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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: tolebrutinib

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • Investigational Site Number :2760001
• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami-Site Number:8400002
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Nucleus Network-Site Number:8400001
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group-NOCCR-Site Number:8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Severe Renal Impairment (RI) group (Part A only); Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition	Drug: tolebrutinib; Pharmaceutical form: Film-coated tablets Route of administration: oral
Experimental: Normal Renal Function group (Part A and B); Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition	Drug: tolebrutinib; Pharmaceutical form: Film-coated tablets Route of administration: oral
Experimental: Moderate RI group (Part B only conditional); Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition	Drug: tolebrutinib; Pharmaceutical form: Film-coated tablets Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK parameters Tolebrutinib: Cmax	Maximum plasma concentration observed (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	Area under the serum concentration versus time curve calculated using the trapezoidal method from time zero to the real time 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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2022
• Primary Completion (Actual): August 2, 2022
• Study Completion (Actual): August 2, 2022

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: POP16399; U1111-1269-6877 (Registry Identifier: ICTRP); 2021-006685-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No