Safety and Pharmacokinetic Study of OMT-28 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The aim of this first-in-human study is to assess the safety, tolerability, PK and exploratory pharmacodynamics (PD) of single and multiple oral ascending doses of OMT-28 in healthy male subjects to support further clinical development of OMT-28 in the indication of atrial fibrillation (AF) and to obtain data on food and gender effects of OMT-28 to guide dosing for Phase II trials.

Detailed Description
-----------------
This first-in-human study will be carried out in one study center involving multiple steps. Up to 100 healthy male and female subjects will be enrolled. The study consists of 4 parts: a single ascending dose (SAD) part a multiple ascending dose (MAD) part a single dose, double cross-over food effect (FE) part. a single dose gender effect part (female subjects group) The safety and PK data will be evaluated by the DSMC after each cohort to decide on further dose escalation.

Official Title
-----------------
A First-in-Human Randomized, Double-blind, Placebo-controlled, Fed-fasted, Gender, Single and Multiple Ascending Oral Dose Study, to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of OMT-28 in Healthy Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: OMT-28
* Other: Matching Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In general good physical health as determined by medical and surgical history, physical examination, 12 lead ECG, vital signs, and clinical laboratory tests Normal blood pressure (Systolic Blood Pressure (SBP) between 100 to 140 mmHg (both inclusive); Diastolic Blood Pressure (DBP) ≥55, ≤89 mmHg) measured after 5 min rest in supine position. SAD, MAD, and FE part: male of 18 to 45 years (inclusive) of age. Gender effect part: female of 18 to 45 years (inclusive) of age. Exclusion Criteria: More than moderate smoker (> 10 cigarettes/day). More than moderate alcohol consumption (> 35 g of ethanol regularly per day or > 245 g regularly per week). Use of any medication One or more key safety laboratory parameters out of normal range Gender effect part Pregnant or breastfeeding women and of childbearing potential Previous assignment to treatment during this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMT-28-SAD<br>OMT-28-SAD, Single ascending dose levels 1 - 3 of OMT-28 (15, 30, 60 mg) Oral, healthy young male | Drug: OMT-28<br>* OMT-28 is a fully synthetic small molecule that belongs to the family of 17,18-epoxyeicosatetraenoic acids (17,18-EEQ) analogs, a natural metabolite of the omega-3 fatty acid eicosapentaenoic acid (EPA).<br>* Other names: 17,18-epoxyeicosatetraenoic acid analog;|
| Experimental: OMT-28-MAD<br>Multiple ascending dose of dose levels 1 - 3 of OMT-28 over 14 days (4, 12, 36 mg) Oral, healthy young male | Drug: OMT-28<br>* OMT-28 is a fully synthetic small molecule that belongs to the family of 17,18-epoxyeicosatetraenoic acids (17,18-EEQ) analogs, a natural metabolite of the omega-3 fatty acid eicosapentaenoic acid (EPA).<br>* Other names: 17,18-epoxyeicosatetraenoic acid analog;|
| Experimental: OMT-28- Food Effect<br>Single dose of OMT-28 (4 mg) Oral, healthy young male | Drug: OMT-28<br>* OMT-28 is a fully synthetic small molecule that belongs to the family of 17,18-epoxyeicosatetraenoic acids (17,18-EEQ) analogs, a natural metabolite of the omega-3 fatty acid eicosapentaenoic acid (EPA).<br>* Other names: 17,18-epoxyeicosatetraenoic acid analog;|
| Experimental: OMT-28-Gender<br>Single dose of OMT-28 (4 mg) Oral, healthy non-child bearing potential female | Drug: OMT-28<br>* OMT-28 is a fully synthetic small molecule that belongs to the family of 17,18-epoxyeicosatetraenoic acids (17,18-EEQ) analogs, a natural metabolite of the omega-3 fatty acid eicosapentaenoic acid (EPA).<br>* Other names: 17,18-epoxyeicosatetraenoic acid analog;|
| Placebo Comparator: Placebo-SAD<br>Single dose levels 1 - 3 of matching placebo, Oral, healthy young male | Other: Matching Placebo<br>* Microcrystalline cellulose<br>* Other names: Microcrystalline cellulose;|
| Placebo Comparator: Placebo MAD<br>Multiple dose levels 1 - 3 of matching placebo over 14 days Oral, healthy young male | Other: Matching Placebo<br>* Microcrystalline cellulose<br>* Other names: Microcrystalline cellulose;|
| Placebo Comparator: Placebo-Gender<br>Single dose of matching Placebo Oral, healthy non-child bearing potential female | Other: Matching Placebo<br>* Microcrystalline cellulose<br>* Other names: Microcrystalline cellulose;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by frequency and nature of treatment-emergent adverse events |  | From Day 1 to Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) measured by AUC0-t of OMT-28 in plasma in the SAD |  | From Day 1 to Day 21 | 
| Pharmacokinetics (PK) measured by AUC0-∞ of OMT-28 in plasma in the SAD |  | From Day 1 to Day 21 | 
| Pharmacokinetics (PK) measured by Cmax of OMT-28 in plasma in the SAD |  | From Day 1 to Day 21 | 
| Pharmacokinetics (PK) measured by AUC0-24h of OMT-28 in plasma after single dosing in the SAD |  | From Day 1 to Day 28 | 
| Pharmacokinetics (PK) measured by AUC0-τ after multiple dosing on Day 7 and 14 in the MAD |  | From Day 7 to Day 14 | 
| Pharmacokinetics (PK) of OMT28 measured Cmax after multiple dosing on Day 7 and 14 in the MAD |  | From Day 7 to Day 14 | 
| Pharmacokinetics (PK) in Food Effect and Gender Part measured by AUC0-t of OMT-28 in plasma |  | From Day 1 to Day 21 (Gender) and Day 28 (F&E) | 
| Pharmacokinetics (PK) in Food Effect and Gender Part measured by AUC0-∞ of OMT-28 in plasma |  | From Day 1 to Day 21 (Gender) and Day 28 (F&E) | 
| Pharmacokinetics (PK) of OMT28 in Food Effect and Gender Part measured by Cmax of OMT-28 in plasma |  | From Day 1 to Day 21 (Gender) and Day 28 (F&E) | 
| Change-from-baseline of QTcF (∆QTcF) |  | From baseline to Day 28 | 
| Change from-baseline of heart rate |  | From baseline to Day 28 | 
| Change from-baseline of PR interval in ECG |  | From baseline to Day 28 | 
| Change from-baseline of QRS interval (∆HR, ∆PR and ∆QRS) |  | From baseline to Day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SAD, OMT-28, Atrial Fibrillation, MAD, First-in-Man, Cardiovascular