A Phase 1, Open-label, Parallel-group Study to Assess the Effect of Steady-state Carbamazepine on the Pharmacokinetics of Ponesimod in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Treatment B: Area Under The Plasma Concentration-time Curve of Ponesimod From Time 0 to 24 Hours Post Dose (AUC [0-24h])
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Treatment A: Ponesimod
Participants will receive up-titrated Ponesimod orally once daily from Day 1 to Day 15.
干预措施: Ponesimod (Drug)
Treatment B: Ponesimod + 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.
干预措施: Ponesimod (Drug)
Treatment B: Ponesimod + 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.
干预措施: Carbamazepine (Drug)
结局指标
主要结局
Treatment B: Area Under The Plasma Concentration-time Curve of Ponesimod From Time 0 to 24 Hours Post Dose (AUC [0-24h])
时间窗: 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
时间窗: 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])
时间窗: 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
时间窗: Pre dose up to 120 hours post dose on Day 22
Cmax is the maximum observed plasma concentration of Ponesimod.
次要结局
- Number of Participants with Treatment Emergent Adverse Events (TEAEs)(Up to Day 27)
- Total Lymphocyte Count(Treatment A: Day 1 (Baseline) and Day 16; Treatment B: Day 1 (Baseline) and Day 23)
- Percentage Change in Lymphocytes From Baseline(Treatment A: Baseline and Day 16, Treatment B: Baseline and Day 23)