Clinical trial NCT05282030: Study to Assess the Plasma Concentration of Tolebrutinib Given as a Tablet to Adult Participants With Renal Impairment Compared to Healthy Participants.
Official title: An Open-label, Multi-center Phase 1 Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Oral Dose in Participants With Renal Impairment and in Matched Participants With Normal Renal Function.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-03-16
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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/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
city: Knoxville
country: United States
facility: Volunteer Research Group-NOCCR Site Number : 8400003
state: Tennessee
city: Kiel
country: Germany
facility: Investigational Site Number : 2760001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: