Hours Post Dose (AUC0-168h) of Omarigliptin Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 (Panel G only), 96, and 168 hours post-dose AUC0-168h is a measure of the total amount of drug in the plasma from the dose to 168 hours after the dose.
Apparent Terminal Half-life (t1/2) of Omarigliptin 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 T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%.
Apparent Total Body Clearance (CL/F) of Omarigliptin Up to 336 hours post-dose 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 Up to 336 hours post-dose 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 Up to 48 hours post-dose 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 Up to 48 hours post-dose 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 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 Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose.
- Secondary Outcome Measures
Name Time Method Number of Participants Experiencing an Adverse Event (AE) From pre-dose to 14 days post-dose (Up to Day 15) 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 Up to Day 15