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

• Sponsor: Sanofi (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT05282030
• Collaborator: (none)
• Enrollment: 48
• Locations: 4
• Arms: 3
• Anticipated Duration (Months): 7.1
• Patients Per Site: 12
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: tolebrutinib	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 23, 2022
• Anticipated Primary Completion Date: Oct 26, 2022
• Anticipated Study Completion Date: Oct 26, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Assessment of PK parameters Tolebrutinib: AUC [From Day 1 to Day 4]

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

2. Assessment of PK parameters M2: AUC [From Day 1 to Day 4]

Secondary Outcome Measures

1. Assessment of PK parameters Tolebrutinib: Cmax [From Day 1 to Day 4]

   Maximum plasma concentration observed (Cmax)

2. Assessment of PK parameters M2: Cmax [From Day 1 to Day 4]

3. 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

4. Assessment of PK parameters M2: AUClast [From Day 1 to Day 4]

5. Number of participants with treatment-emergent adverse events (TEAEs) [From Day 1 to Day 8]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts 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/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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami-Site Number:8400002	Miami	Florida	United States	33014
2	Nucleus Network-Site Number:8400001	Saint Paul	Minnesota	United States	55114
3	Volunteer Research Group-NOCCR-Site Number:8400003	Knoxville	Tennessee	United States	37920
4	Investigational Site Number :2760001	Kiel		Germany	24105

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05282030
• Other Study ID Numbers: POP16399; U1111-1269-6877; 2021-006685-20
• First Posted: Mar 16, 2022
• Last Update Posted: Aug 8, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: Renal Insufficiency

Study Results

No Results Posted as of Aug 8, 2022