A Phase 1, Randomized, Double Blind (3rd Party Open), Placebo-controlled, Sequential Group, Multicentre Study To Evaluate The Multiple Dose Safety, Tolerability, Pharmacokinetics And Pharmacodynamics, of PF-00868554 in Hepatitis C Virus (HCV) Positive Otherwise Healthy Patient Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Plasma Decay Half-Life (t1/2): Day 8
研究概览
简要总结
Assess the safety, tolerability and pharmacokinetics of multiple oral doses of PF-00868554 in HCV positive patient volunteers
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HCV RNA ≥ 100,000 IU/mL at screening
- •Genotype 1a or 1b
排除标准
- •Current or prior treatment with IFN and/or RBV
- •Evidence of decompensated liver disease
研究组 & 干预措施
4
干预措施: PF-00868554 (Drug)
2
干预措施: PF-00868554 (Drug)
3
干预措施: PF-00868554 (Drug)
1
干预措施: PF-00868554 (Drug)
5
干预措施: Placebo (Drug)
结局指标
主要结局
Plasma Decay Half-Life (t1/2): Day 8
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. The t1/2 of PF-04691502 was assessed following repeated oral dose administration for 8 days (multiple dose PK).
Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 8
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose
Maximum Observed Plasma Concentration (Cmax): Day 1
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose for twice daily dose; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 hours post-dose for three times daily dose
Maximum Observed Plasma Concentration (Cmax): Day 8
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose
Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 1
时间窗: 0 to 12 hours, 12 to 24 hours post-dose
Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram \[g\]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.
Day 8 to Day 1 Ratio of the 6 Beta-Hydroxyl Cortisol to Cortisol Ratios
时间窗: -24 to 0 hours (pre-dose) on Day 1 (Day 0); 0 to 24 hours post-dose on Day 8
Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 8
时间窗: 0 to 24 hours post-dose on Day 8
Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
Time to Reach Maximum Observed Plasma Concentration (Tmax): Day 1
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose for twice daily dose; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 hours post-dose for three times daily dose
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 8
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 8 hours for three times daily regimens and 12 hours for the twice daily regimens.
Minimum Observed Plasma Trough Concentration (Cmin): Day 8
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8
The Cmin of PF-04691502 was assessed following repeated oral dose administration for 8 days (multiple dose PK).
Observed Accumulation Ratio (Rac)
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 1; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8
Rac was calculated as, area under the curve from time zero to end of dosing interval on Day 8 (AUCtau) divided by area under the curve from time zero to end of dosing interval on Day 1(AUCtau).
Observed Accumulation Ratio for Cmax (Rac Cmax)
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 1; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 hours post-dose on Day 8
Rac Cmax was calculated as, maximum observed plasma concentration on Day 8 (Cmax) divided by maximum observed plasma concentration on Day 1(Cmax).
Percent of Dose Recovered Unchanged in Urine (Ae%): Day 1
时间窗: 0 to 12 hours, 12 to 24 hours post-dose
Percent of dose recovered unchanged in urine during the dosing interval=100\*(cumulative amount of drug recovered unchanged in urine \[Ae\] divided by dose), where the dosing interval is 12 hours.
Percent of Dose Recovered Unchanged in Urine (Ae%): Day 8
时间窗: 0 to 12 hours, 12 to 24 hours post-dose
Percent of dose recovered unchanged in urine during the dosing interval=100 (cumulative amount of drug recovered unchanged in urine \[Ae\] divided by dose), where the dosing interval is 12 hours.
Ratio of 6 Beta-Hydroxyl Cortisol to Cortisol: Day 1
时间窗: -24 to 0 hours (pre-dose) on Day 1 (Day 0)
Urine 6 beta-hydroxyl cortisol and cortisol concentrations were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau): Day 1
时间窗: 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 hours post-dose for twice daily dose; 0 hours (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 hours post-dose for three times daily dose
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 8 hours for three times daily regimens and 12 hours for the twice daily regimens.
Cumulative Amount of Drug Recovered Unchanged in Urine (Ae): Day 8
时间窗: 0 to 12 hours, 12 to 24 hours post-dose
Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram \[g\]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.
Renal Clearance (CLr): Day 1
时间窗: 0 to 12 hours, 12 to 24 hours post-dose
Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval is 12 hours.
Renal Clearance (CLr): Day 8
时间窗: 0 to 12 hours, 12 to 24 hours post-dose
Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval is 12 hours.
次要结局
- Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at Day 8(Baseline, Day 8)
- Number of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Variants Resistant to PF-00868554(Screening up to Day 8)