A Single and Multiple Ascending-dose Trial of LEO 153339 in Healthy Adults

A Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of LEO 153339 in Healthy Subjects

This is a first-in-human study in adult healthy participants consisting of two parts. In Part 1, participants will receive one dose of study drug (LEO 153339) or placebo; in Part 2, participants will receive multiple doses of study drug or placebo.

The participants will stay in the clinic for 6 days (Part 1) or for 12 days (Part 2) to have the study doctor assess their safety and to investigate how quickly and to what extent LEO 153339 (and the breakdown product) is absorbed, transported, and eliminated from the body.

The purpose is to assess the safety and tolerability of LEO 153339 when compared to a placebo with no active ingredient.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: LEO 153339

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • NZ
    • Groningen, NZ, Netherlands, 9728
      • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Main Inclusion Criteria:

• Healthy adult males and females.
• Age between 18 and 65 years (both inclusive) at screening.
• A body mass index (BMI) between 18.0 and 32.0 kg/m² (both inclusive).
• In good health at screening and/or check-in (Day -2 and Day -1) as judged by the investigator based on medical history, physical examination, vital signs, 12 lead electrocardiogram (ECG), and clinical laboratory evaluations.

Main Exclusion Criteria:

• Male participants sexually active with a woman of childbearing potential who are not willing to use a barrier method of contraception (e.g. condom) from the time of first dose of investigational medicinal product (IMP) until 3 months after the last dose, in conjunction with this female partner using a highly effective form of contraception. For vasectomised male participants, male participants with a female partner with bilateral tubal occlusion or ligation, and heterosexually abstinent male participants (when this is in line with the preferred and usual life style of the participant and not just being without a current partner), no additional contraception is required.
• Female participants who are pregnant, lactating, or of childbearing potential.
• Any surgical or medical condition or cholecystectomy which might significantly alter the absorption, distribution, metabolism, or excretion of any drug.
• Positive polymerase chain reaction (PCR) test for coronavirus disease 2019 (COVID-19) at Day -2 or Day -1 or within 8 weeks prior to screening or check-in, or contact with COVID-19 positive (or suspected) persons within 14 days prior to first dose.
• Treatment with any prescribed or non-prescribed systemic or topical medication within 7 days prior to the first dose of IMP (excluding paracetamol; including herbal remedies), unless, in the opinion of the investigator and the sponsor, the medication will not interfere with the trial procedures or compromise safety.
• Treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within 3 months prior to the first dose of IMP.
• ECG with QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 msec confirmed by repeat measurement at screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort A2 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort A3 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort A4 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort A5 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort A6 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort A7 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Experimental: Cohort B1 LEO 153339; Single ascending dose (Part 1)	Drug: LEO 153339; LEO 153339
Placebo Comparator: All SAD cohorts placebo; Single ascending dose (Part 1), all participants receiving placebo in Cohorts A1-A7 and B1	Drug: Placebo; Placebo
Experimental: Cohort C1 LEO 153339; Multiple ascending doses (Part 2)	Drug: LEO 153339; LEO 153339
Experimental: Cohort C2 LEO 153339; Multiple ascending doses (Part 2)	Drug: LEO 153339; LEO 153339
Experimental: Cohort C3 LEO 153339; Multiple ascending doses (Part 2)	Drug: LEO 153339; LEO 153339
Experimental: Cohort C4 LEO 153339; Multiple ascending doses (Part 2)	Drug: LEO 153339; LEO 153339
Experimental: Cohort C5 LEO 153339; Multiple ascending doses (Part 2)	Drug: LEO 153339; LEO 153339
Experimental: Cohort C6 LEO 153339; Multiple ascending doses (Part 2)	Drug: LEO 153339; LEO 153339
Placebo Comparator: All MAD cohorts placebo; Multiple ascending doses (Part 2, all participants receiving placebo in Cohorts C1-C6)	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-emergent adverse events per subject.	An adverse event will be considered treatment emergent if started after the first dose of investigational medicinal product (IMP) or if started before the first dose of IMP and worsened in severity after first dose of IMP.	4 days per subject (Part 1); 10 days per subject (Part 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of LEO 153339 and LEO 159074 obtained from 0 to 72 hours post-dose in subjects from the single ascending-dose (SAD) cohorts.	The pharmacokinetics of LEO 153339 and LEO 159074 will be evaluated in plasma.	72 hours per subject
Plasma concentration of LEO 153339 and LEO 159074 obtained from Day 1 to Day 7 post-dose with PK profiles on Day 1, Day 5, and Day 7 in subjects from the multiple ascending-dose (MAD) cohorts.	The pharmacokinetics (PK) of LEO 153339 and LEO 159074 will be evaluated in plasma.	10 days per subject

Collaborators and Investigators

• Sponsor: LEO Pharma
• Collaborators: ICON plc

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): July 18, 2022
• Study Completion (Actual): July 18, 2022

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 11, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: LP0200-1495; 2020-005748-51 (EudraCT Number); U1111-1283-2001 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified IPD can be made available to researchers in a closed environment for a specified period of time.
• IPD Sharing Time Frame: Data is available to request after results of the trial are available on leopharmatrials.com
• IPD Sharing Access Criteria: Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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