Clinical trial NCT05254548: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-24
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Four-period, fixed-sequence drug-drug interaction study.
Primary purpose: OTHER

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
timeFrame: Pre-dose through to 24 hours post-dose.
measure: Time to reach Cmax (tmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
timeFrame: Pre-dose through to 24 hours post-dose.
measure: The area under the plasma concentration-time curve from zero to 24 hours (AUC0-24) of flurbiprofen, midazolam and omeprazole.
timeFrame: Pre-dose through to 24 hours post-dose.
measure: The terminal elimination half-life (t½) of each probe substrate: flurbiprofen, midazolam and omeprazole.
timeFrame: Pre-dose through to 24 hours post-dose.
measure: ACT-539313 trough plasma concentrations (Ctrough)
timeFrame: Pre-dose through to 10 days after first dose.
Secondary outcomes:
Other outcomes:
measure: Treatment-emergent adverse events
timeFrame: From study treatment administration on Day 1 up to last assessment at End of Study (Day 17).
measure: Maximum plasma concentration (Cmax) of ACT-539313
timeFrame: Pre-dose through to 24 hours post-dose.
measure: Time to reach Cmax (tmax) of ACT-539313
timeFrame: Pre-dose through to 24 hours after first dose.
measure: Area under the plasma concentration-time curve [AUC(tau)] of ACT-539313
timeFrame: Pre-dose through to 240 hours after first dose.
Locations:
city: Berlin
country: Germany
facility: CRS Clinical Research Services Berlin GmbH
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References: