Pharmacokinetic Interaction Between Diltiazem and ACT-541468 in Healthy Subjects

Study Overview
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Brief Summary
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The main objective of this study is to investigate whether repeated administration of a cardiac medication (diltiazem) can affect the pharmacokinetics (i.e., amount and time of presence in the blood) of ACT-541468

Detailed Description
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Because ACT-541468 appears to be mainly metabolized by CYP3A4, it is deemed of interest to investigate the potential influence of diltiazem, a well-known CYP3A4 inhibitor on the pharmacokinetic profile of ACT-541468. Safety of the concomitant administration of the two drugs will also be assessed

Official Title
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A Single-center, Open-label, Randomized, Two-way Crossover Study to Investigate the Effect of Multiple-dose Diltiazem on the Pharmacokinetics of a Single Dose of 25 mg ACT-541468 in Healthy Male Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: ACT-541468
* Drug: Diltiazem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Body mass index (BMI) between 18.0 and 28.0 kg/m2 (inclusive) at screening Healthy on the basis of physical examination,cardiovascular assessments and laboratory tests Exclusion Criteria: Any contraindication to the study drugs History or presence of any disease or 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 drugs 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence AB<br>During Period 1, subjects receive a single dose of ACT-541468 on Day 1. During Period 2, they receive Diltiazem from Day 1 to Day 7 and a single dose of ACT-541468 on Day 4 | Drug: ACT-541468<br>* Oral capsule (25 mg) as single dose<br>Drug: Diltiazem<br>* Two oral capsules (2 x 120 mg) once daily from Day 1 to Day 7<br>|
| Experimental: Sequence BA<br>During Period 1, subjects receive Diltiazem from Day 1 to Day 7 and a single dose of ACT-541468 on Day 4. During Period 2, they receive a single dose of ACT-541468 on Day 1 | Drug: ACT-541468<br>* Oral capsule (25 mg) as single dose<br>Drug: Diltiazem<br>* Two oral capsules (2 x 120 mg) once daily from Day 1 to Day 7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of ACT-541468 | Cmax will be directly derived from the plasma concentration time curves of ACT-541468 | From baseline to end of study (Day 8 after last study drug intake for sequence AB, Day 5 after last study drug intake for sequence BA) | 
| Time to reach Cmax of ACT-541468 in plasma | tmax will be directly derived from the plasma concentration time curves of ACT-541468 | From baseline to end of study (Day 8 after last study drug intake for sequence AB, Day 5 after last study drug intake for sequence BA | 
| Area under the plasma concentration-time curve (AUC) of ACT-541468 | AUC will be calculated for the following time frame: from time zero to the last measured concentration above the limit of quantification and from time zero to infinitiy | From baseline to end of study (Day 8 after last study drug intake for sequence AB, Day 5 after last study drug intake for sequence BA) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetic, interaction