Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sisunatovir · 5 trials · 3 indications
Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.
Cmax was defined as maximum observed plasma concentration.
Cmax was defined as maximum observed plasma concentration.
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
AUCinf was defined as area under the concentration-time curve from time 0 to infinity.
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
AUClast was calculated using linear/log trapezoidal method. Treatment A = sisunatovir 200 mg PIC under fasted condition; reference treatment. Treatment B = sisunatovir 200 mg WGT under fasted condition; test treatment.
AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. Treatment A = sisunatovir 200 mg PIC under fasted condition; reference treatment. Treatment B = sisunatovir 200 mg WGT under fasted condition; test treatment.
Treatment A = sisunatovir 200 mg PIC under fasted condition; reference treatment. Treatment B = sisunatovir 200 mg WGT under fasted condition; test treatment.
The relationship between sisunatovir plasma concentration and change from baseline in Fridericia's heart-rate corrected QT interval were analyzed using a model-based concentration-QTc analysis consistent with the Scientific White Paper on Concentration-QT Modeling. Baseline was defined as the mean of the 3 averages of the triplicate electrocardiogram (ECG) measurements taken before dosing on Day 1 within each period. Mean and CI statistics were based on the individual (within subject) corrected differences between sisunatovir and placebo exposures.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Arm 1 | EXPERIMENTAL | This only arm will be given as a single dose on Day 1 in a fasted state followed by repeated twice daily doses (200 mg BID, Q12 hours) from Days 4-7 plus 1 morning dose on Day 8 in a fed state |
| Treatment A | EXPERIMENTAL | Part 1: Sisunatovir without rabeprazole |
| Treatment B | ACTIVE_COMPARATOR | Part 1: Sisunatovir with 40 mg rabeprazole |
| Treatment C | ACTIVE_COMPARATOR | Part 2: Sisunatovir suspension without rabeprazole |
| Treatment D | EXPERIMENTAL | Part 2: Sisunatovir suspension with 20 mg rabeprazole |
| Treatment E | EXPERIMENTAL | Part 2: Sisunatovir suspension with 40 mg rabeprazole |
| Part 1 Treatment A | EXPERIMENTAL | 4 capsules of sisunatovir in fasted state |
| Part 1 Treatment B | EXPERIMENTAL | 2 tablets of sisunatovir in fasted state |
| Part 1 Treatment C | EXPERIMENTAL | 2 tablets of sisunatovir with a high-fat meal |
| Part 2 Treatment B | EXPERIMENTAL | 2 tablets of sisunatovir in fasted sate |
| Part 2 Treatment D | EXPERIMENTAL | 2 tablets of sisunatovir with a low-fat meal |
| Group A: Higher dose sisunatovir | EXPERIMENTAL | higher dose of sisunatovir dosed every 12 hours |
| Group B: Lower dose sisunatovir | EXPERIMENTAL | Lower dose of sisunatovir dosed every 12 hours |
| Group C: Placebo | PLACEBO_COMPARATOR | Placebo for sisunatovir dosed every 12 hours |
| Group D: Higher dose of sisunatovir | EXPERIMENTAL | Higher dose of sisunatovir dosed every 12 hours under fasted conditions |
| Group E: sisunatovir palatability | EXPERIMENTAL | Sisunatovir in 4 vehicles (water, saline, apple juice, infant formula) to assess the palatability of sisunatovir in each vehicle. sisunatovir will not be swallowed, participants will swirl and spit to assess various aspects of the taste. |
| Name | Type | Description |
|---|---|---|
| Sisunatovir | DRUG | Will be given as a single dose on Day 1 in a fasted state followed by repeated twice daily doses (200 mg BID, Q12 hours) from Days 4-7 plus 1 morning dose on Day 8 in a fed state |
| Rabeprazole 40 mg | DRUG | Tablets once daily for 7 days |
| Sisunatovir suspension | DRUG | Tablets once daily for 7 days |
| Rabeprazole 20 mg | DRUG | Tablets once daily for 7 days |
| placebo | DRUG | 6 capsules administered Q12 hours for 5 doses |
| moxifloxacin | DRUG | 6 capsules of placebo administered Q12 hours for 4 doses, followed by a single tablet of moxifloxacin |
Inclusion Criteria: * Chinese male and female participants aged 18 to 65 years of age, inclusive, at the time of signing of the informed consent document (ICD). * Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination...
Sisunatovir is an investigational small molecule being studied for respiratory syncytial virus (RSV) infection. It is currently in Phase 1 clinical development, with completed trials in healthy adult participants to assess safety, effects, and palatability.
Sisunatovir is being developed by Pfizer, Inc. (NYSE: PFE). The company is conducting Phase 1 clinical trials to evaluate the drug's safety and effects in healthy participants.
Sisunatovir is in Phase 1 clinical development. All three completed trials were Phase 1 studies in healthy adult participants, and the drug is not yet approved by regulatory authorities.
Sisunatovir has completed three Phase 1 trials: NCT05712460 (safety, effects, and palatability in Belgium), NCT05878522 (effects on QTc interval in the US), and NCT05994963 (comparison of different preparations in Belgium). A fourth trial, NCT06105983, also completed.
Sisunatovir is not known to have alternative names. It is being studied under its own name in clinical trials for respiratory syncytial virus infection.