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

NCT ID: NCT06591845

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-15
• Study Completion Date: 2024-12-31

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.

Detailed Description

This clinical study is a single-center, randomized, partially double-blind, placebo- and active-controlled, four-period crossover design, with healthy subjects comprising the enrolled population. Ziresovir and placebo will be administered in a double-blind manner, while moxifloxacin hydrochloride tablets will be administered in as open-label.

Thirty-two subjects meeting all inclusion criteria and none of the exclusion criteria will be randomized into 1 of 12 dosing sequences, each consisting of 4 periods with an 8-day washout period in-between.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Treatment T (Therapeutic dose)

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)

Group Type: EXPERIMENTAL

Ziresovir 125 mg

Intervention Type: DRUG

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

Treatment ST (Supratherapeutic dose)

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)

Group Type: EXPERIMENTAL

Ziresovir 500 mg

Intervention Type: DRUG

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

Treatment P (Placebo)

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Treatment PC (positive control)

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)

Group Type: ACTIVE_COMPARATOR

Moxifloxacin hydrochloride tablet 400 mg

Intervention Type: DRUG

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

Interventions

Ziresovir 125 mg

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

Intervention Type: DRUG

Ziresovir 500 mg

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Moxifloxacin hydrochloride tablet 400 mg

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. The subject voluntarily signed a written informed consent form.

2. Male or female; between 18 and 50 years old (inclusive).

3. 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).

4. 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.

5. The subject can communicate well with the investigator and is able to complete the study in compliance with the protocol.

Exclusion Criteria

1. 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.

2. 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.

3. Known or suspected malignancy.

4. 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.

5. Subjects who have donated blood or have had a blood loss ≥500 ml within 3 months prior to screening.

6. 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.

7. History of substance abuse (e.g., alcohol, licit or illicit drugs) within 1 year prior to screening.

8. 12-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.

9. Systolic blood pressure (BP) > 140 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg at screening or admission.

10. Serum potassium, calcium, or magnesium levels outside the normal range at screening or admission.

11. Positive blood alcohol test, positive urine cotinine test or positive urine drug abuse screening at screening or admission.

12. Engaged in strenuous exercise within 48 hours before randomization (e.g., marathon running, long-distance cycling, weightlifting).

13. 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).

14. 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).

15. Smoking or use of tobacco or nicotine-containing products within 6 months before screening.

16. Pregnant or lactating women or those with positive blood pregnancy test results.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shanghai Ark Biopharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Han, M.D., M.P.H

Role: PRINCIPAL_INVESTIGATOR

California Clinical Trials Medical Group

Central Contacts

Sally Xiang

Role: CONTACT

sally.xiang@arkbiosciences.com

2150681677

Other Identifiers

AK0529-3004

Identifier Type: -

Identifier Source: org_study_id