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

Study Overview
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Brief Summary
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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.

Official Title
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Interventional, Randomised, Partially Double-blind, Crossover, Positive-controlled, Single-dose Trial Investigating the Effect of LEO 152020 on Cardiac Repolarisation in Healthy Men and Women

Conditions
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Healthy Volunteers, Cardiac Repolarisation

Intervention / Treatment
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* Drug: LEO 152020
* Drug: Moxifloxacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Uncorrected hypokalaemia or hypomagnesaemia at screening or check-in for Treatment Period 1, history of cardiac failure, history of clinically significant/symptomatic bradycardia. (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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 152020 Dose A<br>A single oral dose of LEO 152020 Dose A according to the randomization schedule. | Drug: LEO 152020<br>* Film-coated tablet Route of administration: Orally 50 mg tablets<br>|
| Experimental: LEO 152020 Dose B<br>A single dose of LEO 152020 Dose B according to the randomization schedule. | Drug: LEO 152020<br>* Film-coated tablet Route of administration: Orally 50 mg tablets<br>|
| Active Comparator: Moxifloxacin<br>A single oral dose of moxifloxacin 400 mg according to the randomization schedule. | Drug: Moxifloxacin<br>* Tablet (may be film-coated depending on brand) Route of administration: Orally 400 mg tablet<br>|
| Placebo Comparator: Placebo<br>A single dose of placebo according to the randomization schedule. | Drug: Placebo<br>* Film-coated tablet Route of administration: Orally No active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of Heart Rate (ΔHR) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Change from baseline of QT interval corrected using Fridericia's formula (ΔQTcF) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Change from baseline of Pulse Rate (ΔPR) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Change from baseline of QRS interval (ΔQRS) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Placebo-corrected, change from baseline of Heart Rate (ΔΔHR) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Placebo-corrected, change from baseline of Pulse Rate (ΔΔPR) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Placebo-corrected, change from baseline of QRS interval (ΔΔQRS) | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Categorical outliers for QTcF, HR, PR interval, and QRS duration | 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. | Predose up to 24 hours postdose for each applicable treatment | 
| Maximum observed plasma concentration of LEO 152020 (Cmax) |  | 0 to 24 hours postdose for each applicable treatment | 
| 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 | 
| 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 terminal elimination half-life of LEO 152020 (t1/2) |  | 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) |