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

Renal Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05282030
• Other study ID #: POP16399
• Secondary ID: U1111-1269-68772
• Status: Completed
• Phase: Phase 1
• Start date: March 23, 2022
• Est. completion date: August 2, 2022

Study information

• Verified date: January 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2, 2022
• Est. primary completion date: August 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• tolebrutinib
Pharmaceutical form: Film-coated tablets Route of administration: oral

Locations

Country	Name	City	State
Germany	Investigational Site Number :2760001	Kiel
United States	Volunteer Research Group-NOCCR-Site Number:8400003	Knoxville	Tennessee
United States	Clinical Pharmacology of Miami-Site Number:8400002	Miami	Florida
United States	Nucleus Network-Site Number:8400001	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of PK parameters Tolebrutinib: AUC	Area under the plasma concentration (AUC) versus time curve extrapolated to infinity	From Day 1 to Day 4
Primary	Assessment of PK parameters M2: AUC		From Day 1 to Day 4
Secondary	Assessment of PK parameters Tolebrutinib: Cmax	Maximum plasma concentration observed (Cmax)	From Day 1 to Day 4
Secondary	Assessment of PK parameters M2: Cmax		From Day 1 to Day 4
Secondary	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
Secondary	Assessment of PK parameters M2: AUClast		From Day 1 to Day 4
Secondary	Number of participants with treatment-emergent adverse events (TEAEs)		From Day 1 to Day 8