A Study of Ponesimod in Healthy Adult Participants

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Ponesimod; Drug: Carbamazepine

• Registration Number: NCT05552196
• Lead Sponsor: Janssen Pharmaceutica N.V., Belgium

Brief Summary

The purpose of this study is to evaluate the effect of steady-state carbamazepine (CBZ; a strong pregnane X receptor \[PXR\] agonist) on the pharmacokinetics (PK) of ponesimod following a gradual up-titration regimen in healthy adult participants.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-21
• Study First Submitted QC: 2022-09-21
• Study First Posted: 2022-09-23
• Study Start: 2022-10-18
• Primary Completion: 2023-03-05
• Study Completion: 2023-03-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-25
• Last Update Posted: 2025-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• Body mass index between (BMI) 18-30 kilograms per meter square (kg/m^2)
• Willing and able to adhere to the prohibitions and restrictions.
• Female participants with negative pregnancy test.
• Women of childbearing potential (WOCBP) must use 2 methods of contraception.
• Healthy on the basis of physical examination (including neurological examination and skin examination), Columbia suicide severity rating scale questionnaire (C-SSRS) questionnaire, ophthalmological examination, medical history, vital signs, and 12-lead electrocardiogram (ECG).
• Positive varicella zoster virus (VZV).

Exclusion Criteria

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below 60 milliliter per minute [mL/min]), thyroid disease, neurologic or psychiatric disease, confirmed or suspected macular edema, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results.
• Contraindications to the use of Carbamazepine (CBZ) as per local prescribing information
• Any immunosuppressive treatment within 6 weeks before first study drug administration.
• Lymphopenia (less than 1,000 cells per microliter).
• Received an investigational drug or used an invasive investigational medical device within 30 days before the first study drug intake or received a biological product within 3 months or 5 half-lives (whichever is longer) before the first study drug intake, or is currently enrolled in an investigational study.
• Lack of good/reasonable venous access.
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment B: Ponesimod + Carbamazepine	Ponesimod	Participants will receive up-titrated Carbamazepine from Day 1 to Day 7 and from Day 23 to Day 26. Participants will also receive up-titrated Ponesimod and Carbamazepine from Day 8 to Day 22.
Treatment B: Ponesimod + Carbamazepine	Carbamazepine	Participants will receive up-titrated Carbamazepine from Day 1 to Day 7 and from Day 23 to Day 26. Participants will also receive up-titrated Ponesimod and Carbamazepine from Day 8 to Day 22.
Treatment A: Ponesimod	Ponesimod	Participants will receive up-titrated Ponesimod orally once daily from Day 1 to Day 15.

Primary Outcome Measures

Name	Time	Method
Treatment B: Area Under The Plasma Concentration-time Curve of Ponesimod From Time 0 to 24 Hours Post Dose (AUC [0-24h])	Pre dose up to 120 hours post dose on Day 22	AUC (0-24h) is the plasma concentration-time curve of Ponesimod from time 0 to 24 hours post dose, calculated by linear-linear trapezoidal summation.
Treatment A: Cmax is the maximum Observed Plasma Concentration (Cmax) of Ponesimod	Pre dose up to 120 hours post dose on Day 15	Cmax is the maximum observed plasma concentration of Ponesimod.
Treatment A: Area Under The Plasma Concentration-time Curve of Ponesimod From Time 0 to 24 Hours Post Dose (AUC [0-24h])	Pre dose up to 120 hours post dose on Day 15	AUC (0-24h) is the plasma concentration-time curve of Ponesimod from time 0 to 24 hours post dose, calculated by linear-linear trapezoidal summation.
Treatment B: Cmax is the maximum Observed Plasma Concentration (Cmax) of Ponesimod	Pre dose up to 120 hours post dose on Day 22	Cmax is the maximum observed plasma concentration of Ponesimod.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	Up to Day 27	An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.
Total Lymphocyte Count	Treatment A: Day 1 (Baseline) and Day 16; Treatment B: Day 1 (Baseline) and Day 23	Total lymphocyte count will be reported.
Percentage Change in Lymphocytes From Baseline	Treatment A: Baseline and Day 16, Treatment B: Baseline and Day 23	Percentage change in lymphocytes from baseline will be reported.

Trial Locations

Locations (1)

Clinical Pharmacology Unit; 🇧🇪 Merksem, Belgium