Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single and Multiple Doses of LEO 142397 in Healthy People, Including Japanese

A Randomised, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LEO 142397 in Healthy Subjects

This is the first clinical trial with LEO 142397. The purpose of the trial is to assess the safety and tolerability of LEO 142397, along with the pharmacokinetics (what the body does to the drug) and the pharmacodynamics (what the drug does to the body) in healthy people.

The trial consists of 2 parts:

• In Part 1, participants will receive a single dose of LEO 142397. There will be up to 8 different dose groups.
• In Part 2, participants will receive a daily dose of LEO 142397 for 14 days. There will be up to 6 different dose groups.

Each participant will be enrolled into 1 dose group in either Part 1 or Part 2.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: LEO 142397

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Covance Clinical Research Unit Ltd.

Participation Criteria

Eligibility Criteria

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

Description

Key inclusion Criteria:

• Body mass index of 18.0-32.0 kg/m2, inclusive.

• In good health at screening and check-in as judged by the investigator based on medical history, physical examination, vital signs assessment, 12-lead electrocardiogram, and clinical laboratory evaluations:

  • Aspartate aminotransferase and alanine aminotransferase values ≤1.5 times the upper limit of normal.
  • Congenital nonhaemolytic hyperbilirubinaemia (including suspicion of Gilbert's syndrome) is not acceptable.
  • Haemoglobin value, neutrophil count, and lymphocyte count ≥ the lower limit of normal.
• Female subjects of childbearing potential must use a highly effective form of birth control, in conjunction with adequate barrier contraception, from randomisation until 90 days after the follow-up visit.
• Male subjects with female partner of childbearing potential must use adequate male barrier contraception, in conjunction with a highly effective form of female contraception for the partner, from randomisation until 90 days after the follow-up visit.

Key exclusion criteria:

• Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of any drug.
• Any medication, including St. John's wort, known to chronically alter drug absorption or elimination processes within 30 days prior to the first dose.
• History of any significant infectious disease, as assessed by the investigator, within 2 weeks prior to the first dose.
• Current active tuberculosis based on QuantiFERON-TB Gold test.
• Positive hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus antibodies at screening.
• Electrocardiogram abnormalities at screening or check-in.
• Smoking of >10 cigarettes per day, on average, within the last 3 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single ascending dose Cohort A; Single dose of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort B; Single dose of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort C; 2 single doses, separated by a washout of ≥7 days.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort D; 2 single doses, separated by a washout of ≥7 days.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort E; Single dose of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort F; Single dose of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort G; Single dose of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Single ascending dose Cohort H; Single dose of LEO 142397 or placebo - tentative, female-only cohort (to be included only if the number of women recruited in the remaining cohorts is insufficient to assess the pharmacokinetics of LEO 142397 in women). Dose level ≥ that in Cohort C and ≤ that in Cohort D.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Multiple ascending dose Cohort K; Multiple doses of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Multiple ascending dose Cohort L; Multiple doses of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Multiple ascending dose Cohort M; Multiple doses of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Multiple ascending dose Cohort N; Multiple doses of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Multiple ascending dose Cohort O; Multiple doses of LEO 142397 or placebo.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S
Experimental: Multiple ascending dose Cohort P; Multiple doses of LEO 142397 or placebo in Japanese-only subjects. Same dose level as for Cohort M.	Drug: Placebo; Placebo; Drug: LEO 142397; A compound in development by LEO Pharma A/S

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1. Number of treatment-emergent adverse events per subject		From Day 1 (postdose) up to Day 8
Part 1. Having clinically significant abnormalities in systolic blood pressure	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 8
Part 1. Having clinically significant abnormalities in diastolic blood pressure	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 8
Part 1. Having clinically significant abnormalities in heart rate	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 8
Part 1. Having clinically significant abnormalities in oral body temperature	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 8
Part 1. Having an abnormal ECG	ECG: electrocardiogram. Abnormal ECG (yes/no) defined as: QT interval corrected for heart rate using Fridericia's formula (QTcF) of >450 msec for males / >470 msec for females, or change from baseline of >30 msec	From Day 1 (postdose) up to Day 8
Part 2. Number of treatment-emergent adverse events per subject		From Day 1 (postdose) up to Day 21
Part 2. Having clinically significant abnormalities in systolic blood pressure	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 21
Part 2. Having clinically significant abnormalities in diastolic blood pressure	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 21
Part 2. Having clinically significant abnormalities in heart rate	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 21
Part 2. Having clinically significant abnormalities in oral body temperature	Clinical significance (yes/no) of abnormal values as judged by the investigator	From Day 1 (postdose) up to Day 21
Part 2. Having an abnormal ECG	ECG: electrocardiogram. Abnormal ECG (yes/no) defined as: QT interval corrected for heart rate using Fridericia's formula (QTcF) of >450 msec for males / >470 msec for females, or maximum change from baseline of >30 msec	From Day 1 (postdose) up to Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1. AUC0-∞	AUC0-∞: area under the plasma concentration-time curve from time zero to infinity	Derived from plasma concentration-time profile from 0-48 hours postdose
Part 1. Cmax	Cmax: maximum plasma concentration	Derived from plasma concentration-time profile from 0-48 hours postdose
Part 2. Accumulation ratio		Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14
Part 2. AUC0-24	AUC0-24: area under the plasma concentration-time curve from time zero to 24 hours postdose	Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14
Part 2. Cmax	Cmax: maximum plasma concentration	Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14

Collaborators and Investigators

• Sponsor: LEO Pharma

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2019
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: June 21, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (Actual): June 24, 2019

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 1, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: LP0184-1415; 2018-004470-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data feasibility requests and research proposals are sent to disclosure@leo-pharma.com. If feasibility to share the data from a trial is granted, the ultimate decision is made by an external to the company board (Patient and Scientific Review Board). Data sharing is further subject to signed data sharing agreement. Data will be available in a closed environment for a specified period on time.
• IPD Sharing Access Criteria: External researchers with no commercial interest who provide scientifically sound research proposal
• 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