Respiratory Syncytial Virus Infections
Conditions
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: 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.
Interventions
DRUG200 mg RV521/78 µCi [ 14C]-RV521.
200 mg RV521/78 µCi \[ 14C\]-RV521
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 14C associated with % of administered dose of the total in urine and feces | Day 1 (time 0) to Day 29 | Metabolite Profiling and Identification |
| lambdaz (Rate constant associated with the terminal elimination phase) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| t1/2 (half-life of the terminal elimination phase) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| CL/F (Apparent clearance of the drug from plasma after oral administration) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| Vz/F (Volume of distribution associated with the terminal phase) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| CLR (renal clearance) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| Fe (fraction of administered drug excreted into urine) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| Ae0-t (cumulative amount of 14C excreted into urine from time 0 to the last sampling interval) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| 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)) | Day 1 (time 0) to Day 29 | Mass balance parameters in urinary and fecal excretion of radioactivity |
| Aet (Amount of 14C excreted into urine and feces per sampling interval (in units of mass-equivalents/g)) | Day 1 (time 0) to Day 29 | Mass balance parameters in urinary and fecal excretion of radioactivity |
| Fet (Fraction of 14C excreted into urine and feces per sampling interval (in units of %)) | Day 1 (time 0) to Day 29 | Mass balance parameters in urinary and fecal excretion of radioactivity |
| Fe0-t (Cumulative fraction of 14C excreted into urine or feces from time 0) | Day 1 (time 0) to Day 29 | Mass balance parameters in urinary and fecal excretion of radioactivity |
| 14C associated with % of AUC of the total in plasma | Day 1 (time 0) to Day 29 | Metabolite Profiling and Identification |
| Tmax (Time of maximum observed concentration) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| Cmax (Maximum observed concentration) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| AUC0-inf (Area under the concentration-time curve (AUC) extrapolated to infinity) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| AUC0-last (AUC from the time of dosing to the time of the last measurable concentration) | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneously reported serious AEs (SAEs) during the Treatment Period | Day -1 to Day 29 | Safety and tolerability of a single oral dose of RV521 in healthy male subjects |
| Use of concomitant medications | Day -1 to Day 29 | Safety and tolerability of a single oral dose of RV521 in healthy male subjects |
| Unscheduled assessments as needed for management of AEs | Day -1 to Day 29 | Safety and tolerability of a single oral dose of RV521 in healthy male subjects |
| Clinically significant changes from baseline of any of the following: Vital Signs (blood pressure, heart rate [HR], respiratory rate [RR], and oral temperature) | Day -1 to Day 29 | Safety and tolerability of a single oral dose of RV521 in healthy male subjects |
| Clinically significant changes from baseline of any of the following: 12-lead electrocardiogram (ECD) assessments | Day -1 to Day 29 | Safety and tolerability of a single oral dose of RV521 in healthy male subjects |
| Clinically significant changes from baseline of any of the following: Physical examinations | Day -1 to Day 29 | Safety and tolerability of a single oral dose of RV521 in healthy male subjects |
| Blood/Plasma AUC Ratio | Day 1 (time 0 to Day 29) | AUC0-inf of total 14C in whole blood divided by the AUC0-inf of total 14C in plasma |
| Amount of 14C excreted into nostrils per sampling interval (in units of mass-equivalents/g) | Day 1 (time 0) to Day 29 | Metabolite Profiling and Identification |
| Cumulative amount of 14C excreted into nostrils, urine, and feces from time 0 to the last sampling interval (in units of mass-equivalents/g) | Day 1 (time 0 to Day 29) | Metabolite Profiling and Identification |
| Evaluation of total radioactivity in nasal samples following a single oral administration of [ 14C]-RV521 to healthy male subjects | Day 1 (time 0) to Day 29 | PK parameters of total radioactivity and RV521 following a single oral administration of \[ 14C\]-RV521 to healthy male subjects |
| Structural identification of major metabolites | Day 1 (time 0) to Day 29 | Identification of each metabolite that accounts for ≥10% of circulating radiolabel |
| Spontaneously reported adverse events (AEs) during the Treatment Period | Day -1 to Day 29 | safety and tolerability of a single oral dose of RV521 in healthy male subjects |
Countries
United States
Outcome results
None listed