Clinical trial NCT04627532: Single Ascending Dose Study of Intravenous Infusion of PF 07304814 in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: SAD, Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-11-13
Enrollment: 16
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 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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment emergent treatment-related adverse event(s)
timeFrame: Dosing through follow-up call (28-32 days after last dose of investigational product)
measure: Number of participants with laboratory test findings of potential clinical importance
timeFrame: Dosing through Day 5 of last period
measure: Number of participants with vital signs findings of potential clinical importance
timeFrame: Dosing through Day 5 of last period
measure: Number of participants with ECG findings of potential clinical importance
timeFrame: Dosing through Day 5 of last period
Secondary outcomes:
measure: Plasma Cmax of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma C24 of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma Css of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma AUClast of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma AUCinf of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma AUCinf (dn) of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma Css (dn) of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma t1/2 of PF-07304814 (prodrug) and PF 00835231 (active moiety)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma CL of PF-07304814 (prodrug)
timeFrame: 0-48 hours post the start of dosing
measure: Plasma Vdss of PF-07304814 (prodrug)
timeFrame: 0-48 hours post the start of dosing
measure: PF-00835231 urinary PK: Ae
timeFrame: 0-36 hours post the start of dosing
measure: PF-00835231 urinary PK: Ae%
timeFrame: 0-36 hours post the start of dosing
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: