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NCT Number: NCT06442436

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

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.

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Pharmacology of Miami ( Site 0003), Miami, Florida, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Nemtabrutinib

Drug

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

Primary outcomes

  1. Area Under the Curve from Dosing to Infinity (AUC0-inf) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The AUC0-inf of nemtabrutinib in plasma will be determined in each arm.

  2. Maximum Concentration (Cmax) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The Cmax of nemtabrutinib in plasma will be determined in each arm.

Secondary outcomes

  1. Area Under the Curve from Dosing to last (AUC0-last) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The AUC0-last of nemtabrutinib in plasma will be determined in each arm.

  2. Concentration 24 (C24) Hours Postdose of Nemtabrutinib in Plasma

    Time frame: 24 hours postdose

    The C24 of nemtabrutinib in plasma will be determined in each arm.

  3. Time to Maximum Concentration (Tmax) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The Tmax of nemtabrutinib in plasma will be determined in each arm.

  4. Apparent Terminal Half-life (t1/2) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The t½ of nemtabrutinib in plasma will be determined in each arm.

  5. Apparent Total Clearance (CL/F) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The CL/F of nemtabrutinib in plasma will be determined in each arm.

  6. Apparent Volume of Distribution During Terminal Phase (Vz/F) of Nemtabrutinib in Plasma

    Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192, 240, and 336 hours postdose

    The Vz/F of nemtabrutinib in plasma will be determined in each arm.

  7. Number of Participants who Experience One or More Adverse Events (AEs)

    Time frame: Up to ~15 days

    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.

  8. Number of Participants Who Discontinue From the Study Due to an Adverse Event (AE)

    Time frame: Up to ~15 days

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Toll Free Number

CONTACT

[email protected]

1-888-577-8839

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jun 4, 2024
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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