Study of a Single Intravenous (IV) Dose of MK-3402 in Participants With Impaired Renal Function and in Healthy Controls (MK-3402-004)

Study Overview
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Brief Summary
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The purpose of this study is to compare the plasma and urine pharmacokinetics (PK) of MK-3402 in participants with impaired renal function and healthy control participants, to investigate the extent to which MK-3402 is removed from the plasma by hemodialysis (HD), and evaluate the safety and tolerability of MK-3402 in participants with impaired renal function.

Official Title
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An Open-Label Trial to Evaluate the Pharmacokinetics of MK-3402 Following Administration of a Single IV Dose to Participants With Mild, Moderate, and Severe Renal Impairment and End-Stage Renal Disease

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: MK-3402


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is in good health based on medical history, physical examination, vital signs (VS) measurements, and electrocardiogram (ECG)s performed before randomization. Is in good health based on laboratory safety tests obtained at the screening visit and before administration of the initial dose of study drug. Has a body mass index (BMI) ≥18 kg/m2 and ≤40 kg/m2. BMI = weight (kg)/height (m)2. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of study intervention: Refrain from donating sperm Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) A female participant is eligible to participate if she is a woman of non-childbearing potential. Panel A: Has a baseline estimated glomerular filtration rate (eGFR) ≥60 and <90 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease (MDRD) equation. Panel B: Has a baseline eGFR ≥30 and <60 mL/min/1.73 m2 based on the MDRD equation. Panel C: Has a baseline eGFR ≥15 and <30 mL/min/1.73 m2 based on the MDRD equation. Panels A, B and C: Has had no clinically significant change in renal status at least 1 month prior to dosing and is not currently receiving or has not previously been on hemodialysis (HD). Panel D: Has an eGFR ≥90 mL/min/1.73 m2 based on the MDRD equation. Panel E: Has end stage renal disease (ESRD) and maintained on a stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing. Exclusion Criteria: Panels A, B, C and E: Has a history of any clinically significant concomitant disease or condition (including treatment for such conditions) or diseases whose current condition is considered clinically unstable that, in the opinion of the investigator, could either interfere with the study drug, compromise interpretation of study data, or pose an unacceptable risk to the patient. Panel D: Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events (eg, uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma) may be enrolled in the study at the discretion of the investigator. Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder that would impact study conduct. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator. Has a history of cancer (malignancy). Exceptions: (1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; (2) Other malignancies that have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study, in the opinion of the investigator and with agreement of the Sponsor (eg, malignancies that have been successfully treated ≥10 years prior to the prestudy screening visit). Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food. Is positive for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV). Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit. Panels A, B, C and E: Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies for the prohibited time period. Panel D: Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit. There may be certain medications that are permitted. Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to study drug administration. The window will be derived from the date of the last dose of study medication in the previous study.

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: Panel A: Mild Renal Impairment<br>Participants with mild renal impairment will receive a single dose of 100 mg MK-3402 via intravenous (IV) infusion on Day 1. | Drug: MK-3402<br>* MK-3402 administered as a single dose of 100 mg IV infusion on the following dosage days: Panels A to D: Day 1 Panel E: Day 1 in Periods 1 and 2<br>|
| Experimental: Panel B: Moderate Renal Impairment<br>Participants with moderate renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1. | Drug: MK-3402<br>* MK-3402 administered as a single dose of 100 mg IV infusion on the following dosage days: Panels A to D: Day 1 Panel E: Day 1 in Periods 1 and 2<br>|
| Experimental: Panel C: Severe Renal Impairment<br>Participants with severe renal impairment will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1. | Drug: MK-3402<br>* MK-3402 administered as a single dose of 100 mg IV infusion on the following dosage days: Panels A to D: Day 1 Panel E: Day 1 in Periods 1 and 2<br>|
| Experimental: Panel D: Healthy Participants<br>Healthy matched control participants will receive a single dose of 100 mg MK-3402 via IV infusion on Day 1. | Drug: MK-3402<br>* MK-3402 administered as a single dose of 100 mg IV infusion on the following dosage days: Panels A to D: Day 1 Panel E: Day 1 in Periods 1 and 2<br>|
| Experimental: Panel E: End-Stage Renal Disease (ESRD) Undergoing Hemodialysis<br>Participants with ESRD undergoing HD will receive a single dose of 100 mg MK-3402 via IV infusion after HD on Day 1 of Period 1 and before HD on Day 1 of Period 2. There will be at least a 6-day washout period before dosing in Period 2. | Drug: MK-3402<br>* MK-3402 administered as a single dose of 100 mg IV infusion on the following dosage days: Panels A to D: Day 1 Panel E: Day 1 in Periods 1 and 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Dosing to Infinity (AUC0-inf) of MK-3402 | AUC0-inf is defined as area under the plasma concentration-time curve from dosing to infinity. | Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1 | 
| Plasma Concentration at the End of Infusion (Ceoi) of MK-3402 | Ceoi is defined as the amount of study drug in plasma following IV infusion administration of study drug. Plasma samples were collected at pre-specified time points and Ceoi was assessed. | Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1 | 
| Time to Maximum Plasma Concentration (Tmax) of MK-3402 | Tmax is defined as the time required for a study drug to reach maximum concentration in plasma. Plasma samples were collected at pre-specified time points and Tmax was assessed. | Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1 | 
| Apparent Plasma Half-life (t½) of MK-3402 | t½ is defined as the time required for plasma drug concentration of study drug to decrease by 50% from peak. | Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1 | 
| Apparent Plasma Clearance (CL) of MK-3402 | CL is defined as the time it takes for the study drug to be completely removed from the body's plasma. | Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1 | 
| Volume of Distribution (Vd) of MK-3402 | Vd is defined as the distributed volume of study drug in plasma. | Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug | Up to 15 days | 
| Number of Participants Who Discontinued From Study Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug | Up to 15 days | 
| Dialysis Clearance Based on Plasma (CLDplasma) of MK-3402 | Plasma dialysis samples were to be collected at pre-specified time points to calculate CLDplasma. | Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion | 
| Concentration of Dialysate (CD) of MK-3402 | Plasma dialysis samples were to be collected at pre-specified time points to calculate CD. | Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion | 
| Amount of Drug Recovered From the Dialysate From Plasma (AED) of MK-3402 | Plasma dialysis samples were to be collected at pre-specified time points to calculate AED. | Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion | 
| Percentage of AED (% Dose) of MK-3402 | Plasma dialysis samples were to be collected at pre-specified time points to calculate AED (% dose). | Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion. | 
| Hemodialysis Clearance Based on Plasma (CLD Dialysate) of MK-3402 | Plasma dialysis samples were to be collected at pre-specified time points to measure CLD dialysate. | Panel E, Period 2: Pre-dose and 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after the start of infusion | 
| Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-3402 | Ae0-24 is defined as the amount of study drug unchanged in urine after 0-24 hours. Urine samples were collected at pre-specified intervals and Ae0-24 was assessed. | Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose | 
| Fraction of Dose Recovered in Urine (Fe) of MK-3402 | Fe is defined as the fraction of the dose of study drug in urine. | Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose | 
| Renal Clearance (CLr) of MK-3402 | CLr is defined as the time it takes for the study drug to be completely removed by the kidneys. | Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MK-3402