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

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

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

Study Overview

• Status: Completed
• Conditions: NASH
• Intervention / Treatment: Drug: Aramchol

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Sciences, Mere Way, Ruddington Fields, Ruddington, Nottingham, NG11 6JS, UK.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose administration of Aramchol in Part 1 and Part 2; 6 subjects received Aramchol in Part 1 and Part 2 of the study	Drug: Aramchol; 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.; 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

Collaborators and Investigators

• Sponsor: Galmed Pharmaceuticals Ltd
• Collaborators: Quotient Sciences
• Investigators: Study Director: John Posner, PhD, FRCP, Consultant

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2020
• Primary Completion (Actual): August 11, 2020
• Study Completion (Actual): August 11, 2020

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: Aramchol-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Consideration will be made whether to share any data of this mass balance study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No