Clinical trial NCT03017495: A Clinical Study to Investigate the Potential Interactions Between Food and ACT-541468 and Between ACT-541468 and Midazolam
Official title: A Single-center, Open-label Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 and the Effect of Single- and Multiple-dose ACT-541468 on the Pharmacokinetics of Midazolam and Its Metabolite 1-Hydroxymidazolam in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: food-drug interaction
drug-drug interaction
pharmacokinetics
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2017-01-11
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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).

Eligibility criteria: 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

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-541468
timeFrame: 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
measure: Time to reach Cmax (tmax) of ACT-541468
timeFrame: 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
measure: Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468
timeFrame: 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
measure: Terminal half-life (t1/2) of ACT-541468
timeFrame: 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
measure: Maximum plasma concentration (Cmax) of midazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Time to reach Cmax (tmax) of midazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Area under the plasma concentration-time curve [AUC(0-24)] of midazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Terminal half-life (t1/2) of midazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Maximum plasma concentration (Cmax) of 1-hydroxymidazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Time to reach Cmax (tmax) of 1-hydroxymidazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
measure: Terminal half-life (t1/2) of 1-hydroxymidazolam
timeFrame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Secondary outcomes:
measure: Number of subjects with treatment-emergent adverse events and serious adverse events
timeFrame: From baseline to end-of-study, i.e.,maximum 5 days after Day 8
measure: Maximum plasma concentration (Cmax) of ACT-541468 metabolites
timeFrame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
measure: Time to reach Cmax (tmax) of ACT-541468 metabolites
timeFrame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
measure: Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites
timeFrame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
measure: Terminal half-life (t1/2) of ACT-541468 metabolites
timeFrame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: Investigator Site
Study officials:
affiliation: Actelion
name: Marie-Laure Boof, PhD
role: STUDY_DIRECTOR
References: