Healthy Subjects
Conditions
Keywords
food-drug interaction, drug-drug interaction, pharmacokinetics
Brief summary
The main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate.
Detailed description
Food effect will be assessed by comparing the pharmacokinetic (PK) parameters of a single dose of ACT-541468 under fasted (Treatment B) and fed (Treatment C) conditions. Potential CYP3A4 inhibiting / inducing effects of ACT-541468 will be assessed by comparing the PK parameters of midazolam alone (Treatment A) and midazolam given with a single dose of ACT-541468 (Treatment B) or with multiple doses of ACT-541468 (Treatment D).
Interventions
DRUGMidazolam
2 mg/mL oral solution
DRUGACT-541468
Hard gelatin capsules for oral use at a strength of 25 mg
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent form * Male subjects aged from 18 to 45 years (inclusive) at screening * Body mass index (BMI) from 18.0 to 30.0 kg/m2 (inclusive) at screening * Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests
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 * History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score \< 0 * 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 |
|---|---|---|
| Terminal half-life (t1/2) of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam |
| Area under the plasma concentration-time curve [AUC(0-24)] of midazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | AUC is calculated from time zero to 24 hours post dose |
| Terminal half-life (t1/2) of midazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | t1/2 is calculated from the plasma concentrations-time curves of midazolam |
| Maximum plasma concentration (Cmax) of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam |
| Time to reach Cmax (tmax) of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam |
| Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | AUC is calculated from time zero to 24 hours post dose |
| Maximum plasma concentration (Cmax) of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only | Cmax is directly determined from the plasma concentrations-time curves of ACT-541468 |
| Time to reach Cmax (tmax) of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only | Tmax is directly determined from the plasma concentrations-time curves of ACT-541468 |
| Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only | AUC is calculated from time zero to 24 hours post dose |
| Terminal half-life (t1/2) of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only | t1/2 is calculated from the plasma concentrations-time curves of ACT-541468 |
| Maximum plasma concentration (Cmax) of midazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | Cmax is directly obtained from the plasma concentrations-time curves of midazolam |
| Time to reach Cmax (tmax) of midazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose | Tmax is directly obtained from the plasma concentrations-time curves of midazolam |
Secondary
| Measure | Time frame |
|---|---|
| Maximum plasma concentration (Cmax) of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| Time to reach Cmax (tmax) of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| Terminal half-life (t1/2) of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| Number of subjects with treatment-emergent adverse events and serious adverse events | From baseline to end-of-study, i.e.,maximum 5 days after Day 8 |
Countries
Germany
Outcome results
None listed