A Study to Learn About Effect of Sisunatovir in Healthy Adult Male Participants

[14C] -RV521.HCl - A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion Following a Single Oral Dose in Healthy Male Subjects

The purpose of this clinical trial is to learn about the safety, effects, and tolerability of the study medicine (sisunatovir).

This study is looking for healthy adult participants who meet the following criteria:

1. Males age 18 to 55 years
2. All fertile participants must agree to the use of highly effective contraception
3. Body mass index (BMI) of 18 to 32.0 kg/m2; body weight of 55.0 to 100.0 kg.
4. Participants who are overtly healthy as determined by medical evaluation. This includes medical history, physical examination, blood pressure, pulse rate, standard 12-lead ECG (electrocardiogram), and laboratory tests.

This study will enroll up to 10 participants. All study participants will receive 1 dose of sisunatovir by mouth. The study duration is expected to be about 9 weeks. This includes a 28-day screening period, 16-day inpatient stay, and 2 overnight follow-up visits, if needed.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Drug: 200 mg RV521/78 µCi [ 14C]-RV521.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pharmaron Clinical Pharmacology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (key):

• Males
• Age 18- 55 years
• Body mass index (BMI) 18.0 kg/m2 to 32.0 kg/m2
• Body weight 55.0 kg to 100.0 kg
• Considered to be in good health
• Nonsmoker
• Content of 14C in urine, whole blood, and/or plasma samples does not exceed the general environmental background level of 14C

Exclusion Criteria (key):

• Clinically significant abnormal medical history or any abnormal finding on physical examination, vital signs, ECG, laboratory tests
• History of cancer that has not been in full remission for >5 years
• Acute illness within 14 days prior to Day 1
• History of significant drug allergies
• History or presence of alcohol or drug abuse
• Recent history of incomplete bladder emptying with voiding or awakening more than once at night to void
• Usual habit of <1 or >3 bowel movements per day
• Exposure to radiation for therapeutic, diagnostic, or occupational reasons within the 12 months prior to Day 1.
• Participation in another clinical study in which a [14C]-labeled drug was administered within 1 year prior to Check-in
• Administration of another investigational medication within 60 days (or 5 half-lives, whichever is longer) prior to Day 1
• Participation in an investigational-device study within 60 days prior to Day 1
• Any ECG abnormality considered to be clinically significant by the Investigator
• QTcF interval >450 msec and QRS interval >120 msec
• Family history of long QT syndrome or of unexplained sudden death in a first-degree relative under 50 years of age
• Documented congenital or acquired long QT syndrome
• Presence of clinically significant hypertension
• Presence of clinically significant hypotension
• Loss or donation of more than 500 mL blood within 60 days prior to the Screening
• Excessive consumption of alcohol
• Use of any live vaccinations within 30 days
• Use/consumption of food or drugs known to be moderate or strong cytochrome P450 3A4 (CYP3A4) inducers or potent CYP3A4 inhibitors within 14 days or 5 half-lives, whichever is longer, prior to RV521 administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 200 mg RV521/78 µCi [ 14C]-RV521	Drug: 200 mg RV521/78 µCi [ 14C]-RV521.; 200 mg RV521/78 µCi [ 14C]-RV521

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax (Time of maximum observed concentration)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
Cmax (Maximum observed concentration)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
AUC0-inf (Area under the concentration-time curve (AUC) extrapolated to infinity)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
AUC0-last (AUC from the time of dosing to the time of the last measurable concentration)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
lambdaz (Rate constant associated with the terminal elimination phase)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
t1/2 (half-life of the terminal elimination phase)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
CL/F (Apparent clearance of the drug from plasma after oral administration)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
Vz/F (Volume of distribution associated with the terminal phase)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
CLR (renal clearance)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
Fe (fraction of administered drug excreted into urine)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
Ae0-t (cumulative amount of 14C excreted into urine from time 0 to the last sampling interval)	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
Ae0-t (Cumulative amount of 14C excreted into urine and feces from time 0 to the last sampling interval (in units of mass-equivalents/g))	Mass balance parameters in urinary and fecal excretion of radioactivity	Day 1 (time 0) to Day 29
Aet (Amount of 14C excreted into urine and feces per sampling interval (in units of mass-equivalents/g))	Mass balance parameters in urinary and fecal excretion of radioactivity	Day 1 (time 0) to Day 29
Fet (Fraction of 14C excreted into urine and feces per sampling interval (in units of %))	Mass balance parameters in urinary and fecal excretion of radioactivity	Day 1 (time 0) to Day 29
Fe0-t (Cumulative fraction of 14C excreted into urine or feces from time 0)	Mass balance parameters in urinary and fecal excretion of radioactivity	Day 1 (time 0) to Day 29
14C associated with % of AUC of the total in plasma	Metabolite Profiling and Identification	Day 1 (time 0) to Day 29
14C associated with % of administered dose of the total in urine and feces	Metabolite Profiling and Identification	Day 1 (time 0) to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneously reported adverse events (AEs) during the Treatment Period	safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Spontaneously reported serious AEs (SAEs) during the Treatment Period	Safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Use of concomitant medications	Safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Unscheduled assessments as needed for management of AEs	Safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Clinically significant changes from baseline of any of the following: Vital Signs (blood pressure, heart rate [HR], respiratory rate [RR], and oral temperature)	Safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Clinically significant changes from baseline of any of the following: 12-lead electrocardiogram (ECD) assessments	Safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Clinically significant changes from baseline of any of the following: Physical examinations	Safety and tolerability of a single oral dose of RV521 in healthy male subjects	Day -1 to Day 29
Blood/Plasma AUC Ratio	AUC0-inf of total 14C in whole blood divided by the AUC0-inf of total 14C in plasma	Day 1 (time 0 to Day 29)
Amount of 14C excreted into nostrils per sampling interval (in units of mass-equivalents/g)	Metabolite Profiling and Identification	Day 1 (time 0) to Day 29
Cumulative amount of 14C excreted into nostrils, urine, and feces from time 0 to the last sampling interval (in units of mass-equivalents/g)	Metabolite Profiling and Identification	Day 1 (time 0 to Day 29)
Evaluation of total radioactivity in nasal samples following a single oral administration of [ 14C]-RV521 to healthy male subjects	PK parameters of total radioactivity and RV521 following a single oral administration of [ 14C]-RV521 to healthy male subjects	Day 1 (time 0) to Day 29
Structural identification of major metabolites	Identification of each metabolite that accounts for ≥10% of circulating radiolabel	Day 1 (time 0) to Day 29

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Actual): July 12, 2022
• Study Completion (Actual): July 12, 2022

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: REVC008; C5241008 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No