The purpose of the study is to learn about: * The activity of sisunotavir in the body over a period. It includes the processes by which sisunotavir is absorbed, distributed in the body, localized in the tissues, and removed from the body. * safety and tolerability of sisunatovir (PF-07923568) in Chinese healthy adult participants. This information is being collected to support further clinical development as well as medicine registration in China. This study is seeking for participants who: * are male and female participants aged 18 to 65 years of age. * are male and female participants who are healthy as seen by medical tests. * have body mass index (BMI) of 19 to 27 kg/m2 and a total body weight of more than 50 kilograms (110 pounds). About 12 participants will receive sisunatovir. Four capsules (strength=50 milligrams, 200 milligrams in total) of Sisunatovir will be given on Day 1 on empty stomach. This will be followed by 8 capsules of sisunatovir with 12 hours gap in between four capsules from Days 4 to 7. The participants will have to take 4 capsules of sisunatovir in the morning of 8th day with a meal. The total time of participants will be in the study is about 71 days. This includes the screening visit to the Follow-up contact. In screening visit, participants will be tested to see if they are fit to take part in the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
12
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
Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
Huashan Hospital
Shanghai, Shanghai Municipality, China
Huashan Hospital Fudan University
Shanghai, Shanghai Municipality, China
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 1
Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 4
Cmax was defined as maximum observed plasma concentration.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 8
Cmax was defined as maximum observed plasma concentration.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day 8
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 1
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day1
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 4
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 8
AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 8
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Sisunatovir on Day1
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day1
AUCinf was defined as area under the concentration-time curve from time 0 to infinity.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1
Time to Reach Cmax (Tmax) on Day 1, Day 4 and Day 8
Tmax was defined as time to reach Cmax.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1, and Day 8. 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4.
Terminal Elimination Half-life (t½) on Day 1 and Day 8
t½ was defined as terminal elimination half-life.
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12,14, 24, 48, 72 hours post dose on Day1, and Day 8
Accumulation Ratio for Sisunatovir (Rac)
Rac is defined as: Observed accumulation ratio for AUCtau. Accumulation ratio on AUCtau = AUC12 (Day 8) /AUC12 (Day 4)
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 and Day 8
Accumulation Ratio on Cmax for Sisunatovir (Rac, Cmax)
Accumulation ratio on Cmax =Cmax (Day 8) /Cmax (Day 4)
Time frame: 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 and 0, 1, 2, 3, 4, 5, 6, 8, 10, 12,14, 24, 48, 72 hours post dose on Day 8
Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship with the study intervention. SAE is defined as one of the following: is fatal or life threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. AEs include all SAEs and non-SAEs.
Time frame: From the first dose (Day 1) up to 35 days after the last dose (Day 8) of study intervention (up to 43 days)
Number of Participants With Vital Signs Meeting the Pre-specified Criteria
Blood pressure (BP) and pulse rate were obtained with participant following at least a 5-minute rest in a supine position. Clinical significance of vital signs was determined at the investigator's discretion.
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Time frame: Baseline up to Day 11 (11 days)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet, neutrophils, eosinophils, monocytes, basophils, lymphocytes, leukocytes); clinical chemistry (alanine aminotransferase, albumin, alkaline phosphatase, bilirubin, calcium, carbon dioxide combining power, chloride, creatinine, cystatin C, GFR CKD-EPI serum creatinine 2021, gamma glutamyl transferase, glucose, potassium, sodium, urate, urea). urinalysis (Bilirubin, Glucose, Hemoglobin, Ketones, Leukocyte Esterase, Nitrite, Protein, Urobilinogen, pH).0 indicates no participants with abnormalities of all above lab examination.
Time frame: Baseline up to Day 11 (11 days)
Number of Participants With Electrocardiogram (ECG) Abnormalities
Criteria for ECG abnormalities: maximum PR interval \>=300 milliseconds (msec) and maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 msec and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, maximum QRS interval \>=140 msec and a maximum IFB: Pctchg\>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to \<480 msec, 480 msec to \<500 msec or \>=500 msec and a maximum change of \<=30change\<60 or \>=60 msec from baseline.
Time frame: Baseline up to Day 11 (11 days)