Pulmonary Arterial Hypertension
Conditions
Keywords
pulmonary, high lung artery pressure
Brief summary
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.
Interventions
DRUGPF-07868489
Experimental Treatment
DRUGPlacebo for PF-07868489
Placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
Part A is a sequential study. Part B is a parallel group study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria Part A: * overtly healthy * Body mass index (BMI) of 16 to 32 kg/m2; and a total body weight \>50 kg. Key
Exclusion criteria
Part A: * 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 ≤ 450. * Pre-randomization RHC documenting a minimum of PVR ≥ 400 dyn ∙sec/cm5. Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week24 | Baseline, Week 24 | repeated doses |
| Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters | Baseline up to Day 113 | Part A |
| Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to Day 113. | Part A |
| Number of Participants With Change From Baseline in Laboratory Tests Results | Baseline up to Day 113 | Part A |
| Number of Participants With Vital Sign Abnormalities | Baseline up to Day 113 | Part A |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Decay Half-Life (t1/2) | Day 113 | single dose |
| Minimum Observed Plasma Trough Concentration (Cmin) | Day 253 | repeat doses |
| 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 | single dose |
| 6MWD | Baseline, Week 24 | repeated doses |
| Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Week24 | Baseline, Week 24 | repeated doses |
| 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 | single dose |
| Maximum Observed Plasma Concentration (Cmax) | Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose | single dose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 4-7 days | single dose |
| Incidence of Anti-Drug Antibody (ADA) | Baseline and up to week 16 | single dose |
Countries
Australia, Belgium, China, Czechia, France, Germany, Italy, Japan, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed