Renal Impairment
Conditions
Brief summary
The purpose of this parallel group, Phase 1, open-label, 2-arm study is to assess the effect of severe (Part A) and moderate (Part B, conditional) renal impairment (RI) on pharmacokinetics (PK), safety and tolerability of tolebrutinib tablets compared with normal renal function, in male and female participants aged 18 to 79 years.
Detailed description
The total duration of the study per participant will be up to 38 days including: * A screening period of up to 4 weeks. * A 5-day, open-label treatment period. * Up to 7 days post-treatment follow-up period
Interventions
DRUGtolebrutinib
Pharmaceutical form: Film-coated tablets Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
NON_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 severe RI (Part A): Absolute GFR \<30 mL/min, and not requiring dialysis (based on estimated glomerular filtration rate \[eGFR\] by absolute GFR from the MDRD formula with individual BSA, without race correction), with a variability within +/- 20% between screening and Day -1 assessments. * For participants with moderate RI (Part B conditional): 30 mL/min ≤ absolute GFR ≤59 mL/min (based on estimated glomerular filtration rate \[eGFR\] by absolute GFR from the MDRD formula with individual body surface area (BSA), without race correction), with a variability within +/- 20% between screening and Day -1 assessments * For participants with normal renal function: Absolute GFR ≥ 90 mL/min (based on eGFR by absolute GFR from the MDRD formula with individual BSA, without race correction), with a variability within +/- 20% between screening and Day -1 assessments. 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) between 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 SBP≥30 mmHg within 3 minutes when changing from a supine to a standing position at screening and Day -1 * Blood donation (usually approximately 500 mL), within 2 months before inclusion. * Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month). * History of alcohol or drug abuse within 1 year prior to screening * 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, moderate or mild CYP2C8 inducer or inhibitor, OR a strong, moderate or mild CYP3A inducer, OR a strong, or moderate CYP3A inhibitor, within 14 days before the study treatment administration or 5 half-lives, whichever is longer Specific criteria for participants with RI * Active liver disease, cirrhosis, chronic liver disease, hepatic insufficiency * Acute renal failure (de novo or superimposed to preexisting chronic RI), nephrotic syndrome. * History of or current hematuria of urologic origin that limits the participant's participation in the study * Participant requiring dialysis during the study Specific criteria for participants with normal renal function: \- Any history or presence of clinically relevant hepatic or renal disease 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 AUClast |
| 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
Germany, United States
Outcome results
None listed