HealthyPhase 1NCT03760848
Study of Potential for Drug Interactions Mediated by CYP3A4 Inhibition With Aramchol in Healthy Volunteers
A Phase 1 study testing Aramchol, Midazolam and Atorvastatin in people with Healthy, run by Galmed Pharmaceuticals Ltd at 1 site in United Kingdom.
Trial summary
The trial is an open-label, 2-period, single-sequence assessment of CYP3A4 inhibition by aramchol using the probe substrates midazolam and atorvastatin to assess CYP3A4 activity. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Aramchol, Midazolam and Atorvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Nov 2018to 2 Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male healthy volunteers.
- Aged 18-45 years at time of consent.
- A body mass index (BMI; Quetelet index) in the range 18.0-30.9.
- Ability to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire trial.
- Willingness to give written consent to participate after reading and understanding the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
- Agree to use effective contraception as described in section 9.
- Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication.
- Willingness to give written consent to have data entered into The Overvolunteering Prevention System (TOPS).
Who cannot join
- Volunteers of East Asian descent including, but not limited to, Chinese, Japanese, Korean, Mongolian, and/or Vietnamese
- Be a smoker, or have smoked cigarettes or other tobacco or nicotine products in the last 12 months.
- Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (AP) > Upper Limit of Normal (ULN) at the screening visit. A repeat is allowed on one occasion for determination of eligibility.
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous,
- Presence or history of obstructive sleep apnoea.
Show all 20Show fewer
- History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including gastrointestinal disorder or of oesophageal, gastric, biliary or intestinal surgery (excluding herniotomy and appendectomy).
- Use of anticholinergic or other drugs known to affect gastrointestinal motility during the 7 days before the first dose of trial medication.
- Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness.
- Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines.
- Presence or history of severe adverse reaction to any drug or a history of sensitivity to aramchol, midazolam or atorvastatin, or any excipients in the tablets.
- Use of a prescription medicine or any other medicine or herbal remedy (such as St John's wort) during the 28 days before the first dose of trial medication or use of any other over-the-counter medicine, with the exception of acetaminophen (paracetamol), during the 7 days before the first dose of trial medication.
- Receipt of an investigational product (including prescription medicines) as part of another clinical trial within the 3 months before first admission to this study; in the follow-up period of another clinical trial at the time of screening for this study.
- Presence or history of drug or alcohol abuse, or intake of more than 14 units of alcohol weekly.
- Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 100-140 mm Hg systolic, 50-90 mm Hg diastolic; heart rate 45_90 beats/min, unless judged not clinically significant.
- Possibility that the volunteer will not cooperate with the requirements of the protocol.
- Evidence of drug abuse on urine testing.
- Positive test for hepatitis B, hepatitis C or HIV.
- Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor.
- Objection by General Practitioner (GP) to volunteer entering trial.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Hammersmith Medicines Research (HMR)
London, NW10 7EW
About this study
The trial is an open-label, 2-period, single-sequence assessment of CYP3A4 inhibition by aramchol using the probe substrates midazolam and atorvastatin to assess CYP3A4 activity.
Read the detailed description
Enrolment of 16 subjects is planned. Each subject will take part in 2 study periods.
In Period 1, subjects will receive a single oral dose of 2 mg midazolam on Day 1 and a single oral dose of 40 mg atorvastatin on Day 3.
In Period 2, subjects will receive twice-daily oral doses of 300 mg aramchol (the IMP) for 18 days. During aramchol dosing, subjects will take a single dose of 2 mg midazolam in the morning on Day 10 and 40 mg atorvastatin in the morning on Day 12.
Subjects will be screened within 21 days before their first dose of study medicine. In Period 1, they will remain resident on the ward from Day -1 to Day 10. In Period 2, subjects will be admitted on Day -1 and discharged on Day 19. Subjects will attend a follow-up visit approximately 2 weeks later, on Day 33 (±2 days). There will be an interval of at least 1 day between Periods 1 and 2.
- Conditions
- Healthy
- Being tested
- Aramchol, Midazolam, Atorvastatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AramcholDrug
Aramchol 600 mg
MidazolamDrug
Midazolam 2 mg
AtorvastatinDrug
atorvastatin 40 mg
| Study group | Role | What they receive |
|---|---|---|
| Midazolam, Atorvastatin / Aramchol, Midazolam, Atorvastatin | Other | Midazolam 2 mg -atorvastatin 40 mg /Aramchol 600mg -midazolam 2 mg-atorvastatin 40 mg (MA/MAA) Receives: Drug: Aramchol; Drug: Midazolam; Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Midazolam - cmax
Maximum plasma concentration
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - cmax
Maximum plasma concentration
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - tmax
Time of maximum plasma concentration
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - tmax
Time of maximum plasma concentration
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - Area under the concentration-time curve to last measurable concentration (AUClast)
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - Area under the concentration-time curve to last measurable concentration (AUClast)
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - Area under the concentration-time curve extrapolated to infinite time (AUCinf)
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - Area under the concentration-time curve extrapolated to infinite time (AUCinf)
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - %AUCextrapinf
Percentage of AUC that was extrapolated
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - %AUCextrapinf
Percentage of AUC that was extrapolated
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - t½
Terminal elimination half-life
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - t½
Terminal elimination half-life
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - CL/F
Clearance/fraction of dose absorbed
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - CL/F
Clearance/fraction of dose absorbed
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - VZ/F
Volume of distribution/fraction of dose absorbed
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - VZ/F
Volume of distribution/fraction of dose absorbed
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - MRT
Mean residence time
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - MRT
Mean residence time
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - λz
Terminal rate constant
Measured: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - λz
Terminal rate constant
Measured: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2018
- Study start12 Nov 2018
- Primary completion2 Feb 2019
- Study completion2 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Galmed Pharmaceuticals Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hammersmith Medicines Research, Analyst Research Laboratories, Alderley Analytical Ltd., Diamond Pharma Services Regulatory Affairs Consultancy
- Responsible party
- Sponsor
- Investigators
- Adeep Puri, M.D., Principal investigator, HMR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03760848
- Sponsor's protocol ID
- Aramchol 016
- Status last verified
- Feb 2019
- First submitted
- 22 Nov 2018
- Last updated
- 22 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Potential for Drug Interactions Mediated by CYP3A4 Inhibition With Aramchol in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03760848
- Acronym / sponsor ID
- Aramchol 016
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Galmed Pharmaceuticals LtdIndustry (pharma, biotech, devices)
- Collaborators
- Hammersmith Medicines Research, Analyst Research Laboratories, Alderley Analytical Ltd., Diamond Pharma Services Regulatory Affairs Consultancy
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- 2 Feb 2019 (actual)
- Study completion
- 2 Feb 2019 (actual)
- First posted
- 30 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial is an open-label, 2-period, single-sequence assessment of CYP3A4 inhibition by aramchol using the probe substrates midazolam and atorvastatin to assess CYP3A4 activity.
Detailed description
Enrolment of 16 subjects is planned. Each subject will take part in 2 study periods.
In Period 1, subjects will receive a single oral dose of 2 mg midazolam on Day 1 and a single oral dose of 40 mg atorvastatin on Day 3.
In Period 2, subjects will receive twice-daily oral doses of 300 mg aramchol (the IMP) for 18 days. During aramchol dosing, subjects will take a single dose of 2 mg midazolam in the morning on Day 10 and 40 mg atorvastatin in the morning on Day 12.
Subjects will be screened within 21 days before their first dose of study medicine. In Period 1, they will remain resident on the ward from Day -1 to Day 10. In Period 2, subjects will be admitted on Day -1 and discharged on Day 19. Subjects will attend a follow-up visit approximately 2 weeks later, on Day 33 (±2 days). There will be an interval of at least 1 day between Periods 1 and 2.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Midazolam, Atorvastatin / Aramchol, Midazolam, Atorvastatin | Other | Drug: Aramchol, Drug: Midazolam, Drug: AtorvastatinMidazolam 2 mg -atorvastatin 40 mg /Aramchol 600mg -midazolam 2 mg-atorvastatin 40 mg (MA/MAA) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male healthy volunteers.
- Aged 18-45 years at time of consent.
- A body mass index (BMI; Quetelet index) in the range 18.0-30.9.
- Ability to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire trial.
- Willingness to give written consent to participate after reading and understanding the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
Key exclusion criteria (20 listed)
- Volunteers of East Asian descent including, but not limited to, Chinese, Japanese, Korean, Mongolian, and/or Vietnamese
- Be a smoker, or have smoked cigarettes or other tobacco or nicotine products in the last 12 months.
- Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (AP) > Upper Limit of Normal (ULN) at the screening visit. A repeat is allowed on one occasion for determination of eligibility.
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous,
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 |
|---|---|---|
| AramcholAramchol 600 mg | Drug | Midazolam, Atorvastatin / Aramchol, Midazolam, Atorvastatin |
| MidazolamMidazolam 2 mg | Drug | Midazolam, Atorvastatin / Aramchol, Midazolam, Atorvastatin |
| Atorvastatinatorvastatin 40 mg | Drug | Midazolam, Atorvastatin / Aramchol, Midazolam, Atorvastatin |
Primary outcome
Midazolam - cmax
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Maximum plasma concentration
Atorvastatin - cmax
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Maximum plasma concentration
Midazolam - tmax
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Time of maximum plasma concentration
Atorvastatin - tmax
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Time of maximum plasma concentration
Midazolam - Area under the concentration-time curve to last measurable concentration (AUClast)
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - Area under the concentration-time curve to last measurable concentration (AUClast)
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - Area under the concentration-time curve extrapolated to infinite time (AUCinf)
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Atorvastatin - Area under the concentration-time curve extrapolated to infinite time (AUCinf)
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Midazolam - %AUCextrapinf
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Percentage of AUC that was extrapolated
Atorvastatin - %AUCextrapinf
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Percentage of AUC that was extrapolated
Midazolam - t½
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Terminal elimination half-life
Atorvastatin - t½
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Terminal elimination half-life
Midazolam - CL/F
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Clearance/fraction of dose absorbed
Atorvastatin - CL/F
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Clearance/fraction of dose absorbed
Midazolam - VZ/F
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Volume of distribution/fraction of dose absorbed
Atorvastatin - VZ/F
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Volume of distribution/fraction of dose absorbed
Midazolam - MRT
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Mean residence time
Atorvastatin - MRT
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Mean residence time
Midazolam - λz
Time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.
Terminal rate constant
Atorvastatin - λz
Time frame: Blood samples for assay of atorvastatin will be taken before, and frequently up to 168 hours after each dose.
Terminal rate constant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2019.
- Individual participant dataSharing planned: No
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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.
Adeep Puri, M.D. principal investigator
HMR
1 site 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, Midazolam and Atorvastatin in people with Healthy, run by Galmed Pharmaceuticals Ltd at 1 site in United Kingdom.
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 8 inclusion and 20 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 22 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Midazolam - cmax (time frame: Blood samples for assay of midazolam will be taken before, and frequently up to 48 hours after each dose.). The study lists 20 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 22 Aug 2019.