Phase 1
N=12
A Study to Assess the Safety, Effects and Palatability of Sisunatovir in Healthy Adult Participants
Respiratory Syncytial Viruses
Bottom Line
View on ClinicalTrials.gov: NCT05712460 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Sep 2024
Primary outcome: Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) — 6; 7; 4; 9 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- sisunatovir (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Apr 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
6; 7; 4; 9; 2; 1 | — |
| PRIMARY Number of Participants With Clinical Laboratory Abnormalities: Part 1 |
2; 2; 4; 5 | — |
| PRIMARY Number of Participants With Newly Occurring Notable Abnormal Vital Signs: Part 1 |
0; 1; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings: Part 1 |
0; 0; 0; 1 | — |
| SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 1: Part 1 |
2623; 495.7; 338.4 | — |
| SECONDARY Dose Normalized AUCtau (AUCtau [dn]) for Day 1: Part 1 |
6.554; 2.478; 1.691 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Day 1: Part 1 |
410.8; 72.00; 50.09 | — |
| SECONDARY Dose Normalized Maximum Plasma Concentration (Cmax [dn]) for Day 1: Part 1 |
1.028; 0.3602; 0.2507 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 1: Part 1 |
5.00; 5.00; 5.00 | — |
| SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Day 5: Part 1 |
7244; 787.6; 678.2 | — |
| SECONDARY AUCtau(dn) for Day 5: Part 1 |
18.10; 3.939; 3.388 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) for Day 5: Part 1 |
811.0; 97.89; 76.92 | — |
| SECONDARY Cmax(dn) for Day 5: Part 1 |
2.031; 0.4900; 0.3847 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) for Day 5: Part 1 |
4.00; 5.00; 5.00 | — |
| SECONDARY Apparent Clearance (CL/F) for Day 5: Part 1 |
55.20; 253.9; 295.2 | — |
| SECONDARY Observed Accumulation Ratio (Rac) for AUC for Day 5: Part 1 |
2.757; 1.589; 2.003 | — |
| SECONDARY Observed Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) for Day 5: Part 1 |
1.961; 1.360; 1.534 | — |
| SECONDARY Plasma Decay Half-Life (t1/2) for Day 5: Part 1 |
9.326; 10.87; 11.15 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) for Day 5: Part 1 |
736.1; 3962; 4676 | — |
| SECONDARY AUCtau for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 |
787.6; 678.2 | — |
| SECONDARY Cmax for Day 5: Evaluation of Food Effect (Sisunatovir 200 mg Fed Versus Fasted): Part 1 |
97.89; 76.92 | — |
| SECONDARY Assessment of Overall Liking Based on Palatability Assessment Questionnaire: Part 2 |
74.7; 67.9; 77.6; 65.7; 78.4; 73.4 | — |
| SECONDARY Assessment of Mouth Feel Based on Palatability Assessment Questionnaire: Part 2 |
80.9; 68.4; 66.1; 68.7; 78.5; 75.4 | — |
| SECONDARY Assessment of Bitterness Based on Palatability Assessment Questionnaire: Part 2 |
75.3; 73.5; 76.0; 64.2; 78.8; 75.0 | — |
| SECONDARY Assessment of Tongue/Mouth Burn Based on Palatability Assessment Questionnaire: Part 2 |
22.6; 17.9; 20.5; 26.3; 32.6; 24.1 | — |
| SECONDARY Assessment of Sourness Based on Palatability Assessment Questionnaire: Part 2 |
53.5; 32.8; 45.5; 34.6; 52.3; 45.5 | — |
| SECONDARY Assessment of Saltiness Based on Palatability Assessment Questionnaire: Part 2 |
34.8; 26.7; 36.0; 56.4; 39.1; 34.8 | — |
| SECONDARY Assessment of Sweetness on Palatability Assessment Questionnaire: Part 2 |
16.5; 43.9; 36.7; 26.3; 21.7; 36.6 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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.
- 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.
- Body mass index (BMI) of 17.5 to 35 kg/m2; and a total body weight >50 kg (110 lb).
Exclusion Criteria
- 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).
- 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.
- 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.
- A positive urine drug test, confirmed by a repeat test, if deemed necessary.
- 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.
- Standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
- 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) 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.
Data sourced from ClinicalTrials.gov (NCT05712460). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.