Clinical trial NCT03995550: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single and Multiple Doses of LEO 142397 in Healthy People, Including Japanese
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Healthy
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2019-06-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1. Number of treatment-emergent adverse events per subject
timeFrame: From Day 1 (postdose) up to Day 8
measure: Part 1. Having clinically significant abnormalities in systolic blood pressure
timeFrame: From Day 1 (postdose) up to Day 8
measure: Part 1. Having clinically significant abnormalities in diastolic blood pressure
timeFrame: From Day 1 (postdose) up to Day 8
measure: Part 1. Having clinically significant abnormalities in heart rate
timeFrame: From Day 1 (postdose) up to Day 8
measure: Part 1. Having clinically significant abnormalities in oral body temperature
timeFrame: From Day 1 (postdose) up to Day 8
measure: Part 1. Having an abnormal ECG
timeFrame: From Day 1 (postdose) up to Day 8
measure: Part 2. Number of treatment-emergent adverse events per subject
timeFrame: From Day 1 (postdose) up to Day 21
measure: Part 2. Having clinically significant abnormalities in systolic blood pressure
timeFrame: From Day 1 (postdose) up to Day 21
measure: Part 2. Having clinically significant abnormalities in diastolic blood pressure
timeFrame: From Day 1 (postdose) up to Day 21
measure: Part 2. Having clinically significant abnormalities in heart rate
timeFrame: From Day 1 (postdose) up to Day 21
measure: Part 2. Having clinically significant abnormalities in oral body temperature
timeFrame: From Day 1 (postdose) up to Day 21
measure: Part 2. Having an abnormal ECG
timeFrame: From Day 1 (postdose) up to Day 21
Secondary outcomes:
measure: Part 1. AUC0-∞
timeFrame: Derived from plasma concentration-time profile from 0-48 hours postdose
measure: Part 1. Cmax
timeFrame: Derived from plasma concentration-time profile from 0-48 hours postdose
measure: Part 2. Accumulation ratio
timeFrame: Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14
measure: Part 2. AUC0-24
timeFrame: Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14
measure: Part 2. Cmax
timeFrame: Derived from plasma concentration-time profile from 0-24 hours postdose on Day 1 and Day 14
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit Ltd.
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References: