Clinical trial NCT04788017: A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Ziresovir in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Group, Single Ascending Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Ziresovir in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-03-09
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This is a randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics (PK) of ziresovir following a single ascending oral dose administration in healthy adult subjects under fasted conditions.

Detailed description: Up to 3 dose cohorts are planned. The ziresovir dose level of each cohort is determined based on the collective clinical and nonclinical data of ziresovir.

The proposed dose levels of Cohorts 1, 2 and 3 are 300 mg and up to 600 mg and up to 900 mg, respectively.

A total of up to 24 subjects will be randomized with 18 subjects to receive active drug and 6 subjects to receive placebo in a double-blind fashion. Eight subjects will be randomized in each dose cohort, with 6 subjects to receive active drug and 2 subjects o receive placebo.

Eligibility criteria: Inclusion Criteria:

1. Capable of giving written informed consent and complying with study procedures;
2. Between the ages of 18 and 55 years, inclusive;
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg;
4. Female subjects must have a negative pregnancy test result at screening;
5. Considered healthy by the Investigator, based on subject's reported medical history, full physical examination, 12-lead ECG, and vital signs;
6. Willing and being able to adhere to study restrictions and to be confined at the Clinical Research Unit.

Exclusion Criteria:

1. Clinically significant reported history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
2. Poor venous access;
3. Taken an investigational drug or participated in a clinical trial evaluating an investigational drug or device within 30 days (or 5 half-lives) prior to the study drug dose, whichever is longer;
4. Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the study drug dose;
5. Major surgery or hospitalization within 6 months prior to screening that in the Investigator's opinion would put the subject or study conduct at risk, or have any scheduled surgery or hospitalization during the study period;
6. Any condition or finding that in the Investigator's opinion would put the subject or study conduct at risk if the subject were to participate in the study.

Primary outcomes:
measure: numbers of all AEs
timeFrame: through study completion, an average of 22 days
measure: percentages of all AEs
timeFrame: through study completion, an average of 22 days
measure: change from baseline in systolic and diastolic blood pressure
timeFrame: screen/day -1/day 1/day 2/day 3/day4
measure: change from baseline in pulse rate
timeFrame: screen/day -1/day 1/day 2/day 3/day4
measure: change from baseline in respiratory rate
timeFrame: screen/day -1/day 1/day 2/day 3/day4
measure: change from baseline in oral temperature
timeFrame: screen/day -1/day 1/day 2/day 3/day4
measure: change from baseline in Prothrombin time/International Normalized Ratio
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Thrombin time
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in activated Partial Thromboplastin time
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Hemoglobin (Hgb) count
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Hematocrit (Hct)
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Platelet count
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Red blood cell (RBC) count
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in White blood cell (WBC) count with differential
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Specific gravity from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in pH from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Protein from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Glucose from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Ketones from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Bilirubin from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Blood from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Nitrites from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Leukocytes from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in Urobilinogen from urinalysis
timeFrame: screen/day -1/day 2/day4
measure: Incidence of abnormal Microscopic urine analysis
timeFrame: screen/day -1/day 2/day4
measure: change from baseline in heart rate-corrected QT interval from resting 12-lead ECGs
timeFrame: screen/day -1/day1/day2/day4
measure: change from baseline in heart rate from resting 12-lead ECGs
timeFrame: screen/day -1/day1/day2/day4
measure: change from baseline in QRS intervals from resting 12-lead ECGs
timeFrame: screen/day -1/day1/day2/day4
measure: change from baseline in treatment-emergent T-wave morphology from resting 12-lead ECGs
timeFrame: screen/day -1/day1/day2/day4
measure: change from baseline in appearance of U-waves from resting 12-lead ECGs
timeFrame: screen/day -1/day1/day2/day4
measure: Incidence of abnormal physical findings
timeFrame: screen/day -1/day2/day3/day4
Secondary outcomes:
measure: To characterize the drug concentration of ziresovir following single ascending doses by oral administration in healthy adult male and female subjects
timeFrame: 0 (within 90 minutes prior to dosing) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours post-dose
Other outcomes:
Locations:
city: Secaucus
country: United States
facility: Frontage
state: New Jersey
Study officials:
affiliation: Ark Biosciences
name: Jimmy Gu
role: STUDY_DIRECTOR
References: