Pharmacokinetic Interaction Between Diltiazem and ACT-541468 in Healthy Subjects

Sponsor

Idorsia Pharmaceuticals Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT02526888

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: ACT-541468 Drug: Diltiazem	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Nov 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Maximum plasma concentration (Cmax) 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)]
Cmax will be directly derived from the plasma concentration time curves of ACT-541468
Time to reach Cmax of ACT-541468 in plasma [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]
tmax will be directly derived from the plasma concentration time curves of ACT-541468
Area under the plasma concentration-time curve (AUC) 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)]
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

Other Outcome Measures

Incidence of safety events of interest [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)]
Events of interest are any abnormalities in ECG, vital signs or laboratory test results
Incidence of adverse events [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)]
Number of participants with any adverse events, including laboratory abnormalities

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CRS Clinical Research Services Kiel GmbH	Kiel		Germany	24105

Sponsors and Collaborators

Idorsia Pharmaceuticals Ltd.

Investigators

Study Director: Marie-Laure Boof, PhD, Actelion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Idorsia Pharmaceuticals Ltd.

ClinicalTrials.gov Identifier:

NCT02526888

Other Study ID Numbers:

AC-078-103

First Posted:

Aug 18, 2015

Last Update Posted:

Jul 10, 2018

Last Verified:

Jul 1, 2018

Keywords provided by Idorsia Pharmaceuticals Ltd.

pharmacokinetic

interaction

Additional relevant MeSH terms:

Diltiazem

Study Results

No Results Posted as of Jul 10, 2018