Chronic obstructive pulmonary disease (COPD) MedDRA version: 21.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Code: EP395
Pharmaceutical Form: Capsule
INN or Proposed INN: n.a.
CAS Number: n.a.
Current Sponsor code: EP395
Other descriptive name: EP395
Concentration unit: mg milligram(s)
Concentration
Sponsors
EpiEndo Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to understand the information on the nature, the scope, and the relevance of the study, and to provide voluntary, written informed consent to participate in the study before any study-related procedures 2. Men and women, aged =45 years 3. Women of childbearing potential must: a. have a negative pregnancy test (blood) at Screening and (urine) Day 1 b. 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, during study participation and until 90 days after the last investigational product (IP) intake. c. agree to abstain from breast feeding during the study participation and for 90 days after the last IP intake. 4. Men must agree to use a condom during sexual intercourse with women of childbearing potential during treatment and for 90 days after the last IP intake and should not donate sperm during this time 5. Diagnosed with COPD for at least 2 years with FEV1/forced vital capacity (FVC) ratio =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. History or presence of any clinically relevant medical condition including laboratory test abnormality or planned surgery that in the investigator’s opinion could affect the patient’s safety or interfere with the objectives of the study 2. Exacerbation of COPD in the 3 months before Screening 3. Change in medication for COPD in the 3 months before Screening 4. Lung function at Screening that in the investigator’s opinion would indicate not safe to perform sputum induction or bronchoscopy (bronchoscopy applicable only in a subset of patients) 5. History of or active tuberculosis 6. Malignancy within the past 5 years, except removed basal cell carcinoma and resected benign colonic polyps 7. Clinically significant abnormality on 12-lead ECG including prolonged corrected QTcF (>450 msec in men or >470 msec in women); based on triplicate) at Screening and Day 1 pre-dose 8. Absolute estimated glomerular filtration rate ([eGFR cystatin C + eGFR creatinine]/2) 1.5 x ULN at Screening 10. Use (including prescription, over-the-counter, herbal or dietary) of cytochrome P450 (CYP) inducers within 28 days before first dosing, or strong or moderate inhibitors of CYP3A4 (including dietary eg, grapefruit juice) or P-glycoprotein (Pgp) inhibitors or oral narrow therapeutic index (TI) Pgp substrates (eg, digoxin) within 14 days before first dosing 11. Use of macrolide, roflumilast, or oral corticosteroid (OCS) within 28 days before Screening 12. Ongoing antibiotic treatment at Screening 13. Use of home oxygen or home-based non-invasive ventilation 3 months before Screening 14. Use of a biological therapy within 3 months before Screening 15. Use of herbal remedies within 28 days before first dose until follow up 16. Live vaccine within 28 days or any other vaccine within 14 days before first dose until 28 days after final dose of the IP (with the exception of COVID-19 booster and flu vaccination; see Previous and concomitant medications and therapies) 17. Positive hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus 1 or 2 antibodies at Screening 18. Positive test result for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on Day 1 19. Positive drugs of abuse test at Screening, including cotinine only in ex-smokers for at least 3 months 20. Use of e-cigarettes and vapes 21. History of alcohol or drug misuse within 12 months before Screening 22. Pregnant and lactating women 23. Prior recovery from recent infection, including but not limited to COVID 19 within the last 30 days before first dosing with IP 24. Known hypersensitivity to macrolides or EP395 or any of the excipients (dicalcium phosphate, croscarmellose sodium, magnesium stearate, microcrystalline cellulose) 25. Participation in a study of an experimental drug within 5 half-lives or 3 months before Screening, whichever is longer 26. Dependent subjects of the sponsor or investigator (eg, employees, relatives) 27. Patients without the capacity to understand the nature and risks of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of repeat doses of EP395 in patients with COPD;Secondary Objective: Secondary objectives: • To assess the effect of EP395 on lung inflammation • To assess the effect of EP395 on systemic inflammation • To assess the effect of EP395 on lung function • To assess the systemic exposure to EP395 • To assess the effect of EP395 on quality of life Exploratory objectives: • To assess the effect of EP395 on mechanistic biomarkers • To assess the effects of EP395 on the microbiome ;Primary end point(s): Adverse events (AEs), vital signs, laboratory safety tests, 12-lead electrocardiograms (ECGs), physical examinations;Timepoint(s) of evaluation of this end point: Throughout treatment phase and follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Sputum cells (total and differential) and inflammatory mediators including interleukin (IL) 8, tumour necrosis factor (TNF)-a, IL-6, IL 1ß, macrophage inflammatory protein (MIP) 1a, MIP-1ß, monocyte chemotactic protein (MCP)-1, surfactant protein D (SP-D), granulocyte macrophage colony-stimulating factor (GM-CSF), IL-23, IL-33, IL-25, IL-10, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, CXC motif chemokine ligand (CXCL)1, myeloperoxidase (MPO) 2) Blood inflammatory markers including fibrinogen (FBG), C-reactive protein (CRP), TNF-a, IL-6, a2 macroglobulin 3) Forced expiratory volume in 1 second (FEV1) 4) Plasma levels of EP395 5) St George’s respiratory questionnaire (SGRQ) and Exacerbations of COPD tool (EXACT)-respiratory symptoms (E-RS) Exploratory end points: 6) Blood biomarkers including SP-D, thymic stromal lymphopoietin (TSLP), Clara cell protein (CC)-16, Krebs von den Lungen (KL)-6, MMP-7, cancer antigen (CA)19-9, CA125, soluble cluster of differentiation (sCD)163, sCD14 7) Bronchial brushing (gene expression including KIAA1177/CEMIB) and lavage including cells (total and differential), TNF a, IL-6, IL-1ß, IL-8, MIP-1a, MIP-1ß, MCP-1, SP-D, GM-CSF, IL 23, IL-33, IL-25, IL 10, albumin, and protein (and optionally: gene expression in bronchoalveolar lavage [BAL] cells) 8) Polyinosinic:polycytidylic acid (poly I:C) stimulation of bronchial epithelial cells (BECs) 9) Microbiome in BAL fluid (BALF), bronchial brushing samples and sputum (if sufficient sample available) ;Timepoint(s) of evaluation of this end point: 1) Screening, D1, D42, D70, D84 2) D1, D42, D84 3) Screening, D1, D28, D56, D84 4) D14, D28, D42, D56, D70, D80, D84 5) SGRQ: Screening, D1, D28, D56, D84; E-RS: daily throughout study participation Exploratory end points: 6) D1, D42, D84 7) D-05, D80 8) D-05, D80 9) D-05, D80 | — |
Countries
Germany, United Kingdom
Contacts
Public ContactProject Manager Kate Hanrott
EpiEndo Pharmaceuticals
Outcome results
None listed