Clinical trial NCT05434091: A First-In-Human Study of the Study Medicine, Called PF-07291177, in Healthy Adult Participants
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO CONTROLLED, 4-PERIOD, CROSSOVER, FIRST-IN-HUMAN STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SINGLE ASCENDING ORAL DOSES OF PF 07291177 ADMINISTERED TO HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Healthy Participants
Keywords: PF-07291177
Single ascending dose
Transthyretin
Retinol binding protein
Healthy participants
Safety
Tolerability
Pharmacokinetics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-06-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to learn about the safety, tolerability (the extent to which side effects can be tolerated), and plasma pharmacokinetics (PK) (PK helps us understand how the drug is changed and eliminated from body after you take it) of PF-07291177 after administration of escalating, single, doses by mouth.

Detailed description: The purpose of the study is to learn about the safety, the extent to which side effects can be tolerated, and plasma pharmacokinetics (PK) (PK helps us understand how the drug is changed and eliminated from your body after you take it) of PF-07291177 after administration of escalating, single, doses by mouth.

Each participant in this study is planned to undergo up to 4 treatment periods receiving up to 3 doses of PF 07291177 and 1 dose of placebo.

Precautionary sentinel dosing will be used in this study. Two participants (1 receiving PF 07291177 and 1 receiving placebo) within a period will be dosed initially before the remaining participants of that period are dosed.

This study is seeking :

* Female participants of non-child bearing potential and males must be 18 to 60 years of age, inclusive, at the time of signing the ICD
* Female participants of non-child bearing potential and males who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

Eligibility criteria: This study is seeking participants who are:

1. Female participants of non-child bearing potential and males must be 18 to 60 years of age, inclusive, at the time of signing the inform consent documents.
2. Female participants of non-child bearing potential and males who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

This study is not seeking participants who have:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to coronavirus disease 2019 (COVID-19) pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
3. 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/strong cytochrome P450 3A inducers or time-dependent inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
4. Received a COVID-19 vaccine within 7 days before screening or any visit in which a safety lab is planned, or who are to be vaccinated with a COVID-19 vaccine within 7 days before screening or any visit in which a safety lab is planned.
5. 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 study intervention used in this study (whichever is longer).
6. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
7. Renal impairment as defined by an estimated glomerular filtration rate (eGFR) \<75 mL/min/1.73m2
8. Standard 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, complete left bundle branch block (LBBB), signs of an acute or indeterminate age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is \>450 ms, this interval should be rate corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting.
9. ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

   * Aspartate aminotransferase or Alanine aminotransferase level ≥1.25× upper limit of normal (ULN);
   * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
10. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
11. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Baseline up to 35 days after last dose of study intervention (approximately 11 weeks)
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Baseline up to 10 days after last dose of study intervention (approximately 5 weeks)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to 10 days after last dose of study intervention (approximately 5 weeks)
measure: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
timeFrame: Baseline up to 10 days after last dose of study intervention (approximately 5 weeks)
measure: Number of Participants With Clinically-Significant Change From Baseline in Neurological Examination Findings
timeFrame: Baseline up to 10 days after last dose of study intervention (approximately 5 weeks)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-07291177
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 post-dose in each period
measure: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-07291177
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 post-dose in each period
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07291177
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 post-dose in each period
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07291177
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 post-dose in each period
measure: Plasma Half-Life (t1/2) of PF-07291177
timeFrame: Hour 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 post-dose in each period
Other outcomes:
Locations:
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: