A Trial to Investigate the Safety, Tolerability, and Drug Levels in Blood After Single and Multiple Doses of LEO 32731 in Healthy People

NCT ID: NCT03812198

Last Updated: 2019-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-22
• Study Completion Date: 2019-06-13

Brief Summary

This is a phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of 4 different oral formulations of LEO 32731 in healthy subjects. The trial will be conducted in 3 parts at a single site. Each eligible subject will be enrolled into 1 group only and will participate in 3 treatment periods.

Detailed Description

Part 1 will evaluate the pharmacokinetics of single doses of 4 test formulations of LEO 32731 compared with a reference formulation. Part 2 will evaluate the effect of food on the pharmacokinetics of selected test formulations of LEO 32731. Part 3 will evaluate the tolerability and safety of selected test formulations of LEO 32731 after multiple dosing.

Based on data from Part 1, up to 3 formulations will be taken forward to Part 2. If none of the formulations are considered appropriate to take forward to Part 2, the trial will stop after Part 1. Similarly, based on data from Part 2, up to 2 formulations will be taken forward to Part 3. If none of the formulations are considered appropriate to take forward to Part 3, the trial will stop after Part 2.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group 1-1

Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 modified release tablet; LEO 32731 blend, hard capsule; LEO 32731 API hard capsule (reference formulation).

Group Type: ACTIVE_COMPARATOR

LEO 32731 modified release tablet

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of tablets with approximately 240 mL of water at room temperature.

LEO 32731 blend, hard capsule

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

LEO 32731 API, hard capsule

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

Group 1-2

Part 1: Subjects will receive 3 doses of LEO 32731 in different formulations, as follows (1 dose per formulation/treatment period): LEO 32731 soft capsule; LEO 32731 gastro-resistant capsule; LEO 32731 API hard capsule (reference formulation).

Group Type: ACTIVE_COMPARATOR

LEO 32731 API, hard capsule

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

LEO 32731 soft capsule

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

LEO 32731 gastro-resistant capsule

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

Group 2-1

Part 2: Subjects will receive 3 doses of the same LEO 32731 formulation under different conditions, as follow (1 dose per condition/treatment period): fasted, after low-fat breakfast, after high-fat breakfast.

The formulation depends on the outcome of Part 1.

Group Type: EXPERIMENTAL

LEO 32731

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Group 2-2

Part 2: Subjects will receive 3 doses of the same LEO 32731 formulation under different conditions, as follow (1 dose per condition/treatment period): fasted, after low-fat breakfast, after high-fat breakfast.

The formulation depends on the outcome of Part 1.

Group Type: EXPERIMENTAL

LEO 32731

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Group 2-3

Part 2: Subjects will receive 3 doses of the same LEO 32731 formulation under different conditions, as follow (1 dose per condition/treatment period): fasted, after low-fat breakfast, after high-fat breakfast.

The formulation depends on the outcome of Part 1.

Group Type: EXPERIMENTAL

LEO 32731

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Group 3-1

Subjects will be dosed twice daily from Days 1-17 (morning dose only on Day 17) with LEO 32731 or placebo. The formulation depends on the outcome of Part 2.

Group Type: PLACEBO_COMPARATOR

LEO 32731

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Placebo

Intervention Type: OTHER

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Group 3-2

Subjects will be dosed twice daily from Days 1-17 (morning dose only on Day 17) with LEO 32731 or placebo. The formulation depends on the outcome of Part 2.

Group Type: PLACEBO_COMPARATOR

LEO 32731

Intervention Type: DRUG

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Placebo

Intervention Type: OTHER

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Interventions

LEO 32731 modified release tablet

At each dosing, subjects will swallow the appropriate number of tablets with approximately 240 mL of water at room temperature.

Intervention Type: DRUG

LEO 32731 blend, hard capsule

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

Intervention Type: DRUG

LEO 32731 API, hard capsule

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

Intervention Type: DRUG

LEO 32731 soft capsule

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

Intervention Type: DRUG

LEO 32731 gastro-resistant capsule

At each dosing, subjects will swallow the appropriate number of capsules with approximately 240 mL of water at room temperature.

Intervention Type: DRUG

LEO 32731

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Intervention Type: DRUG

Placebo

At each dosing, subjects will swallow the appropriate number of tablets or capsules with approximately 240 mL of water at room temperature.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 18 to 65 years, inclusive.
• Body mass index of 18.5 to 29.9 kg/m2, inclusive.
• In good health, at the discretion of the investigator, as determined by: medical history, physical examination, vital sign assessment (specifically, blood pressure must be within normal reference range), 12-lead ECG, clinical laboratory evaluations, aspartate aminotransferase and alanine aminotransferase not above the upper limit of normal (Gilbert's syndrome is not acceptable).
• Female subjects of childbearing potential must be willing to use a highly effective form of birth control in conjunction with a barrier method of contraception throughout the trial and for at least 90 days after final follow-up.
• Male subjects with a female partner of childbearing potential must be willing to use a highly effective form of birth control in conjunction with male barrier method of contraception (i.e. male condom with spermicide) throughout the trial and for at least 90 days after final follow-up.

Exclusion Criteria

• Systemic or topical treatment within 14 days prior to first dose administration unless in the opinion of the investigator the medication will not interfere with the trial procedures or compromise safety.
• Any medications, including St. John's wort, known to chronically alter drug absorption or elimination processes within 30 days prior to first dose administration.
• Subjects who smoke more than an average of 10 cigarettes per day.
• History of chronic alcohol or drug abuse within 12 months prior to screening.
• Subjects with ≥3 bowel movements per day.
• Any disorder which is not stable and could: Affect the safety of the subject throughout the trial; Influence the findings of the trial; Impede the subject's ability to complete the trial. Examples include but are not limited to cardiovascular, GI, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immunological, and psychiatric disorders and major physical impairment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

LEO Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Expert

Role: STUDY_DIRECTOR

LEO Pharma

Locations

LEO Pharma Investigational Site

Leeds, , United Kingdom

Countries

United Kingdom

Other Identifiers

2018-003282-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LP0058-1442

Identifier Type: -

Identifier Source: org_study_id