HealthyPhase 1NCT05254548
A Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on What the Body Does to Flurbiprofen, Omeprazole, Midazolam in Healthy Subjects
A Phase 1 study testing ACT-539313, Flurbiprofen and Omeprazole in people with Healthy, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
Trial summary
A study to investigate the effect of single and repeated oral doses of ACT-539313 on what the body does to flurbiprofen, omeprazole, midazolam in healthy participants. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- ACT-539313, Flurbiprofen and Omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteGermany
- Study dates
- 18 Feb 2022to 13 Apr 2022
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
- Healthy male or female subjects aged between 18 and 45 years (inclusive) at Screening.
- Body Mass Index of 18.5 to 28.0 kg/m2 (inclusive) at Screening.
- Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (from Screening, during the entire study, and for at least 30 days after study treatment intake) a highly effective method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must have been initiated at least 1 month before treatment administration.
- Women of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a FSH test), with previous bilateral salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, uterine agenesis.
- 12-lead ECG (including QT: < 450 milliseconds [for males] and < 470 milliseconds [for females] without clinically relevant abnormalities, measured after 5 min in the supine position at Screening and on Day -1.
Who cannot join
- Pregnant or lactating women.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis, i.e. outside the reference ranges (< 0.9 lower limit of normal and > 1.1 upper limit of normal; except for relevant hepatic parameters [Alanine Aminotransferase (ALT), Aspartate Aminotransferase Test (AST), bilirubin] which must not exceed the upper limit of normal), at Screening and on Day -1.
- History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- Acute, ongoing, recurrent, or chronic systemic disease with the ability to interfere with the evaluation of the study results.
- Prior history of severe respiratory failure, acute respiratory depression, or sleep apnea.
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- Prior history of peptic ulcer disease and/or gastrointestinal bleeding.
- Prior history of asthma, urticaria, or other allergic type reactions after taking acetylsalicylic acid or other NSAIDs.
- History of cardiovascular thrombotic events (including myocardial infarction and stroke) and coronary artery bypass graft surgery.
- Participation in a clinical study involving study treatment administered within 3 months (or 5 t 1/2 of the study treatment administered [whichever is longer]) prior to screening or in more than 4 clinical studies within 1 year prior to Screening.
- Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St. John's Wort, homeopathic preparations, vitamins, and minerals; with the exception of ibuprofen [1200 mg/day] or paracetamol [up to 1500 mg/day] up until Day -1) within 3 weeks (or 5 t1/2 [whichever is longer]) prior to first study treatment administration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Open-label, Four-period, Fixed-sequence Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on the Pharmacokinetics of Flurbiprofen, Omeprazole, Midazolam, and Their Respective Metabolites in Healthy Subjects
A study to investigate the effect of single and repeated oral doses of ACT-539313 on what the body does to flurbiprofen, omeprazole, midazolam in healthy participants.
Read the detailed description
A screening evaluation will be performed within 3 to 28 days (or within 10 to 28 days for women of childbearing potential) before first study treatment administration. Prior to any screening assessment, participants must sign the informed consent form.
Eligibility will be based on the results of the Screening and Day -1 assessments.
The participants will be confined to the study site from the morning of Day -1 until the morning of Day 2, from the morning of Day 7 until the morning of Day 9 and from the morning of Day 14 until the morning of Day 16. Participants will return to the study site for the End of Study examination on Day 17.
- Conditions
- Healthy
- Being tested
- ACT-539313, Flurbiprofen, Omeprazole, Midazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT-539313Drug
100 mg ACT-539313 (hard capsules) will be administered twice per day in period 2 (morning and evening of Day 8), period 3 (morning and evening of Day 9 to 14) and period 4 (morning and evening of Day 15).
FlurbiprofenDrug
One daily dose of flurbiprofen 50 mg will be administered in period 1 (morning of Day 1), period 2 (morning of Day 8), and period 4 (morning of Day 15).
OmeprazoleDrug
A single dose of omeprazole 20 mg will be administered in period 1 (morning of Day 1), period 2 (morning of Day 8), and period 4 (morning of Day 15).
MidazolamDrug
A single dose of midazolam 2 mg will be administered in period 1 (morning of Day 1), period 2 (morning of Day 8), and period 4 (morning of Day 15).
| Study group | Role | What they receive |
|---|---|---|
| ACT-539313 with or without a standard combination (probe substrate) | Experimental | Treatment arm has 4 in-house treatment periods. In Treatment Period 1, participants will receive a single oral dose of the standardized combination (probe substrate: containing flurbiprofen [50 mg], midazolam [2 mg] and omeprazole 20 [mg]) on Day 1. Participants will be discharged from the study site on Day 2 and will be re-admitted on Day 7. In Treatment Period 2 (morning of Day 8) a first oral dose of 100 mg ACT-539313 will be administered. One hour later a single oral dose of the probe substrate will be administered. In the evening of Day 8, a second oral dose of 100 mg ACT-539313 will be administered. During Treatment Period 3 (morning of Day 9, ending on the evening of Day 14) oral doses of 100 mg ACT-539313 will be administered in the morning and evening. In Treatment Period 4 (Day 15), a single oral dose of 100 mg ACT-539313 together with the probe substrate will be administered. The participants will receive the last dose of ACT-539313 in the evening of Day 15. Receives: Drug: ACT-539313; Drug: Flurbiprofen; Drug: Omeprazole; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
Measured: Pre-dose through to 24 hours post-dose.
Time to reach Cmax (tmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
Measured: Pre-dose through to 24 hours post-dose.
The area under the plasma concentration-time curve from zero to 24 hours (AUC0-24) of flurbiprofen, midazolam and omeprazole.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
Measured: Pre-dose through to 24 hours post-dose.
The terminal elimination half-life (t½) of each probe substrate: flurbiprofen, midazolam and omeprazole.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
Measured: Pre-dose through to 24 hours post-dose.
ACT-539313 trough plasma concentrations (Ctrough)
In periods 2, 3 and 4 the plasma pharmacokinetic parameters of ACT-539313 will be measured prior to the next dose being administered in the morning.
Measured: Pre-dose through to 10 days after first dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2022
- Study start18 Feb 2022
- Primary completion13 Apr 2022
- Study completion13 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Sequential
- Model description
- Four-period, fixed-sequence drug-drug interaction study.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Idorsia Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05254548
- Sponsor's protocol ID
- ID-082-103
- Other IDs
- 2021-006214-36
- Status last verified
- May 2022
- First submitted
- 15 Feb 2022
- Last updated
- 4 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Berger B, Kaufmann P, Berse M, Treiber A, Grignaschi N, Dingemanse J. Effect of nivasorexant (ACT-539313), a selective orexin-1-receptor antagonist, on multiple cytochrome P450 probe substrates in vitro and in vivo using a cocktail approach in healthy subjects. Pharmacol Res Perspect. 2023 Oct;11(5):e01143. doi: 10.1002/prp2.1143.
PubMed 37800597
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Four-period, Fixed-sequence Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on the Pharmacokinetics of Flurbiprofen, Omeprazole, Midazolam, and Their Respective Metabolites in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05254548
- Acronym / sponsor ID
- ID-082-103
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 18 Feb 2022 (actual)
- Primary completion
- 13 Apr 2022 (actual)
- Study completion
- 13 Apr 2022 (actual)
- First posted
- 24 Feb 2022 (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.
A study to investigate the effect of single and repeated oral doses of ACT-539313 on what the body does to flurbiprofen, omeprazole, midazolam in healthy participants.
Detailed description
A screening evaluation will be performed within 3 to 28 days (or within 10 to 28 days for women of childbearing potential) before first study treatment administration. Prior to any screening assessment, participants must sign the informed consent form.
Eligibility will be based on the results of the Screening and Day -1 assessments.
The participants will be confined to the study site from the morning of Day -1 until the morning of Day 2, from the morning of Day 7 until the morning of Day 9 and from the morning of Day 14 until the morning of Day 16. Participants will return to the study site for the End of Study examination on Day 17.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Four-period, fixed-sequence drug-drug interaction study.
| Arm | Type | Receives |
|---|---|---|
| ACT-539313 with or without a standard combination (probe substrate) | Experimental | Drug: ACT-539313, Drug: Flurbiprofen, Drug: Omeprazole, Drug: MidazolamTreatment arm has 4 in-house treatment periods. In Treatment Period 1, participants will receive a single oral dose of the standardized combination (probe substrate: containing flurbiprofen [50 mg], midazolam [2 mg] and omeprazole 20 [mg]) on Day 1. Participants will be discharged from the study site on Day 2 and will be re-admitted on Day 7. In Treatment Period 2 (morning of Day 8) a first oral dose of 100 mg ACT-539313 will be administered. One hour later a single oral dose of the probe substrate will be administered. In the evening of Day 8, a second oral dose of 100 mg ACT-539313 will be administered. During Treatment Period 3 (morning of Day 9, ending on the evening of Day 14) oral doses of 100 mg ACT-539313 will be administered in the morning and evening. In Treatment Period 4 (Day 15), a single oral dose of 100 mg ACT-539313 together with the probe substrate will be administered. The participants will receive the last dose of ACT-539313 in the evening of Day 15. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
- Healthy male or female subjects aged between 18 and 45 years (inclusive) at Screening.
- Body Mass Index of 18.5 to 28.0 kg/m2 (inclusive) at Screening.
- Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (from Screening, during the entire study, and for at least 30 days after study treatment intake) a highly effective method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must have been initiated at least 1 month before treatment administration.
- Women of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a FSH test), with previous bilateral salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, uterine agenesis.
Key exclusion criteria (11 listed)
- Pregnant or lactating women.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis, i.e. outside the reference ranges (< 0.9 lower limit of normal and > 1.1 upper limit of normal; except for relevant hepatic parameters [Alanine Aminotransferase (ALT), Aspartate Aminotransferase Test (AST), bilirubin] which must not exceed the upper limit of normal), at Screening and on Day -1.
- History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- Acute, ongoing, recurrent, or chronic systemic disease with the ability to interfere with the evaluation of the study results.
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 |
|---|---|---|
| ACT-539313100 mg ACT-539313 (hard capsules) will be administered twice per day in period 2 (morning and evening of Day 8), period 3 (morning and evening of Day 9 to 14) and period 4 (morning and evening of Day 15). | Drug | ACT-539313 with or without a standard combination (probe substrate) |
| FlurbiprofenOne daily dose of flurbiprofen 50 mg will be administered in period 1 (morning of Day 1), period 2 (morning of Day 8), and period 4 (morning of Day 15). | Drug | ACT-539313 with or without a standard combination (probe substrate) |
| OmeprazoleA single dose of omeprazole 20 mg will be administered in period 1 (morning of Day 1), period 2 (morning of Day 8), and period 4 (morning of Day 15). | Drug | ACT-539313 with or without a standard combination (probe substrate) |
| MidazolamA single dose of midazolam 2 mg will be administered in period 1 (morning of Day 1), period 2 (morning of Day 8), and period 4 (morning of Day 15). | Drug | ACT-539313 with or without a standard combination (probe substrate) |
Primary outcome
Maximum plasma concentration (Cmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
Time frame: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
Time to reach Cmax (tmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
Time frame: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
The area under the plasma concentration-time curve from zero to 24 hours (AUC0-24) of flurbiprofen, midazolam and omeprazole.
Time frame: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
The terminal elimination half-life (t½) of each probe substrate: flurbiprofen, midazolam and omeprazole.
Time frame: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
ACT-539313 trough plasma concentrations (Ctrough)
Time frame: Pre-dose through to 10 days after first dose.
In periods 2, 3 and 4 the plasma pharmacokinetic parameters of ACT-539313 will be measured prior to the next dose being administered in the morning.
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 4 May 2022.
- Derived from this study: PubMed 37800597Berger B, Kaufmann P, Berse M, Treiber A, Grignaschi N, Dingemanse J. Effect of nivasorexant (ACT-539313), a selective orexin-1-receptor antagonist, on multiple cytochrome P450 probe substrates in vitro and in vivo using a cocktail approach in healthy subjects. Pharmacol Res Perspect. 2023 Oct;11(5):e01143. doi: 10.1002/prp2.1143.
- 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.
Clinical Trials study director
Idorsia Pharmaceuticals Ltd.
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 ACT-539313, Flurbiprofen and Omeprazole in people with Healthy, 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 6 inclusion and 11 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 4 May 2022. 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 each probe substrate: flurbiprofen, midazolam and omeprazole. (time frame: Pre-dose through to 24 hours post-dose.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05254548, which also lists 1 linked publication.
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 4 May 2022.