Healthy SubjectsPhase 1NCT03017495
A Clinical Study to Investigate the Potential Interactions Between Food and ACT-541468 and Between ACT-541468 and Midazolam
A Phase 1 study testing Midazolam and ACT-541468 in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
Trial summary
The main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate. 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 Subjects
- What is being tested?
- Midazolam and ACT-541468
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jan 2017to 1 Feb 2017
- 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
- Signed informed consent form
- Male subjects aged from 18 to 45 years (inclusive) at screening
- Body mass index (BMI) from 18.0 to 30.0 kg/m2 (inclusive) at screening
- Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests
Who cannot join
- Any contraindication to the study treatments
- History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments
- History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0
- Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Open-label Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 and the Effect of Single- and Multiple-dose ACT-541468 on the Pharmacokinetics of Midazolam and Its Metabolite 1-Hydroxymidazolam in Healthy Male Subjects
The main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate.
Read the detailed description
Food effect will be assessed by comparing the pharmacokinetic (PK) parameters of a single dose of ACT-541468 under fasted (Treatment B) and fed (Treatment C) conditions.
Potential CYP3A4 inhibiting / inducing effects of ACT-541468 will be assessed by comparing the PK parameters of midazolam alone (Treatment A) and midazolam given with a single dose of ACT-541468 (Treatment B) or with multiple doses of ACT-541468 (Treatment D).
- Conditions
- Healthy Subjects
- Being tested
- Midazolam, ACT-541468
- Keywords
- food-drug interaction, drug-drug interaction, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
2 mg/mL oral solution
ACT-541468Drug
Hard gelatin capsules for oral use at a strength of 25 mg
| Study group | Role | What they receive |
|---|---|---|
| Food effect and Drug-Drug interaction | Experimental | Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted). Receives: Drug: Midazolam; Drug: ACT-541468 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax) of ACT-541468
Cmax is directly determined from the plasma concentrations-time curves of ACT-541468
Measured: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Time to reach Cmax (tmax) of ACT-541468
Tmax is directly determined from the plasma concentrations-time curves of ACT-541468
Measured: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468
AUC is calculated from time zero to 24 hours post dose
Measured: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Terminal half-life (t1/2) of ACT-541468
t1/2 is calculated from the plasma concentrations-time curves of ACT-541468
Measured: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Maximum plasma concentration (Cmax) of midazolam
Cmax is directly obtained from the plasma concentrations-time curves of midazolam
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Time to reach Cmax (tmax) of midazolam
Tmax is directly obtained from the plasma concentrations-time curves of midazolam
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Area under the plasma concentration-time curve [AUC(0-24)] of midazolam
AUC is calculated from time zero to 24 hours post dose
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Terminal half-life (t1/2) of midazolam
t1/2 is calculated from the plasma concentrations-time curves of midazolam
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Maximum plasma concentration (Cmax) of 1-hydroxymidazolam
Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Time to reach Cmax (tmax) of 1-hydroxymidazolam
Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam
AUC is calculated from time zero to 24 hours post dose
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Terminal half-life (t1/2) of 1-hydroxymidazolam
t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam
Measured: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Secondary outcomes (5)
Number of subjects with treatment-emergent adverse events and serious adverse events
Measured: From baseline to end-of-study, i.e.,maximum 5 days after Day 8
Maximum plasma concentration (Cmax) of ACT-541468 metabolites
Measured: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Time to reach Cmax (tmax) of ACT-541468 metabolites
Measured: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites
Measured: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Terminal half-life (t1/2) of ACT-541468 metabolites
Measured: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2017 (estimated)
- Study start1 Jan 2017
- Primary completion1 Feb 2017
- Study completion1 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy SubjectsStudies 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marie-Laure Boof, PhD, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03017495
- Sponsor's protocol ID
- AC-078-104
- Other IDs
- 2016-003490-18, 2016
- Status last verified
- Jul 2018
- First submitted
- 10 Jan 2017
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 and the Effect of Single- and Multiple-dose ACT-541468 on the Pharmacokinetics of Midazolam and Its Metabolite 1-Hydroxymidazolam in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT03017495
- Acronym / sponsor ID
- AC-078-104
- Conditions
- Healthy Subjects
- Keywords
- food-drug interaction, drug-drug interaction, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 1 Feb 2017 (actual)
- Study completion
- 1 Feb 2017 (actual)
- First posted
- 11 Jan 2017 (estimated)
- 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 main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate.
Detailed description
Food effect will be assessed by comparing the pharmacokinetic (PK) parameters of a single dose of ACT-541468 under fasted (Treatment B) and fed (Treatment C) conditions.
Potential CYP3A4 inhibiting / inducing effects of ACT-541468 will be assessed by comparing the PK parameters of midazolam alone (Treatment A) and midazolam given with a single dose of ACT-541468 (Treatment B) or with multiple doses of ACT-541468 (Treatment D).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Food effect and Drug-Drug interaction | Experimental | Drug: Midazolam, Drug: ACT-541468Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Signed informed consent form
- Male subjects aged from 18 to 45 years (inclusive) at screening
- Body mass index (BMI) from 18.0 to 30.0 kg/m2 (inclusive) at screening
- Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests
Key exclusion criteria (4 listed)
- Any contraindication to the study treatments
- History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments
- History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0
- Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol
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 |
|---|---|---|
| Midazolam2 mg/mL oral solution | Drug | Food effect and Drug-Drug interaction |
| ACT-541468Hard gelatin capsules for oral use at a strength of 25 mg | Drug | Food effect and Drug-Drug interaction |
Primary outcome
Maximum plasma concentration (Cmax) of ACT-541468
Time frame: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Cmax is directly determined from the plasma concentrations-time curves of ACT-541468
Time to reach Cmax (tmax) of ACT-541468
Time frame: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
Tmax is directly determined from the plasma concentrations-time curves of ACT-541468
Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468
Time frame: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
AUC is calculated from time zero to 24 hours post dose
Terminal half-life (t1/2) of ACT-541468
Time frame: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only
t1/2 is calculated from the plasma concentrations-time curves of ACT-541468
Maximum plasma concentration (Cmax) of midazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Cmax is directly obtained from the plasma concentrations-time curves of midazolam
Time to reach Cmax (tmax) of midazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Tmax is directly obtained from the plasma concentrations-time curves of midazolam
Area under the plasma concentration-time curve [AUC(0-24)] of midazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
AUC is calculated from time zero to 24 hours post dose
Terminal half-life (t1/2) of midazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
t1/2 is calculated from the plasma concentrations-time curves of midazolam
Maximum plasma concentration (Cmax) of 1-hydroxymidazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam
Time to reach Cmax (tmax) of 1-hydroxymidazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam
Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
AUC is calculated from time zero to 24 hours post dose
Terminal half-life (t1/2) of 1-hydroxymidazolam
Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam
5 secondary outcomes
Number of subjects with treatment-emergent adverse events and serious adverse events
Time frame: From baseline to end-of-study, i.e.,maximum 5 days after Day 8
Maximum plasma concentration (Cmax) of ACT-541468 metabolites
Time frame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Time to reach Cmax (tmax) of ACT-541468 metabolites
Time frame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites
Time frame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Terminal half-life (t1/2) of ACT-541468 metabolites
Time frame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
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 10 Jul 2018.
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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.
Marie-Laure Boof, PhD study director
Actelion
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 Midazolam and ACT-541468 in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
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 4 inclusion and 4 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 10 Jul 2018. 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 Germany. 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?
Maximum plasma concentration (Cmax) of ACT-541468 (time frame: PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only). The study lists 12 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 10 Jul 2018.