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

LEO Pharma

Status and phase: Withdrawn; Phase 1

Conditions: Healthy

Treatments: Drug: LEO 142397; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03995550

LP0184-1415

2018-004470-10 (EudraCT Number)

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

0 participants in 14 patient groups

Single ascending dose Cohort A

Experimental group

Description:

Single dose of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort B

Experimental group

Description:

Single dose of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort C

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort D

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort E

Experimental group

Description:

Single dose of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort F

Experimental group

Description:

Single dose of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort G

Experimental group

Description:

Single dose of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Single ascending dose Cohort H

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: LEO 142397

Multiple ascending dose Cohort K

Experimental group

Description:

Multiple doses of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Multiple ascending dose Cohort L

Experimental group

Description:

Multiple doses of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Multiple ascending dose Cohort M

Experimental group

Description:

Multiple doses of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Multiple ascending dose Cohort N

Experimental group

Description:

Multiple doses of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Multiple ascending dose Cohort O

Experimental group

Description:

Multiple doses of LEO 142397 or placebo.

Treatment:

Drug: Placebo

Drug: LEO 142397

Multiple ascending dose Cohort P

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: LEO 142397