Healthy Subjects
Conditions
Keywords
selexipag, pharmacokinetics, midazolam
Brief summary
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)
Detailed description
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).
Interventions
DRUGMidazolam
Single oral dose of 7.5 mg midazolam (tablet)
DRUGSelexipag
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. )
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Signed informed consent form * Age from 18 to 45 years (inclusive) at screening * Body mass index (BMI) from 18.0 to 28.0 kg/m2 (inclusive) at screening * Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests Key
Exclusion criteria
* Any contraindication to the study treatments * History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments * Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf) of midazolam following administration of midazolam alone and in combination with selexipag | From pre-dose up to 24 hours after midazolam admisnitration for each treatment period | 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 |
| Cmax of midazolam following administration of midazolam alone and in combination with selexipag | From pre-dose up to 24 hours after midazolam admisnitration for each treatment period | Cmax is the maximum observed plasma concentration and is directly derived from the individual plasma concentration time curves of midazolam |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf) of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag | 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 | From pre-dose up to 24 hours after midazolam admisnitration | tmax is the time to reach Cmax of midazolam and its metabolite (1-hydroxymidazolam), respectively |
| Trough concentration of selexipag and its metabolite ACT-333679 at steady-state | Days 1, 4, 7, 10,12 and 13 | Trough concentrations are measured before morning administration of selexipag |
| t½ of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag. | From pre-dose up to 24 hours after midazolam admisnitration | 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 |
| Cmax of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag | From pre-dose up to 24 hours after midazolam admisnitration | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events and serious adverse events | Up to 39 days (from Day 1 of Period 1 to end of study of Period 2) | 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 |
Countries
France
Outcome results
None listed