A PHASE 1 / 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SINGLE ESCALATING DOSES OF PF-07868489 IN HEALTHY ADULT PARTICIPANTS AND, ADDITIONALLY, CLINICAL ACTIVITY OF REPEAT DOSES IN PARTICIPANTS WITH PULMONARY ARTERIAL HYPERTENSION
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 97
- 试验地点
- 105
- 主要终点
- Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of the study is to learn how the study medicine called PF-07868489 is tolerated and acts in healthy adult people and people with pulmonary arterial hypertension (PAH).
Part A:
An investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose study to assess the safety, tolerability, and pharmacokinetics (PK) of PF-07868489 in healthy adult participants.
Part B:
A 24-week, randomized, double blind, placebo-controlled study to assess the safety, tolerability, PK, and pharmacodynamics (PD) of PF-07868489 in adult participants with PAH.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part A is an investigator- and participant-blind, sponsor-open, placebo-controlled, single ascending dose.
Part B is a 24-week, randomized, double blind, placebo-controlled study.
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
- •overtly healthy
- •Body mass index (BMI) of 16 to 32 kg/m2; and a total body weight >50 kg.
排除标准
- •clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, infections or allergic disease.
- •smoking more than 10 cigarettes (or equivalent) per day or smoking history ≥10 pack-years.
- •Key Inclusion Criteria Part B:
- •diagnosis of pulmonary arterial hypertension (PAH)
- •stable dose of standard of care PAH vasodilators
- •BMI 16 to 40 kg/m2; and a total body weight >45 kg.
- •6MWD ≥ 150 and ≤
- •Pre-randomization RHC documenting a minimum of PVR ≥ 400 dyn ∙sec/cm
- •Key Exclusion Criteria Part B:
- •Any medical or psychiatric condition or laboratory abnormality.
- •Stopped receiving pulmonary hypertension chronic general supportive therapy 90 days prior to Day
- •Pulmonary capillary wedge pressure > 15 mmHg on right heart catheterization (RHC) conducted during Screening.
- •History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in investigational product.
- •Major surgery within 8 weeks prior to randomization.
- •Participants who smoke more than 10 cigarettes (or equivalent) per day or has a smoking history ≥10 pack-years.
研究组 & 干预措施
Placebo
single subcutaneous injection (Part A); 6 subcutaneous injections at regular intervals (Part B)
干预措施: Placebo for PF-07868489 (Drug)
PF-07868489
single subcutaneous injection (Part A); 6 subcutaneous injections at regular intervals (Part B)
干预措施: PF-07868489 (Drug)
结局指标
主要结局
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to Day 253
Part B
Number of Participants With Change From Baseline in Laboratory Tests Results
时间窗: Baseline up to Day 253
Part B
Number of Participants With Vital Sign Abnormalities
时间窗: Baseline up to Day 253
Part B
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
时间窗: Baseline up to Day 253
Part B
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to Day 113.
Part A
Number of Participants With Change From Baseline in Laboratory Tests Results
时间窗: Baseline up to Day 113
Part A
Number of Participants With Vital Sign Abnormalities
时间窗: Baseline up to Day 113
Part A
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
时间窗: Baseline up to Day 113
Part A
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week24
时间窗: Baseline, Week 24
repeated doses
Number of Participants With Change From Baseline in Laboratory Tests Results
时间窗: Baseline up to Day 253
Part B
Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to Day 253
Part B
Number of Participants With Vital Sign Abnormalities
时间窗: Baseline up to Day 253
Part B
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
时间窗: Baseline up to Day 253
Part B
次要结局
- Maximum Observed Plasma Concentration (Cmax)(Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(4-7 days)
- Incidence of Anti-Drug Antibody (ADA)(Baseline and up to Day 253)
- Plasma Decay Half-Life (t1/2)(Day 253)
- Minimum Observed Plasma Trough Concentration (Cmin)(Day 253)
- 6MWD(Baseline, Week 24)
- Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast)(Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)(Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose)
- Incidence of Anti-Drug Antibody (ADA)(Baseline and up to week 16)
- Plasma Decay Half-Life (t1/2)(Day 113)
- Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast)(Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)(Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose)
- Maximum Observed Plasma Concentration (Cmax)(Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(4-7 days)
- Incidence of Anti-Drug Antibody (ADA)(Baseline and up to Day 253)
- Plasma Decay Half-Life (t1/2)(Day 253)
- Minimum Observed Plasma Trough Concentration (Cmin)(Day 253)
- Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Week24(Baseline, Week 24)
- 6MWD(Baseline, Week 24)