Clinical trial NCT02479204: Clinical Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441
Official title: Single-center, Open-label, Randomized, Multiple-dose, Parallel-group Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441 Combined With Calcium-channel Blocker (Diltiazem) or Beta-blocker (Atenolol) Treatment in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: safety
heart rate
pharmacokinetics
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2015-06-24
Enrollment: 10
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of the study is to investigate the safety of the concomitant administration of ACT-334441 with cardiovascular drugs.

Detailed description: The study will consist of two parts: a pilot part (Part A) that will be completed prior to the start of the main part (Part B). The Subjects who will participate in Part A are excluded from Part B.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
* Women of childbearing potential must have a negative pregnancy test and they must use reliable methods of contraception
* Healthy on the basis of physical examination,cardiovascular assessments and laboratory tests

Exclusion Criteria:

* Pregnant or lactating women
* 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
* Any clinically significant abnormalities in laboratory tests, vital signs, ECG variables and pulmonary variables
* 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

Primary outcomes:
measure: PR intervals measured by 12-lead ECG (Part A + Part B)
timeFrame: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B)
measure: Heart rate (HR) measured by 12-lead ECG (PArt A + Part B)
timeFrame: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B)
measure: Hourly mean heart rate (HR) measured by 24-hour Holter ECG
timeFrame: Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B
Secondary outcomes:
measure: Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B)
timeFrame: Blood samples from Day 1 to Day 20 for the PK profile of diltiazem and atenolol, and from Day 8 to Day 21 for the PK profile of ACT-334441.
measure: Maximum plasma concentration (Cmax) for ACT-334441, diltiazem and atenolol (Part B)
timeFrame: From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444.
measure: Time to reach the maximum plasma concentration (tmax) for ACT-334441, diltiazem and atenolol (Part B)
timeFrame: From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444
measure: Terminal half-life [t(1/2)] of ACT-334441, diltiazem and atenolol (Part B)
timeFrame: From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444
measure: Trough plasma levels (Ctrough) of of ACT-334441, diltiazem and atenolol (Part B)
timeFrame: From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444
measure: Number of subjects with adverse events as a measure of safety
timeFrame: From baseline to end of study [Day 20-23 (Part A), Day 556-59 (Part B)]
Other outcomes:
measure: Lymphocyte count as a measure of immunomodulation (Part A + Part B)
timeFrame: Day 1, Day 6, Day 12 and Day 20 (Part A); Day 1 and Day 8 toDay 16 (Part B)
Locations:
city: Rennes
country: France
facility: BIOTRIAL
Study officials:
References: