Single Ascending Dose Study of Intravenous Infusion of PF 07304814 in Healthy Adult Participants

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO CONTROLLED, DOSE ESCALATION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE ASCENDING DOSES OF PF-07304814 ADMINISTERED AS A 24-H IV INFUSION IN HEALTHY ADULT PARTICIPANTS

The current study is the second clinical administration with PF-07304814, the phosphate prodrug of the active moiety PF-00835231, and the first in healthy adult participants. It is to evaluate safety, tolerability and PK of single escalating doses of PF 07304814 given as a 24-h IV infusion.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-07304814; Drug: Placebo

Detailed Description

The current study is the second clinical administration with PF-07304814, the phosphate prodrug of the active moiety PF-00835231, and the first in healthy adult participants. It is to evaluate safety, tolerability and PK of single escalating doses of PF 07304814 given as a 24-h IV infusion. This is a randomized, double-blind, sponsor-open, placebo-controlled trial. There will be 2 cohorts with a total of approximately 16 participants planned (approximately 8 participants in each cohort).

• Study Type: Interventional
• Enrollment (Actual): 16
• 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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female participants must be 18 to 60 years of age. All fertile participants must agree to use a highly effective method of contraception.
• Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

• Capable of giving signed informed consent.

Exclusion Criteria

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation.
• History of venous thromboembolic event, including deep venous thrombosis or pulmonary embolism.
• 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
• Previous administration with an investigational drug 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).
• A positive urine drug test at screening or admission and confirmed by repeat test, if deemed necessary.
• Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
• Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment; PF-07304814 assignment	Drug: PF-07304814; Participants will receive PF-07304814
PLACEBO_COMPARATOR: Placebo; Placebo assigned	Drug: Placebo; Participants will recieve placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment emergent treatment-related adverse event(s)	Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs	Dosing through follow-up call (28-32 days after last dose of investigational product)
Number of participants with laboratory test findings of potential clinical importance	Percentage of subjects with laboratory abnormalities	Dosing through Day 5 of last period
Number of participants with vital signs findings of potential clinical importance	blood pressure, pulse rate, temperature, respiration rate	Dosing through Day 5 of last period
Number of participants with ECG findings of potential clinical importance	Number of subjects with change from baseline in electrocardiogram (ECG) parameters	Dosing through Day 5 of last period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Cmax of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Maximum plasma concentration	0-48 hours post the start of dosing
Plasma C24 of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Plasma concentration at the end of infusion (24 hours post the start of infusion)	0-48 hours post the start of dosing
Plasma Css of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Plasma steady state concertation	0-48 hours post the start of dosing
Plasma AUClast of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Area under the serum concentration time profile from time zero to the time of the last quantifiable concentration.	0-48 hours post the start of dosing
Plasma AUCinf of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Area under the serum concentration time profile from time zero to infinity.	0-48 hours post the start of dosing
Plasma AUCinf (dn) of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Dose normalized AUCinf	0-48 hours post the start of dosing
Plasma Css (dn) of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Dose normalized Css	0-48 hours post the start of dosing
Plasma t1/2 of PF-07304814 (prodrug) and PF 00835231 (active moiety)	Terminal half life	0-48 hours post the start of dosing
Plasma CL of PF-07304814 (prodrug)	Clearance	0-48 hours post the start of dosing
Plasma Vdss of PF-07304814 (prodrug)	Volume of distribution at steady state	0-48 hours post the start of dosing
PF-00835231 urinary PK: Ae	Amount of unchanged drug excreted in urine over collection interval	0-36 hours post the start of dosing
PF-00835231 urinary PK: Ae%	Percent of dose excreted in urine as unchanged drug over the collection interval.	0-36 hours post the start of dosing

Collaborators and Investigators

• Sponsor: 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 23, 2020
• Primary Completion (ACTUAL): December 17, 2020
• Study Completion (ACTUAL): December 17, 2020

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: November 8, 2020
• First Posted (ACTUAL): November 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 6, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: SAD, Healthy
• Other Study ID Numbers: C4611007

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