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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Ziresovir; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ziresovir; 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; 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; Other Names: AK0529
Placebo Comparator: placebo; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Ark Biosciences Inc.
• Investigators: Study Director: Jimmy Gu, Ark Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): June 14, 2021
• Study Completion (Actual): July 22, 2021

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: March 4, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 13, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Ziresovir
• Other Study ID Numbers: AK0529-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No