Clinical trial NCT04756531: STUDY OF PF-07321332 IN HEALTHY PARTICIPANTS
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF 07321332 IN HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-02-16
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Detailed description: Combined 5-part study. Part-1: Single Ascending dose Part-2: Multiple Ascending Dose Part-3: Relative bioavailability and food effect Part-4: Metabolism and Excretion Part-5: Supra-therapeutic Exposure Part-1,2 and 5 are double blind, sponsor open and Part-3 and 4 are open label study.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD
timeFrame: Post the single dose of study intervention till up to 36 days
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD
timeFrame: Baseline up to Day 2 of the final period
measure: Number of Participants With Laboratory Abnormalities in PART-1: SAD
timeFrame: Baseline up to Day 4 of the final period
measure: Number of Participants With TEAEs in PART-2:MAD
timeFrame: Post first dose till up to 45 days after last dose of study intervention
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD
timeFrame: Baseline up to Day 12
measure: Number of Participants With Laboratory Abnormalities in PART-2: MAD
timeFrame: Baseline up to Day 12
measure: 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
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: 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
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME
timeFrame: Day 1 to Day 11
measure: Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME
timeFrame: Day 1 to Day 11
measure: Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME
timeFrame: Day 1 to Day 11
measure: Number of Participants With TEAEs in PART-5: SE
timeFrame: Post first dose till up to 36 days after last dose of study intervention
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE
timeFrame: Baseline up to Day 5 of the final period
measure: Number of Participants With Laboratory Abnormalities in PART-5: SE
timeFrame: Baseline up to Day 5 of the final period
Secondary outcomes:
measure: Cmax of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: AUClast of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: AUCinf of PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Apparent Volume of Distribution (Vz/F) in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Apparent Clearance (CL/F) in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
measure: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10
timeFrame: Pre-dose to 12 hours post-dose on Day 10
measure: Renal Clearance (CLr) in PART-2: MAD on Day 10
timeFrame: Pre-dose to 12 hours post-dose on Day 10
measure: AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Tmax of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: CL/F of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Vz/F of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: t1/2 of Plasma PF-07321332 in PART-3: rBA/FE
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
measure: Number of Participants With TEAEs in PART-3: rBA/FE
timeFrame: Post the single dose of study intervention till up to 36 days
measure: Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE
timeFrame: Baseline up to Day 3
measure: Cmax of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Tmax of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: AUClast of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: AUCinf of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: CL/F of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Vz/F of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: t1/2 of Plasma PF-07321332 in PART-4: ME
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
measure: Number of Participants With TEAEs in PART-4: ME
timeFrame: Post the single dose of study intervention till up to 36 days
measure: Number of Participants With Laboratory Abnormalities in PART-4: ME
timeFrame: Baseline up to Day 11
measure: Cmax of Plasma PF-07321332 in PART-5: SE
timeFrame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
measure: Tmax of Plasma PF-07321332 in PART-5: SE
timeFrame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
measure: AUClast of Plasma PF-07321332 in PART-5: SE
timeFrame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
measure: AUCinf of Plasma PF-07321332 in PART-5: SE
timeFrame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
measure: t1/2 of Plasma PF-07321332 in PART-5: SE
timeFrame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.