Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects

NCT06591845 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: AK0529-3004
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-center, randomized, partially double-blind, placebo and active-controlled, 4-period crossover design thorough QT/QTc (TQT) clinical study to evaluate the effects of ziresovir on cardiac repolarization in healthy subjects.

Conditions

Healthy Volunteers

Keywords

QT/QTc (TQT) Clinical Study

Outcome Measures

Primary Outcomes (1)

• Change from baseline QTcF (ΔQTcF)

  The primary ECG endpoint is the change from baseline in the QT interval corrected for heart rate (HR) using the Fridericia method (ΔQTcF).

  Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period

Secondary Outcomes (8)

• Change from baseline in QTc

  Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period

• Change from baseline in HR, PR, and QRS

  Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period

• Incidence of treatment-emergent adverse events (TEAEs) and changes in laboratory safety tests, vital signs, and ECGs.

  Up to Day 8 of each treatment period (up to 31 days)

• Treatment-emergent changes in ECG Morphology

  Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period

• Categorical outliers for QTcF/QTcI/QTcS, HR, PR, and QRS.

  Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period

Study Arms (4)

Treatment T (Therapeutic dose)

EXPERIMENTAL

The subjects will receive a ziresovir 125 mg as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4)

Drug: Ziresovir 125 mg

Treatment ST (Supratherapeutic dose)

EXPERIMENTAL

The subjects will receive a ziresovir 500 mg as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4)

Drug: Ziresovir 500 mg

Treatment P (Placebo)

PLACEBO COMPARATOR

The subjects will receive a placebo as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4)

Drug: Placebo

Treatment PC (positive control)

ACTIVE COMPARATOR

The subjects will receive a moxifloxacin hydrochloride tablet 400 mg as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4)

Drug: Moxifloxacin hydrochloride tablet 400 mg

Interventions

Ziresovir 125 mg DRUG

Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral

Treatment T (Therapeutic dose)

Ziresovir 500 mg DRUG

Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral

Treatment ST (Supratherapeutic dose)

Placebo DRUG

Active Substance: Placebo, Pharmaceutical Form: Suspension, Route of Administration: Oral

Treatment P (Placebo)

Moxifloxacin hydrochloride tablet 400 mg DRUG

Active Substance: Moxifloxacin hydrochloride Pharmaceutical Form: Tablet Route of Administration: Oral

Treatment PC (positive control)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject voluntarily signed a written informed consent form.
• Male or female; between 18 and 50 years old (inclusive).
• Male subjects weighing ≥50 kg, female subjects weighing ≥45 kg, body mass index (BMI) between 19.0 and 30.0 kg/m2 (inclusive), BMI= weight (kg)/height2 (m2).
• Healthy, as defined by no clinically significant or relevant abnormalities identified by vital signs, physical examination, laboratory examination items, ECG, and other trial-related examinations at screening, admission or baseline day of each period as assessed by the investigator.
• The subject can communicate well with the investigator and is able to complete the study in compliance with the protocol.

You may not qualify if:

• History of or evidence of clinically significant disorder, condition or disease not otherwise excluded that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• History of cardiovascular disease or risk factors for Torsade de Pointes (TdP) at screening, including but not limited to: unexplained syncope; heart failure; cardiomyopathy; hypertension; angina pectoris; myocardial infarction; hypokalemia; bradycardia or sick sinus syndrome; cardiac conduction abnormalities; personal or family history of long QT syndrome (LQTS); or family history of sudden death.
• Known or suspected malignancy.
• Known allergic reactions to study intervention (e.g., ziresovir or its drug excipients, moxifloxacin, fluoroquinolone antibiotics) or history of clinically significant multiple or severe drug allergies, food allergies.
• Subjects who have donated blood or have had a blood loss ≥500 ml within 3 months prior to screening.
• Subjects who have participated in a clinical trial evaluating an investigational drug or device within 30 days or 5 half-lives (whichever is longer) prior to screening.
• History of substance abuse (e.g., alcohol, licit or illicit drugs) within 1 year prior to screening.
• lead ECG at screening or admission exceeding criteria: PR\>220 ms, QRS\>120 ms, HR\< 50 bpm or \>100 bpm, QTcF \>450 ms (male and female) (The mean of 3 triplicate ECGs timepoint measurement); or ECG abnormalities that are considered by the investigator to be abnormal and clinically significant.
• Systolic blood pressure (BP) \> 140 mmHg or \< 90 mmHg, or diastolic BP \> 90 mmHg at screening or admission.
• Serum potassium, calcium, or magnesium levels outside the normal range at screening or admission.
• Positive blood alcohol test, positive urine cotinine test or positive urine drug abuse screening at screening or admission.
• Engaged in strenuous exercise within 48 hours before randomization (e.g., marathon running, long-distance cycling, weightlifting).
• Intake of caffeinated beverages or food within 48 hours before randomization or a history of high caffeine consumption (e.g., in the last 3 months drinking \>5 cups of coffee/day).
• History of alcoholism or regular alcohol consumption within 1 year prior to screening, defined as more than 14 units (male) or 7 units (female) of alcohol per week (1 unit =360 mL of beer or 45 mL of spirits containing 40% alcohol or 150 mL of wine).
• Smoking or use of tobacco or nicotine-containing products within 6 months before screening.

Sponsors & Collaborators

• Shanghai Ark Biopharmaceutical Co., Ltd.: lead

MeSH Terms

Interventions

ziresovir; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David Han, M.D., M.P.H

  California Clinical Trials Medical Group

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sally Xiang

CONTACT

2150681677; sally.xiang@arkbiosciences.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Partially Double-Blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This clinical study will last for a total of 59 days, including a 26-day screening period, admission day (Day -2) preceding the first treatment period, 4 treatment periods with 8 days washout in-between and a safety follow-up period (7 ± 1 days after the last dose).

Study Record Dates

• First Submitted: September 4, 2024
• First Posted: September 19, 2024
• Study Start: September 15, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share