Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to determine the safety profile of single and multiple doses of EB8018 in healthy male subjects, to determine the pharmacokinetic profile of single and multiple doses of EB8018 in healthy male subjects and to assess preliminary effects of EB8018 on the healthy male gut microbiome.
Detailed description
Crohn's Disease is a chronic inflammatory disease of the gastrointestinal tract. Emerging evidence suggests that the microbiome plays an important role in triggering an abnormal mucosal immune response in patients with Crohn's Disease. Independent studies have demonstrated an imbalance of the microbiome with a significant increase of E coli with invasive properties, termed adherent-invasive E coli (AIEC). These AIEC bacteria attach to the gut wall of susceptible patients via the fimbrial adhesion protein FimH, and subsequently trigger inflammation by invading and proliferating within the gut wall. EB8018 is an oral small molecule that is designed to block FimH thereby preventing the entry of AIEC into the gut wall thereby disarming the bacteria without disrupting the gut microbiome.
Interventions
DRUGMultiple Ascending Doses of EB8018
DRUGSingle Ascending Doses of EB8018
DRUGSingle Ascending Doses of placebo
Sponsors
Quotient Clinical
Enterome
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males * Age ≥ 18 to ≤ 55 years of age * Body mass index of 19.0 to 30.0 kg/m2 * Normal ECG, showing no clinically relevant deviations, as judged by the investigator (QTcF ≤450 ms)
Exclusion criteria
* Subjects who have received any Investigational Medicinal Product in a clinical research study within the previous 3 months. * History of any drug or alcohol abuse in the past 2 years * Regular alcohol consumption in males \>21 units per week * Current smokers and those who have smoked within the last 12 months * Positive drugs of abuse test result * Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever, even inactive, is not allowed. * Chronic infection or acute significant infection or fever within the previous 5 weeks prior to the start of IMP administration * Malignancy or prior malignancy, with a disease-free interval of less than 5 years after diagnosis and intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Related Adverse Event, including Abnormal Laboratory Events to evaluate the safety and tolerability profile of single ascending and multiple ascending doses of EB8018 compared with placebo in healthy subjects | Between screening and 7-10 days after the last dose | The variables for analysis will be the difference of EB8018 compared with placebo for incidence, severity and type of adverse events, including changes in vital signs, physical examinations, laboratory safety tests and ECGs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The amount of EB8018 in stool | Between predose and 48 hours after the (last) dose | To characterize the amount of EB8018 in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects |
| The amount of EB8018 in plasma | Between Day 1 predose and 48 hours after the (last) dose | To characterize the amount of EB8018 in plasma over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects |
| The amount of EB8018 in urine | Between Day 1 predose and 48 hours after the (last) dose | To characterize the amount of EB8018 in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects |
| Analysis of microbiome richness | Between predose and 48 hours after the (last) dose | To compare the abundance of gene richness, all phyla and certain species such as E. Coli |
Countries
United Kingdom
Outcome results
None listed