Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults

Phase 1

Completed

• Conditions: COPD; Chronic Obstructive Pulmonary Disease
• Interventions: Drug: EP395; Drug: Placebo

• Registration Number: NCT05516316
• Lead Sponsor: EpiEndo Pharmaceuticals

Brief Summary

This study aims to assess the effect of EP395 against an induced inflammation of the lung. In addition, further data about the safety and tolerability of EP395 will be collected.

To investigate the efficacy of EP395 at the end of the treatment with EP395 or placebo (dummy), all participants will inhale a lipopolysaccharide (a molecule composed of sugar and fat) that artificially induces an acute inflammation of the airways. It is assumed that participants who received EP395 will show less inflammation of the airways than participants who received placebo.

Detailed Description

This is a study to assess the pharmacological effect of repeated doses of EP395 in healthy subjects with the aim to assess the effects of EP395 on lung and blood markers of inflammation after inhaled lipopolysaccharide (LPS), and the safety, tolerability, and systemic exposure of EP395.

The study will be randomised in a 1:1 ratio to take either high dose EP395 or placebo as oral capsules once daily for 21 days starting on Day 1 with scheduled visits at Days 7, 14, and 21 for assessments of safety and tolerability and systemic exposure of EP395. At Day 21, 2 hours after the last investigational product (IP) intake, participants will undergo an inhaled LPS challenge to induce airway inflammation, which will be followed by bronchoscopy and BAL 6 hours later. A final safety follow-up visit will be performed at Day 37.

If the data from the high dose EP395 arm (variability, effect size) indicate that it may be possible to detect effects on IL-8 at a lower dose of EP395, an additional lower dose EP395 arm will be added.

Study Timeline

• Study First Submitted: 2022-08-16
• Study First Submitted QC: 2022-08-23
• Study First Posted: 2022-08-25
• Study Start: 2022-10-11
• Status Verified: 2023-06
• Primary Completion: 2023-06-21
• Study Completion: 2023-06-21
• Last Update Submitted: 2023-06-22
• Last Update Posted: 2023-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

1. History or presence of any clinically relevant medical condition that could affect the participant's safety or interfere with the objectives of the study

2. Presence or history of lung disease, eg, asthma, chronic obstructive pulmonary disease

3. Clinically significant abnormality on 12-lead ECG including prolonged corrected QT interval by Fredericia (>450 msec men or >470 msec women)

4. Use of prescribed or nonprescribed medications or herbal remedies within 28 days of first dosing and during the study with the exception of

   1. hormone replacement therapy (HRT)
   2. contraception
   3. occasional use of paracetamol

5. Positive hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or -2 antibodies

6. Positive drugs of abuse, smoking, or alcohol test at Screening

7. History of alcohol or drug misuse

8. Pregnant and lactating women

9. Prior recovery from recent infection, including but not limited to COVID-19, within the last 14 days before first dosing with IP

10. History of hypersensitivity to any constituents of the IMP or LPS

11. Any clinically significant allergy

12. Participation in a clinical study with an IP within 3 months or 5 half-lives before first dosing, whichever is longer

13. Employees of the sponsor or employees or relatives of the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EP395 high dose	EP395	EP395 in repeated doses. Orally, once-daily administration of 3 EP395 capsules for 21 days
EP395 low dose	EP395	EP395 in repeated doses. Orally, once-daily administration of 1 EP395 capsule and 2 placebo capsules for 21 days
Placebo	Placebo	Matched placebo capsule, once-daily administration of 3 placebo capsules for 21 days

Primary Outcome Measures

Name	Time	Method
Bronchoalveolar lavage fluid interleukin 8 at Day 21	Day 21

Secondary Outcome Measures

Name	Time	Method
ECG ventricular rate	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Assessment of laboratory values (blood biochemistry)	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Vital signs: Systolic and diastolic blood pressure	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Assessment of laboratory values (haematology)	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Exhaled particles IL-6 and IL-8	Day 21 (±2 days)
ECG RR interval	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
ECG PR interval	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Assessment of blood coagulation	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
BALF cell count (total and differential) and mediators	Day 21 (±2 days)	Including tumour necrosis factor (TNF)-α, IL-6, IL-1β, macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemotactic protein-1, intercellular adhesion molecule-1, surfactant protein (SP)-D, granulocyte macrophage colony-stimulating factor, IL-23, IL-33, IL-25, IL-10, albumin, and protein
ECG QRS duration	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
ECG QT interval (uncorrected)	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
ECG QTcF intervals	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Urinalysis	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Vital signs: Body temperature	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Plasma EP395	Day 7 (±2 days) [only applicable for trough levels of EP395], Day 14 (±2 days) and Day 21 (±2 days)
Height and weight	Screening (Day -21 to Day -1), Day 37 (±3 days)	BMI will be calculated from height and weight measurements
Standard routine physical examination	Screening (Day -21 to Day -1), Days 1, Day 21 (±2 days), Day 37 (±3 days)	A standard routine physical body examination will be performed and abnormal physical examination results will be evaluated and reported as AEs.
Assessment of adverse event (AE) occurrence	From Screening (Day -21 to Day -1), to Day 37 (±3 days)
Vital signs: Pulse	Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)	Absolute values and changes from baseline will be summarized for all assessed time points
Blood inflammatory markers including C-reactive protein, TNF-α, IL-6, IL-8, and α2-macroglobulin	Day 21 (±2 days)

Trial Locations

Locations (1)

Fraunhofer Institute for Toxicology and Experimental Medicine ITEM; 🇩🇪 Hannover, Germany