STUDY OF PF-07321332 IN HEALTHY PARTICIPANTS

• ClinicalTrials.gov Identifier: NCT04756531
• Recruitment Status: Completed
• First Posted: February 16, 2021
• Last Update Posted: September 13, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Participants	Drug: PF-07321332 Dose 1; Drug: PF-07321332 Dose 2; Drug: PF-07321332 Dose 3; Drug: PF-07321332 Dose 4; Drug: PF-07321332 Dose 5; Drug: PF-07321332 Dose 4 or Placebo (Fed)	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• 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
• Actual Study Start Date: February 11, 2021
• Actual Primary Completion Date: September 1, 2021
• Actual Study Completion Date: September 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: PF-07321332 Dose 1; Dose level 1 of PF-07321332	Drug: PF-07321332 Dose 1; PF-07321332 Dose 1 or Placebo
Experimental: PF-07321332 Dose 2; Dose level 2 of PF-07321332	Drug: PF-07321332 Dose 2; PF-07321332 Dose 2 or Placebo
Experimental: PF-07321332 Dose 3; Dose level 3 of PF-07321332	Drug: PF-07321332 Dose 3; PF-07321332 Dose 3 or Placebo
Experimental: PF-07321332 Dose 4; Dose level 4 of PF-07321332	Drug: PF-07321332 Dose 4; PF-07321332 Dose 4 or Placebo
Experimental: PF-07321332 Dose 5; Dose level 5 of PF-07321332	Drug: PF-07321332 Dose 5; PF-07321332 Dose 5 or Placebo
Experimental: PF-07321332 Dose 4 (Fed); Dose level 4 of PF-07321332 with high fat meal	Drug: PF-07321332 Dose 4 or Placebo (Fed); PF-07321332 Dose 5 or Placebo with high fat meal

Outcome Measures

Primary Outcome Measures :

1. Number of participants with Treatment Emergent Adverse Events (TEAEs) in single ascending dose (SAD) [ Time Frame: Day 1 to Day 4 ]
   An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment
2. Number of Participants With Clinically Significant Change From Baseline in Vital Signs in SAD [ Time Frame: Day 1 to Day 4 ]
3. Number of Participants With Laboratory Abnormalities in SAD [ Time Frame: Day 1 to Day 4 ]
4. Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in SAD [ Time Frame: Day 1 to Day 4 ]
   Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG
5. Number of participants with TEAEs in multiple ascending dose (MAD) [ Time Frame: Day 1 to Day 12 ]
   An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment
6. Number of Participants With Clinically Significant Change From Baseline in Vital Signs in MAD [ Time Frame: Day 1 to Day 12 ]
   Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), temperature, respiratory rate and pulse rate.
7. Number of Participants With Laboratory Abnormalities in MAD [ Time Frame: Day 1 to Day 12 ]
8. Number of Participants with Clinically Significant Change From Baseline in ECGs Findings in MAD [ Time Frame: Day 1 to Day 12 ]
   Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG
9. Total % cumulative recovery of drug related material in metabolism and excretion (ME) [ Time Frame: Day 1 to Day 11 ]
   Drug related material excreted in urine and feces combined
10. The ratio of AUClast in relative bioavailability (RBA) [ Time Frame: Day 1 to Day 3 ]
    The ratio of AUClast of test vs reference formulation
11. The ratio of Cmax in RBA [ Time Frame: Day 1 to Day 3 ]
    The ratio of Cmax of test vs reference formulation
12. Number of participants with Treatment Emergent Adverse Events (TEAEs) in supratherapeutic exposure (SE) [ Time Frame: Day 1 to Day 5 ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment
13. Number of Participants With Clinically Significant Change From Baseline in Vital Signs in SE [ Time Frame: Day 1 to Day 5 ]
14. Number of Participants With Laboratory Abnormalities in SE [ Time Frame: Day 1 to Day 5 ]
15. Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in SE [ Time Frame: Day 1 to Day 5 ]
    Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG

Secondary Outcome Measures :

1. Maximum Plasma Concentration (Cmax) in SAD [ Time Frame: Day 1 to Day 4 ]
   The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations
2. Dose Normalized Maximum Plasma Concentration (Cmax[dn]) in SAD [ Time Frame: Day 1 to Day 4 ]
   Cmax(dn) = Cmax / dose.
3. Time for Cmax (Tmax) in SAD [ Time Frame: Day 1 to Day 4 ]
   Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.
4. Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in SAD [ Time Frame: Day 1 to Day 4 ]
   AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.
5. Dose Normalized Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast[dn]) in SAD [ Time Frame: Day 1 to Day 4 ]
   AUClast /dose
6. Cmax in MAD-Day 1 [ Time Frame: Day 1 Pre-dose (0 hours) to 12 hours ]
   Observed Cmax is estimated based on the plasma concentrations
7. Cmax(dn) in MAD-Day 1 [ Time Frame: Day 1 Pre-dose (0 hours) to 12 hours ]
   Cmax/dose is summarized by dosing regimen.
8. Cmax in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
   Observed Cmax is estimated based on the plasma concentrations
9. Dose Normalized Maximum Plasma Concentration (Cmax[dn]) in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
   Cmax/dose is summarized by dosing regimen.
10. Cmax in MAD-Day 10 [ Time Frame: Day 10 (0h) Pre-dose (0 hours) to 12 hours ]
    Observed Cmax is estimated based on the plasma concentrations
11. Dose Normalized Maximum Plasma Concentration (Cmax[dn]) in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Cmax/dose is summarized by dosing regimen.
12. Time for Cmax (Tmax) in MAD-Day 1 [ Time Frame: Day 1 Pre-dose (0 hours) to 12 hours ]
    Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.
13. Tmax in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.
14. Tmax in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.
15. Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau) in MAD-Day 1 [ Time Frame: Day 1 Pre-dose (0 hours) to 12 hours ]
    AUCtau is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for three times daily (TID) dosing and 12 hours for twice daily (BID) dosing. It is determined by linear/log trapezoidal method.
16. Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau[dn]) in MAD-Day 1 [ Time Frame: Day 1 Pre-dose (0 hours) to 12 hours ]
    AUCtau/dose is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for TID dosing and 12 hours for BID dosing. I
17. AUCtau in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    AUCtau is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for TID dosing and 12 hours for BID dosing. It is determined by linear/log trapezoidal method.
18. AUCtau(dn) in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    AUCtau/dose is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for TID dosing and 12 hours for BID dosing. I
19. AUCtau in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    AUCtau is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for TID dosing and 12 hours for BID dosing. It is determined by linear/log trapezoidal method.
20. Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau[dn]) in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    AUCtau/dose is summarized by dosing regimen and period. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval is 8 hours for TID dosing and 12 hours for BID dosing. I
21. Lowest Concentration Observed During the Dosing Interval tau (Cmin) in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    Cmin is observed directly from data. It is summarized by dosing regimen. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval tau is 8 hours for TID dosing and 12 hours for BID dosing.
22. Cmin in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Cmin is observed directly from data. It is summarized by dosing regimen. Dosing interval is the interval tau between administration of doses of drug. In this study, the dosing interval tau is 8 hours for TID dosing and 12 hours for BID dosing.
23. t½ in MAD-Day 10 [ Time Frame: Day 10 Pre dose (0 hours) to Day 12 (48 hours post dose) ]
    t1/2 is summarized by dosing regimen . It is determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline is used in the regression.
24. Vz/F in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. VZ/F after oral dose is influenced by the fraction absorbed.
25. Peak Trough Ratio (PTR) in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen .
26. PTR in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen .
27. Observed Accumulation Ratio Based on AUC (Rac) in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    Rac = AUCtau,ss / AUCtau,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac = AUCtau(Day 5) / AUCtau(Day 1). Rac is summarized by dosing regimen.
28. Rac in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Rac = AUCtau,ss / AUCtau,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac = AUCtau(Day 10) / AUCtau(Day 1). Rac is summarized by dosing regimen.
29. Observed Accumulation Ratio Based on Cmax (Rac,Cmax) in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    Rac,Cmax = Cmax,ss / Cmax,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac,Cmax = Cmax(Day5) / Cmax(Day 1). Rac,Cmax is summarized by dosing regimen.
30. Rac,Cmax in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Rac,Cmax = Cmax,ss / Cmax,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac,Cmax = Cmax(Day10) / Cmax(Day 1). Rac,Cmax is summarized by dosing regimen.
31. CL/F in MAD-Day 5 [ Time Frame: Day 5 Pre-dose (0 hours) to 12 hours ]
    CL/F is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. calculated as Dose/AUC tau. Dosing interval (tau) is 8 h for TID dosing and 12 h for BID dosing.
32. CL/F in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    CL/F is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. calculated as Dose/AUC tau. Dosing interval (tau) is 8 h for TID dosing and 12 h for BID dosing.
33. Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval tau Hours Post-Dose (Aetau) in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Sum of (urine volume × urine concentration) for each collection over the dosing interval tau. Dosing interval (tau) is 8h for TID and 12 h for BID dosing.
34. Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval tau Hours Post-Dose (Aetau%) in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Aetau% = Aetau / Dose * 100. Aetau% is summarized by dosing regimen. Dosing interval (tau) is 8h for TID and 12 h for BID dosing.
35. Renal Clearance (Clr) in MAD-Day 10 [ Time Frame: Day 10 Pre-dose (0 hours) to 12 hours ]
    Renal clearance is calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval is 8 hours for TID dosing and 12 hours for BID dosing.
36. Maximum Plasma Concentration (Cmax) in Metabolism and Excretion (ME) [ Time Frame: Day 1 to Day 11 ]
    The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations
37. Time for Cmax (Tmax) in Metabolism and Excretion (ME) [ Time Frame: Day 1 to Day 11 ]
    Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.
38. Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in Metabolism and Excretion (ME) [ Time Frame: Day 1 to Day 11 ]
    AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.
39. Maximum Plasma Concentration (Cmax) in SE [ Time Frame: Day 1 to Day 5 ]
    The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations
40. Time for Cmax (Tmax) in SE [ Time Frame: Day 1 to Day 5 ]
    Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.
41. Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in SE [ Time Frame: Day 1 to Day 5 ]
    AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Connecticut

New Haven Clinical Research Unit

New Haven, Connecticut, United States, 06511

Belgium

Brussels Clinical Research Unit

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

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] June 24, 2021

Statistical Analysis Plan  [PDF] August 25, 2021

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04756531
• Other Study ID Numbers: C4671001; 2020-006073-30 ( EudraCT Number )
• First Posted: February 16, 2021
• Last Update Posted: September 13, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Nirmatrelvir; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents