Respiratory Syncytial Viruses
Conditions
Keywords
RSV, respiratory syncytial virus
Brief summary
This study is seeking healthy participants who are: 1. Aged 18 to 65 years of age. All fertile participants must agree to use a highly effective method of contraception. 2. Male and female 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. 3. BMI (body mass index) of 17.5 to 35 kg/m2; and a total body weight \>50 kg (110 lb). This study will consist of up to 2 cohorts (groups of participants).: Cohort 1 is a randomized, 2-part, crossover cohort. Part 1 has 3 periods. Periods 1 and 2 are to evaluate the safety and effects of sisunatovir. Participants will take sisunatovir tablets or placebo by mouth once every 12 hours. A placebo looks like the study medicine but does not contain any active medicine in it. Period 3 is an open label period to evaluate the food effect of the planned higher dose of sisunatovir. Participants will take the planned higher dose sisunatovir tablets every 12 hours. In Part 2, participants will take sisunatovir prepared in 4 different vehicles (water, infant formula, apple juice, and saline) to assess how palatable each form is. Participants will complete a questionnaire after tasting each form of sisunatovir. The palatability questionnaire will be completed for each vehicle, the questionnaire asks participants to assess each vehicle at 4 different time increments after tasting. At least 60 minutes will pass between tasting each vehicle. Period 4 may start after the last PK draw of Period 3. A minimum 7-day washout period will occur between the last dose of Periods 1 and 2 and the first dose of Periods 2 and 3. We will assess the safety of participants following each study period and doses and adjust the doses for subsequent study periods as needed. Cohort 2 is an optional cohort; the design of Cohort 2 is the same as Part 1 of Cohort 1. Dose levels studied in Cohort 2 will be determined after the completion of Cohort 1. Participants will take part in this study for approximately 2 months, excluding the screening period. During this time there are 3 separate 7-day in-patient stays at the study clinic and a follow-up phone call that takes place 28-35 days after the last dose of study medicine.
Interventions
DRUGsisunatovir
Sisunatovir is an orally administered RSV F-protein inhibitor being developed to target viral-host cell fusion for the treatment of adult and pediatric patients with RSV
DRUGPlacebo
Placebo for sisunatovir
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants aged 18 to 65 years of age, inclusive, at the time of signing of the informed consent document (ICD). • All fertile participants must agree to use a highly effective method of contraception. 2. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, including blood pressure, pulse rate, standard 12-lead electrocardiogram (ECG), and laboratory tests. 3. Body mass index (BMI) of 17.5 to 35 kg/m2; and a total body weight \>50 kg (110 lb).
Exclusion criteria
1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 2. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality, or other conditions or situations related to Coronavirus Disease 2019 (COVID-19) pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 3. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention with the exception of moderate/strong CYP3A inducers or time dependent inhibitors which are prohibited within 14 days plus 5 half lives prior to the first dose of study intervention. 4. A positive urine drug test, confirmed by a repeat test, if deemed necessary. 5. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. 6. Standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. 7. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary: * glomerular filtration rate (GFR) \<60 mL/min/1.73m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; * Aspartate Aminotransferase (AST) or Alanine Transaminase (ALT) level ≥1.5 x upper limit of normal (ULN); * Gamma-glutamyl transferase (Gamma-GT)\> ULN; * Alkaline phosphatase \> ULN; * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From start of treatment to 28-35 days after last dose (maximum upto 66 days) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred following start of treatment. |
| Number of Participants With Clinical Laboratory Abnormalities: Part 1 | Up to Day 5 | Laboratory tests included haematology (Monocytes \[10\^9/L\] increase: \> 1.2\* upper limit of normal \[ULN\] and Monocytes/Leukocytes \[percentage\] {%}:\> 1.2\* ULN); clinical chemistry (serum) included Alanine Aminotransferase (units per liter \[U/L\]):\> 3.0\* ULN and Bicarbonate (milliequivalents per liter) (mEq/L): \>1.1\* ULN and in urinalysis (urine Hemoglobin (Scalar) more than equal to (\>=) 1, urine Bilirubin (Scalar) \>= 1, Hyaline Casts (/Low power field \[LPF\]) \>= 1. Number of participants with any clinical laboratory abnormalities is reported in this outcome. |
| Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1 | Up to Day 5 | Supine blood pressure (BP) was measured with the participant's arm supported at the level of the heart and recorded after approximately 5 minutes of rest. Pulse rate was measured in the brachial/radial artery. Notable abnormal vital sign categories included: Systolic BP: \<90 millimeter of mercury \[mmHg\]; Systolic BP change from baseline: maximum increase and decrease \>=30 mmHg; Diastolic BP \<50 mmHg; Diastolic BP change from baseline: maximum decrease and increase ≥20 mmHg; pulse rate \<40 and \>120 beats per minute. Number of participants with newly occurring notable abnormal vital sign (i.e. change in supine systolic BP \>=30 millimeter of mercury \[mmHg\] increase) is reported in this outcome measure. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1 | Up to Day 7 | Standard 12-lead ECGs utilizing limb leads were used to measure PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF), and QRS complex. ECG was performed after the participant had rested quietly for at least 5 minutes in a supine position. Clinical significance was determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 1: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 | Area under the concentration-time profile from time zero to time tau (the dosing interval), where tau = 12 hours for twice a day (BID) dosing. |
| Dose Normalized AUCtau (AUCtau [dn]) for Day 1: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 | AUCtau(dn) was calculated as AUCtau/Dose. |
| Maximum Observed Plasma Concentration (Cmax) for Day 1: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 | — |
| Dose Normalized Maximum Plasma Concentration (Cmax [dn]) for Day 1: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 | Cmax(dn) was calculated as Cmax/Dose. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 1: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 5 | Area under the concentration-time profile from time zero to time tau (the dosing interval), where tau = 12 hours for BID dosing. |
| AUCtau(dn) for Day 5: Part 1 | Pre-dose, 1, 2, 3,4, 5, 6, 8 and 12 hours post-dose on Day 5 | AUCtau(dn) was calculated as AUCtau/Dose. |
| Maximum Observed Plasma Concentration (Cmax) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | — |
| Cmax(dn) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | Cmax(dn) was calculated as Cmax/Dose. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | — |
| Apparent Clearance (CL/F) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | CL/F was calculated as Dose/AUCtau. |
| Observed Accumulation Ratio (Rac) for AUC for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 and Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 5 | Rac for AUC was calculated as AUCtau Day5/AUCtau Day1. |
| Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 and Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | Rac,Cmax was calculated as Cmax Day5/Cmax Day1. |
| Plasma Decay Half-Life (t1/2) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | — |
| Apparent Volume of Distribution (Vz/F) for Day 5: Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | Vz/F was calculated as Dose/(AUCtau \* kel \[Terminal phase rate constant\]). |
| AUCtau for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 5 | — |
| Cmax for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5 | — |
| Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of overall liking by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated less overall liking. |
| Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of mouth feel by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated worse mouth feel. |
| Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of bitterness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more bitterness. |
| Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of tongue/mouth burn by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more tongue/mouth burn. |
| Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of sourness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated increase in sourness. |
| Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of saltiness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more saltiness. |
| Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle | Participants were required to answer the palatability attribute of sweetness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), Participants were required to answer the palatability attribute of sweetness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more sweetness. |
Countries
Belgium
Participant flow
Recruitment details
This study was planned to be conducted in 2 cohorts: Cohort 1 and optional Cohort 2. Cohort 1 had 2 parts, Part 1 had 3 periods (Period 1, 2, 3) and Part 2 had 4 periods (Period 4, 5, 6, 7). The optional cohort 2 was not conducted based on the findings for Cohort 1.
Pre-assignment details
A total of 12 participants were enrolled at 1 site in Brussels.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants who were randomized to either of the treatment sequence and received Sisunatovir 400 mg, Fed (A) Sisunatovir 200 mg, Fed (B), Placebo, Fed (treatment C), Sisunatovir 200 mg, Fasted (D), Sisunatovir 200 mg, Fed (treatment L), Sisunatovir 50 mg, Water (E), Sisunatovir 50 mg, Formula (F), Sisunatovir 50 mg, Apple Juice (G), Sisunatovir 50 mg, Saline (H) in any of the treatment periods were included. Participants were administered either Sisunatovir 200 mg in the fed state, Sisunatovir 400 mg in the fed state or placebo in fed state in Period 1 and 2, Sisunatovir 200 mg in fasted state in Period 3 and tasted Sisunatovir 50 mg capsule in either water, formula, apple juice or saline in Periods 4 to 7. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 Period 3 (4 Days) | Refused further treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 43.3 Years STANDARD_DEVIATION 10.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 6 / 6 | 7 / 12 | 4 / 6 | 9 / 11 | 2 / 11 | 1 / 11 | 0 / 11 | 2 / 11 |
| serious Total, serious adverse events | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 11 |
Outcome results
Primary
Number of Participants With Clinical Laboratory Abnormalities: Part 1
Laboratory tests included haematology (Monocytes \[10\^9/L\] increase: \> 1.2\* upper limit of normal \[ULN\] and Monocytes/Leukocytes \[percentage\] {%}:\> 1.2\* ULN); clinical chemistry (serum) included Alanine Aminotransferase (units per liter \[U/L\]):\> 3.0\* ULN and Bicarbonate (milliequivalents per liter) (mEq/L): \>1.1\* ULN and in urinalysis (urine Hemoglobin (Scalar) more than equal to (\>=) 1, urine Bilirubin (Scalar) \>= 1, Hyaline Casts (/Low power field \[LPF\]) \>= 1. Number of participants with any clinical laboratory abnormalities is reported in this outcome.
Time frame: Up to Day 5
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Number of Participants With Clinical Laboratory Abnormalities: Part 1 | 2 Participants |
| Part 1: Sisunatovir 200 mg, Fed | Number of Participants With Clinical Laboratory Abnormalities: Part 1 | 2 Participants |
| Part 1: Placebo, Fed | Number of Participants With Clinical Laboratory Abnormalities: Part 1 | 4 Participants |
| Part 1: Sisunatovir 200 mg, Fasted | Number of Participants With Clinical Laboratory Abnormalities: Part 1 | 5 Participants |
Primary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1
Standard 12-lead ECGs utilizing limb leads were used to measure PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF), and QRS complex. ECG was performed after the participant had rested quietly for at least 5 minutes in a supine position. Clinical significance was determined by the investigator.
Time frame: Up to Day 7
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1 | 0 Participants |
| Part 1: Sisunatovir 200 mg, Fed | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1 | 0 Participants |
| Part 1: Placebo, Fed | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1 | 0 Participants |
| Part 1: Sisunatovir 200 mg, Fasted | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1 | 1 Participants |
Primary
Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1
Supine blood pressure (BP) was measured with the participant's arm supported at the level of the heart and recorded after approximately 5 minutes of rest. Pulse rate was measured in the brachial/radial artery. Notable abnormal vital sign categories included: Systolic BP: \<90 millimeter of mercury \[mmHg\]; Systolic BP change from baseline: maximum increase and decrease \>=30 mmHg; Diastolic BP \<50 mmHg; Diastolic BP change from baseline: maximum decrease and increase ≥20 mmHg; pulse rate \<40 and \>120 beats per minute. Number of participants with newly occurring notable abnormal vital sign (i.e. change in supine systolic BP \>=30 millimeter of mercury \[mmHg\] increase) is reported in this outcome measure.
Time frame: Up to Day 5
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1 | 0 Participants |
| Part 1: Sisunatovir 200 mg, Fed | Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1 | 1 Participants |
| Part 1: Placebo, Fed | Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1 | 0 Participants |
| Part 1: Sisunatovir 200 mg, Fasted | Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1 | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred following start of treatment.
Time frame: From start of treatment to 28-35 days after last dose (maximum upto 66 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Part 1: Sisunatovir 200 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Part 1: Placebo, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Part 1: Sisunatovir 200 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 9 Participants |
| Part 2: Sisunatovir 50 mg, Water | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Part 2: Sisunatovir 50 mg, Formula | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| Part 2: Sisunatovir 50 mg, Apple Juice | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| Part 2: Sisunatovir 50 mg, Saline | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Apparent Clearance (CL/F) for Day 5: Part 1
CL/F was calculated as Dose/AUCtau.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Apparent Clearance (CL/F) for Day 5: Part 1 | 55.20 Liter/hour | Geometric Coefficient of Variation 47 |
| Part 1: Sisunatovir 200 mg, Fed | Apparent Clearance (CL/F) for Day 5: Part 1 | 253.9 Liter/hour | Geometric Coefficient of Variation 57 |
| Part 1: Placebo, Fed | Apparent Clearance (CL/F) for Day 5: Part 1 | 295.2 Liter/hour | Geometric Coefficient of Variation 50 |
Secondary
Apparent Volume of Distribution (Vz/F) for Day 5: Part 1
Vz/F was calculated as Dose/(AUCtau \* kel \[Terminal phase rate constant\]).
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Apparent Volume of Distribution (Vz/F) for Day 5: Part 1 | 736.1 Liter | Geometric Coefficient of Variation 63 |
| Part 1: Sisunatovir 200 mg, Fed | Apparent Volume of Distribution (Vz/F) for Day 5: Part 1 | 3962 Liter | Geometric Coefficient of Variation 63 |
| Part 1: Placebo, Fed | Apparent Volume of Distribution (Vz/F) for Day 5: Part 1 | 4676 Liter | Geometric Coefficient of Variation 60 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 1: Part 1
Area under the concentration-time profile from time zero to time tau (the dosing interval), where tau = 12 hours for twice a day (BID) dosing.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1
Population: Pharmacokinetic (PK) parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 1: Part 1 | 2623 Nanogram*hour/ milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| Part 1: Sisunatovir 200 mg, Fed | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 1: Part 1 | 495.7 Nanogram*hour/ milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48 |
| Part 1: Placebo, Fed | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 1: Part 1 | 338.4 Nanogram*hour/ milliliter (ng*hr/mL) | Geometric Coefficient of Variation 72 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 5: Part 1
Area under the concentration-time profile from time zero to time tau (the dosing interval), where tau = 12 hours for BID dosing.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 5: Part 1 | 7244 Nanogram*hour/ milliliter (ng*hr/mL) | Geometric Coefficient of Variation 47 |
| Part 1: Sisunatovir 200 mg, Fed | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 5: Part 1 | 787.6 Nanogram*hour/ milliliter (ng*hr/mL) | Geometric Coefficient of Variation 57 |
| Part 1: Placebo, Fed | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 5: Part 1 | 678.2 Nanogram*hour/ milliliter (ng*hr/mL) | Geometric Coefficient of Variation 51 |
Secondary
Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of bitterness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more bitterness.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 78.8 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 77.9 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 75.3 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 76.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 77.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 73.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 68.7 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 75.0 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 75.9 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 73.1 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 76.0 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 76.0 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 64.2 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 59.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 53.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 58.1 Units on a scale |
Secondary
Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of mouth feel by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated worse mouth feel.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 76.9 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 78.5 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 79.1 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 80.9 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 76.7 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 68.4 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 75.4 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 69.0 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 66.1 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 67.5 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 69.8 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 69.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 60.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 70.1 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 54.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 68.7 Units on a scale |
Secondary
Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of overall liking by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated less overall liking.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 78.4 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 75.0 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 74.7 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 77.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 73.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 73.4 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 67.9 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 64.9 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 70.1 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 71.9 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 69.8 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 77.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 65.7 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 62.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 55.0 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 63.0 Units on a scale |
Secondary
Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of saltiness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more saltiness.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 34.8 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 39.1 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 33.4 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 32.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 34.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 30.0 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 32.1 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 26.7 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 30.6 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 38.3 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 29.2 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 36.0 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 46.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 49.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 56.4 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 46.8 Units on a scale |
Secondary
Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of sourness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated increase in sourness.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 52.3 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 49.5 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 50.3 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 53.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 32.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 35.7 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 38.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 45.5 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 44.9 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 45.5 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 44.0 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 46.9 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 34.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 28.8 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 29.2 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 29.1 Units on a scale |
Secondary
Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of sweetness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), Participants were required to answer the palatability attribute of sweetness by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more sweetness.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 20.6 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 21.7 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 22.2 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 1 minute | 16.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 1 minute | 43.9 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 36.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 27.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 33.5 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 1 minute | 36.7 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 27.6 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 26.5 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 29.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 25.2 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 25.0 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 25.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 | 1 minute | 26.3 Units on a scale |
Secondary
Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2
Participants were required to answer the palatability attribute of tongue/mouth burn by providing a mark on the colour bar. The data was rescaled to a score ranging from 0 (good) to 100 (bad), where higher scores indicated more tongue/mouth burn.
Time frame: 1 minute (immediately following dose), 5,10 and 20 minutes after tasting dose in each vehicle
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 35.8 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 22.6 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 38.6 Units on a scale |
| Part 1: Sisunatovir 400 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 32.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 17.9 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 25.0 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 24.1 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 23.6 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 23.1 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 25.3 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 21.2 Units on a scale |
| Part 1: Placebo, Fed | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 20.5 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 10 minutes | 24.6 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 20 minutes | 24.4 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 1 minute | 26.3 Units on a scale |
| Part 1: Sisunatovir 200 mg, Fasted | Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 | 5 minutes | 26.5 Units on a scale |
Secondary
AUCtau(dn) for Day 5: Part 1
AUCtau(dn) was calculated as AUCtau/Dose.
Time frame: Pre-dose, 1, 2, 3,4, 5, 6, 8 and 12 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | AUCtau(dn) for Day 5: Part 1 | 18.10 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 47 |
| Part 1: Sisunatovir 200 mg, Fed | AUCtau(dn) for Day 5: Part 1 | 3.939 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 57 |
| Part 1: Placebo, Fed | AUCtau(dn) for Day 5: Part 1 | 3.388 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 51 |
Secondary
AUCtau for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | AUCtau for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 | 787.6 ng*hr/mL | Geometric Coefficient of Variation 57 |
| Part 1: Sisunatovir 200 mg, Fed | AUCtau for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 | 678.2 ng*hr/mL | Geometric Coefficient of Variation 51 |
90% CI: [106.87, 150.1]
Secondary
Cmax(dn) for Day 5: Part 1
Cmax(dn) was calculated as Cmax/Dose.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Cmax(dn) for Day 5: Part 1 | 2.031 ng/mL/mg | Geometric Coefficient of Variation 41 |
| Part 1: Sisunatovir 200 mg, Fed | Cmax(dn) for Day 5: Part 1 | 0.4900 ng/mL/mg | Geometric Coefficient of Variation 52 |
| Part 1: Placebo, Fed | Cmax(dn) for Day 5: Part 1 | 0.3847 ng/mL/mg | Geometric Coefficient of Variation 53 |
Secondary
Cmax for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Cmax for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 | 97.89 ng/mL | Geometric Coefficient of Variation 52 |
| Part 1: Sisunatovir 200 mg, Fed | Cmax for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 | 76.92 ng/mL | Geometric Coefficient of Variation 53 |
90% CI: [117.2, 174.32]
Secondary
Dose Normalized AUCtau (AUCtau [dn]) for Day 1: Part 1
AUCtau(dn) was calculated as AUCtau/Dose.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Dose Normalized AUCtau (AUCtau [dn]) for Day 1: Part 1 | 6.554 Nanogram*hour/ milliliter/milligram | Geometric Coefficient of Variation 30 |
| Part 1: Sisunatovir 200 mg, Fed | Dose Normalized AUCtau (AUCtau [dn]) for Day 1: Part 1 | 2.478 Nanogram*hour/ milliliter/milligram | Geometric Coefficient of Variation 48 |
| Part 1: Placebo, Fed | Dose Normalized AUCtau (AUCtau [dn]) for Day 1: Part 1 | 1.691 Nanogram*hour/ milliliter/milligram | Geometric Coefficient of Variation 72 |
Secondary
Dose Normalized Maximum Plasma Concentration (Cmax [dn]) for Day 1: Part 1
Cmax(dn) was calculated as Cmax/Dose.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) for Day 1: Part 1 | 1.028 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 20 |
| Part 1: Sisunatovir 200 mg, Fed | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) for Day 1: Part 1 | 0.3602 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 47 |
| Part 1: Placebo, Fed | Dose Normalized Maximum Plasma Concentration (Cmax [dn]) for Day 1: Part 1 | 0.2507 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 77 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Day 1: Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Maximum Observed Plasma Concentration (Cmax) for Day 1: Part 1 | 410.8 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| Part 1: Sisunatovir 200 mg, Fed | Maximum Observed Plasma Concentration (Cmax) for Day 1: Part 1 | 72.00 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Part 1: Placebo, Fed | Maximum Observed Plasma Concentration (Cmax) for Day 1: Part 1 | 50.09 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 77 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Day 5: Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Maximum Observed Plasma Concentration (Cmax) for Day 5: Part 1 | 811.0 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Part 1: Sisunatovir 200 mg, Fed | Maximum Observed Plasma Concentration (Cmax) for Day 5: Part 1 | 97.89 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
| Part 1: Placebo, Fed | Maximum Observed Plasma Concentration (Cmax) for Day 5: Part 1 | 76.92 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 53 |
Secondary
Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) for Day 5: Part 1
Rac,Cmax was calculated as Cmax Day5/Cmax Day1.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 and Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) for Day 5: Part 1 | 1.961 Ratio | Geometric Coefficient of Variation 25 |
| Part 1: Sisunatovir 200 mg, Fed | Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) for Day 5: Part 1 | 1.360 Ratio | Geometric Coefficient of Variation 25 |
| Part 1: Placebo, Fed | Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) for Day 5: Part 1 | 1.534 Ratio | Geometric Coefficient of Variation 69 |
Secondary
Observed Accumulation Ratio (Rac) for AUC for Day 5: Part 1
Rac for AUC was calculated as AUCtau Day5/AUCtau Day1.
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1 and Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Observed Accumulation Ratio (Rac) for AUC for Day 5: Part 1 | 2.757 Ratio | Geometric Coefficient of Variation 24 |
| Part 1: Sisunatovir 200 mg, Fed | Observed Accumulation Ratio (Rac) for AUC for Day 5: Part 1 | 1.589 Ratio | Geometric Coefficient of Variation 22 |
| Part 1: Placebo, Fed | Observed Accumulation Ratio (Rac) for AUC for Day 5: Part 1 | 2.003 Ratio | Geometric Coefficient of Variation 63 |
Secondary
Plasma Decay Half-Life (t1/2) for Day 5: Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Plasma Decay Half-Life (t1/2) for Day 5: Part 1 | 9.326 Hour | Standard Deviation 1.2781 |
| Part 1: Sisunatovir 200 mg, Fed | Plasma Decay Half-Life (t1/2) for Day 5: Part 1 | 10.87 Hour | Standard Deviation 0.96844 |
| Part 1: Placebo, Fed | Plasma Decay Half-Life (t1/2) for Day 5: Part 1 | 11.15 Hour | Standard Deviation 2.0984 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 1: Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 1
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 1: Part 1 | 5.00 Hour |
| Part 1: Sisunatovir 200 mg, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 1: Part 1 | 5.00 Hour |
| Part 1: Placebo, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 1: Part 1 | 5.00 Hour |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 5: Part 1
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36 and 48 hours post-dose on Day 5
Population: PK parameter analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Here, Number of Participants Analyzed' signifies participants evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sisunatovir 400 mg, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 5: Part 1 | 4.00 Hour |
| Part 1: Sisunatovir 200 mg, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 5: Part 1 | 5.00 Hour |
| Part 1: Placebo, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 5: Part 1 | 5.00 Hour |