Hepatic ImpairmentPhase 1NCT04480827
Open-Label Study to Evaluate the Safety, Tolerability, and PK of Aramchol in Subjects With Hepatic Impairment
A Phase 1 study testing Aramchol free acid tablet 600mg, single dose and Aramchol free acid tablet 300mg, bid in people with Hepatic Impairment, run by Galmed Research and Development, Ltd. at 3 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Aramchol free acid tablet 600mg, single dose and Aramchol free acid tablet 300mg, bid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Feb 2020to 24 Mar 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- The subject agrees to comply with all protocol requirements.
- The subject is able to provide written informed consent.
- Additional Inclusion Criteria for Healthy Subjects Only (Cohort D):
- 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.
- Additional Inclusion Criteria for Subjects With Hepatic Impairment Only (Cohorts A, B, and C):
- 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.
Who cannot join
- 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.
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- 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.
- For additional exclusion criteria specific to hepatic impaired subjects and healthy volunteers, see protocol.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Alliance for Multispecialty Research
Knoxville, Tennessee, 37920
Division of Clinical Pharmacology, University of Miami
Miami, Florida, 33136
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Aramchol in Subjects With Hepatic Impairment
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
Read the detailed description
Each of the 2 parts of the study consisted of a screening period, a check in day, a treatment period, and an end of study (EOS) visit.
In Part 1 (single-dose): 39 subjects were enrolled: 8 subjects each in the mild (Cohort A), moderate (Cohort B), and severe (Cohort C) hepatic impairment cohorts and 15 healthy control subjects with normal hepatic function (Cohort D). Enrollment of 8 subjects with mild hepatic impairment (Cohort A) proceeded only if there is evidence of reduced clearance of aramchol in Cohort B. Assignment to cohorts A to C, was according to Child Pugh classification system.
Serial blood samples for PK analysis of aramchol concentrations in plasma were collected before dosing (0 hour) and up to 168 hours for healthy subjects and 240 hours for hepatically impaired subjects after administration of aramchol.
In Part 2 (multiple-dose), a cohort of 4 subjects comprising of mild, 7 moderate , as well as a cohort of 7 healthy volunteers was administered with aramchol as multiple doses to obtain the PK profile of aramchol at steady state. Aramchol was given twice daily for 12 days. Trough blood samples for analysis of aramchol plasma concentrations was collected before the AM dose on several days and at intervals to 12 hours after the AM dose on Day 12.
- Conditions
- Hepatic Impairment
- Being tested
- Aramchol free acid tablet 600mg, single dose, Aramchol free acid tablet 300mg, bid
- Keywords
- Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aramchol free acid tablet 600mg, single doseDrug
Also called Cholan-24-oic acid 7,12-dihydroxy3-[(1- oxoeicosyl)amino]-(3β,5β,7α,12α) salt with N-methyl-(D)-glucamine
Aramchol free acid tablet 600mg, single dose
Aramchol free acid tablet 300mg, bidDrug
Also called Cholan-24-oic acid 7,12-dihydroxy3-[(1- oxoeicosyl)amino]-(3β,5β,7α,12α) salt with N-methyl-(D)-glucamine
Aramchol acid tablet 300mg, bid for 12 days
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Mild Hepatic Impairment (Cohort A) | Experimental | 8 mild hepatic impaired subjects Receives: Drug: Aramchol free acid tablet 600mg, single dose |
| Part 1: Moderate Hepatic Impairment (Cohort B) | Experimental | 8 moderate hepatic impaired subjects Receives: Drug: Aramchol free acid tablet 600mg, single dose |
| Part 1: Severe Hepatic Impairment (Cohort C) | Experimental | 8 severe hepatic impaired subjects Receives: Drug: Aramchol free acid tablet 600mg, single dose |
| Part 1: Healthy Volunteers (Cohort D) | Experimental | 15 matched healthy volunteers Receives: Drug: Aramchol free acid tablet 600mg, single dose |
| Part 2: Mild Hepatic Impairment Cohort | Experimental | 4 mild hepatic impaired subjects Receives: Drug: Aramchol free acid tablet 300mg, bid |
| Part 2: Moderate Hepatic Impairment Cohort | Experimental | 7 moderate hepatic impaired subjects Receives: Drug: Aramchol free acid tablet 300mg, bid |
| Part 2: Healthy Volunteers Cohort | Experimental | 7 matched healthy volunteers Receives: Drug: Aramchol free acid tablet 300mg, bid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: Day 11
Secondary outcomes (1)
Number of Subjects With Significant TEAEs
The number of significant treatment-related adverse events
Measured: Part 1: up to 22 days; Part 2: up to 27 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start13 Feb 2020
- Primary completion24 Mar 2022
- Study completion24 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Galmed Research and Development, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yossi Gilgun-Sherki, PhD, MBA, Study director, Executive Drug Development Consultant
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04480827
- Sponsor's protocol ID
- Aramchol-019
- Status last verified
- Sep 2022
- First submitted
- 2 Jun 2020
- Last updated
- 14 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Aramchol in Subjects With Hepatic Impairment
- ClinicalTrials.gov ID
- NCT04480827
- Acronym / sponsor ID
- Aramchol-019
- Conditions
- Hepatic Impairment
- Keywords
- Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Galmed Research and Development, Ltd.Industry (pharma, biotech, devices)
- Study start
- 13 Feb 2020 (actual)
- Primary completion
- 24 Mar 2022 (actual)
- Study completion
- 24 Mar 2022 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Posted 14 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Each of the 2 parts of the study consisted of a screening period, a check in day, a treatment period, and an end of study (EOS) visit.
In Part 1 (single-dose): 39 subjects were enrolled: 8 subjects each in the mild (Cohort A), moderate (Cohort B), and severe (Cohort C) hepatic impairment cohorts and 15 healthy control subjects with normal hepatic function (Cohort D). Enrollment of 8 subjects with mild hepatic impairment (Cohort A) proceeded only if there is evidence of reduced clearance of aramchol in Cohort B. Assignment to cohorts A to C, was according to Child Pugh classification system.
Serial blood samples for PK analysis of aramchol concentrations in plasma were collected before dosing (0 hour) and up to 168 hours for healthy subjects and 240 hours for hepatically impaired subjects after administration of aramchol.
In Part 2 (multiple-dose), a cohort of 4 subjects comprising of mild, 7 moderate , as well as a cohort of 7 healthy volunteers was administered with aramchol as multiple doses to obtain the PK profile of aramchol at steady state. Aramchol was given twice daily for 12 days. Trough blood samples for analysis of aramchol plasma concentrations was collected before the AM dose on several days and at intervals to 12 hours after the AM dose on Day 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part 1: Mild Hepatic Impairment (Cohort A) | Experimental | Drug: Aramchol free acid tablet 600mg, single dose8 mild hepatic impaired subjects |
| Part 1: Moderate Hepatic Impairment (Cohort B) | Experimental | Drug: Aramchol free acid tablet 600mg, single dose8 moderate hepatic impaired subjects |
| Part 1: Severe Hepatic Impairment (Cohort C) | Experimental | Drug: Aramchol free acid tablet 600mg, single dose8 severe hepatic impaired subjects |
| Part 1: Healthy Volunteers (Cohort D) | Experimental | Drug: Aramchol free acid tablet 600mg, single dose15 matched healthy volunteers |
| Part 2: Mild Hepatic Impairment Cohort | Experimental | Drug: Aramchol free acid tablet 300mg, bid4 mild hepatic impaired subjects |
| Part 2: Moderate Hepatic Impairment Cohort | Experimental | Drug: Aramchol free acid tablet 300mg, bid7 moderate hepatic impaired subjects |
| Part 2: Healthy Volunteers Cohort | Experimental | Drug: Aramchol free acid tablet 300mg, bid7 matched healthy volunteers |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aramchol free acid tablet 600mg, single doseAlso: Cholan-24-oic acid 7,12-dihydroxy3-[(1- oxoeicosyl)amino]-(3β,5β,7α,12α) salt with N-methyl-(D)-glucamineAramchol free acid tablet 600mg, single dose | Drug | 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, bidAlso: Cholan-24-oic acid 7,12-dihydroxy3-[(1- oxoeicosyl)amino]-(3β,5β,7α,12α) salt with N-methyl-(D)-glucamineAramchol acid tablet 300mg, bid for 12 days | Drug | Part 2: Healthy Volunteers Cohort, Part 2: Mild Hepatic Impairment Cohort, Part 2: Moderate Hepatic Impairment Cohort |
Primary outcome
AUC0-tau, Steady State
Time frame: Day 12
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
Cmax,ss
Time frame: Day 12
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
Apparent Total Oral Clearance, Single Dose
Time frame: Day 11
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
1 secondary outcome
Number of Subjects With Significant TEAEs
Time frame: Part 1: up to 22 days; Part 2: up to 27 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Hepatic Impairment
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yossi Gilgun-Sherki, PhD, MBA study director
Executive Drug Development Consultant
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aramchol free acid tablet 600mg, single dose and Aramchol free acid tablet 300mg, bid in people with Hepatic Impairment, run by Galmed Research and Development, Ltd. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC0-tau, Steady State (time frame: Day 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2024.