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

EpiEndo Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Chronic Obstructive Pulmonary Disease; COPD

Treatments: Drug: EP395; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05516316

EP395-002

2021-005867-28 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

1. Willing and able to understand the information on the nature, the scope and the relevance of the clinical study, and to provide voluntary, written informed consent to participate in the study before any study-related procedures

2. Men and women, aged ≥18 and ≤55 years

3. Women of childbearing potential must:

   1. have a negative pregnancy test (blood) at Screening.
   2. agree to use, and be able to comply with, highly effective measures of contraceptive control (failure rate less than 1% per year when used consistently and correctly) without interruption, from Screening until 90 days after the last IP intake.

4. Men must agree to use contraception (barrier method) during sexual intercourse with women of childbearing potential during treatment until 90 days after the last IP intake and should not donate sperm during this time.

5. In good health as determined by medical history and screening investigations, as judged by the investigator

6. Body mass index of ≥19 and ≤33 kg/m2

7. Normal spirometry (forced expiratory volume in 1 second [FEV1] >80% predicted and FEV1/forced vital capacity >70%)

8. Non-smoker or former smoker with <10 pack years who had stopped smoking (including e-cigarettes) for at least 6 months before Screening.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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49 participants in 3 patient groups, including a placebo group

EP395 high dose

Experimental group

Description:

EP395 in repeated doses. Orally, once-daily administration of 3 EP395 capsules for 21 days

Treatment:

Drug: EP395

EP395 low dose

Experimental group

Description:

EP395 in repeated doses. Orally, once-daily administration of 1 EP395 capsule and 2 placebo capsules for 21 days

Treatment:

Drug: EP395

Placebo

Placebo Comparator group

Description:

Matched placebo capsule, once-daily administration of 3 placebo capsules for 21 days

Treatment:

Drug: Placebo