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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: PF-07304814

• Registration Number: NCT04627532
• Lead Sponsor: Pfizer

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-10-21
• Study Start: 2020-10-23
• Study First Submitted QC: 2020-11-08
• Study First Posted: 2020-11-13
• Status Verified: 2020-12
• Primary Completion: 2020-12-17
• Study Completion: 2020-12-17
• Last Update Submitted: 2021-01-04
• Last Update Posted: 2021-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo assigned
Treatment	PF-07304814	PF-07304814 assignment

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

New Haven Clinical Research Unit; 🇺🇸 New Haven, Connecticut, United States