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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LEO 153339
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |