A Study to Learn How the Study Medicine Called Sisunatovir is Tolerated and Acts in the Bodies of Chinese Healthy Adults.
- Registration Number
- NCT05987072
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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, standard 12-lead ECG, and laboratory tests.
- Body mass index (BMI) of 19 to 27 kg/m2; and a total body weight >50 kg (110 lb).
- 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).
- Any 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 cytochrome P4503A (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 (eg, QTc corrected using Fridericia's formula [QTcF] >450 ms, complete left bundle branch block [LBBB], signs of an acute or indeterminate- age myocardial infarction, ST-segment and T-wave [ST-T] interval changes suggestive of myocardial ischemia, second- or thirddegree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is >450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or quantitative restrictions (QRS) exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer interpreted- ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
- 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 chronic kidney disease epidemiology (CKD-EPI equation);
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.05 × upper limit of normal (ULN);
- Gamma-glutamyl transferase (GGT) > 1.05 × ULN;
- Alkaline phosphatase > 1.05 × ULN;
- Total bilirubin level ≥1.05 × 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 Sisunatovir 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
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 1 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1 Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 4 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 Cmax was defined as maximum observed plasma concentration.
Maximum Observed Plasma Concentration (Cmax) of Sisunatovir on Day 8 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day 8 Cmax was defined as maximum observed plasma concentration.
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 1 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day1 AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 4 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Area Under the Plasma Concentration-time Profile From Time Zero to Time 12 Hours (AUC12) of Sisunatovir on Day 8 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 8 AUC12 was defined as area under the concentration-time curve from time zero to 12 hours.
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Sisunatovir on Day1 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1 AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day1 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 48, 72 hours post dose on Day1 AUCinf was defined as area under the concentration-time curve from time 0 to infinity.
- Secondary Outcome Measures
Name Time Method Time to Reach Cmax (Tmax) on Day 1, Day 4 and Day 8 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. Tmax was defined as time to reach Cmax.
Terminal Elimination Half-life (t½) on Day 1 and Day 8 0, 1, 2, 3, 4, 5, 6, 8, 10, 12,14, 24, 48, 72 hours post dose on Day1, and Day 8 t½ was defined as terminal elimination half-life.
Accumulation Ratio for Sisunatovir (Rac) 0, 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose on Day 4 and Day 8 Rac is defined as: Observed accumulation ratio for AUCtau. Accumulation ratio on AUCtau = AUC12 (Day 8) /AUC12 (Day 4)
Accumulation Ratio on Cmax for Sisunatovir (Rac, Cmax) 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 Accumulation ratio on Cmax =Cmax (Day 8) /Cmax (Day 4)
Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs) From the first dose (Day 1) up to 35 days after the last dose (Day 8) of study intervention (up to 43 days) 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.
Number of Participants With Vital Signs Meeting the Pre-specified Criteria Baseline up to Day 11 (11 days) 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.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Baseline up to Day 11 (11 days) 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.
Number of Participants With Electrocardiogram (ECG) Abnormalities Baseline up to Day 11 (11 days) 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.
Trial Locations
- Locations (3)
Huashan Hospital
🇨🇳Shanghai, Shanghai, China
Huashan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
Huashan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China