Hepatic Function Abnormal
Conditions
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
Interventions
DRUGtolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of PK parameters Tolebrutinib: AUC | From Day 1 to Day 4 | Area under the plasma concentration (AUC) versus time curve extrapolated to infinity |
| Assessment of PK parameters M2: AUC | From Day 1 to Day 4 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of PK parameters Tolebrutinib: AUClast | From Day 1 to Day 4 | Area under the serum concentration versus time curve calculated using the trapezoidal method from time zero to the real time Tlast |
| Assessment of PK parameters Tolebrutinib: Cmax | From Day 1 to Day 4 | Maximum plasma concentration observed (Cmax) |
| Number of participants with treatment-emergent adverse events (TEAEs) | From Day 1 to Day 8 | — |
| Assessment of PK parameters M2: AUClast | From Day 1 to Day 4 | — |
| Assessment of PK parameters M2: Cmax | From Day 1 to Day 4 | — |
Countries
United States
Outcome results
None listed