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

Study Overview
=================
Brief Summary
-----------------
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: Males age 18 to 55 years All fertile participants must agree to the use of highly effective contraception Body mass index (BMI) of 18 to 32.0 kg/m2; body weight of 55.0 to 100.0 kg. 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.

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

Conditions
-----------------
Respiratory Syncytial Virus Infections

Intervention / Treatment
-----------------
* Drug: 200 mg RV521/78 µCi [ 14C]-RV521.


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 mg RV521/78 µCi [ 14C]-RV521<br>200 mg RV521/78 µCi [ 14C]-RV521 | Drug: 200 mg RV521/78 µCi [ 14C]-RV521.<br>* 200 mg RV521/78 µCi [ 14C]-RV521<br>|

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 |