Healthy
Conditions
Keywords
SAD, Healthy
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).
Interventions
DRUGPF-07304814
Participants will receive PF-07304814
DRUGPlacebo
Participants will recieve placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 (dn) of PF-07304814 (prodrug) and PF 00835231 (active moiety) | 0-48 hours post the start of dosing | Dose normalized AUCinf |
| Plasma Css (dn) of PF-07304814 (prodrug) and PF 00835231 (active moiety) | 0-48 hours post the start of dosing | Dose normalized Css |
| Plasma t1/2 of PF-07304814 (prodrug) and PF 00835231 (active moiety) | 0-48 hours post the start of dosing | Terminal half life |
| 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. |
| 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 | Amount of unchanged drug excreted in urine over collection interval |
| 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 CL of PF-07304814 (prodrug) | 0-48 hours post the start of dosing | Clearance |
| Plasma Cmax of PF-07304814 (prodrug) and PF 00835231 (active moiety) | 0-48 hours post the start of dosing | Maximum plasma concentration |
| 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 Css of PF-07304814 (prodrug) and PF 00835231 (active moiety) | 0-48 hours post the start of dosing | Plasma steady state concertation |
Countries
United States
Outcome results
None listed