Back to resultsClinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults
Primary Purpose
Chronic Obstructive Pulmonary Disease, COPD
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
EP395
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease
Eligibility Criteria
- 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
- Men and women, aged ≥18 and ≤55 years
Women of childbearing potential must:
- have a negative pregnancy test (blood) at Screening.
- 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.
- 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.
- In good health as determined by medical history and screening investigations, as judged by the investigator
- Body mass index of ≥19 and ≤33 kg/m2
- Normal spirometry (forced expiratory volume in 1 second [FEV1] >80% predicted and FEV1/forced vital capacity >70%)
- 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:
- History or presence of any clinically relevant medical condition that could affect the participant's safety or interfere with the objectives of the study
- Presence or history of lung disease, eg, asthma, chronic obstructive pulmonary disease
- Clinically significant abnormality on 12-lead ECG including prolonged corrected QT interval by Fredericia (>450 msec men or >470 msec women)
Use of prescribed or nonprescribed medications or herbal remedies within 28 days of first dosing and during the study with the exception of
- hormone replacement therapy (HRT)
- contraception
- occasional use of paracetamol
- Positive hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or -2 antibodies
- Positive drugs of abuse, smoking, or alcohol test at Screening
- History of alcohol or drug misuse
- Pregnant and lactating women
- Prior recovery from recent infection, including but not limited to COVID-19, within the last 14 days before first dosing with IP
- History of hypersensitivity to any constituents of the IMP or LPS
- Any clinically significant allergy
- Participation in a clinical study with an IP within 3 months or 5 half-lives before first dosing, whichever is longer
- Employees of the sponsor or employees or relatives of the investigator
Sites / Locations
- Fraunhofer Institute for Toxicology and Experimental Medicine ITEM
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
EP395 high dose
EP395 low dose
Placebo
Arm Description
EP395 in repeated doses. Orally, once-daily administration of 3 EP395 capsules for 21 days
EP395 in repeated doses. Orally, once-daily administration of 1 EP395 capsule and 2 placebo capsules for 21 days
Matched placebo capsule, once-daily administration of 3 placebo capsules for 21 days
Outcomes
Primary Outcome Measures
Bronchoalveolar lavage fluid interleukin 8 at Day 21
Secondary Outcome Measures
ECG ventricular rate
Absolute values and changes from baseline will be summarized for all assessed time points
ECG RR interval
Absolute values and changes from baseline will be summarized for all assessed time points
ECG PR interval
Absolute values and changes from baseline will be summarized for all assessed time points
ECG QRS duration
Absolute values and changes from baseline will be summarized for all assessed time points
ECG QT interval (uncorrected)
Absolute values and changes from baseline will be summarized for all assessed time points
ECG QTcF intervals
Absolute values and changes from baseline will be summarized for all assessed time points
Assessment of laboratory values (haematology)
Absolute values and changes from baseline will be summarized for all assessed time points
Assessment of laboratory values (blood biochemistry)
Absolute values and changes from baseline will be summarized for all assessed time points
Assessment of blood coagulation
Absolute values and changes from baseline will be summarized for all assessed time points
Urinalysis
Absolute values and changes from baseline will be summarized for all assessed time points
Vital signs: Systolic and diastolic blood pressure
Absolute values and changes from baseline will be summarized for all assessed time points
Vital signs: Pulse
Absolute values and changes from baseline will be summarized for all assessed time points
Vital signs: Body temperature
Absolute values and changes from baseline will be summarized for all assessed time points
Height and weight
BMI will be calculated from height and weight measurements
Standard routine physical examination
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
BALF cell count (total and differential) and mediators
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
Exhaled particles IL-6 and IL-8
Blood inflammatory markers including C-reactive protein, TNF-α, IL-6, IL-8, and α2-macroglobulin
Plasma EP395
Full Information
NCT ID
NCT05516316
First Posted
August 16, 2022
Last Updated
June 22, 2023
Sponsor
EpiEndo Pharmaceuticals
Collaborators
FGK Clinical Research GmbH
1. Study Identification
Unique Protocol Identification Number
NCT05516316
Brief Title
Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults
Official Title
A Randomised, Double-blind, Placebo-controlled Proof-of-pharmacology Study of EP395 in Healthy Adults
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 11, 2022 (Actual)
Primary Completion Date
June 21, 2023 (Actual)
Study Completion Date
June 21, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EpiEndo Pharmaceuticals
Collaborators
FGK Clinical Research GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease, COPD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
The study is double-blind, placebo-controlled and parallel-group in design.
Masking
ParticipantInvestigator
Masking Description
During the study, study participants, investigators, the sponsor, and all other persons involved in the conduct of the study will be blinded to treatment.
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EP395 high dose
Arm Type
Experimental
Arm Description
EP395 in repeated doses. Orally, once-daily administration of 3 EP395 capsules for 21 days
Arm Title
EP395 low dose
Arm Type
Experimental
Arm Description
EP395 in repeated doses. Orally, once-daily administration of 1 EP395 capsule and 2 placebo capsules for 21 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matched placebo capsule, once-daily administration of 3 placebo capsules for 21 days
Intervention Type
Drug
Intervention Name(s)
EP395
Intervention Description
Capsule for oral use
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsule for oral use
Primary Outcome Measure Information:
Title
Bronchoalveolar lavage fluid interleukin 8 at Day 21
Time Frame
Day 21
Secondary Outcome Measure Information:
Title
ECG ventricular rate
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
ECG RR interval
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
ECG PR interval
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
ECG QRS duration
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
ECG QT interval (uncorrected)
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
ECG QTcF intervals
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
Assessment of laboratory values (haematology)
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
Assessment of laboratory values (blood biochemistry)
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
Assessment of blood coagulation
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
Urinalysis
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days), Day 37 (±3 days)
Title
Vital signs: Systolic and diastolic blood pressure
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)
Title
Vital signs: Pulse
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)
Title
Vital signs: Body temperature
Description
Absolute values and changes from baseline will be summarized for all assessed time points
Time Frame
Screening (Day -21 to Day -1), Days 1, 7 (±2 days), 14 (±2 days), Day 21 (±2 days)
Title
Height and weight
Description
BMI will be calculated from height and weight measurements
Time Frame
Screening (Day -21 to Day -1), Day 37 (±3 days)
Title
Standard routine physical examination
Description
A standard routine physical body examination will be performed and abnormal physical examination results will be evaluated and reported as AEs.
Time Frame
Screening (Day -21 to Day -1), Days 1, Day 21 (±2 days), Day 37 (±3 days)
Title
Assessment of adverse event (AE) occurrence
Time Frame
From Screening (Day -21 to Day -1), to Day 37 (±3 days)
Title
BALF cell count (total and differential) and mediators
Description
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
Time Frame
Day 21 (±2 days)
Title
Exhaled particles IL-6 and IL-8
Time Frame
Day 21 (±2 days)
Title
Blood inflammatory markers including C-reactive protein, TNF-α, IL-6, IL-8, and α2-macroglobulin
Time Frame
Day 21 (±2 days)
Title
Plasma EP395
Time Frame
Day 7 (±2 days) [only applicable for trough levels of EP395], Day 14 (±2 days) and Day 21 (±2 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Men and women, aged ≥18 and ≤55 years
Women of childbearing potential must:
have a negative pregnancy test (blood) at Screening.
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.
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.
In good health as determined by medical history and screening investigations, as judged by the investigator
Body mass index of ≥19 and ≤33 kg/m2
Normal spirometry (forced expiratory volume in 1 second [FEV1] >80% predicted and FEV1/forced vital capacity >70%)
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:
History or presence of any clinically relevant medical condition that could affect the participant's safety or interfere with the objectives of the study
Presence or history of lung disease, eg, asthma, chronic obstructive pulmonary disease
Clinically significant abnormality on 12-lead ECG including prolonged corrected QT interval by Fredericia (>450 msec men or >470 msec women)
Use of prescribed or nonprescribed medications or herbal remedies within 28 days of first dosing and during the study with the exception of
hormone replacement therapy (HRT)
contraception
occasional use of paracetamol
Positive hepatitis B surface antigen, hepatitis C antibodies, HIV-1 or -2 antibodies
Positive drugs of abuse, smoking, or alcohol test at Screening
History of alcohol or drug misuse
Pregnant and lactating women
Prior recovery from recent infection, including but not limited to COVID-19, within the last 14 days before first dosing with IP
History of hypersensitivity to any constituents of the IMP or LPS
Any clinically significant allergy
Participation in a clinical study with an IP within 3 months or 5 half-lives before first dosing, whichever is longer
Employees of the sponsor or employees or relatives of the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Hohlfeld, Prof. Dr.
Organizational Affiliation
Fraunhofer Institute for Toxicology and Experimental Medicine ITEM
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fraunhofer Institute for Toxicology and Experimental Medicine ITEM
City
Hannover
ZIP/Postal Code
30625
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Clinical Trial Comparing the Pharmacological Effects of EP395 With Placebo in Healthy Adults
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