A Phase I, open-label, single-sequence, two-part, two-period, drug-drug interaction study to assess the effect of itraconazole and phenytoin on the pharmacokinetics of a single oral dose of LXE408 in healthy participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- To investigate the effect of multiple doses of CYP3A inhibitor, itraconazole, at 200 mg QD on the PK of a single 50 mg oral dose of LXE408 in healthy participants.
研究概览
简要总结
The purpose of this study is to evaluate the effect of co-administration of itraconazole, a strong cytochrome P450 CYP3A inhibitor, or co-administration of phenytoin, a strong CYP3A inducer on the pharmacokinetics (PK) of a single 50mg dose of LXE408. In addition, the safety and tolerability of a single dose of LXE408 with or without the co-administration of itraconazole or phenytoin will be evaluated. The study will be conducted in healthy participants. type of the treatment is oral drug administration and study type is interventional study.
This study is an open-label, single-sequence, two-part, two-period, crossover drug-drug interaction (DDI) study designed to evaluate the PK of a single-dose of 50 mg LXE408 in healthy participants when given alone and during multiple dosing of 200 mg itraconazole QD (Part 1) or phenytoin 100 mg TID (Part 2). The study consists of 2 separate and independent parts, Part 1 and Part 2, with 2 separate groups of participants enrolled. Each of the 2 study parts comprises a screening period of up to 28 days, a baseline evaluation (on Day -1 of Period 1) and 2 treatment periods. Participants who meet the eligibility criteria at the screening and baseline assessments on Day-1 of Period 1 will be admitted to the study site and will remain domiciled until the Study Completion (End of Study, EOS). A participant will be enrolled in either of the parts.
Approximately 20 male or female participants 18 to 55 years of age will be enrolled and dosed with the aim to have at least 16 evaluable participants in each part. Additional participants may be enrolled if participants discontinue from the study for reasons other than safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Subjects willing to adhere to the protocol requirements and to provide written informed consent prior to participation in the study.
- •2.Healthy male or non-childbearing potential female participants 18 to 55 years of age inclusive at screening.
- •3.In good health as determined by no clinically significant findings from past medical history, physical examination, vital signs, chest X-rays, 2D-ECHO, ECG, and clinical laboratory tests during screening and/or baseline.
- •4.Participants must weigh at least 50.0 kg with a body mass index (BMI) within the range of 18.0 to 29.9 kg/m2, inclusive, at screening.
- •5.At screening and baseline, vital signs (systolic and diastolic blood pressure, body temperature and pulse rate) will be assessed in the sitting position and again (when required) in the standing position.
- •Vital signs after sitting 3 minutes in a quiet environment must be within the following ranges: oral body temperature between 35.0-37.5°C, systolic blood pressure between 90-139 mm Hg, diastolic blood pressure between 50-89 mm Hg, and pulse rate between 50-100 bpm.
排除标准
- •1.History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants.
- •2.Participants who have received other investigational drugs within 5 half-lives or within 30 days or until the expected pharmacodynamic effect has returned to baseline prior to initial dosing, whichever is longer.
- •3.History of hypersensitivity to the investigational compounds (LXE408, Itraconazole or Phenytoin)/compound class or excipients being used in this study 4.Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 30 days after stopping study treatment.
- •5.Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 1.2 × upper limit of normal (ULN) and ≥ 1.5 × ULN total bilirubin OR any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin at screening 6.Any single parameter of amylase or lipase above 1.0 x ULN, or any history or presence of clinical symptoms suggestive of pancreatitis.
- •7.History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine (creatinine level above 1.5x ULN) or blood urea, or abnormal urinary constituents (e.g. proteinuria, microscopy confirmed hematuria) at screening.
结局指标
主要结局
To investigate the effect of multiple doses of CYP3A inhibitor, itraconazole, at 200 mg QD on the PK of a single 50 mg oral dose of LXE408 in healthy participants.
时间窗: Primary PK parameters of LXE408 in plasma such as AUClast, AUCinf, AUC0-t (as appropriate), Cmax and Tmax. | Secondary plasma PK parameters of LXE408 including AUC0-24, CL/F, Vz/F and T1/2 as feasible. | [Part 1 & Part 2 in Period 1: From dose (0h) up to 120h. | Part 1 in Period 2: From Pre-dose (0h) up to 264h. | Part 2 in Period 2: From Pre-dose (0h) up to 120h.]
To investigate the effect of multiple doses of CYP3A inducer, phenytoin, at 100 mg TID on the PK of a single 50 mg oral dose of LXE408 in healthy participants
时间窗: Primary PK parameters of LXE408 in plasma such as AUClast, AUCinf, AUC0-t (as appropriate), Cmax and Tmax. | Secondary plasma PK parameters of LXE408 including AUC0-24, CL/F, Vz/F and T1/2 as feasible. | [Part 1 & Part 2 in Period 1: From dose (0h) up to 120h. | Part 1 in Period 2: From Pre-dose (0h) up to 264h. | Part 2 in Period 2: From Pre-dose (0h) up to 120h.]
次要结局
- To assess the safety & tolerability of a single 50 mg oral dose of LXE408 given alone & with multiple doses of itraconazole at 200 mg QD in healthy participants.
研究者
Murugananthan K
Novartis Healthcare Private Limited