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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-006214-36 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACT-539313 | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Treatment-emergent adverse events | All adverse events will be collected, however, adverse events occurring during the in-between period (from end of period 1 up to first study treatment administration in period 2, are not considered as treatment-emergent adverse events. | From study treatment administration on Day 1 up to last assessment at End of Study (Day 17). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Idorsia Pharmaceuticals Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRS Clinical Research Services Berlin GmbH | Berlin | 13353 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37800597 | Derived | 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. |
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Four-period, fixed-sequence drug-drug interaction study.
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| Flurbiprofen | 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). |
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| Omeprazole | 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). |
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| Midazolam | 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). |
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| 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. | Pre-dose through to 10 days after first dose. |
| Maximum plasma concentration (Cmax) of ACT-539313 | In periods 2 (Day 8 and 9) and period 4 (Day 15, 16 and 17) the plasma pharmacokinetic parameters of ACT-539313 will be derived by non-compartmental analysis of the plasma concentration-time profiles. Cmax will be analyzed in periods 2 and 4 with the administration of probe substrate. In period 4 the Cmax will be determined after steady state ACT-539313 concentrations have been reached. | Pre-dose through to 24 hours post-dose. |
| Time to reach Cmax (tmax) of ACT-539313 | In periods 2 (Day 8 and 9) and period 4 (Day 15, 16 and 17) the plasma pharmacokinetic parameters of ACT-539313 will be derived by non-compartmental analysis of the plasma concentration-time profiles. tmax will be analyzed in periods 2 and 4 with the administration of probe substrate. In period 4 the tmax will be determined after steady state ACT-539313 concentrations have been reached. | Pre-dose through to 24 hours after first dose. |
| Area under the plasma concentration-time curve [AUC(tau)] of ACT-539313 | In periods 2 (Day 8 and 9), period 3 (Day 10 to Day 15) and period 4 (Day 15, 16 and 17) plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze ACT-539313 concentrations. AUC(tau) will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification. | Pre-dose through to 240 hours after first dose. |
| ID | Term |
|---|---|
| C000721594 | ACT-539313 |
| D005480 | Flurbiprofen |
| D009853 | Omeprazole |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
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