Single and multiple ascending dose study of EP395
Research type
Research Study
Full title
A First-in Man, Phase I study investigating the safety and tolerability of EP395 in healthy volunteers
IRAS ID
284977
Contact name
Maria Bech
Contact email
Sponsor organisation
Epiendo Pharmacueticals
Eudract number
2020-002583-31
Duration of Study in the UK
0 years, 9 months, 15 days
Research summary
Research Summary
The study drug, EP395, is a potential new drug being developed for the treatment of chronic lung conditions such as Chronic Obstructive Pulmonary Disease (COPD).
Patients with chronic lung disease can often suffer periods of worsenings in their conditions (known as exacerbations) which lead to poorer medical outcomes, increased symptoms and high medical costs. Long term use of a type of drug called macrolides (a common type of medication known largely as an antibiotic) has been shown to reduce the number of exacerbations in patients with chronic lung conditions such as COPD and asthma. However, a potential risk associated with long term macrolide use is antibiotic resistance.
EP395 is one of a potential new class of drugs called ‘barriolides’ which are a type of macrolide. Barriolides such as EP395 retain anti-inflammatory and barrier protective properties for the lungs but lack anti-bacterial effect compared to existing macrolides (for example azithromycin) at clinical doses.
This is the first study with EP395 in humans and is designed to study the safety, tolerability and pharmacokinetic properties (levels of study drug in the body) following single ascending doses (Part A) and multiple ascending doses (Part B) in healthy subjects.
A randomized, double-blind, placebo-controlled design has been selected to allow for unbiased analysis of safety and tolerability data. The study will be conducted in a dose escalation format in order to characterise doses that are anticipated to be safe and efficacious in the treatment of COPD and other inflammatory lung diseases. Dose escalation will be based on safety, tolerability, and available PK data from previous cohorts.
The target indication for EP395 is reduction of exacerbations in COPD patients in combination with standard treatment.Summary of Results
A total of 40 healthy participants were enrolled into Part A of the study and 30 healthy participants into Part B of the study.
All doses of EP395 (single doses of 20 mg, 120 mg, 300 mg, and 750 mg [fasted], single dose of 300 mg [fed], and multiple doses of 120 mg, 250 mg, and 375 mg [once daily for 28 days]) were well tolerated.
The overall incidence of side effects reported after EP395 was administered (treatment emergent adverse events ‘TEAEs’) was low; no severe or serious TEAEs were reported and no TEAEs led to withdrawal, discontinuation of treatment, or death. The majority of TEAEs were not considered related to study treatment by the Investigator ; a total of 3 mild TEAEs (excessive sweating, throat irritation, and upper abdominal pain) all reported in Part B of the study were considered related to study treatment.
Heart monitoring (Part A only) and hearing assessments showed no clinically significant abnormalities and there were no clinically relevant abnormal findings attributable to EP395 treatment following other safety assessments.
Following single and multiple once daily oral dosing of EP395 to healthy participants, Pharmacokinetic data indicated that:
• EP395 was rapidly absorbed.
• The terminal half-lives (time it takes for the concentration of EP395 to be reduced by 50%) were, on average, 72-76 hours following 28 days repeated dosing.
• A small proportion of the dose was excreted in urine.
• Food decreased the exposure of EP395 in plasma to 68% of the levels under fasted conditions.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
20/NW/0272
Date of REC Opinion
17 Sep 2020
REC opinion
Favourable Opinion