Evaluating nemtabrutinib in patients with moderate liver impairment

A Study to Evaluate the Pharmacokinetics of Nemtabrutinib in Participants With Moderate Hepatic Impairment

This study is testing how a new drug called nemtabrutinib works in people with moderate liver problems to see if it's safe and how their bodies process it compared to healthy individuals.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Merck Sharp & Dohme LLC (industry)
• Drugs / interventions: nemtabrutinib
• Locations: 3 sites (Miami, Florida and 2 other locations)
• Trial ID: NCT06442436 on ClinicalTrials.gov

What this trial studies

This study aims to assess the pharmacokinetics of nemtabrutinib after a single oral dose in participants with moderate hepatic impairment compared to healthy controls. It will also evaluate the safety and tolerability of the drug in this specific population. Participants must have stable chronic hepatic impairment and meet specific health criteria to be eligible for the study. The study is interventional and is classified as Phase 1.

Who should consider this trial

Good fit: Ideal candidates are individuals with moderate hepatic impairment classified as Child-Pugh class B who are in general good health otherwise.

Not a fit: Patients with significant conditions affecting drug absorption or those with severe hepatic impairment will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the safe use of nemtabrutinib for patients with moderate hepatic impairment.

How similar studies have performed: While this specific approach is novel, similar studies evaluating drug pharmacokinetics in hepatic impairment have shown varying degrees of success.

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 AND/OR the participant has moderate impairment by the National Cancer Institution Organ Dysfunction Working Group (NCI-ODWG) 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).

Where this trial is running

Miami, Florida and 2 other locations

• Clinical Pharmacology of Miami ( Site 0003) — Miami, Florida, United States (RECRUITING)
• Orlando Clinical Research Center ( Site 0001) — Orlando, Florida, United States (RECRUITING)
• Texas Liver Institute ( Site 0002) — San Antonio, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Toll Free Number

Conditions: Hepatic Impairment