Pharmacokinetic Interaction Between Diltiazem and ACT-541468 in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: ACT-541468; Drug: Diltiazem

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • CRS Clinical Research Services Kiel GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; 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; Oral capsule (25 mg) as single dose; Drug: Diltiazem; Two oral capsules (2 x 120 mg) once daily from Day 1 to Day 7
Experimental: Sequence BA; 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; Oral capsule (25 mg) as single dose; Drug: Diltiazem; Two oral capsules (2 x 120 mg) once daily from Day 1 to Day 7

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of safety events of interest	Events of interest are any abnormalities in ECG, vital signs or laboratory test results	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)
Incidence of adverse events	Number of participants with any adverse events, including laboratory abnormalities	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)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: August 14, 2015
• First Submitted That Met QC Criteria: August 17, 2015
• First Posted (Estimate): August 18, 2015

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: pharmacokinetic; interaction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Diltiazem
• Other Study ID Numbers: AC-078-103