- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT06591845
Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects
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
Studieoversikt
Status
Forhold
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
California
-
Glendale, California, Forente stater, 91206
- California Clinical Trials Medical Group, Inc.
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
- 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.
- Pregnant or lactating women or those with positive blood pregnancy test results.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Enkelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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)
|
Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral
|
|
Eksperimentell: 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)
|
Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral
|
|
Placebo komparator: 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)
|
Active Substance: Placebo, Pharmaceutical Form: Suspension, Route of Administration: Oral
|
|
Aktiv komparator: 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)
|
Active Substance: Moxifloxacin hydrochloride Pharmaceutical Form: Tablet Route of Administration: Oral
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change from baseline QTcF (ΔQTcF)
Tidsramme: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
|
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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change from baseline in QTc
Tidsramme: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
|
Change from baseline in QTc using correction methods not chosen as the primary correction method if a substantial HR effect is observed
|
Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
|
|
Change from baseline in HR, PR, and QRS
Tidsramme: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
|
Change-from-baseline in HR, PR and QRS (ΔHR, ΔPR and ΔQRS).
|
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.
Tidsramme: Up to Day 8 of each treatment period (up to 31 days)
|
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
Tidsramme: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
|
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.
Tidsramme: 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
|
|
Maximum observed plasma concentration (Cmax) of ziresovir
Tidsramme: 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
|
PK parameters of ziresovir and its metabolites including maximum observed plasma concentration (Cmax).
|
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
|
|
Terminal elimination half-life (t1/2) of ziresovir.
Tidsramme: 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.
|
PK parameters of ziresovir and its metabolites including terminal elimination half-life (t1/2).
|
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.
|
|
Area under the curve (AUC) of ziresovir.
Tidsramme: 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.
|
PK parameters of ziresovir and its metabolites including area under the curve (AUC).
|
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.
|
Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: David Han, M.D., M.P.H, California Clinical Trials Medical Group
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- AK0529-3004
Plan for individuelle deltakerdata (IPD)
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