Clinical trial NCT06591845: Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects
Official title: A Single-Center, Randomized, Partially Double-Blind, Placebo- and Active-Controlled, Four-period Crossover, Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: QT/QTc (TQT) Clinical Study
Lead sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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).
Primary purpose: TREATMENT

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.

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\&amp;gt;220 ms, QRS\&amp;gt;120 ms, HR\&amp;lt; 50 bpm or \&amp;gt;100 bpm, QTcF \&amp;gt;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) \&amp;gt; 140 mmHg or \&amp;lt; 90 mmHg, or diastolic BP \&amp;gt; 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 \&amp;gt;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.

Primary outcomes:
measure: Change from baseline QTcF (ΔQTcF)
timeFrame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
Secondary outcomes:
measure: Change from baseline in QTc
timeFrame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
measure: Change from baseline in HR, PR, and QRS
timeFrame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
measure: Incidence of treatment-emergent adverse events (TEAEs) and changes in laboratory safety tests, vital signs, and ECGs.
timeFrame: Up to Day 8 of each treatment period (up to 31 days)
measure: Treatment-emergent changes in ECG Morphology
timeFrame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
measure: Categorical outliers for QTcF/QTcI/QTcS, HR, PR, and QRS.
timeFrame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
measure: Maximum observed plasma concentration (Cmax) of ziresovir
timeFrame: Pre-dose within 1 hour and at 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, and 72 hours post-dose during each period
measure: Terminal elimination half-life (t1/2) of ziresovir.
timeFrame: Pre-dose within 1 hour and at 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, and 72 hours post-dose during each period.
measure: Area under the curve (AUC) of ziresovir.
timeFrame: Pre-dose within 1 hour and at 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, and 72 hours post-dose during each period.
Other outcomes:
Locations:
Study officials:
affiliation: California Clinical Trials Medical Group
name: David Han, M.D., M.P.H
role: PRINCIPAL_INVESTIGATOR
References: