NCT01835197已完成1 期
A Phase 1, Within Cohort, Randomized, Double Blind, Third-Party Open, Placebo-Controlled, Single- And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-04965842 In Healthy Western and Japanese Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations
研究概览
简要总结
This single- and multiple-ascending dose study is the first evaluation of PF-04965842, a Janus kinase1 (JAK1) inhibitor, in humans. The goal is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy Western and Japanese subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive.
- •Females must be of non-child bearing potential and either at least 1 year post menopausal (FSH ≥40 IU/L), or have documented hysterectomy (with or without bilateral oophrectomy) at least 6 months prior to study day
- •Subjects willing to defer receiving prophylactic immunizations (e.g. influenza or pneumococcal vaccines) during the study.
- •Absolute lymphocyte count must be greater than or equal to the lower limit of the laboratory reference range.
- •Subjects enrolled in Cohort 8 must have four Japanese grandparents born in Japan.
排除标准
- •Evidence or history of clinically significant hematological, renal, , pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- •History of hepatitis or positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBc Ab) or hepatitis C antibodies (HCV).
- •Clinically significant abnormality on chest X-ray performed at screening or within 3 months of screening date; or history of tuberculosis or active or latent or inadequately treated infection.
研究组 & 干预措施
SAD Cohorts 1-8 Experimental Arm
Experimental
干预措施: PF-04965842 (Drug)
SAD Cohorts 1-8 Placebo Arm
Placebo Comparator
干预措施: Placebo (Drug)
MAD Cohorts 3 through 5 Experimental Arm
Experimental
干预措施: PF-04965842 (Drug)
MAD Cohorts 3 through 5 Placebo Arm
Placebo Comparator
干预措施: Placebo (Drug)
MAD Cohorts 6 and 7 Experimental Arm
Experimental
干预措施: PF-04965842 (Drug)
MAD Cohorts 6 and 7 Placebo Arm
Placebo Comparator
干预措施: Placebo (Drug)
MAD Cohort 8 Experimental Arm
Experimental
干预措施: PF-04965842 (Drug)
MAD Cohort 8 Placebo Arm
Placebo Comparator
干预措施: Placebo (Drug)
MAD Cohort 9 Experimental Arm
Experimental
干预措施: PF-04965842 (Drug)
MAD Cohort 9 Placebo Arm
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Changes from baseline vital signs (blood pressure, pulse rate, oral temperature and respiration rate) and physical examinations
时间窗: 6 weeks
Changes from baseline in 12 lead ECG parameters
时间窗: 6 weeks
Quantitative changes in ECG intervals
Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events
时间窗: 6 weeks
Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology (with white blood cell count differentials, platelets, PT and aPTT), chemistry, fasting glucose, urinalysis
时间窗: 6 weeks
Change from baseline in immunoglobulin levels
时间窗: 6 weeks
Quantitative IgG, IgA, IgM, and IgE levels
24-hour urine creatinine clearance (Single Ascending Dose Period)
时间窗: Baseline, Day 1
24-hour urine creatinine clearance (Multiple Ascending Dose Period)
时间窗: Baseline, Day 1
次要结局
- Complement Level: C3(6 weeks)
- Complement Level: C4(6 weeks)
- Complement Level: C3A(6 weeks)
- Complement Level: Bb(6 weeks)
- Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Infinity (AUCinf(dn))(8 days)
- Multiple Ascending Dose: Accumulation Ratio based on Cmax (Rac(Cmax))(6 weeks)
- Urinary Pharmacokinetics; for twice-a-day dosing, amount of PF-0496842 excreted unchanged in 12 hours (AE12)(6 weeks)
- Urinary Pharmacokinetics; for twice-a-day dosing, percent of PF-0496842 excreted unchanged in 12 hours (AE12%)(6 weeks)
- Multiple Ascending Dose: Apparent Volume of Distribution at Steady State (Vz/F)(6 weeks)
- Multiple Ascending Dose: Apparent Total Body Clearance (CL/F)(6 weeks)
- Urinary Pharmacokinetics; for once-a-day dosing, amount of PF-0496842 excreted unchanged in 24 hours (AE24)(6 weeks)
- Urinary Pharmacokinetics; for once-a-day dosing, percent of PF-0496842 excreted unchanged in 24 hours (AE24%)(6 weeks)
- Renal Clearance (CLr)(6 weeks)
- High-Sensitivity C-Reactive Protein (hsCRP)(6 weeks)
- Neutrophil counts(6 weeks)
- Reticulocyte counts(6 weeks)
- Complement Level: CH50(6 weeks)
- Single Ascending Dose: Apparent Total Body Clearance (CL/F)(8 days)
- Multiple Ascending Dose: Maximum Observed Plasma Concentration (Cmax)(6 weeks)
- Multiple Ascending Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax)(6 weeks)
- Multiple Ascending Dose: Dose-normalized Maximum Observed Plasma Concentration (Cmax(dn))(6 weeks)
- Multiple Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau(dn))(6 weeks)
- Multiple Ascending Dose: Accumulation Ratio based on AUC predicted (Rss)(6 weeks)
- Multiple Ascending Dose: Accumulation Ration based on AUC observed (Rac)(6 weeks)
- Multiple Ascending Dose: Plasma Decay Half-Life (t1/2)(6 weeks)
- Multiple Ascending Dose: Peak to Trough Fluctuation (PTF)(6 weeks)
- Single Ascending Dose: Dose-normalized Area Under the Curve to the end of the dosing period (AUCtau(dn))(8 days)
- Single Ascending Dose: Area Under the Curve From Time Zero to Infinity (AUCinf)(8 days)
- Single Ascending Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(8 days)
- Single Ascending Dose: Dose-normalized Maximum Observed Plasma Concentration (Cmax(dn))(8 days)
- Single Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau)(8 days)
- Single Ascending Dose: Dose-normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn))(8 days)
- Single Ascending Dose: Plasma Decay Half-Life (t1/2)(8 days)
- Multiple Ascending Dose: Area Under the Curve to the end of the dosing period (AUCtau)(6 weeks)
- Single Ascending Dose: Apparent Volume of Distribution (Vz/F)(8 days)
- Single Ascending Dose: Maximum Observed Plasma Concentration (Cmax)(8 days)
研究者
研究点 (1)
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