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

July 6, 2018 updated by: Idorsia Pharmaceuticals Ltd.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Kiel, Germany, 24105
        • Investigator Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Food effect and Drug-Drug interaction
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).
Drug: Midazolam
2 mg/mL oral solution
Drug: ACT-541468
Hard gelatin capsules for oral use at a strength of 25 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax) 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
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
Time to reach Cmax (tmax) 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
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
Area under the plasma concentration-time curve [AUC(0-24)] 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
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
Terminal half-life (t1/2) 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
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
Maximum plasma concentration (Cmax) 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
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
Time to reach Cmax (tmax) 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
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
Area under the plasma concentration-time curve [AUC(0-24)] 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
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
Terminal half-life (t1/2) 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
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
Maximum plasma concentration (Cmax) of 1-hydroxymidazolam
Time Frame: 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
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 1-hydroxymidazolam
Time Frame: 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
PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam
Time Frame: 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
PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose
Terminal half-life (t1/2) of 1-hydroxymidazolam
Time Frame: 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
PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
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
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
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
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
PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Idorsia Pharmaceuticals Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 10, 2017

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 11, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 10, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AC-078-104
  • 2016-003490-18 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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