Open-Label Study to Evaluate the Safety, Tolerability, and PK of Aramchol in Subjects With Hepatic Impairment

NCT04480827 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Aramchol-019
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

Brief Summary

Phase 1, multicenter, open-label, 2-part, single- and multiple-dose study designed to assess the effect of hepatic insufficiency on the PK of aramchol

Conditions

Hepatic Impairment

Keywords

Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• AUC0-tau, Steady State

  AUC from time 0 to the dosing interval tau measured at steady state. Blood was collected at the following time points: before dosing (0 hour) and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 48, 72, 96, 120, 144, 168, 192, and 240 hours

  Day 12

• Cmax,ss

  Maximum plasma concentrations (Cmax,ss) Blood was collected at the following time points: before dosing (0 hour) and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 48, 72, 96, 120, 144, 168, 192, and 240 hours

  Day 12

• Apparent Total Oral Clearance, Single Dose

  CL/F measured after single dose in Part 1 Blood was collected at the following time points: before dosing (0 hour) and at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 18, 24, 48, 72, 96, 120, 144, 168, 192, and 240 hours

  Day 11

Secondary Outcomes (1)

• Number of Subjects With Significant TEAEs

  Part 1: up to 22 days; Part 2: up to 27 days

Study Arms (7)

Part 1: Mild Hepatic Impairment (Cohort A)

EXPERIMENTAL

8 mild hepatic impaired subjects

Drug: Aramchol free acid tablet 600mg, single dose

Part 1: Moderate Hepatic Impairment (Cohort B)

EXPERIMENTAL

8 moderate hepatic impaired subjects

Drug: Aramchol free acid tablet 600mg, single dose

Part 1: Severe Hepatic Impairment (Cohort C)

EXPERIMENTAL

8 severe hepatic impaired subjects

Drug: Aramchol free acid tablet 600mg, single dose

Part 1: Healthy Volunteers (Cohort D)

EXPERIMENTAL

15 matched healthy volunteers

Drug: Aramchol free acid tablet 600mg, single dose

Part 2: Mild Hepatic Impairment Cohort

EXPERIMENTAL

4 mild hepatic impaired subjects

Drug: Aramchol free acid tablet 300mg, bid

Part 2: Moderate Hepatic Impairment Cohort

EXPERIMENTAL

7 moderate hepatic impaired subjects

Drug: Aramchol free acid tablet 300mg, bid

Part 2: Healthy Volunteers Cohort

EXPERIMENTAL

7 matched healthy volunteers

Drug: Aramchol free acid tablet 300mg, bid

Interventions

Aramchol free acid tablet 600mg, single dose DRUG

Aramchol free acid tablet 600mg, single dose

Also known as: Cholan-24-oic acid 7,12-dihydroxy3-[(1- oxoeicosyl)amino]-(3β,5β,7α,12α) salt with N-methyl-(D)-glucamine

Part 1: Healthy Volunteers (Cohort D); Part 1: Mild Hepatic Impairment (Cohort A); Part 1: Moderate Hepatic Impairment (Cohort B); Part 1: Severe Hepatic Impairment (Cohort C)

Aramchol free acid tablet 300mg, bid DRUG

Aramchol acid tablet 300mg, bid for 12 days

Also known as: Cholan-24-oic acid 7,12-dihydroxy3-[(1- oxoeicosyl)amino]-(3β,5β,7α,12α) salt with N-methyl-(D)-glucamine

Part 2: Healthy Volunteers Cohort; Part 2: Mild Hepatic Impairment Cohort; Part 2: Moderate Hepatic Impairment Cohort

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject is male or female 18 to 79 years of age, inclusive.
• The subject has a body mass index of 19 to 40 kg/m2, inclusive, at screening.
• Females of childbearing potential must practice a highly effective method of contraception throughout the study period and for 1 month after treatment discontinuation.
• Male subjects with female partners of childbearing potential must be vasectomized, be willing to use an acceptable method of birth control, or practice abstinence during the study.
• The subject has a resting pulse rate of ≥40 and \<100 beats per minute with no clinically significant deviation as judged by the investigator.
• The subject has a QT interval corrected for heart rate using Fridericia's formula of \<500 msec.
• The subject agrees to comply with all protocol requirements.
• The subject is able to provide written informed consent.
• The subject has normal hepatic function.
• The subject has a resting blood pressure of 90 to 150 mm Hg (systolic) and 50 to 100 mm Hg (diastolic).
• The subject is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings.
• The subject has cirrhosis with evidence of impaired liver function. The etiology of the cirrhosis may be alcoholic, autoimmune, nonalcoholic steatohepatitis, or chronic viral hepatitis type B or C.
• The subject has chronic (more than 6 months) and stable hepatic impairment (ie, no acute episodes of illness within 30 days before screening due to deterioration of hepatic function) as assessed by a Child-Pugh classification score of mild (5 to 6 points), moderate (7 to 9 points), or severe (10 to 15 points).
• The subject has a resting blood pressure of 90 to 155 mm Hg (systolic) and 50 to 100 mm Hg (diastolic).
• The subject is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12 lead ECG results, and physical examination findings, except for findings that, as judged by the investigator, are consistent with the subject's hepatic impairment or other stable concomitant medical conditions.

You may not qualify if:

• The subject has a history or clinical manifestations of a significant neurological, renal, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, or psychiatric disease that would preclude study participation, as judged by the investigator.
• The subject has a positive test result for human immunodeficiency virus type 1 or 2 antibodies at screening.
• The subject has a history of drug abuse within 3 months before screening.
• The subject has a history of alcoholism within 3 months before screening, or excessive alcohol consumption (regular alcohol intake \>15 units per week) (1 unit is equal to approximately ½ pint \[200 mL\] of beer, 1 small glass \[100 mL\] of wine, or 1 measure \[25 mL\] of spirits).
• The subject smokes \>10 cigarettes daily and is unwilling to reduce to \<5 daily from the time of screening through the last PK sample.
• The subject is unable or unwilling to abstain from alcohol, caffeine, xanthine containing beverages or food (eg, coffee, tea, chocolate, and caffeinated sodas, colas), grapefruit, grapefruit juice, Seville oranges, or products containing any of these, from 48 hours prior to study drug dosing until discharge.
• The subject is involved in strenuous activity or contact sports within 24 hours of the first dose of study drug or during the study.
• The subject has donated blood or blood products \>450 mL within 3 months before the first dose of study drug.
• The subject has a presence or history of relevant drug and/or food allergies (ie, allergy to aramchol, cholic acid, or any excipients, or any significant food allergy.
• The subject has received study drug in another investigational study within 30 days of dosing.
• In the opinion of the investigator, the subject is not suitable for entry into the study.

Sponsors & Collaborators

• Galmed Research and Development, Ltd.: lead

Study Sites (3)

Division of Clinical Pharmacology, University of Miami

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Alliance for Multispecialty Research

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Interventions

Salts; Meglumine; BID protein, human

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Hexosamines; Amino Sugars; Carbohydrates

Results Point of Contact

• Title: Dr. Yossi Gilgun-Sherki
• Organization: Galmed Pharmaceuticals

yossigs@galmedpharma.com

972.3.693.8448

Study Officials

• Yossi Gilgun-Sherki, PhD, MBA

  Executive Drug Development Consultant

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: July 21, 2020
• Study Start: February 13, 2020
• Primary Completion: March 24, 2022
• Study Completion: March 24, 2022
• Last Updated: August 14, 2024
• Results First Posted: August 14, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)