Clinical trial NCT05652647: A Study to Understand How the Study Medicine (PF-07081532) is Processed and Eliminated in Healthy Men
Official title: A PHASE 1, OPEN-LABEL, 2-PERIOD, FIXED SEQUENCE STUDY TO INVESTIGATE THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF [14C]PF-07081532 AND TO ASSESS THE ABSOLUTE BIOAVAILABILITY AND FRACTION ABSORBED OF PF-07081532 IN HEALTHY MALE PARTICIPANTS USING A [14C]-MICROTRACER APPROACH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Absorption
Distribution
Metabolism
Elimination
Bioavailability
Fraction absorbed
Mass balance
Healthy Males
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-12-15
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this clinical trial is to learn about how much PF-07081532 will be taken up and processed by healthy male participants. The study consists of two parts, called study periods. In Period 1, participants will take one dose of PF-07081532 by mouth. In Period 2, participants will take one dose by mouth and one dose as an injection through a vein at the study clinic.

In Period 1, participants will stay at the clinic site for up to 21 days. In Period 2, they will stay at the clinic site for 7 days. During their stays, participants will have their blood, urine, and feces collected by the study doctors several times. We will measure the level of PF-07081532 in participants' blood, urine, and feces samples. This will help us know how much the study medicine is getting taken in by the body. At the end of the study, participants will be contacted by phone to check in. Participants will be involved in this study for about 12 weeks.


Eligibility criteria: Key Eligibility criteria for this study include, but are not limited to the following:

Inclusion criteria:

Healthy Male participants must be 18 to 60 years of age, inclusive.

Overtly healthy as determined by medical evaluation including medical history, physical examination, blood pressure and pulse rate measurement, standard 12-lead ECG, and laboratory tests.

BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).

Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures

Exclusion criteria:

History of irregular bowel movements (eg, irritable bowel syndrome, frequent episodes of diarrhea, or constipation defined by less than 1 bowel movement on average per 2 days) or lactose intolerance

Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).

Previous administration with an investigational product (drug or vaccine) within 90 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.

Primary outcomes:
measure: Total Recovery of Radioactivity in Urine, Feces and Both Routes Combined, as Percentage of Orally Administered Radioactive Dose of [14C]PF-07081532
timeFrame: 360 hours
measure: Relative Abundance of [14C]PF-07081532 and Its Metabolites in Plasma After A Single Oral Dose of [14]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hours [hrs]) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, and 72 hrs post Period 1 Day 1 dosing
measure: Relative Abundance of [14C]PF-07081532 and Its Metabolites in Urine and Feces After A Single Oral Dose of [14]PF-07081532 in Period 1
timeFrame: 96 hours for urine samples and 144 hours for feces samples
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: AUClast of PF-07081532 After A Single Oral Dose of [14]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Plasma Maximum Observed Concentration (Cmax) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Plasma Cmax of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Plasma Time to Reach Cmax (Tmax) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Area Under the Plasma Concentration-Time Curve to Infinity (AUCinf) of Total [14C] After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: AUCinf of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Plasma Elimination Half Life (t1/2) of Total [14C] and PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Apparent Clearance of Drug From Plasma (CL/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Plasma Apparent Volume of Distribution (Vz/F) of PF-07081532 After A Single Oral Dose of [14C]PF-07081532 in Period 1
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs and 144 hrs post Period 1 Day 1 dosing
measure: Plasma AUClast of [14C]PF-07081532 Following Intravenous (IV) Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Dose-Normalized Plasma AUClast (AUClast(dn) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma Cmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Dose-Normalized Plasma Cmax (Cmax (dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma Tmax of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma AUCinf of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Dose-Normalized Plasma AUCinf (AUCinf(dn)) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma t1/2 of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma Clearance (CL) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma Steady-State Volume of Distribution (Vss) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Plasma Mean Residence Time (MRT) of [14C]PF-07081532 Following IV Administration of [14C]PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.17 hrs, 0.25 hrs, 0.33 hrs, 0.5 hrs, 1 hr, 3 hrs, 5 hrs, 7 hrs, 9 hrs, 11 hrs, 14 hrs, 23 hrs, 35 hrs, 47 hrs, 71 hrs, 95 hrs, 119 hrs and 143 hrs post IV dosing of [14C]PF-07081532 on Period 2 Day 1
measure: Absolute Oral Bioavailability (F) of PF-07081532 in Period 2
timeFrame: Pre-dose (0 hrs) and 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 15 hrs, 24 hrs, 36 hrs, 48 hrs, 72hrs, 96 hrs, 120 hrs and 144 hrs post oral dosing of unlabeled PF-07081532 on Period 2 Day 1
measure: Fraction Absorbed (Fa) of PF-07081532
timeFrame: Day 1 to Day 7 for both Period 1 and Period 2
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Maximum of 11 weeks
measure: Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
timeFrame: Maximum of 11 weeks
measure: Number of Participants With Post-Baseline Vital Signs Data Meeting Pre-Defined Criteria
timeFrame: Maximum of 11 weeks
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Criteria
timeFrame: Maximum of 11 weeks
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: PRA Health Sciences
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: