A Clinical Study to Investigate the Potential Interactions Between Food and ACT-541468 and Between ACT-541468 and Midazolam
- Registration Number
- NCT03017495
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Food effect and Drug-Drug interaction Midazolam Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted). Food effect and Drug-Drug interaction ACT-541468 Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted).
- Primary Outcome Measures
Name Time Method 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 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
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
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
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
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
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (1)
Investigator Site
🇩🇪Kiel, Germany