STUDY OF PF-07321332 IN HEALTHY PARTICIPANTS

NCT04756531 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C46710012020-006073-30
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 2

Brief Summary

A Phase 1, double blind, sponsor open, single and multiple ascending dose study to evaluate safety, tolerability and pharmacokinetics of PF-07321332 in healthy participants.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (15)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD

  An Adverse Event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. A 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.

  Post the single dose of study intervention till up to 36 days

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD

  Vital signs (temperature, respiratory rate, pulse rate \[PR\], systolic blood pressure \[SBP\], and diastolic blood pressure \[DBP\]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 millimeters of mercury (mm Hg), increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 beats per minute (bpm) or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of study intervention and had at least 1 assessment undertaken post treatment.

  Baseline up to Day 2 of the final period

• Number of Participants With Laboratory Abnormalities in PART-1: SAD

  Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, Severe Acute Respiratory Syndrome Coronavirus 2 \[SARS-CoV-2\] reverse transcription polymerase chain reaction \[RT-PCR\], estimated glomerular filtration rate \[eGFR\], pregnancy test \[beta human chorionic gonadotropin \[b-hCG\]\], activated partial thromboplastin time \[aPTT\], prothrombin time \[PT\] - international normalized ratio \[INR\], fibrinogen, thyroid stimulating hormone \[TSH\], Free thyroxine \[T4\]). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.

  Baseline up to Day 4 of the final period

• Number of Participants With TEAEs in PART-2:MAD

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.

  Post first dose till up to 45 days after last dose of study intervention

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD

  Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 mm Hg, increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 bpm or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion.

  Baseline up to Day 12

• Number of Participants With Laboratory Abnormalities in PART-2: MAD

  Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.

  Baseline up to Day 12

• Area Under the Plasma Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Tablet Formulation and Suspension in PART-3: rBA/FE

  AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.

  Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose

• Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Tablet Formulation and Suspension in PART-3: rBA/FE

  AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet\] /Reference \[suspension\]) and 90% CI for the ratio.

  Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose

• Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE

  Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet\] /Reference \[suspension\]) and 90% CI for the ratio.

  Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose

• Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME

  Total recovery of drug-related material excreted in urine, expressed as a percent of total dose administered, measured by fluorine-19 nuclear magnetic resonance (19F-NMR).

  Day 1 to Day 11

• Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME

  Total recovery of drug-related material excreted in feces, expressed as a percent of total dose administered, measured by 19F-NMR.

  Day 1 to Day 11

• Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME

  Total recovery of drug-related material excreted in urine and feces combined, expressed as a percent of total dose administered, measured by 19F-NMR.

  Day 1 to Day 11

• Number of Participants With TEAEs in PART-5: SE

  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.

  Post first dose till up to 36 days after last dose of study intervention

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE

  Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 mm Hg, increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 bpm or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion.

  Baseline up to Day 5 of the final period

• Number of Participants With Laboratory Abnormalities in PART-5: SE

  Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.

  Baseline up to Day 5 of the final period

Secondary Outcomes (52)

• Cmax of Plasma PF-07321332 in PART-1: SAD

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose

• Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose

• AUClast of Plasma PF-07321332 in PART-1: SAD

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose

• AUCinf of PF-07321332 in PART-1: SAD

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose

• Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose

Study Arms (6)

PF-07321332 Dose 1

EXPERIMENTAL

Dose level 1 of PF-07321332

Drug: PF-07321332 Dose 1

PF-07321332 Dose 2

EXPERIMENTAL

Dose level 2 of PF-07321332

Drug: PF-07321332 Dose 2

PF-07321332 Dose 3

EXPERIMENTAL

Dose level 3 of PF-07321332

Drug: PF-07321332 Dose 3

PF-07321332 Dose 4

EXPERIMENTAL

Dose level 4 of PF-07321332

Drug: PF-07321332 Dose 4

PF-07321332 Dose 5

EXPERIMENTAL

Dose level 5 of PF-07321332

Drug: PF-07321332 Dose 5

PF-07321332 Dose 4 (Fed)

EXPERIMENTAL

Dose level 4 of PF-07321332 with high fat meal

Drug: PF-07321332 Dose 4 or Placebo (Fed)

Interventions

PF-07321332 Dose 1 DRUG

PF-07321332 Dose 1 or Placebo

PF-07321332 Dose 1

PF-07321332 Dose 2 DRUG

PF-07321332 Dose 2 or Placebo

PF-07321332 Dose 2

PF-07321332 Dose 3 DRUG

PF-07321332 Dose 3 or Placebo

PF-07321332 Dose 3

PF-07321332 Dose 4 DRUG

PF-07321332 Dose 4 or Placebo

PF-07321332 Dose 4

PF-07321332 Dose 5 DRUG

PF-07321332 Dose 5 or Placebo

PF-07321332 Dose 5

PF-07321332 Dose 4 or Placebo (Fed) DRUG

PF-07321332 Dose 5 or Placebo with high fat meal

PF-07321332 Dose 4 (Fed)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female subjects between ages of 18-60 years. Male only in part-4.
• Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight \>50kg (110lbs)
• Japanese subjects who have four Japanese biologic grandparents born in Japan

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, intestinal resection).
• Positive test result for SARS-CoV-2 infection at the time of screening or Day-1.
• Have received COVID-19 vaccine within 7 days before screening or have received only one of the 2 required doses of COVID-19 vaccine
• Use of tobacco or nicotine containing products in excess of the equivalents of 5 cigarettes per day or 2 chews of tobacco per day

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Publications (1)

• Singh RSP, Toussi SS, Hackman F, Chan PL, Rao R, Allen R, Van Eyck L, Pawlak S, Kadar EP, Clark F, Shi H, Anderson AS, Binks M, Menon S, Nucci G, Bergman A. Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir. Clin Pharmacol Ther. 2022 Jul;112(1):101-111. doi: 10.1002/cpt.2603. Epub 2022 May 4.

  PMID: 35388471 DERIVED

Related Links

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

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 16, 2021
• Study Start: February 11, 2021
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); BE (1)