Clinical trial NCT06137742: A Study to Learn About the Study Medicine Called PF-07868489 in Healthy Adult People and in People With Pulmonary Arterial Hypertension
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: pulmonary
high lung artery pressure
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A is a sequential study. Part B is a parallel group study.
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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 32 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 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 1.
* 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.

Primary outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 113.
measure: Number of Participants With Change From Baseline in Laboratory Tests Results
timeFrame: Baseline up to Day 113
measure: Number of Participants With Vital Sign Abnormalities
timeFrame: Baseline up to Day 113
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to Day 113
measure: Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 253
measure: Number of Participants With Change From Baseline in Laboratory Tests Results
timeFrame: Baseline up to Day 253
measure: Number of Participants With Vital Sign Abnormalities
timeFrame: Baseline up to Day 253
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to Day 253
measure: Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Week24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
timeFrame: Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
timeFrame: Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre dose, 8, 12, 24, 48,72,96,168,336 hours post dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: 4-7 days
measure: Incidence of Anti-Drug Antibody (ADA)
timeFrame: Baseline and up to week 16
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Day 113
measure: Minimum Observed Plasma Trough Concentration (Cmin)
timeFrame: Day 253
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Day 253
measure: Incidence of Anti-Drug Antibody (ADA)
timeFrame: Baseline and up to Day 253
measure: PVR
timeFrame: Baseline, Week 24
measure: 6MWD
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kawasaki
country: Japan
facility: St. Marianna University Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Kanagawa
country: Japan
facility: Yokohama City University Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Namdong-gu
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon-gwangyeoksi [incheon]
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [seoul]
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: London, CITY OF
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: