To demonstrate that multiple-dose administration of oral therapeutic and supratherapeutic doses of aprocitentan do not have a clinically relevant effect on the QT interval.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
48
Repeated administration of a 25 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation.
Repeated administration of a 100 mg oral dose of aprocitentan, once daily from Day 1 to Day 10, followed by 18 days of observation.
Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 10, followed by 18 days of observation.
CRS Clinical Research Services Mannheim GmbH
Mannheim, Baden-Wurttemberg, Germany
Placebo-corrected change from baseline in QT interval corrected with Fridericia's formula (ΔΔQTcF)
Time frame: Multiple predefined time points related to study treatment administration on Day 1 and Day 10 to 11 of each treatment.
Aprocitentan trough plasma concentrations (Ctrough)
Time frame: Day 2 to Day 9
Aprocitentan plasma Cmax, first dose
Time frame: Pre-defined times on the first dosing day (Day 1) up to 15 hours after last dose
Aprocitentan plasma Cmax, steady state
Time frame: Pre-defined times on the last dosing day (Day 10) up to 15 hours after last dose
Area under the plasma concentration-time curve (AUCτ) during a dosage interval (τ) of aprocitentan
Time frame: Day 1 to Day 10
Aprocitentan attainment of steady-state conditions
Time frame: Day 1 to Day 10
Accumulation index between the first and the last dosing day of aprocitentan
Time frame: Day 1; Day 10
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Repeated administration of an oral dose of aprocitentan-matching placebo, once daily from Day 1 to Day 9. On Day 10, oral administration of one single 400 mg moxifloxacin tablet open-label, followed by 18 days of observation.