Clinical trial NCT06442436: A Study of Nemtabrutinib in Participants With Moderate Hepatic Impairment (MK-1026-015)
Official title: A Study to Evaluate the Pharmacokinetics of Nemtabrutinib in Participants With Moderate Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment (HI)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-06-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the plasma pharmacokinetics (PK) of nemabrutinib (MK-1026) following a single oral dose of nemtabrutinib in participants with moderate hepatic impairment to that of healthy matched control participants and to evaluate the safety and tolerability of nemtabrutinib.


Eligibility criteria: Inclusion Criteria:

* Has a body mass index (BMI) between 18.0 and 40.0 kg/m2, inclusive.
* Is assigned male or female sex at birth. Participants assigned female sex at birth must not be pregnant or breast feeding and must be of nonchild bearing potential.
* Who agrees to use contraception.
* Has provided documented informed consent for the study.
* Has a diagnosis of chronic (\>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic impairment with features of cirrhosis due to any etiology (moderate HI only).
* Has moderate hepatic impairment (class B) by the Child-Pugh classification system (moderate HI only).
* Is in general good health (except for Moderate HI).

Exclusion Criteria:

* Has a clinically significant condition that may affect absorption of the study drug in the opinion of the investigator, including gastric restrictions and bariatric surgery (eg, gastric bypass).
* 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 of the last 5 years.
* Has a history of cancer (malignancy).
* Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (systemic allergic reaction) to prescription or nonprescription drugs or food.
* Had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy.
* Has received any vaccine starting from 14 days prior to study or is scheduled to receive any vaccine through 30 days following study intervention.
* Was dosed in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to check-in (Day -1).
* Is under the age of consent.
* Is heavy smoker or heavy user of nicotine-containing products (\>20 cigarettes or equivalent/day).
* Is regular user of cannabis or any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months.
* Consumes greater than 3 servings of alcoholic beverages per day.
* Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, (1 serving is approximately equivalent to 120 mg of caffeine) energy drinks, or other caffeinated beverages per day.
* Is unwilling to comply with the study restrictions.
* Has a history or illness that in the opinion of the investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study (moderate HI only).
* Has a history of recent variceal bleeds (for moderate HI only).
* Has evidence of hepatorenal syndrome (for moderate HI only).
* Has fluctuating or rapidly deteriorating hepatic function within the prestudy period, in the opinion of the investigator (for moderate HI only).
* Is not in sufficient health, with regard to stability of HI, to undergo participation in the study with anticipated survival of \<3 months, in keeping with a Model for End-Stage Liver Disease (MELD) score of ≥25 (for moderate HI only).
* Has a history of liver or other solid organ transplantation (for moderate HI only).
* Has an active infection requiring systemic therapy (for moderate HI only).
* Who requires paracentesis more often than 2 times per month (for moderate HI only).
* Has a transjugular intrahepatic portosystemic shunt and/or has undergone portacaval shunting (for moderate HI only).
* Has encephalopathy Grade 3 or worse within 28 days before administration of study intervention (for moderate HI only).
* Has received antiviral and/or immune modulating therapy for hepatitis B virus (HBV) or hepatitis C virus (HCV) within 90 days prior to study start (for moderate HI only).
* Is positive for human immunodeficiency virus (HIV)-1 or HIV-2 or using HIV protease inhibitors (for moderate HI only).
* Is positive for HBV (for moderate HI only).
* Is positive for HCV (for moderate HI only).
* Is taking medications to treat chronic medical conditions and has not been on a stable regimen for at least 1 month and/or is unable to withhold the use of the medication(s) for the prohibited period of time in study (for moderate HI only).
* Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological (history of a bleeding disorder, abnormal bleeding or a hereditary or acquired coagulation or platelet disorder), hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke, intracranial hemorrhage, and chronic seizures) abnormalities or diseases (for healthy control participants only).
* Has positive test(s) for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or HIV at the prestudy (screening) visit (for healthy control participants only).
* Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies (for healthy control participants only).

Primary outcomes:
measure: Area Under the Curve from Dosing to Infinity (AUC0-inf) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
measure: Maximum Concentration (Cmax) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Secondary outcomes:
measure: Area Under the Curve from Dosing to last (AUC0-last) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
measure: Concentration 24 (C24) Hours Postdose of Nemtabrutinib in Plasma
timeFrame: 24 hours postdose
measure: Time to Maximum Concentration (Tmax) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
measure: Apparent Terminal Half-life (t1/2) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
measure: Apparent Total Clearance (CL/F) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
measure: Apparent Volume of Distribution During Terminal Phase (Vz/F) of Nemtabrutinib in Plasma
timeFrame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
measure: Number of Participants who Experience One or More Adverse Events (AEs)
timeFrame: Up to ~15 days
measure: Number of Participants Who Discontinue From the Study Due to an Adverse Event (AE)
timeFrame: Up to ~15 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami ( Site 0003)
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0001)
state: Florida
city: San Antonio
country: United States
facility: Texas Liver Institute ( Site 0002)
state: Texas
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: