First in Man Evaluation of Single and Multiple Doses of Oral ATX2417

Study Overview
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Brief Summary
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First in man evaluation of single and multiple doses of compound ATX2417 in healthy male volunteers. A double blind placebo controlled parallel group ascending dose design; up to five dose levels for the single dose and up to two dose levels for the multiple dose (8 days of dosing). Subjects will be screened to assure normal health prior to inclusion in the trial and will be monitored for safety (adverse events, vital signs, ECGs, safety labs) and pharmacokinetic profile. A fasted/fed comparison will also be included in the single ascending dose part of the trial.

Detailed Description
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The study consists of two parts, A (single ascending dose including fasted/fed comparison) and B (multiple ascending dose). Part B will be conducted after a thorough review by the Sponsor and the Principal Investigator of the data arising from part A. Part A This will be a randomised, double blind, placebo controlled, parallel group titration of up to seven single dose levels of ATX2417. In each cohort, six subjects will receive active compound and two will receive placebo in a randomised fashion. At each dose level, 2 subjects (1 subject will receive ATX2417 and 1 subject will receive placebo) will be dosed on Day 1 and the remaining 6 subjects will be dosed at least 24 hours later. Safety and pharmacokinetic observations will be made. There will be a minimum of two weeks between the first dosing day at each dose level. Safety and ATX2417 pharmacokinetic data will be reviewed prior to each dose escalation and, based on pharmacokinetic data, it is also possible to decrease the dose if the pharmacokinetic profile so indicates. This part will also include an assessment of the effect of a high fat breakfast on the absorption and pharmacokinetic profile of ATX 2417, performed at a dose predicted to be associated with therapeutic plasma concentrations. Part B Following completion of Part A, and selection of appropriate dose levels, Part B will be performed. This will be a randomised, double blind, placebo controlled, parallel group study of up to two dose levels of ATX2417 given once daily for eight days. In each cohort, six subjects will receive active compound and two will receive placebo in a randomised fashion. Safety and pharmacokinetic observations will be made.

Official Title
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Double Blind Randomised Placebo Controlled Evaluation of Single and Multiple Oral Doses of ATX2417 in Man and Effect of Food

Conditions
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Allergy

Intervention / Treatment
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* Drug: ATX2417
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects, any racial group Able to comply with the protocol Subjects with a Body Mass Index (BMI) of 21-28 (BMI = Body weight (kg) / (Height (m)2) Exclusion Criteria: A history of gastrointestinal disorder likely to influence drug absorption Receipt of any medication including over the counter preparations and vitamins within 14 days of the first dose of study drug with the exception of paracetamol up to a maximum of 2 g daily Evidence of clinically significant renal, hepatic, cardiovascular or metabolic dysfunction A history of drug or alcohol abuse Inability to communicate well with the investigator (i.e., language problem, poor mental development or impaired cerebral function)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Active Comparator: Single dose level 1 active<br>Six subjects ATX2417 I mg tablet once. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Single dose level 2 active<br>Six subjects ATX2417 2x1 mg tablet once. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Single dose level 3 active<br>Six subjects ATX2417 5 mg tablet once. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Single dose level 4 active<br>Six subjects ATX2417 4x5 mg tablets once. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Single dose level 5 active<br>Six subjects ATX2417 to be determined. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Multiple dose level 1 active<br>Six subjects ATX2417 dose to be determined once daily for 8 days. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Multiple dose level 2 active<br>Six subjects ATX2417 dose to be determined once daily for 8 days. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 1 placebo<br>Two subjects one placebo tablet once. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 2 placebo<br>Two subjects one placebo tablet x2 once. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 3 placebo<br>Two subjects one placebo tablet once. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 4 placebo<br>Two subjects two placebo tablets once. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 5 placebo<br>Two subjects four placebo tablets once. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Multiple dose level 1 placebo<br>Two subjects matching placebo(s) once daily for 8 days | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Multiple dose level 2 placebo<br>Two subjects matching placebo(s) once daily for 8 days. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Single dose level 6 active<br>Six subjects ATX2417 to be determined. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Active Comparator: Single dose level 7 active<br>Six subjects ATX2417 to be determined. | Drug: ATX2417<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 6 placebo<br>Six subjects placeboto be determined. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|
| Placebo Comparator: Single dose level 7 placebo<br>Six subjects placebo to be determined. | Drug: Placebo<br>* Randomised double blind parallel group ascending dose assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability | Number of subjects with adverse events | 120 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t | Area under concentration time curve at 120 hours | 120 hours after single dose | 
| AUC0-t | Area under concentration time curve at 120 hours | 120 hours after eighth dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergy