A First-in-human Study of Single Doses of PF-07328948 Which is Given to Healthy Adult Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-07328948; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants will receive up to 4 dose levels of PF-07328948 single dose and up to 2 single doses of matching placebo. Doses will be administered as oral suspensions and each dose level is to be determined.	Drug: PF-07328948; investigational drug administered orally; Drug: Placebo; Placebo matching active drug administered orally
Experimental: Cohort 2; Participants will receive up to 4 dose levels of PF-07328948 single dose and up to 2 single doses of matching placebo. Doses will be administered as oral suspensions and each dose level is to be determined.	Drug: PF-07328948; investigational drug administered orally; Drug: Placebo; Placebo matching active drug administered orally
Experimental: Cohort 3; Participants will receive up to 4 dose levels of PF-07328948 single dose and up to 2 single doses of matching placebo. Doses will be administered as oral suspensions and each dose level is to be determined.	Drug: PF-07328948; investigational drug administered orally; Drug: Placebo; Placebo matching active drug administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An adverse event is considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were flagged as TEAEs. The algorithm did not consider any events that started prior to the first dose date. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality	Pre-defined categorical criteria for laboratory abnormalities included: lymphocytes/Leukocytes <0.8 x lower limit of normal (LLN) or >1.2 x upper limit of normal (ULN); Neutrophils <0.8 x LLN; Neutrophils/Leukocytes <0.8 x LLN; Eosinophils/Leukocytes >1.2 x ULN; Monocytes/Leukocytes >1.2 x ULN; Bilirubin >1.5 x ULN; Indirect Bilirubin >1.5 x ULN; Ketones (Scalar) ≥1; URINE Hemoglobin (Scalar) ≥1; URINE Bilirubin (Scalar) ≥1; Leukocyte Esterase (Scalar) ≥1; and Bacteria (/HPF) >20.	Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria	Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (≥) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP ≥ 20 mmHg.	Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria	ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) ≥300 millisecond (msec), b) ≥25% increase when baseline is > 200 msec or ≥50% increase when baseline is less than or equal to (≤) 200 msec. 2. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) ≥140 msec, b) ≥50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and ≤480 msec, b) >480 msec and ≤500 msec, c) >500 msec, d) >30 msec and ≤60 msec increase from baseline, e) >60 msec increase from baseline	Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate)	Maximum increase from baseline in ECG Mean Heart Rate was reported.	Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval)	Maximum increase from baseline in PR Interval, QRS Duration, and QTcF Interval was reported.	Day 1-8 per period, along with the 28-35 day post-final dose follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration Observed in Plasma (Cmax)	Maximum observed plasma PF-07328948 concentration. Observed directly from data.	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)
Time to Achieve Cmax (Tmax)	Observed directly from data as time of first occurrence.	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)
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration. It was determined by using linear/Log trapezoidal method.	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)
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf)	Area under the plasma concentration-time curve from time 0 extrapolated to infinite time. AUCinf = AUClast + (Clast*/kel), where Clast* is the predicted plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis, and Kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, AUClast = Area under the plasma concentration time-curve from zero to the last measured concentration.	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)
Terminal Half-Life (t1/2) of PF-07328948	Terminal elimination half-life. t1/2 = Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log linear decline will be used in the regression.	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)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): May 3, 2023
• Study Completion (Actual): May 3, 2023

Study Registration Dates

• First Submitted: October 13, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: C4921001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No