This two-part study was designed to evaluate the pharmacokinetics (PK) of single and multiple doses of apremilast in healthy adult Korean males.
The study will consist of two parts. Part 1 will evaluate the PK of ascending single doses of apremilast. Part 2 will evaluate the PK of apremilast when administered as multiple doses over 14 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Tablet for oral administration
Tablet for oral administration
Seoul National University Hospital
Seoul, South Korea
Part 1: Maximum Observed Plasma Concentration (Cmax) of Apremilast
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) for Apremilast
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
Part 1: Terminal Elimination Half-life (T1/2) for Apremilast
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
Part 1: Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
Part 1: Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)
Time frame: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
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Part 2: Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) for Apremilast
Area under the plasma concentration-time curve during a dosage interval (tau) at steady state, where tau is 12 hours.
Time frame: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose
Part 2: Maximum Observed Plasma Concentration (Cmax) of Apremilast
Time frame: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose
Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
Time frame: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose
Part 2: Terminal Elimination Half-life (T1/2) for Apremilast
Time frame: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose
Part 2: Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)
Time frame: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose
Part 2: Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)
Time frame: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose
Part 2: Ratio of Accumulation
Ratio of accumulation calculated as Day 14 AUC0-τ / Day 1 AUC0-τ
Time frame: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose, and on day 14 only at 24, 36, 48, 60, and 72 hours after the morning dose
Number of Participants With Treatment-emergent Adverse Events (AEs)
Time frame: Part 1, up to 40 days; Part 2, up to 24 days