A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN HEALTHY ADULT MALE PARTICIPANTS TO ASSESS THE EXTENT OF EXCRETION, ABSOLUTE BIOAVAILABILITY, FRACTION ABSORBED, AND PHARMACOKINETICS OF [14C]PF-06865571 USING A 14C-MICROTRACER APPROACH
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Total Recovery of Radioactivity in Urine as Percentage of Total Radioactive Dose of PF-06865571 Administered
研究概览
简要总结
This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose study of PF-06865571 in healthy male participants to characterize the ADME properties of [14C]PF-06865571 following oral administration; and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration of unlabeled PF-06865571 and IV administration of [14C]PF-06865571.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male participants, 18 to 60 years of age, inclusive, at the time of signing the informed consent document.
- •Male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac tests.
- •Participants who are nonsmoking for at least 3 months at the time of signing the informed consent document.
- •BMI of 17.5 to 30.4 kg/m2, inclusive; and a total body weight >50 kg (110 lb).
排除标准
- •Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
- •History of irregular bowel movements including irritable bowel syndrome or frequent episodes of diarrhea or constipation, defined by less than 1 bowel movement on average per 2 days, or lactose intolerance.
- •History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg,or HCVAb. Hepatitis B vaccination is allowed.
- •History of SARS-CoV-2 PCR or antibody (eg, IgG, IgM, etc) positive result would necessitate accompanying history of asymptomatic state for at least 6 months prior to screening.
- •Use of prescription or nonprescription drugs.
- •Previous administration with an unapproved drug within 60 days preceding the first dose of study intervention used in this study.
- •A positive urine drug test.
- •A positive urine cotinine test.
- •A positive COVID-19 (SARS-CoV-2) PCR test.
- •Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
研究组 & 干预措施
Study arm
One arm of healthy male participants administered a single oral dose of [14C]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of [14C]PF-06865571 three hours later.
干预措施: Oral [14C]PF-06865571 (Drug)
Study arm
One arm of healthy male participants administered a single oral dose of [14C]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of [14C]PF-06865571 three hours later.
干预措施: Oral PF-06865571 (Drug)
Study arm
One arm of healthy male participants administered a single oral dose of [14C]PF-06865571; followed by a single dose of unlabeled PF-06865571, and IV administration of [14C]PF-06865571 three hours later.
干预措施: IV [14C]PF-06865571 (Drug)
结局指标
主要结局
Total Recovery of Radioactivity in Urine as Percentage of Total Radioactive Dose of PF-06865571 Administered
时间窗: Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
The total recovery of radioactivity in urine was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in urine in Period 1 and Period 2 were reported.
Total Recovery of Radioactivity in Feces as Percentage of Total Radioactive Dose of PF-06865571 Administered
时间窗: Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
The total recovery of radioactivity in feces was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in feces in Period 1 and Period 2 were reported.
Total Recovery of Radioactivity in Total Excreta (Urine + Feces) as Percentage of Total Radioactive Dose of PF-06865571 Administered
时间窗: Period 1: Day -1 to maximum Day 21; Period 2: Day 1 to maximum Day 3
The total recovery of radioactivity in the combination of urine and feces was listed and summarized using descriptive statistics. In this outcome measure, the percentages of dose excreted in total excreta (urine + feces) in Period 1 and Period 2 were reported.
Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Plasma in Period 1
时间窗: Period 1: 0, 0.5, 3, 6, 12, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
Plasma samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in plasma, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-06865571 in plasma based on \[14C\] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Urine in Period 1
时间窗: Period 1: Day -1 to maximum Day 21
Urine samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in urine, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in urine based on \[14C\] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Feces in Period 1
时间窗: Period 1: Day -1 to maximum Day 21
Fecal samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in feces, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-06865571 in feces based on \[14C\] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Plasma in Period 1
时间窗: Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6)
Plasma samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in plasma, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in plasma based on \[14C\] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Relative Abundance (Mean Value) of Metabolites of Radiolabeled PF-06865571 in Urine in Period 1
时间窗: Period 1: Day -1 to maximum Day 21
Urine samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in urine, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of the metabolites of \[14C\]PF-06865571 in urine based on \[14C\] quantitation was reported. The metabolites included 487, 391, 412, 556, M6 (PF-07822633), M7 (PF-07911964), 584, M1 (PF-06878236), 426, M4 (PF-06887477), 600, M5 (PF-06885984) and M2 (PF-06868609). The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
Relative Abundance (Mean Value) of Radiolabeled PF-06865571 in Feces in Period 1
时间窗: Period 1: Day -1 to maximum Day 21
Fecal samples were analyzed for radiolabeled PF-06865571 and its metabolites. \[14C\]PF-06865571 and the major metabolites in feces, after oral administration of 300 mg \[14C\]PF-06865571 were identified. In this outcome measure, relative abundance of radiolabeled PF-06865571 in feces based on \[14C\] quantitation was reported. The measure type was the mean value based on pooled sampling, which means blood samples from the 6 participants were pooled together and then analyzed as 1 sample, thus the confidence interval could not be calculated. Therefore, "Number" is selected as the Measure Type.
次要结局
- Maximum Plasma Concentration (Cmax) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- Area Under the Plasma Concentration-time Profile From Time Zero to Time of The Last Quantifiable Concentration (AUClast) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- AUClast of Intravenous (IV) Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Tmax of IV Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- AUCinf of Oral PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- t1/2 of Oral PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- AUCinf of IV Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Systemic Clearance (CL) of IV Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Steady State Volume of Distribution (Vss) of IV Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Dose-Normalized AUCinf (AUCinf[dn]) of Oral Unlabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- AUCinf(dn) of IV Microtracer of Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Absolute Oral Bioavailability (F) of Oral Unlabeled and IV Radiolabeled PF-06865571 for Plasma AUCinf(dn) in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Cmax of IV Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Percentage of Total 14C in Urine Following Oral Administration (%14C_Urine_PO) of Radiolabeled PF-06865571 in Period 1(Period 1: up to 48 hours post-dose (Day 1 to Day 3))
- Percentage of Total 14C in Urine Following IV Microtracer Administration (%14C_Urine_IV) of Radiolabeled PF-06865571 in Period 2(Period 2: up to 48 hours post-dose (Day 1 to Day 3))
- Time for Cmax (Tmax) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- Terminal Elimination Half-life (t1/2) of Total Radioactivity of [14C]PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- AUClast of Oral PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- Tmax of Oral PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- Cmax of Oral PF-06865571 in Plasma in Period 1(Period 1: 0, 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 and 120 hours post-dose (Day 1 to Day 6))
- t1/2 of IV Radiolabeled PF-06865571 in Plasma in Period 2(Period 2: -3, 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 3, 6, 9, 13, 21, 33 and 45 hours post-dose (Day 1 to Day 3))
- Fraction Absorbed (Fa) for Percentage of Excretion of Total 14C in Urine for Oral and IV Radiolabeled PF-06865571(Period 1 and Period 2: up to 48 hours post-dose (Day 1 to Day 3))