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

NCT05282030 | Completed Phase 1 FDA Drug

• 3 other identifiers: POP16399U1111-1269-68772021-006685-20
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 4

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.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (2)

• Assessment of PK parameters Tolebrutinib: AUC

  Area under the plasma concentration (AUC) versus time curve extrapolated to infinity

  From Day 1 to Day 4

• Assessment of PK parameters M2: AUC

  From Day 1 to Day 4

Secondary Outcomes (5)

• Assessment of PK parameters Tolebrutinib: Cmax

  From Day 1 to Day 4

• Assessment of PK parameters M2: Cmax

  From Day 1 to Day 4

• Assessment of PK parameters Tolebrutinib: AUClast

  From Day 1 to Day 4

• Assessment of PK parameters M2: AUClast

  From Day 1 to Day 4

• Number of participants with treatment-emergent adverse events (TEAEs)

  From Day 1 to Day 8

Study Arms (3)

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

EXPERIMENTAL

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

Drug: tolebrutinib

Normal Renal Function group (Part A and B)

EXPERIMENTAL

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

Drug: tolebrutinib

Moderate RI group (Part B only conditional)

EXPERIMENTAL

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

Drug: tolebrutinib

Interventions

tolebrutinib DRUG

Pharmaceutical form: Film-coated tablets Route of administration: oral

Moderate RI group (Part B only conditional); Normal Renal Function group (Part A and B); Severe Renal Impairment (RI) group (Part A only)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.
• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Clinical Pharmacology of Miami Site Number : 8400002

Miami, Florida, 33014, United States

Location

Nucleus Network Site Number : 8400001

Saint Paul, Minnesota, 55114, United States

Location

Volunteer Research Group-NOCCR Site Number : 8400003

Knoxville, Tennessee, 37920, United States

Location

Investigational Site Number : 2760001

Kiel, 24105, Germany

Location

Related Links

• POP16399 Plain language Results Summary

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 16, 2022
• Study Start: March 10, 2022
• Primary Completion: August 2, 2022
• Study Completion: August 2, 2022
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (3); DE (1)