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

NCT03995550 | Withdrawn Phase 1

• 2 other identifiers: LP0184-14152018-004470-10
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (5)

• Part 1. AUC0-∞

  Derived from plasma concentration-time profile from 0-48 hours postdose

• Part 1. Cmax

  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

  Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14

• Part 2. Cmax

  Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14

Study Arms (14)

Single ascending dose Cohort A

EXPERIMENTAL

Single dose of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort B

EXPERIMENTAL

Single dose of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort C

EXPERIMENTAL

2 single doses, separated by a washout of ≥7 days.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort D

EXPERIMENTAL

2 single doses, separated by a washout of ≥7 days.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort E

EXPERIMENTAL

Single dose of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort F

EXPERIMENTAL

Single dose of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort G

EXPERIMENTAL

Single dose of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Single ascending dose Cohort H

EXPERIMENTAL

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: LEO 142397; Drug: Placebo

Multiple ascending dose Cohort K

EXPERIMENTAL

Multiple doses of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Multiple ascending dose Cohort L

EXPERIMENTAL

Multiple doses of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Multiple ascending dose Cohort M

EXPERIMENTAL

Multiple doses of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Multiple ascending dose Cohort N

EXPERIMENTAL

Multiple doses of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Multiple ascending dose Cohort O

EXPERIMENTAL

Multiple doses of LEO 142397 or placebo.

Drug: LEO 142397; Drug: Placebo

Multiple ascending dose Cohort P

EXPERIMENTAL

Multiple doses of LEO 142397 or placebo in Japanese-only subjects. Same dose level as for Cohort M.

Drug: LEO 142397; Drug: Placebo

Interventions

LEO 142397 DRUG

A compound in development by LEO Pharma A/S

Multiple ascending dose Cohort K; Multiple ascending dose Cohort L; Multiple ascending dose Cohort M; Multiple ascending dose Cohort N; Multiple ascending dose Cohort O; Multiple ascending dose Cohort P; Single ascending dose Cohort A; Single ascending dose Cohort B; Single ascending dose Cohort C; Single ascending dose Cohort D; Single ascending dose Cohort E; Single ascending dose Cohort F; Single ascending dose Cohort G; Single ascending dose Cohort H

Placebo DRUG

Placebo

Multiple ascending dose Cohort K; Multiple ascending dose Cohort L; Multiple ascending dose Cohort M; Multiple ascending dose Cohort N; Multiple ascending dose Cohort O; Multiple ascending dose Cohort P; Single ascending dose Cohort A; Single ascending dose Cohort B; Single ascending dose Cohort C; Single ascending dose Cohort D; Single ascending dose Cohort E; Single ascending dose Cohort F; Single ascending dose Cohort G; Single ascending dose Cohort H

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (1)

Covance Clinical Research Unit Ltd.

Leeds, LS2 9LH, United Kingdom

Location

Study Officials

• Medical Expert

  LEO Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2019
• First Posted: June 24, 2019
• Study Start: July 3, 2019
• Primary Completion: January 27, 2020
• Study Completion: July 16, 2020
• Last Updated: May 1, 2026

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)