Clinical Study to Investigate Safety and Effects on Heart Rate, Blood Pressure, and Pharmacokinetic Interactions of ACT-334441
- Conditions
- Healthy Subjects
- Interventions
- Registration Number
- NCT02479204
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 10
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A ACT-334441 + diltiazem Diltiazem ER 4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6 Part A ACT-334441 + atenolol ACT-334441 2 mg 4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6 Part A ACT-334441 + atenolol Atenolol 4 subjects will receive 50 mg of atenolol once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6 Part B ACT-334441 + diltiazem Placebo 12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 Part B ACT-334441 + diltiazem Diltiazem ER 12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 Part A ACT-334441 + diltiazem ACT-334441 2 mg 4 subjects will receive 240 mg of diltiazem once daily for 6 days, and a concomitant single administration of ACT-334441 2 mg on Day 6 Part B ACT-334441 + atenolol Placebo 12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 Part B ACT-334441 + diltiazem ACT-334441 4 mg 12 subjects will receive 240 mg of diltiazem (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 Part B ACT-334441 + atenolol ACT-334441 4 mg 12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15 Part B ACT-334441 + atenolol Atenolol 12 subjects will receive 50 mg of atenolol (once daily) from day 1 to day 15, placebo once on day 6, and ACT-334441 4 mg (once daily) from day 8 to day 15
- Primary Outcome Measures
Name Time Method Hourly mean heart rate (HR) measured by 24-hour Holter ECG Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B Absolute and change from baseline in hourly mean HR on each day of measurement
PR intervals measured by 12-lead ECG (Part A + Part B) Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B) Absolute PR intervals and corresponding changes from baseline at the different days of measurement
Heart rate (HR) measured by 12-lead ECG (PArt A + Part B) Days 1 and 6 (Part A); Days 1, 6, 8, 9, 15, and 16 (Part B) Absolute heart rates at the different days of measurement
- Secondary Outcome Measures
Name Time Method Number of subjects with adverse events as a measure of safety From baseline to end of study [Day 20-23 (Part A), Day 556-59 (Part B)] An AE is defined as any unfavorable and unintended sign, including an abnormal laboratory finding, symptom or disease, that occurs during the course of the study, whether or not considered related to the study drug
Areas under the plasma concentration-time curves (AUC) for ACT-334441, diltiazem and atenolol (Part B) 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. AUCs will be calculated will be calculated according to the linear trapezoidal rule for the following periods: from zero to time t of the last measured concentration above the limit of quantification, from zero to 24h after study drug administration, from zero to infinity)
Trough plasma levels (Ctrough) of of ACT-334441, diltiazem and atenolol (Part B) From Day 1 to Day 15 for diltiazem and atenolol; from Day 8 to Day 15 for ACT-33444 Ctrough will be used to determine the attainment of steady state conditions
Time to reach the maximum plasma concentration (tmax) for ACT-334441, diltiazem and atenolol (Part B) From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444 The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective tmax
Terminal half-life [t(1/2)] of ACT-334441, diltiazem and atenolol (Part B) From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444 Time required for the plasma concentration of a drug to decrease by 50% in the final stage of its elimination
Maximum plasma concentration (Cmax) for ACT-334441, diltiazem and atenolol (Part B) From Day 1 to Day 20 for diltiazem and atenolol; from Day 8 to Day 21 for ACT-33444. The measured individual concentrations of ACT-334441, diltiazem and atenolol will be used to obtain their respective Cmax
Trial Locations
- Locations (1)
BIOTRIAL
🇫🇷Rennes, France