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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03017495
• Other study ID #: AC-078-104
• Secondary ID: 2016-003490-18
• Status: Completed
• Phase: Phase 1
• Start date: January 1, 2017
• Est. completion date: February 1, 2017

Study information

• Verified date: July 2018
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 1, 2017
• Est. primary completion date: February 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Midazolam
2 mg/mL oral solution
• ACT-541468
Hard gelatin capsules for oral use at a strength of 25 mg

Locations

Country	Name	City	State
Germany	Investigator Site	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of ACT-541468	Cmax is directly determined from the plasma concentrations-time curves 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
Primary	Time to reach Cmax (tmax) of ACT-541468	Tmax is directly determined from the plasma concentrations-time curves 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
Primary	Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468	AUC is calculated from time zero to 24 hours post dose	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
Primary	Terminal half-life (t1/2) of ACT-541468	t1/2 is calculated from the plasma concentrations-time curves 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
Primary	Maximum plasma concentration (Cmax) of midazolam	Cmax is directly obtained from the plasma concentrations-time curves of midazolam	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Time to reach Cmax (tmax) of midazolam	Tmax is directly obtained from the plasma concentrations-time curves of midazolam	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Area under the plasma concentration-time curve [AUC(0-24)] of midazolam	AUC is calculated from time zero to 24 hours post dose	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Terminal half-life (t1/2) of midazolam	t1/2 is calculated from the plasma concentrations-time curves of midazolam	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Maximum plasma concentration (Cmax) of 1-hydroxymidazolam	Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Time to reach Cmax (tmax) of 1-hydroxymidazolam	Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam	AUC is calculated from time zero to 24 hours post dose	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Primary	Terminal half-life (t1/2) of 1-hydroxymidazolam	t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam	PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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