Clinical trial NCT04678505: Study of a Single Intravenous (IV) Dose of MK-3402 in Participants With Impaired Renal Function and in Healthy Controls (MK-3402-004)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: MK-3402
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-12-22
Enrollment: 9
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Curve From Dosing to Infinity (AUC0-inf) of MK-3402
timeFrame: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
measure: Plasma Concentration at the End of Infusion (Ceoi) of MK-3402
timeFrame: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
measure: Time to Maximum Plasma Concentration (Tmax) of MK-3402
timeFrame: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
measure: Apparent Plasma Half-life (t½) of MK-3402
timeFrame: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
measure: Apparent Plasma Clearance (CL) of MK-3402
timeFrame: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
measure: Volume of Distribution (Vd) of MK-3402
timeFrame: Predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, and 48 hours postdose on Day 1
Secondary outcomes:
measure: Number of Participants With Adverse Events (AE)
timeFrame: Up to 15 days
measure: Number of Participants Who Discontinued From Study Due to an AE
timeFrame: Up to 15 days
measure: Dialysis Clearance Based on Plasma (CLDplasma) of MK-3402
timeFrame: 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
measure: Concentration of Dialysate (CD) of MK-3402
timeFrame: 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
measure: Amount of Drug Recovered From the Dialysate From Plasma (AED) of MK-3402
timeFrame: 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
measure: Percentage of AED (% Dose) of MK-3402
timeFrame: 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.
measure: Hemodialysis Clearance Based on Plasma (CLD Dialysate) of MK-3402
timeFrame: 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
measure: Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-3402
timeFrame: Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose
measure: Fraction of Dose Recovered in Urine (Fe) of MK-3402
timeFrame: Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose
measure: Renal Clearance (CLr) of MK-3402
timeFrame: Pre-dose and 0-4, 4-8, 8-12, and 12-24 hours postdose
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0001)
state: Florida
city: Saint Paul
country: United States
facility: Prism Clinical Research, LLC ( Site 0002)
state: Minnesota
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: