A First Time in Human Study in Healthy Volunteers and Patients

Study Overview
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Brief Summary
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A multi-part study to investigate the safety, tolerability and local and systemic pharmacokinetics of V565

Official Title
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A Four Part, Phase 1, First Time in Human, Single Centre Study in Healthy Male Subjects, Patient Volunteers With Crohn's Disease and in Healthy Patient Volunteers With a Terminal Ileostomy

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: V565
* Drug: V565
* Drug: Placebo
* Drug: V565
* Drug: V565


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parts 1 and 2 Adult male subjects aged 18 to 45 years inclusive. Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive. Body weight between 50.0 and 100.0 kg inclusive. Subjects who are healthy as determined by pre study medical history, physical examination and 12-lead ECG, and clinical laboratory tests Part 3 Adult male or female subjects aged 18 to 65 years. Ileostomy for a minimum of 18 months for a non malignant disease indication. A BMI between 18.0 and 32.0 kg/m2 inclusive. Body weight between 50.0 and 100.0 kg inclusive. Subjects who are healthy as determined by pre study medical history, physical examination and 12-lead ECG, and clinical laboratory tests Part 4 Adult male or female subjects aged 18 to 65 years. A confirmed diagnosis of Crohn's disease for a minimum of 6 months. A BMI between 15.0 and 32.0 kg/m2 inclusive. Subjects who have no other significant co-morbidity (other than those associated with Crohn's disease). Subjects whose medical history, physical examination, clinical laboratory test results and 12-lead ECG have no clinically relevant abnormalities (other than those associated with Crohn's disease). Exclusion Criteria: Parts 1 and 2 A clinically significant abnormal medical history or clinically significant abnormal physical examination, including history of febrile illness within 1 week prior to the first dose. A history of severe allergies, non-allergic drug reactions, or multiple drug allergies. A known hypersensitivity to TNF inhibitors or any of the inactive ingredients of the study treatment. A history of significant gastrointestinal (GI) disease, including GI motility disorders, GI malignancy or of polyposis coli. Previous surgery to the GI tract with the exception of appendectomy. A history of malignancy. Any other condition which in the investigator's opinion will interfere with the trial or interpretation of the results. Part 3 A history of Crohn's disease. A clinically significant abnormal medical history (other than the condition leading to ileostomy) or clinically significant abnormal physical examination, including history of febrile illness within 1 week prior to the first dose. A history of severe allergies, non-allergic drug reactions, or multiple drug allergies. A known hypersensitivity or contraindication to TNF inhibitors or any of the inactive ingredients of the study treatment. A known history of heart disease. Any clinical evidence of active inflammatory bowel disease. Any other condition which in the investigator's opinion will interfere with the trial or interpretation of the results. Part 4 Subjects with severe Crohn's disease such as: those requiring surgery; those with a current abscess; those with a non inflammatory stricture; those with a history of obstruction. Having ever received anti-TNF-α therapy or other biologics. Required an increase in dose of either steroids or immunosuppressant therapy within the past 6 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Single ascending dose of oral V565 | Drug: V565<br>* single ascending dose of V565<br>|
| Experimental: Part 2 - V565<br>Single dose level of oral V565 TID for 14 days | Drug: V565<br>* Multiple dose<br>|
| Placebo Comparator: Part 1 and 2 - placebo<br>Oral placebo single dose (Part 1) or TID for 14 days (Part 2) | Drug: Placebo<br>* Single and multiple dose<br>|
| Experimental: Part 3<br>Single dose of V565 in patient volunteers | Drug: V565<br>* Open-label single dose<br>|
| Experimental: Part 4<br>Single ascending dose of V565 in patients with Crohn's Disease | Drug: V565<br>* Open-label single ascending dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety & tolerability: treatment-emergent AEs including clinically significant changes in physical examinations, safety lab tests, ECGs or vital signs |  | Up to 14 days | 
| Measurement of the concentrations of V565 in ileal fluid following a single dose |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of pharmacokinetic parameter of V565: Cmax |  | 72 hours | 
| Evaluation of pharmacokinetic parameter of V565: AUC |  | 72 hours | 
| Evaluation of pharmacokinetic parameter of V565: tmax |  | 72 hours |