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

NCT ID: NCT05254548

Last Updated: 2022-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-18
• Study Completion Date: 2022-04-13

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.

Conditions

Healthy

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

ACT-539313 with or without a standard combination (probe substrate)

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.

Group Type: EXPERIMENTAL

ACT-539313

Intervention Type: DRUG

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).

Flurbiprofen

Intervention Type: DRUG

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).

Omeprazole

Intervention Type: DRUG

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).

Midazolam

Intervention Type: DRUG

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).

Interventions

ACT-539313

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).

Intervention Type: DRUG

Flurbiprofen

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).

Intervention Type: DRUG

Omeprazole

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).

Intervention Type: DRUG

Midazolam

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).

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Idorsia Pharmaceuticals Ltd.

Locations

CRS Clinical Research Services Berlin GmbH

Berlin, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 37800597 (View on PubMed)

Other Identifiers

2021-006214-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ID-082-103

Identifier Type: -

Identifier Source: org_study_id