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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label, Two-Part, Single-Dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of MK-3102 in Patients With Impaired Renal Function

Conditions
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Chronic Renal Insufficiency, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Omarigliptin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Mild Renal Impairment (Panel A)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 1: Control to Match Panel A (Panel B)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 1: Moderate Renal Impairment (Panel C)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 1: Control to Match Panel C (Panel D)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 1: Severe Renal Impairment (Panel E)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 1: Control to Match Panel E (Panel F)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 2: End-stage Renal Disease needing hemodialysis (Panel G)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|
| Experimental: Part 2: Control to Match Panel G (Panel H)<br> | Drug: Omarigliptin<br>* Single oral dose of 3 mg (3 x 1-mg capsules)<br>* Other names: MK-3102;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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). | Up to 336 hours post-dose | 
| Renal Clearance (CLr) of Omarigliptin | 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. | Up to 336 hours post-dose | 
| Fraction of Dose Excreted Unchanged in Urine Through 48 Hours Post-dose (fe48h) of Omarigliptin | fe48h is expressed as percentage of omarigliptin not metabolized and excreted in urine. fe48h was only determined for Panels A-F. | Up to 48 hours post-dose | 
| Cumulative Amount of Drug Excreted in Urine Over 48 Hours (Ae0-48h) of Omarigliptin | 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. | Up to 48 hours post-dose | 
| Time to Maximum Concentration (Tmax) of Omarigliptin | Tmax is a measure of the time to reach the maximum drug plasma concentration post-dose. | 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 | 
| Apparent Terminal Half-life (t1/2) of Omarigliptin | T1/2 is the time required for the maximum concentration of a drug in the plasma to decrease by 50%. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Adverse Event (AE) | 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. | From pre-dose to 14 days post-dose (Up to Day 15) | 
| Number of Participants Withdrawn From Study |  | Up to Day 15 |