A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN SUBJECTS WITH RENAL IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL RENAL FUNCTION
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)
研究概览
简要总结
This study is a phase 1 non-randomized, open-label, single-dose, parallel-group study of PF 04965842 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with moderate renal impairment (Part 2).
详细描述
This is a Phase 1 non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-04965842 after a single 200 mg oral dose. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted and approximately 8 subjects with moderate renal impairment will be enrolled. The total duration of participation from the Screening Visit to Day 4 will be a maximum of 31 days and from the Screening Visit to Follow-up Contact/Visit will be a maximum of 67 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Breath alcohol test at Screening and Day -1 must be negative.
- •Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m2; and a total body weight >50 kg (110 lb).
- •Additional inclusion criteria for subjects with renal impairment:
- •Meet the following eGFR criteria during the screening period based on the MDRD equation:
- •Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.
- •Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and <60 mL/min.
- •Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
- •Stable concomitant drug regimen.
排除标准
- •Renal transplant recipients.
- •Urinary incontinence without catheterization.
- •Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days prior to baseline, history of disseminated herpes simplex infection or recurrent or disseminated herpes zoster.
- •Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
- •History of or current positive results for human immunodeficiency virus, Hepatitis B, Hepatitis C.
- •Additional exclusion criteria for subjects with renal impairment:
- •Subjects requiring hemodialysis and peritoneal dialysis.
- •Screening BP ≥ 180 mm Hg (systolic) or ≥ 110 mm Hg (diastolic).
- •Screening supine 12-lead ECG demonstrating QTcF >470 msec or a QRS interval >120 msec.
研究组 & 干预措施
PF-04965842
PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor
干预措施: PF-04965842 (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)
时间窗: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)
时间窗: 0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
时间窗: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
Maximum observed plasma PF-04965842 concentration.
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)
时间窗: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)
时间窗: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842
时间窗: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline up to Follow-Up (Day 36))
- Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)(Baseline, post-dose on Day 1, Day 2 and Day 4.)
- Number of Participants With Clinically Significant Vital Sign Values(Day 1 (pre-dose) and Day 4)
- Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values(Baseline, post-dose on Day 1 and on Day 4)