A Study of Nemtabrutinib in Participants With Moderate Hepatic Impairment (MK-1026-015)

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

The purpose of this study is to compare the plasma pharmacokinetics (PK) of nemtabrutinib (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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment (HI)
• Intervention / Treatment: Drug: Nemtabrutinib

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33172
      • Clinical Pharmacology of Miami ( Site 0003)
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center ( Site 0001)
  • Texas
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute ( Site 0002)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A; Participants with moderate hepatic impairment will receive a single oral dose of 25 mg nemtabrutinib on Day 1.	Drug: Nemtabrutinib; 25 mg nemtabrutinib (1 x 5 mg and 1 x 20 mg tablets) administered orally as a single dose.; Other Names: MK-1026; ARQ 531
Experimental: Panel B; Healthy control participants will receive a single oral dose of 25 mg nemtabrutinib on Day 1.	Drug: Nemtabrutinib; 25 mg nemtabrutinib (1 x 5 mg and 1 x 20 mg tablets) administered orally as a single dose.; Other Names: MK-1026; ARQ 531

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve from Dosing to Infinity (AUC0-inf) of Nemtabrutinib in Plasma	The AUC0-inf of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Maximum Concentration (Cmax) of Nemtabrutinib in Plasma	The Cmax of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve from Dosing to last (AUC0-last) of Nemtabrutinib in Plasma	The AUC0-last of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Concentration 24 (C24) Hours Postdose of Nemtabrutinib in Plasma	The C24 of nemtabrutinib in plasma will be determined in each arm.	24 hours postdose
Time to Maximum Concentration (Tmax) of Nemtabrutinib in Plasma	The Tmax of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Apparent Terminal Half-life (t1/2) of Nemtabrutinib in Plasma	The t½ of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Apparent Total Clearance (CL/F) of Nemtabrutinib in Plasma	The CL/F of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Nemtabrutinib in Plasma	The Vz/F of nemtabrutinib in plasma will be determined in each arm.	Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose
Number of Participants who Experience One or More Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported.	Up to ~15 days
Number of Participants Who Discontinue From the Study Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to an AE will be reported.	Up to ~15 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2024
• Primary Completion (Actual): August 13, 2026
• Study Completion (Actual): August 13, 2026

Study Registration Dates

• First Submitted: May 29, 2024
• First Submitted That Met QC Criteria: May 29, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; ARQ531
• Other Study ID Numbers: 1026-015; MK-1026-015 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No