First-in-Human Single and Multiple Dose of EB8018

Healthy Volunteers Clinical Trial

Official title:

A Randomised, Double-Blind, Placebo-Controlled Study of a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) of a FimH Antagonist, EB8018, in Healthy Volunteers.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02998190
• Other study ID #: EBFIM116
• Status: Completed
• Phase: Phase 1
• First received: December 13, 2016
• Last updated: February 12, 2018
• Start date: November 2016
• Est. completion date: August 2017

Study information

• Verified date: February 2018
• Source: Enterome
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Single Ascending Doses of EB8018

• Single Ascending Doses of placebo

• Multiple Ascending Doses of EB8018

• Multiple Ascending Doses of placebo

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Ruddington	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
Enterome	Quotient Clinical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Between screening and 7-10 days after the last dose
Secondary	The amount of EB8018 in plasma	To characterize the amount of EB8018 in plasma over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects	Between Day 1 predose and 48 hours after the (last) dose
Secondary	The amount of EB8018 in urine	To characterize the amount of EB8018 in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects	Between Day 1 predose and 48 hours after the (last) dose
Secondary	The amount of EB8018 in stool	To characterize the amount of EB8018 in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects	Between predose and 48 hours after the (last) dose
Secondary	Analysis of microbiome richness	To compare the abundance of gene richness, all phyla and certain species such as E. Coli	Between predose and 48 hours after the (last) dose