An Open-Label Study of the Effect of Tesetaxel on the QTc Interval and the Effect of Food, Itraconazole, and Rifampin on Tesetaxel Pharmacokinetics in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 93
- 试验地点
- 3
- 主要终点
- All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval
研究概览
简要总结
This is a 3-cohort, multicenter, Phase 1 study of the effect of tesetaxel, an investigational, orally administered taxane, on the corrected QT (QTc) interval and the potential effect of food, a cytochrome P450 (CYP) 3A inhibitor (itraconazole), and a CYP3A inducer (rifampin) on tesetaxel pharmacokinetics (PK) in adult patients with advanced solid tumors.
详细描述
Cohort 1:
Cohort 1 is a 2-period, 2-sequence, crossover study designed to assess the effect of food on the PK of tesetaxel and tesetaxel metabolites. Patients were randomized in a 1:2 ratio to receive tesetaxel on Day 1 of two 21-day cycles under fed and fasting conditions in one of two opposing sequences (Sequence 1A and Sequence 1B).
Cohort 2:
Cohort 2 is a 2-period, single-sequence, crossover study designed to assess the potential PK drug-drug interaction (DDI) of a strong CYP3A inhibitor (itraconazole) on tesetaxel and tesetaxel metabolites. Patients receive tesetaxel during Cycle 1 followed by a reduced dose of tesetaxel plus itraconazole during Cycle 2.
Cohort 3:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male patients at least 18 years of age
- •Histologically or cytologically confirmed solid tumor
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- •Adequate cardiac conduction by ECG
- •Adequate bone marrow, hepatic, and renal function
排除标准
- •Presence of risk factors for QTc prolongation
- •Presence of neuropathy Grade > 1
- •Anticancer treatment ≤ 14 days prior to randomization
- •Major surgery ≤ 28 days prior to randomization
- •Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of:
- •A moderate or strong inhibitor or inducer of CYP3A
- •A CYP3A substrate with a narrow therapeutic range or that is contraindicated with either itraconazole or rifampin
研究组 & 干预措施
Cohort 1, Sequence 1A: Fed then fasted
Cycle 1: Tesetaxel on Day 1 of a 21-day cycle under fed conditions
Cycle 2: Tesetaxel on Day 1 of a 21-day cycle under fasted conditions
干预措施: Tesetaxel (Drug)
Cohort 1, Sequence 1B: Fasted then fed
Cycle 1: Tesetaxel on Day 1 of a 21-day cycle under fasted conditions
Cycle 2: Tesetaxel on Day 1 of a 21-day cycle under fed conditions
干预措施: Tesetaxel (Drug)
Cohort 2: Tesetaxel plus itraconazole
Cycle 1: Tesetaxel on Day 1 of a 21-day cycle
Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and itraconazole on Day -3 through Day 14 of a 21-day cycle
干预措施: Tesetaxel (Drug)
Cohort 2: Tesetaxel plus itraconazole
Cycle 1: Tesetaxel on Day 1 of a 21-day cycle
Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and itraconazole on Day -3 through Day 14 of a 21-day cycle
干预措施: Itraconazole (Drug)
Cohort 3: Tesetaxel plus rifampin
Cycle 1: Tesetaxel on Day 1 of a 21-day cycle
Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and rifampin on Day -6 through Day 14 of a 21-day cycle
干预措施: Tesetaxel (Drug)
Cohort 3: Tesetaxel plus rifampin
Cycle 1: Tesetaxel on Day 1 of a 21-day cycle
Cycle 2: Tesetaxel on Day 1 of a 21-day cycle and rifampin on Day -6 through Day 14 of a 21-day cycle
干预措施: Rifampin (Drug)
结局指标
主要结局
All Cohorts: The change from baseline in Fridericia's corrected QT (ΔQTcF) interval
时间窗: Approximately 3 weeks
Cohort 2: AUC from 0 to 336 hours (AUC0-336h) for tesetaxel in the presence and absence of itraconazole
时间窗: Approximately 6 weeks
Cohort 1, Sequences 1A and 1B: Maximum observed plasma concentration (Cmax) for tesetaxel under fed and fasted conditions
时间窗: Approximately 6 weeks
Cohort 1, Sequences 1A and 1B: Area under the plasma concentration-time curve from 0 to the last measurable plasma concentration (AUC0-t) for tesetaxel under fed and fasted conditions
时间窗: Approximately 6 weeks
Cohort 2: Cmax for tesetaxel in the presence and absence of itraconazole
时间窗: Approximately 6 weeks
Cohort 3: AUC0-336h for tesetaxel in the presence and absence of rifampin
时间窗: Approximately 6 weeks
Cohort 3: Cmax for tesetaxel in the presence and absence of rifampin
时间窗: Approximately 6 weeks
次要结局
- All Cohorts: Cmax for tesetaxel metabolites(Approximately 6 weeks)
- All Cohorts: Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs)(Baseline through 30 days after last administration of Study treatment)
- All Cohorts: AUC for tesetaxel metabolites(Approximately 6 weeks)