A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of PF-07899895 Administered as Immediate and Modified Release Formulations in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- AE observed after single or multiple doses
研究概览
简要总结
The purposes of the study are as follows:
- To understand how safe and tolerable are different amounts of study medicine (PF-07899895).
- To measure the amount of PF-07899895 in blood after the medicine is taken by mouth.
The study is seeking participants who:
- Are male or female of 18 to 65 years of age.
- Are in good health condition.
- Have not had viral infections (HIV, HBV, or HCV). HIV, human immunodeficiency virus. - HBV, human hepatitis B virus. HCV, human hepatitis C virus.
- Have tested negative for tuberculosis.
Participants will receive either PF-07899895 or placebo (dummy pill) by chance. In the first part of the study (Part A):
- each participant will receive a total of up to 5 doses of the medicine or placebo with at least 5 days between each dose.
- after each dose, participants will stay in study clinic for 3 to5 days.
In the second part of the study (Part B):
- each participant will need to take 10 days of dosing and will stay in the study clinic for clinical checks for 13 days.
In the third part of the study (Part C):
- In SD cohort, each participant will receive a total of up to 5 doses of the medicine or placebo with at least 7 days between each dose. After each dose, participants will stay in study clinic for 5 days.
- In MD cohorts, each participant will need to take 10 days of dosing and will stay in the study clinic for clinical checks for 13 days.
The planned duration of participation from screening to follow-up in:
- Part A of the study is up to 15 to 18 weeks.
- Part B of the study is up to 11 weeks.
- Part C of the study is up to 15 to 18 weeks. Participants will also have their blood collected by the study doctors for several times.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants, male or female, must be 18 to 65 years of age, inclusive, at the time of signing the ICD.
- •BMI of 16 to 32 kg/m2; and a total body weight>50 kg (110 lb).
- •Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs assessments, oral temperature, 12-lead ECGs, and laboratory tests.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
- •Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, bowel resection) or gastrointestinal (GI) transit time (eg, constipation).
- •History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb); positive or indeterminate QuantiFERON test for tuberculosis. Hepatitis B vaccination is allowed.
- •Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •History of undesired reactions to the sun (photosensitivity).
- •Recent exposure to live or attenuated vaccines within 28 days of the screening visit.
- •Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention, with the exception of moderate or strong cytochrome P450 3A (CYP3A) inducers or inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
- •Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of PF-07899895 used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
研究组 & 干预措施
PF-07899895
Participants will receive single or multiple ascending oral doses of PF-07899895.
干预措施: PF-07899895 (Drug)
Placebo
Participants will receive matching placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
AE observed after single or multiple doses
时间窗: Day 1 up to Day 28 (Part A)/Day 1 up to Day 38 (Part B)
number of participants experience AE or SAEs.
Laboratory abnormalities following single or multiple ascending doses
时间窗: Day 1 up to Day 28 (Part A)/Day 1 up to Day 38 (Part B)
number of participants with laboratory abnormalities
Vital sign changes following single or multiple ascending doses
时间窗: Day 1 up to Day 28 (Part A)/Day 1 up to Day 38 (Part B)
Number of participants with change from baseline in vital signs
ECG changes following single or multiple ascending doses
时间窗: Day 1 up to Day 28 (Part A)/Day 1 up to Day 38 (Part B)
Number of participants with change from baseline in electrocardiogram (ECG) parameters
Changes in physical examination after single or multiple ascending doses
时间窗: Day 1 up to Day 28 (Part A)/Day 1 up to Day 38 (Part B)
Number of participants with change from baseline in physical examinations (PE)
次要结局
- Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast)(Day 1 up to Day 3 (Part A))
- Dose normalized AUClast divided by dose (AUClast(dn))(Day 1 up to Day 3 (Part A))
- Maximum Observed Plasma Concentration (Cmax)(Day 1 (Part A)/Day 1 and Day 10 (Part B))
- Dose normalized Cmax divided by dose (Cmax(dn))(Day 1 (Part A)/Day 1 and Day 10 (Part B))
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Day 1 (Part A)/Day 1 and Day 10 (Part B))
- Area under the concentration time-profile from time 0 extrapolated to infinity (AUCinf)(Day 1 up to Day 3 (Part A))
- Dose normalized AUCinf divided by dose (AUCinf(dn))(Day 1 up to Day 3 (Part A))
- Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half (t½)(Day 1 up to Day 3 (Part A)/Day 10 up to Day 12 (Part B))
- Apparent clearance (CL/F)(Day 1 up to Day 3 (Part A)/Day 10 up to Day 12 (Part B))
- Apparent volume of distribution after oral dose is influenced by the fraction absorbed (Vz/F)(Day 1 up to Day 3 (Part A)/Day 10 up to Day 12 (Part B))
- Area under the concentration-time curve from time 0 to time tau, where tau=24 hrs (AUCtau)(Day 1 and Day 12 (Part B))
- Dose normalized AUCtau divided by dose (AUCtau(dn))(Day 1 and Day 12 (Part B))
- Observed accumulation ratio for Rac for AUC(Day 1 and Day 12 (Part B))
- Observed accumulation ratio for Cmax (Rac,Cmax)(Day 1 and Day 12 (Part B))