A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-05221304 IN ADULT SUBJECTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITHOUT HEPATIC IMPAIRMENT
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304
研究概览
简要总结
Hepatic impairment PK study
详细描述
This is a non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (total and unbound) of PF-05221304 after a single oral dose administered in the fed state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •All subjects -
- •Adults <18 years of age and >70 years of age
- •BMI < 17.5 and > 35.4 kg/m2
- •HIV positive
- •Conditions that affect drug absorption
- •Positive breath alcohol test
- •Healthy/ those without hepatic impairment -
- •Known or suspected hepatic impairment
- •Evidence of Hepatitis B or C
- •On any chronic medications
- •Those with varying degrees of hepatic impairment -
- •Not meeting Classification A, B, or C of hepatic impairment based on Child-Pugh Classification
- •Evidence of Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy
- •Recent GI bleed
- •Moderate or severe renal impairment
- •Hepatic encephalopathy Grade 3 or higher
研究组 & 干预措施
Cohort 4_Severe impairment
Single, 25 mg dose of PF-05221304
干预措施: PF-05221304 (Drug)
Cohort 3_Moderate impairment
Single, 25 mg dose of PF-05221304
干预措施: PF-05221304 (Drug)
Cohort 1_Without impairment
Single, 25 mg dose of PF-05221304
干预措施: PF-05221304 (Drug)
Cohort 2_Mild impairment
Single, 25 mg dose of PF-05221304
干预措施: PF-05221304 (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304
时间窗: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 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.
Unbound AUCinf (AUCinf,u) of PF-05221304
时间窗: 4 hours postdose
AUCinf,u was calculated by fu\*AUCinf.
Fraction Unbound (fu) of PF-05221304
时间窗: 4 hours postdose
fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Unbound Cmax (Cmax,u) of PF-05221304
时间窗: 4 hours postdose
Cmax,u was calculated by fu\*Cmax.
Maximum Plasma Concentration (Cmax) of PF-05221304
时间窗: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Cmax was observed directly from data.
次要结局
- Unbound CL/F (CLu/F) of PF-05221304(4 hours postdose)
- Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304(0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose)
- Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304(0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose)
- Unbound AUClast ( AUClast,u) of PF-05221304(4 hours postdose)
- Apparent Clearance After Oral Dose (CL/F) of PF-05221304(0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose)
- Terminal Half-Life ( t½) of PF-05221304(0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Approximately 30 days)
- Number of Participants With Clinical Significant Findings in Vital Signs(7 days)
- Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data(7 days)
- Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304(0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose)
- Unbound Vz/F (Vz,u/F) of PF-05221304(4 hours postdose)
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology(7 days)
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry(7 days)
- Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis(7 days)