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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000856-83 | EudraCT Number |
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The primary purpose of this study is to evaluate the effect of repeated doses of selexipag on the pharmacokinetics of a single oral dose of midazolam (i.e., how long and how much midazolam is present in the blood)
In order to exclude an inductive effect of selexipag in the gastrointestinal tract, this study aims at investigating the effect of selexipag on the PK of midazolam, a sensitive substrate of both hepatic and intestinal cytochrome P450 3A4 (CYP3A4).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence AB | Experimental | Subjects participate in two study periods: During the first period, they receive a single oral dose of midazolam on Day 1. During the second period, they receive oral selexipag alone from Day 1 to Day 11 and selexipag + midazolam on Day 12. There is a washout period of 14 to 21 days between the two periods. |
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| Sequence BA | Experimental | Subjects participate in two study periods: During the first period, they receive oral selexipag alone from Day 1 to Day 11 and selexipag + midazolam on Day 12. During the second period, they receive a single oral dose of midazolam on Day 1. There is a washout period of 14 to 21 days between the two periods. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | Single oral dose of 7.5 mg midazolam (tablet) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of midazolam following administration of midazolam alone and in combination with selexipag | Cmax is the maximum observed plasma concentration and is directly derived from the individual plasma concentration time curves of midazolam | From pre-dose up to 24 hours after midazolam admisnitration for each treatment period |
| AUC(0-inf) of midazolam following administration of midazolam alone and in combination with selexipag | AUC(0-inf) is the area under the plasma concentration-time curves of midazolam, calculated from time 0 (pre-dose) to the extrapolated infinite time | From pre-dose up to 24 hours after midazolam admisnitration for each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag | From pre-dose up to 24 hours after midazolam admisnitration | |
| AUC(0-inf) of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-emergent adverse events and serious adverse events | A treatment-emergent AE is any AE temporally associated with the use of a study treatment, whether or not considered related to the study treatment | Up to 39 days (from Day 1 of Period 1 to end of study of Period 2) |
Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pierre-Eric Juif, PhD | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Gières | 38610 | France |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| C523468 | selexipag |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Selexipag |
| Drug |
Oral administration of selexipag (200 µg film-coated tablet) for 12 consecutive days (with a titration scheme from 400 to 1600 μg b.i.d. ) |
|
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| From pre-dose up to 24 hours after midazolam admisnitration |
| tmax of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag | tmax is the time to reach Cmax of midazolam and its metabolite (1-hydroxymidazolam), respectively | From pre-dose up to 24 hours after midazolam admisnitration |
| t½ of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag. | t½ is the terminla half-life of midazolam and its metabolite (1-hydroxymidazolam), and corresponds to the period of time required for the concentration levels of midazolam and its metabolite to be reduced by one-half, respectively | From pre-dose up to 24 hours after midazolam admisnitration |
| Trough concentration of selexipag and its metabolite ACT-333679 at steady-state | Trough concentrations are measured before morning administration of selexipag | Days 1, 4, 7, 10,12 and 13 |
| D006571 | Heterocyclic Compounds |