Study to Assess the Plasma Concentration of Tolebrutinib Given as a Tablet to Adult Participants With Renal Impairment Compared to Healthy Participants.

Sanofi

Status and phase: Completed; Phase 1

Conditions: Renal Impairment

Treatments: Drug: tolebrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05282030

2021-006685-20 (EudraCT Number)

U1111-1269-6877 (Registry Identifier)

POP16399

Details and patient eligibility

About

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.

Full 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

Enrollment: 22 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 3 patient groups

Severe Renal Impairment (RI) group (Part A only)

Experimental group

Description:

Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition

Treatment:

Drug: tolebrutinib

Normal Renal Function group (Part A and B)

Experimental group

Description:

Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition

Treatment:

Drug: tolebrutinib

Moderate RI group (Part B only conditional)

Experimental group

Description:

Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition

Treatment:

Drug: tolebrutinib