A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Ziresovir in Healthy Subjects

NCT04788017 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AK0529-3001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (31)

• numbers of all AEs

  The Common Terminology Criteria for Adverse Events (CTCAE) Version 5 will be used to grade AEs

  through study completion, an average of 22 days

• percentages of all AEs

  The Common Terminology Criteria for Adverse Events (CTCAE) Version 5 will be used to grade AEs

  through study completion, an average of 22 days

• change from baseline in systolic and diastolic blood pressure

  blood pressure in millimeter of mercury

  screen/day -1/day 1/day 2/day 3/day4

• change from baseline in pulse rate

  pulse rate in times per minute

  screen/day -1/day 1/day 2/day 3/day4

• change from baseline in respiratory rate

  respiratory rate in times per minute

  screen/day -1/day 1/day 2/day 3/day4

• change from baseline in oral temperature

  oral temperature in degree

  screen/day -1/day 1/day 2/day 3/day4

• change from baseline in Prothrombin time/International Normalized Ratio

  INR is calculated from the PT and allows for worldwide standardization of results.

  screen/day -1/day 2/day4

• change from baseline in Thrombin time

  Thrombin time in seconds

  screen/day -1/day 2/day4

• change from baseline in activated Partial Thromboplastin time

  activated Partial Thromboplastin time in seconds

  screen/day -1/day 2/day4

• change from baseline in Hemoglobin (Hgb) count

  Hemoglobin (Hgb) in gram per liter

  screen/day -1/day 2/day4

• change from baseline in Hematocrit (Hct)

  screen/day -1/day 2/day4

• change from baseline in Platelet count

  Platelet count per liter

  screen/day -1/day 2/day4

• change from baseline in Red blood cell (RBC) count

  screen/day -1/day 2/day4

• change from baseline in White blood cell (WBC) count with differential

  screen/day -1/day 2/day4

• change from baseline in Specific gravity from urinalysis

  screen/day -1/day 2/day4

• change from baseline in pH from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Protein from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Glucose from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Ketones from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Bilirubin from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Blood from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Nitrites from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Leukocytes from urinalysis

  screen/day -1/day 2/day4

• change from baseline in Urobilinogen from urinalysis

  screen/day -1/day 2/day4

• Incidence of abnormal Microscopic urine analysis

  screen/day -1/day 2/day4

• change from baseline in heart rate-corrected QT interval from resting 12-lead ECGs

  ECGs will be performed after the subject has been supine for at least 5 minutes

  screen/day -1/day1/day2/day4

• change from baseline in heart rate from resting 12-lead ECGs

  ECGs will be performed after the subject has been supine for at least 5 minutes

  screen/day -1/day1/day2/day4

• change from baseline in QRS intervals from resting 12-lead ECGs

  ECGs will be performed after the subject has been supine for at least 5 minutes

  screen/day -1/day1/day2/day4

• change from baseline in treatment-emergent T-wave morphology from resting 12-lead ECGs

  ECGs will be performed after the subject has been supine for at least 5 minutes

  screen/day -1/day1/day2/day4

• change from baseline in appearance of U-waves from resting 12-lead ECGs

  ECGs will be performed after the subject has been supine for at least 5 minutes

  screen/day -1/day1/day2/day4

• Incidence of abnormal physical findings

  full physical examination will be conducted at screening and an abbreviated physical exam will be conducted on Day -1 and Day 2. A symptom-directed physical exam will be conducted on Day 3 and Day 4.

  screen/day -1/day2/day3/day4

Secondary Outcomes (1)

• To characterize the drug concentration of ziresovir following single ascending doses by oral administration in healthy adult male and female subjects

  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

Study Arms (2)

ziresovir

ACTIVE COMPARATOR

The study drugs will be administered to subjects by CRU staff at approximately 8:00 a.m. (± 1 hour), following an overnight fast. Immediately following administration of the assigned dose of the study drugs, subjects will be given water such that their water consumption is approximately 240 mL as follows: * If administered 60 mL as the study drug dose, follow with approximately 180 mL water. * If administered 120 mL as the study drug dose, follow with approximately 120 mL water. * If administered 180 mL as the study drug dose, follow with approximately 60 mL water.

Drug: Ziresovir

placebo

PLACEBO COMPARATOR

The study drugs will be administered to subjects by CRU staff at approximately 8:00 a.m. (± 1 hour), following an overnight fast. Immediately following administration of the assigned dose of the study drugs, subjects will be given water such that their water consumption is approximately 240 mL as follows: * If administered 60 mL as the study drug dose, follow with approximately 180 mL water. * If administered 120 mL as the study drug dose, follow with approximately 120 mL water. * If administered 180 mL as the study drug dose, follow with approximately 60 mL water.

Other: Placebo

Interventions

Ziresovir DRUG

Planned treatments are: * Cohort 1: 300 mg of ziresovir * Cohort 2: up to 600 mg of ziresovir * Cohort 3: up to 900 mg of ziresovir

Also known as: AK0529

ziresovir

Placebo OTHER

Planned treatments are: * Cohort 1: 300 mg of placebo * Cohort 2: up to 600 mg of placebo * Cohort 3: up to 900 mg of placebo

placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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;
• Poor venous access;
• 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;
• Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the study drug dose;
• 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;
• 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.

Sponsors & Collaborators

• Shanghai Ark Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

Frontage

Secaucus, New Jersey, 07094, United States

Location

MeSH Terms

Interventions

ziresovir

Study Officials

• Jimmy Gu

  Ark Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: March 9, 2021
• Study Start: March 24, 2021
• Primary Completion: June 14, 2021
• Study Completion: July 22, 2021
• Last Updated: February 15, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)