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

Phase 1

Completed

• Conditions: NASH
• Interventions: Drug: Aramchol

• Registration Number: NCT05874336
• Lead Sponsor: Galmed Pharmaceuticals Ltd

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.

Study Timeline

• Study Start: 2020-06-17
• Primary Completion: 2020-08-11
• Study Completion: 2020-08-11
• Status Verified: 2023-04
• Study First Submitted: 2023-04-24
• Study First Submitted QC: 2023-05-23
• Last Update Submitted: 2023-05-23
• Study First Posted: 2023-05-24
• Last Update Posted: 2023-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

1. Healthy males
2. Aged 35 to 64 years at the time of signing informed consent
3. Body mass index (BMI) of 18.0 to 35.0 kg/m2 as measured at screening
4. Must be willing and able to communicate and participate in the whole study
5. Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)
6. Must provide written informed consent
7. Must agree to adhere to the contraception requirements

Exclusion Criteria

1. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1
2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee
3. History of any drug or alcohol abuse in the past 2 years
4. 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)
5. A confirmed positive alcohol breath test at screening or each admission
6. 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
7. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
8. Subjects with pregnant or lactating partners
9. 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
10. Participation in any study involving administration of any [14C]-labelled compound within 12 months prior to dosing in Part 1 of this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single dose administration of Aramchol in Part 1 and Part 2	Aramchol	6 subjects received Aramchol in Part 1 and Part 2 of the study

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Safety- Adverse events	10 days	Assess and characterize the number of participants with adverse events
Chemical structure of each metabolite accounting for more than 10%	10 days	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
PK- Maximum observed concentration (Cmax)	10 days	Investigate the plasma Maximum observed concentration (Cmax) of Aramchol
Safety- Clinical laboratory parameters	10 days	Assess and characterize the number of participants with clinically significant changes in clinical laboratory parameters
Routes and rates of elimination	10 days	Determine the routes and rates of elimination of \[14C\]-Aramchol in excreta
PK- Area under the concentration-time curve (AUC)	10 days	Investigate the plasma Area under the concentration-time curve (AUC) of Aramchol
PK- Total body clearance (CL)	10 days	Investigate the Total body clearance (CL) of Aramchol
PK- Time of maximum observed concentration (Tmax)	10 days	Investigate the plasma Time of maximum observed concentration (Tmax) of Aramchol

Trial Locations

Locations (1)

Quotient Sciences, Mere Way, Ruddington Fields, Ruddington, Nottingham, NG11 6JS, UK.; 🇬🇧 Nottingham, United Kingdom