An Open-Label, Two-Part Study Designed to Assess the Absolute Bioavailability and Mass Balance of Aramchol

Study Overview
=================
Brief Summary
-----------------
A two-part open-label study to assess the absolute bioavailability of aramchol and the mass balance recovery, metabolite profile and identification of metabolite structures for [14C]-aramchol in healthy male subjects

Detailed Description
-----------------
A two-part open-label study to assess the absolute bioavailability of aramchol and the mass balance recovery, metabolite profile and identification of metabolite structures for [14C]-aramchol in healthy male subjects. A subject was considered evaluable in Part 1 if they provided PK samples for up to a minimum of 120 h after first investigational medicinal product (IMP) administration. A subject was considered evaluable in Part 2 if they provided biological samples for up to a minimum of 144 h after IMP administration or demonstrated >90% mass balance recovery, or <1% of the administered dose eliminated in excreta for 2 consecutive days, whichever was sooner.

Official Title
-----------------
An Open-Label, Two-Part Study Designed to Assess the Absolute Bioavailability of Aramchol and to Determine the Mass Balance Recovery, Metabolite Profile and Metabolite Identification to Healthy Male Subjects

Conditions
-----------------
NASH

Intervention / Treatment
-----------------
* Drug: Aramchol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males Aged 35 to 64 years at the time of signing informed consent Body mass index (BMI) of 18.0 to 35.0 kg/m2 as measured at screening Must be willing and able to communicate and participate in the whole study Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day) Must provide written informed consent Must agree to adhere to the contraception requirements Exclusion Criteria: Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1 Subjects who are study site employees, or immediate family members of a study site or sponsor employee History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type) A confirmed positive alcohol breath test at screening or each admission Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or each admission Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months Subjects with pregnant or lactating partners Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study Participation in any study involving administration of any [14C]-labelled compound within 12 months prior to dosing in Part 1 of this study

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 64 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose administration of Aramchol in Part 1 and Part 2<br>6 subjects received Aramchol in Part 1 and Part 2 of the study | Drug: Aramchol<br>* Aramchol free acid (3β-arachidylamido-7α,12α-dihydroxy-5β-cholan-24-oic acid) is a synthetic small molecule, produced by conjugation of cholic acid (bile acid) and arachidic acid (saturated fatty acid) linked by a stable amide bond.<br>* Other names: Aramchol free acid (3β-arachidylamido-7α,12α-dihydroxy-5β-cholan-24-oic acid);|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute bioavailability | Measure the AUC(0-inf) of orally and intravenously (IV) administered Aramchol | 10 days | 
| Mass balance recovery | Assess the mass balance recovery of total amounts of radioactivity excreted in urine and feces | 10 days | 
| Metabolite profiling | Assess the potential metabolites of Aramchol and determine their chemical structure in plasma, urine and fecal samples | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Routes and rates of elimination | Determine the routes and rates of elimination of [14C]-Aramchol in excreta | 10 days | 
| Chemical structure of each metabolite accounting for more than 10% | Identify the chemical structure of each metabolite accounting for more than 10% by area under the curve (AUC) of circulating total radioactivity or 10% of the dose in urine and feces | 10 days | 
| PK- Area under the concentration-time curve (AUC) | Investigate the plasma Area under the concentration-time curve (AUC) of Aramchol | 10 days | 
| PK- Time of maximum observed concentration (Tmax) | Investigate the plasma Time of maximum observed concentration (Tmax) of Aramchol | 10 days | 
| PK- Maximum observed concentration (Cmax) | Investigate the plasma Maximum observed concentration (Cmax) of Aramchol | 10 days | 
| PK- Total body clearance (CL) | Investigate the Total body clearance (CL) of Aramchol | 10 days | 
| Safety- Adverse events | Assess and characterize the number of participants with adverse events | 10 days | 
| Safety- Clinical laboratory parameters | Assess and characterize the number of participants with clinically significant changes in clinical laboratory parameters | 10 days |