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A Trial to Evaluate the Effect of LEO 152020 on the Heart of Healthy People

Phase 1
Completed
Conditions
Healthy Volunteers
Cardiac Repolarisation
Interventions
Registration Number
NCT05508776
Lead Sponsor
JW Pharmaceutical
Brief Summary

The trial medicine (LEO 152020) is being developed to treat people with eczema.

The aims of this trial are to find out about:

* How the trial medicine affects participant's heart rhythm.

* How much of the trial medicine is absorbed into the bloodstream, and how quickly the body gets rid of it.

* The safety of the trial medicine and any side effects that might be related to it.

The trial will last up to 45 days, and there will be up to 6 visits.

Four treatment periods are planned for this trial. In each treatment period, participant will receive a single dose of the trial medicine at dose A, trial medicine at dose B, dummy tablet, or an approved medication named moxifloxacin (used for the treatment of bacterial infections). The order of these 4 treatment periods is chosen at random. Participant will receive all 4 treatments; it is only the order of the treatments that is random.

There will be 6 trial visits and they will include 1 screening visit, 4 treatment period visits and 1 final, follow-up visit at the clinic. The 4 treatment period visits will last for 3 days, from Day -1 (check-in to the clinic) to Day 2 (check-out of the clinic). There will be a period of at least 3 days between the 4 dosing occasions.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
Inclusion Criteria
  • Men or women between 18 and 55 years of age, inclusive, at screening.
  • Body mass index between 18.0 and 30.0 kg/m2, inclusive.
  • In good health at screening and check-in (as applicable) for Treatment Period 1, as assessed by the investigator (or designee) based on medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g. suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable).
  • Female subjects of childbearing potential must be willing to comply with the contraception requirements.
Exclusion Criteria
  • ECG with any clinically relevant abnormality, such as QTcF >450 ms (males) or >460 ms (females), QRS duration >110 ms, or PR interval >220 ms.

  • Subjects at risk for Torsades de pointes based on any of the following:

    1. Uncorrected hypokalaemia or hypomagnesaemia at screening or check-in for Treatment Period 1, history of cardiac failure, history of clinically significant/symptomatic bradycardia.
    2. (Congenital) long QT syndrome or family history of idiopathic sudden death.
  • Known history of ventricular arrhythmias.

  • Second- or third-degree atrioventricular block.

  • Use or intend to use any medications or products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to check-in for Treatment Period 1, considered to potentially impact subject safety or the objectives of the trial, as determined by the investigator (or designee).

  • Use of tobacco- or nicotine-containing products within 3 months prior to check-in for Treatment Period 1, or positive cotinine at screening or check-in for Treatment Period 1.

Other protocol defined criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
LEO 152020 Dose ALEO 152020A single oral dose of LEO 152020 Dose A according to the randomization schedule.
LEO 152020 Dose BLEO 152020A single dose of LEO 152020 Dose B according to the randomization schedule.
MoxifloxacinMoxifloxacinA single oral dose of moxifloxacin 400 mg according to the randomization schedule.
PlaceboPlaceboA single dose of placebo according to the randomization schedule.
Primary Outcome Measures
NameTimeMethod
Placebo-corrected change from baseline of LEO 152020 using QT interval corrected using Fridericia's formula (ΔΔQTcF)Predose up to 24 hours postdose for each applicable treatment
Secondary Outcome Measures
NameTimeMethod
Change from baseline of Heart Rate (ΔHR)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Change from baseline of QT interval corrected using Fridericia's formula (ΔQTcF)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Change from baseline of Pulse Rate (ΔPR)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Placebo-corrected, change from baseline of Heart Rate (ΔΔHR)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Placebo-corrected, change from baseline of Pulse Rate (ΔΔPR)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Time to maximum plasma concentration of LEO 152020 (tmax)0 to 24 hours postdose for each applicable treatment
Area under the plasma concentration-time curve from time 0 to 24 hours postdose of LEO 152020 (AUC0-24).0 to 24 hours postdose for each applicable treatment
Apparent terminal elimination half-life of LEO 152020 (t1/2)0 to 24 hours postdose for each applicable treatment
Change from baseline of QRS interval (ΔQRS)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Categorical outliers for QTcF, HR, PR interval, and QRS durationPredose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Maximum observed plasma concentration of LEO 152020 (Cmax)0 to 24 hours postdose for each applicable treatment
Placebo-corrected, change from baseline of QRS interval (ΔΔQRS)Predose up to 24 hours postdose for each applicable treatment

A continuous 12-lead electrocardiogram recording (Holter) will be performed for at least 25 hours, starting 1 hour predose on Day 1 and encompassing the entire period from prior to the first (predose) extraction time point until after the last (24 hours postdose) extraction time point.

Area under the plasma concentration-time curve from time 0 to the time of last observed quantifiable concentration of LEO 152020 (AUC0-tlast)0 to 24 hours postdose for each applicable treatment
Area under the plasma concentration-time curve from time 0 extrapolated to infinity of LEO 152020 (AUC0-∞)0 to 24 hours postdose for each applicable treatment
Apparent total plasma clearance of LEO 152020 (CL/F)0 to 24 hours postdose for each applicable treatment
Apparent volume of distribution during the terminal phase (Vz/F)0 to 24 hours postdose for each applicable treatment
Number of treatment-emergent adverse events (AEs)Dosing on Day 1 of Treatment Period 1 to follow-up. (Up to 17 days)

Trial Locations

Locations (1)

LEO Investigational Site

🇬🇧

Leeds, United Kingdom

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