A PHASE 1, SINGLE DOSE OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS OF LORLATINIB IN SUBJECTS WITH IMPAIRED RENAL FUNCTION
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib
研究概览
简要总结
This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment.
详细描述
This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment. Each subject will receive a single oral dose of lorlatinib administered in the fasted state. Subjects with mild, moderate, and severe renal impairment will be enrolled and normal healthy subjects will be enrolled as matched controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female subjects of non-childbearing potential
- •Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
- •Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
- •Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Demonstrate stable renal function
排除标准
- •Renal allograft recipients
- •Any condition possibly affecting drug absorption (eg, gastrectomy)
- •A positive urine drug test
- •History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
- •Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer).
- •Screening supine triplicate 12 lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec
- •Second-degree or third-degree AV block (unless paced) or baseline PR interval >180 msec at any time prior to dosing of study treatment.
- •Abnormalities in clinical laboratory tests at screening
- •Pregnant or breastfeeding female subjects
- •History of HIV, Hepatitis B, Hepatitis C, HIT, sensitivity to heparin
- •Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation
研究组 & 干预措施
Mild
Mild renal impairment
干预措施: Lorlatinib (Drug)
Moderate
Moderate renal impairment
干预措施: Lorlatinib (Drug)
Severe
Severe renal impairment
干预措施: Lorlatinib (Drug)
Normal
Normal renal function
干预措施: Lorlatinib (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
AUCinf was calculated by AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration; Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Maximum Observed Plasma Concentration (Cmax) of Lorlatinib
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Cmax was observed directly from data.
次要结局
- Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria(Baseline up to 28 days after last dose of study treatment (approximately 29 days))
- Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria(Screening, Day -1, 0 hours (pre-dose), 1 hour, 2 hours, 4 hours, 24 hours and 120 hours postdose.)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline up to 28 days after last dose of study treatment (approximately 29 days))
- Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormalities(Screening, Day -1, Day 2 and Day 6)