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

NCT03812198 | Completed Phase 1 DMC

• 2 other identifiers: LP0058-14422018-003282-34
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

healthy

Outcome Measures

Primary Outcomes (9)

• Part 1. AUC0-∞

  AUC0-∞: Area under the plasma concentration-time curve from time 0 extrapolated to infinity

  Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1

• Part 1. Relative bioavailability (F-rel)

  F-rel: AUC0 ∞ test formulations/AUC0-∞ reference formulation (derived from the statistical analysis of AUC0-∞)

  Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1

• Part 1. C-max

  C-max: Maximum observed plasma concentration

  Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1

• Part 1. t-max

  t-max: Time to reach maximum observed plasma concentration

  Calculated using concentration data collected from predose to 48 hours postdose for each treatment period in Part 1

• Part 2. AUC0-∞

  AUC0-∞: Area under the plasma concentration-time curve from time 0 extrapolated to infinity

  Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2

• Part 2. Relative bioavailability (F-rel)

  F-rel: AUC0 ∞ test formulations/AUC0-∞ reference formulation (derived from the statistical analysis of AUC0-∞)

  Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2

• Part 2. C-max

  C-max: Maximum observed plasma concentration

  Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2

• Part 2. t-max

  t-max: Time to reach maximum observed plasma concentration

  Calculated using concentration data collected from predose to 72 hours postdose for each treatment period in Part 2

• Part 3. Number of GI-related AEs and number of subjects with GI-related AEs during the treatment period

  AEs: adverse events; GI: gastrointestinal

  From Day 1 (first dose) to Day 19 (end of treatment period) in Part 3

Secondary Outcomes (35)

• Part 1. Number of GI-related AEs and number of subjects with GI-related AEs during each combination of treatment and period.

  24 days (from first dose in first treatment period until end of last treatment period) in Part 1

• Part 1. Number of total AEs and number of subjects with AEs during each combination of treatment and period

  24 days (from first dose in first treatment period until end of last treatment period) in Part 1

• Part 1. Number of subjects with systolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'

  At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose

• Part 1. Number of subjects with diastolic blood pressure in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'

  At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose

• Part 1. Number of subjects with pulse rate in each of the following categories: 'normal', 'abnormal, not clinically significant', 'abnormal, clinically significant'

  At screening and during each treatment period in Part 1: predose, 4 hours, 24 hours, and 48 hours postdose

Study Arms (7)

Group 1-1

ACTIVE COMPARATOR

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).

Drug: LEO 32731 modified release tablet; Drug: LEO 32731 blend, hard capsule; Drug: LEO 32731 API, hard capsule

Group 1-2

ACTIVE COMPARATOR

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).

Drug: LEO 32731 API, hard capsule; Drug: LEO 32731 soft capsule; Drug: LEO 32731 gastro-resistant capsule

Group 2-1

EXPERIMENTAL

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.

Drug: LEO 32731

Group 2-2

EXPERIMENTAL

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.

Drug: LEO 32731

Group 2-3

EXPERIMENTAL

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.

Drug: LEO 32731

Group 3-1

PLACEBO COMPARATOR

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.

Drug: LEO 32731; Other: Placebo

Group 3-2

PLACEBO COMPARATOR

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.

Drug: LEO 32731; Other: Placebo

Interventions

LEO 32731 modified release tablet DRUG

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

Group 1-1

LEO 32731 blend, hard capsule DRUG

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

Group 1-1

LEO 32731 API, hard capsule DRUG

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

Group 1-1; Group 1-2

LEO 32731 soft capsule DRUG

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

Group 1-2

LEO 32731 gastro-resistant capsule DRUG

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

Group 1-2

LEO 32731 DRUG

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

Group 2-1; Group 2-2; Group 2-3; Group 3-1; Group 3-2

Placebo OTHER

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

Group 3-1; Group 3-2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (1)

LEO Pharma Investigational Site

Leeds, United Kingdom

Location

MeSH Terms

Interventions

Hardness

Intervention Hierarchy (Ancestors)

Mechanical Phenomena; Physical Phenomena

Study Officials

• Medical Expert

  LEO Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 3-part, single (open-label) and multiple (double-blind, placebo-controlled)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 (single dose, cross-over) Part 2 (single dose, cross-over with food effect evaluation) Part 3 (multiple dose, parallel)

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 23, 2019
• Study Start: January 22, 2019
• Primary Completion: June 13, 2019
• Study Completion: June 13, 2019
• Last Updated: July 1, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Access Criteria: External researchers with no commercial interest who provide scientifically sound research proposal

Locations

GB (1)