Clinical trial NCT05283915: Study to Assess the Plasma Concentration of Tolebrutinib Given as a Tablet to Adult Participants With Mild Hepatic Impairment Compared to Participants With Normal Hepatic Function
Official title: An Open-label Phase 1, Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Dose in Adult Participants With Mild Hepatic Impairment, and in Matched Participants With Normal Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Function Abnormal
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-03-17
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this parallel group, Phase 1, open-label, 2-arm, single dose, multi-center study is to assess the effect of mild hepatic impairment on pharmacokinetics (PK), safety and tolerability of tolebrutinib compared with normal hepatic function, in male and female participants aged 18 to 79 years.

Detailed description: The total duration of the study per participant is up to 41 days including:

* A screening period of up to 4 weeks (Days -28 to -2)
* A 5-day, open-label treatment period
* Up to 7 days post-treatment follow-up period

Eligibility criteria: Inclusion Criteria:

For participants with mild hepatic impairment

* Stable chronic liver disease assessed by medical history, physical examination, and laboratory values
* Child-Pugh total score ranging from 5 to 6, inclusive.
* Laboratory parameters within the acceptable range for participants with hepatic impairment; however, estimated glomerular filtration rate (eGFR) should be above or equal to 60 mL/min

For all participants

* Body weight between 50.0 and 115.0 kg, inclusive, if male, between 40.0 and 100 kg, inclusive, if female, and body mass index (BMI) within the range 18 to 40 kg/m2, inclusive, at screening.
* Participant with platelet count ≥150 000/μL at the screening visit and at Day -1

Exclusion Criteria:

For all participants :

* Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥30 mmHg within 3 minutes when changing from supine to standing position at screening and Day -1
* Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month).
* History of drug or alcohol abuse within 1 year before inclusion.
* Smoking regularly more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 8 cigarettes per day during the institutionalization.
* Any consumption of citrus fruits (grapefruit, orange, etc) or their juices within 72 hours before inclusion.
* Use of any herbal medicines 2 weeks before IMP administration
* Treatment with a strong or moderate CYP3A inhibitors, a strong, moderate or mild CYP2C8 inhibitors OR CYP3A, CYP2C8 inducers within 14 days before the study treatment administration or 5 half-lives, whichever is longer

Specific for participants with mild hepatic impairment:

* Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic, renal, infectious disease, moderate or severe hepatic impairment (Child-Pugh total score greater than or equal to 7), or signs of acute illness.
* Hepatocarcinoma.
* Acute liver disease.
* Hepatic encephalopathy Grade 2, 3, and 4.
* Esophageal bleeding which is caused by esophageal varices within 3 months before inclusion.

NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Primary outcomes:
measure: Assessment of PK parameters Tolebrutinib: AUC
timeFrame: From Day 1 to Day 4
measure: Assessment of PK parameters M2: AUC
timeFrame: From Day 1 to Day 4
Secondary outcomes:
measure: Assessment of PK parameters Tolebrutinib: Cmax
timeFrame: From Day 1 to Day 4
measure: Assessment of PK parameters M2: Cmax
timeFrame: From Day 1 to Day 4
measure: Assessment of PK parameters Tolebrutinib: AUClast
timeFrame: From Day 1 to Day 4
measure: Assessment of PK parameters M2: AUClast
timeFrame: From Day 1 to Day 4
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: From Day 1 to Day 8
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami Site Number : 8400002
state: Florida
city: Saint Paul
country: United States
facility: Nucleus Network Site Number : 8400001
state: Minnesota
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: