A Study to Investigate the Pharmacokinetics and Safety of Remibrutinib in Participants With Hepatic Impairment Compared With Matched Healthy Participants

NCT05753592 | Completed Phase 1

• 2 other identifiers: CLOU064A21012022-001936-27
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This was a Phase 1, open-label study to evaluate the PK, safety, and tolerability after administration of multiple doses of remibrutinib in participants with mild, moderate, or severe hepatic impairment (HI) compared to pooled matched healthy control participants with normal hepatic function.

Conditions

Hepatic Impairment

Keywords

Remibrutinib (LOU064); Hepatic Impairment (HI); Pharmacokinetic (PK); Safety; Tolerability; Child-Pugh

Outcome Measures

Primary Outcomes (5)

• Cmax,ss

  The maximum (peak) observed blood concentration following multiple-dose administration (mass/volume)

  72 hours

• AUCtau

  The area under the curve (AUC) from time zero to the end of the dosing interval tau (12 hours) following multiple-dose administration

  72 hours

• AUClast,ss

  The area under the curve (AUC) from time zero to the last measurable blood concentration sampling time (Tlast) following multiple-dose administration (mass\*time/volume)

  72 hours

• Tmax,ss

  The time to reach maximum (peak) blood concentration following multiple-dose administration (time)

  72 hours

• T1/2

  The elimination half-life associated with the terminal slope (lambda\_z) of a semi logarithmic concentration-time curve (time)

  72 hours

Secondary Outcomes (4)

• Number of participants with adverse events

  8 days

• Unbound fraction; Cmax,ss,u

  8 days

• Unbound fraction; AUCtau,u

  8 days

• Unbound fraction; AUClast,ss,u

  8 days

Study Arms (2)

Part 1; LOU064 (Remibrutinib)

EXPERIMENTAL

Mild and Moderate HI participants and matching healthy participants

Drug: Part 1; LOU064 (Remibrutinib)

Part 2; LOU064 (Remibrutinib)

EXPERIMENTAL

Severe HI participants and matching healthy participants

Drug: Part 2; LOU064 (Remibrutinib)

Interventions

Part 1; LOU064 (Remibrutinib) DRUG

25 mg remibrutinib (5.5 days)

Part 1; LOU064 (Remibrutinib)

Part 2; LOU064 (Remibrutinib) DRUG

25 mg remibrutinib (5.5 days)

Part 2; LOU064 (Remibrutinib)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants
• Signed informed consent was obtained prior to participation in the study.
• Male and non-childbearing potential female\* participants 18 to 70 years of age, inclusive, at Screening.
• Women of non-childbearing potential were defined as women who were post menopausal or had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks prior to first dosing of study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman was confirmed by follow-up hormone level assessment was she considered not of childbearing potential. Women were considered post-menopausal if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms).
• Must have been a non-smoker or a light smoker who smoked no more than 10 cigarettes (or equivalent) per day, at Screening. Smokers must have agreed to smoke no more than 5 cigarettes (or equivalent) per day from check-in until after Study Completion evaluations.
• Must have been able to communicate well with the investigator and to understand and comply with the requirements of the study.
• Participants with mild, moderate, and severe HI (Groups 1, 2 and 3)
• Must have weighed at least 50 kg to participate in the study and must have had a body mass index (BMI) within the range of 18.0 to 35.0 kg/m2, inclusive, at Screening.
• Seated vital signs must have been within the following ranges at Screening and Baseline:
• body temperature, 35.0 to 37.5°C, inclusive
• systolic blood pressure (BP), 90 to 160 mmHg, inclusive
• diastolic BP, 50 to 100 mmHg, inclusive
• pulse rate, 50 to 110 bpm, inclusive
• Had impaired hepatic function as defined by the Child-Pugh classification for severity of liver disease and had a Child-Pugh score in line with one of the following HI groups at Screening:
• Group 1; mild (Class A); Child-Pugh score 5-6, inclusive

You may not qualify if:

• All participants
• Use of other investigational drugs within 5 half-lives or 30 days prior to first dosing of study treatment, whichever was longer.
• History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
• History or presence of malignancy of any organ system (other than treated localized basal cell or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years of Screening, regardless of whether there was evidence of local recurrence or metastases.
• History of immunodeficiency diseases or had a positive human immunodeficiency virus (HIV) test result at Screening.
• History or presence of any ongoing, chronic, or recurrent infectious disease (including tuberculosis, atypical mycobacterioses, listeriosis, aspergillosis).
• Female participants who were of childbearing potential, defined as all women physiologically capable of becoming pregnant.
• Female participants who were pregnant or nursing (lactating). Pregnancy was defined as the state of a female participant after conception and until termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test at Screening or Baseline.
• Use of prohibited prescription or non-prescription medication or supplement.
• Received any live vaccine within 8 weeks prior to first dosing of study treatment.
• Received any coronavirus disease-2019 (COVID-19) vaccines within 2 weeks prior to first dosing of study treatment.
• Clinical signs and symptoms consistent with COVID-19 (e.g., fever, dry cough, dyspnea, sore throat, fatigue) or confirmed infection by appropriate laboratory test within 2 weeks prior to Screening or tested positive during the Screening period before study site check in.
• History or presence of significant bleeding risk or any coagulation disorder.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing of study treatment, or longer if required by local regulation.
• Any surgical or medical condition which could have significantly altered the absorption, distribution, metabolism or excretion of drugs (apart from cholecystectomy), or which could have jeopardized the participants in case of participation in the study.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Miskolc, Baz, H-3529, Hungary

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Interventions

remibrutinib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: March 3, 2023
• Study Start: October 31, 2022
• Primary Completion: December 14, 2023
• Study Completion: December 17, 2023
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)