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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Cardiac Repolarisation
• Intervention / Treatment: Drug: LEO 152020; Drug: Moxifloxacin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • LEO Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: JW Pharmaceutical
• Collaborators: LEO Pharma
• Investigators: Study Director: Medical Expert, LEO Pharma

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2022
• Primary Completion (Actual): December 28, 2022
• Study Completion (Actual): December 28, 2022

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: LP0190-2212; U1111-1279-4625 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Access Criteria: Data sharing is subject to approved scientifically sound research proposal and signed data agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No