A Clinical Study to Investigate the Potential Interactions Between Food and ACT-541468 and Between ACT-541468 and Midazolam

Idorsia Pharmaceuticals Ltd.20 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Subjects

Interventions

MidazolamDRUG

2 mg/mL oral solution

ACT-541468DRUG

Hard gelatin capsules for oral use at a strength of 25 mg

Eligibility

Sex: MALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Investigator Site

Kiel, Germany

Outcomes

Primary Outcomes

Maximum plasma concentration (Cmax) of ACT-541468

Cmax is directly determined from the plasma concentrations-time curves of ACT-541468

Time frame: 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

Time to reach Cmax (tmax) of ACT-541468

Tmax is directly determined from the plasma concentrations-time curves of ACT-541468

Time frame: 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

Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468

AUC is calculated from time zero to 24 hours post dose

Time frame: 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

Terminal half-life (t1/2) of ACT-541468

t1/2 is calculated from the plasma concentrations-time curves of ACT-541468

Time frame: 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

Maximum plasma concentration (Cmax) of midazolam

Cmax is directly obtained from the plasma concentrations-time curves of midazolam

Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

Time to reach Cmax (tmax) of midazolam

Tmax is directly obtained from the plasma concentrations-time curves of midazolam

Time frame: PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of subjects with treatment-emergent adverse events and serious adverse events

Time frame: From baseline to end-of-study, i.e.,maximum 5 days after Day 8

Maximum plasma concentration (Cmax) of ACT-541468 metabolites

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose