STUDY OF PF-07321332 IN HEALTHY PARTICIPANTS

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04756531
• Other study ID #: C4671001
• Secondary ID: 2020-006073-30
• Status: Completed
• Phase: Phase 1
• Start date: February 11, 2021
• Est. completion date: September 1, 2021

Study information

• Verified date: September 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: September 1, 2021
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• PF-07321332 Dose 1
PF-07321332 Dose 1 or Placebo
• PF-07321332 Dose 2
PF-07321332 Dose 2 or Placebo
• PF-07321332 Dose 3
PF-07321332 Dose 3 or Placebo
• PF-07321332 Dose 4
PF-07321332 Dose 4 or Placebo
• PF-07321332 Dose 5
PF-07321332 Dose 5 or Placebo
• PF-07321332 Dose 4 or Placebo (Fed)
PF-07321332 Dose 5 or Placebo with high fat meal

Locations

Country	Name	City	State
Belgium	Brussels Clinical Research Unit	Brussels	Bruxelles-capitale, Région DE
United States	New Haven Clinical Research Unit	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Treatment Emergent Adverse Events (TEAEs) in single ascending dose (SAD)	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	Day 1 to Day 4
Primary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs in SAD		Day 1 to Day 4
Primary	Number of Participants With Laboratory Abnormalities in SAD		Day 1 to Day 4
Primary	Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in SAD	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	Day 1 to Day 4
Primary	Number of participants with TEAEs in multiple ascending dose (MAD)	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	Day 1 to Day 12
Primary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs in MAD	Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), temperature, respiratory rate and pulse rate.	Day 1 to Day 12
Primary	Number of Participants With Laboratory Abnormalities in MAD		Day 1 to Day 12
Primary	Number of Participants with Clinically Significant Change From Baseline in ECGs Findings in MAD	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	Day 1 to Day 12
Primary	Total % cumulative recovery of drug related material in metabolism and excretion (ME)	Drug related material excreted in urine and feces combined	Day 1 to Day 11
Primary	The ratio of AUClast in relative bioavailability (RBA)	The ratio of AUClast of test vs reference formulation	Day 1 to Day 3
Primary	The ratio of Cmax in RBA	The ratio of Cmax of test vs reference formulation	Day 1 to Day 3
Primary	Number of participants with Treatment Emergent Adverse Events (TEAEs) in supratherapeutic exposure (SE)	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	Day 1 to Day 5
Primary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs in SE		Day 1 to Day 5
Primary	Number of Participants With Laboratory Abnormalities in SE		Day 1 to Day 5
Primary	Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in SE	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	Day 1 to Day 5
Secondary	Maximum Plasma Concentration (Cmax) in SAD	The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations	Day 1 to Day 4
Secondary	Dose Normalized Maximum Plasma Concentration (Cmax[dn]) in SAD	Cmax(dn) = Cmax / dose.	Day 1 to Day 4
Secondary	Time for Cmax (Tmax) in SAD	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	Day 1 to Day 4
Secondary	Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in SAD	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1 to Day 4
Secondary	Dose Normalized Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast[dn]) in SAD	AUClast /dose	Day 1 to Day 4
Secondary	Cmax in MAD-Day 1	Observed Cmax is estimated based on the plasma concentrations	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	Cmax(dn) in MAD-Day 1	Cmax/dose is summarized by dosing regimen.	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	Cmax in MAD-Day 5	Observed Cmax is estimated based on the plasma concentrations	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Dose Normalized Maximum Plasma Concentration (Cmax[dn]) in MAD-Day 5	Cmax/dose is summarized by dosing regimen.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Cmax in MAD-Day 10	Observed Cmax is estimated based on the plasma concentrations	Day 10 (0h) Pre-dose (0 hours) to 12 hours
Secondary	Dose Normalized Maximum Plasma Concentration (Cmax[dn]) in MAD-Day 10	Cmax/dose is summarized by dosing regimen.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Time for Cmax (Tmax) in MAD-Day 1	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	Tmax in MAD-Day 5	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Tmax in MAD-Day 10	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau) in MAD-Day 1	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.	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau[dn]) in MAD-Day 1	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	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	AUCtau in MAD-Day 5	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.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	AUCtau(dn) in MAD-Day 5	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	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	AUCtau in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Dose Normalized Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUCtau[dn]) in MAD-Day 10	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	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Lowest Concentration Observed During the Dosing Interval tau (Cmin) in MAD-Day 5	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.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Cmin in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	t½ in MAD-Day 10	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.	Day 10 Pre dose (0 hours) to Day 12 (48 hours post dose)
Secondary	Vz/F in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Peak Trough Ratio (PTR) in MAD-Day 5	PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen .	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	PTR in MAD-Day 10	PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen .	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Observed Accumulation Ratio Based on AUC (Rac) in MAD-Day 5	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.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Rac in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Observed Accumulation Ratio Based on Cmax (Rac,Cmax) in MAD-Day 5	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.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Rac,Cmax in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	CL/F in MAD-Day 5	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.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	CL/F in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval tau Hours Post-Dose (Aetau) in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval tau Hours Post-Dose (Aetau%) in MAD-Day 10	Aetau% = Aetau / Dose * 100. Aetau% is summarized by dosing regimen. Dosing interval (tau) is 8h for TID and 12 h for BID dosing.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Renal Clearance (Clr) in MAD-Day 10	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.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Maximum Plasma Concentration (Cmax) in Metabolism and Excretion (ME)	The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations	Day 1 to Day 11
Secondary	Time for Cmax (Tmax) in Metabolism and Excretion (ME)	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	Day 1 to Day 11
Secondary	Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in Metabolism and Excretion (ME)	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1 to Day 11
Secondary	Maximum Plasma Concentration (Cmax) in SE	The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations	Day 1 to Day 5
Secondary	Time for Cmax (Tmax) in SE	Tmax was summarized by dosing regimen. It was observed directly from data as time of first occurrence.	Day 1 to Day 5
Secondary	Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in SE	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1 to Day 5

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