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

Shanghai Ark Biopharmaceutical

Status and phase: Not yet enrolling; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Ziresovir 500 mg; Drug: Placebo; Drug: Moxifloxacin hydrochloride tablet 400 mg; Drug: Ziresovir 125 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT06591845

AK0529-3004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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32 participants in 4 patient groups, including a placebo group

Treatment T (Therapeutic dose)

Experimental group

Description:

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)

Treatment:

Drug: Ziresovir 125 mg

Treatment ST (Supratherapeutic dose)

Experimental group

Description:

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)

Treatment:

Drug: Ziresovir 500 mg

Treatment P (Placebo)

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo

Treatment PC (positive control)

Active Comparator group

Description:

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)

Treatment:

Drug: Moxifloxacin hydrochloride tablet 400 mg