Clinical trial NCT05654181: A First-in-human Study of Single Doses of PF-07328948 Which is Given to 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-07328948 ADMINISTERED TO HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 20
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: This study is the first clinical study with PF-07328948. The safety, tolerability, and plasma pharmacokinetics and pharmacodynamics of PF-07328948 after administration of escalating, single, oral doses will be evaluated.


Eligibility criteria: Inclusion Criteria:

1. Female participants of non-childbearing potential and males must be 18 to 60 years of age, inclusive, at the time of signing the Informed Consent Document (ICD).
2. Female participants of non-childbearing 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.

Exclusion Criteria:

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).

   * Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
   * History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb, or HCVAb. Hepatitis B vaccination is allowed.
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 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.
4. Receipt of a COVID-19 vaccine within 7 days before screening or within 7 days before any visit in which a safety lab is planned. Vaccination with a COVID 19 vaccine that occurs greater than 7 days from either screening or any visit in which a safety lab is planned is permitted.
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 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 eGFR \<75 mL/min/1.73m2 calculated using CKD EPI SCr formulas.
8. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, complete LBBB, signs of an acute or indeterminate age myocardial infarction, STT 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. Participants with 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:

   * AST or ALT level ≥1.25× 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 Reporting Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
measure: Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality
timeFrame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
measure: Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria
timeFrame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria
timeFrame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
measure: Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate)
timeFrame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
measure: Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval)
timeFrame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Secondary outcomes:
measure: Maximum Concentration Observed in Plasma (Cmax)
timeFrame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
measure: Time to Achieve Cmax (Tmax)
timeFrame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast)
timeFrame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
timeFrame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
measure: Terminal Half-Life (t1/2) of PF-07328948
timeFrame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: