Healthy Subjects
Conditions
Keywords
safety, heart rate, pharmacokinetics
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.
Interventions
DRUGACT-334441 2 mg
capsule containing ACT-334441 at a strength of 2 mg
DRUGACT-334441 4 mg
capsule containing ACT-334441 at a strength of 4 mg
DRUGPlacebo
ACT-33441-matching placebo
DRUGAtenolol
film-coated tablet containing atenolol at a strength of 50 mg
DRUGDiltiazem ER
film-coated tablet containing diltiazem at a strength of of 120 mg
Sponsors
Viatris Innovation GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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) |
| 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 |
Other
| Measure | Time frame |
|---|---|
| Lymphocyte count as a measure of immunomodulation (Part A + Part B) | Day 1, Day 6, Day 12 and Day 20 (Part A); Day 1 and Day 8 toDay 16 (Part B) |
Countries
France
Outcome results
None listed