The purpose of this study is to assess how much of apremilast is found in the blood unchanged when administered as an oral suspension compared to when it is administered as a tablet formulation. The effect of food on apremilast oral suspension will also be evaluated. In addition, information on the safety and tolerability of apremilast will be obtained.
This is a phase 1, open-label, randomized, three-period, six-sequence crossover study in healthy subjects. The study will consist of a screening phase, baseline (Day -1), three study periods, and a follow-up phone call. Each study period will be four days in duration (Day 1 through Day 4) followed by a five-day washout between doses. Eligible participants will be admitted into the study center on Day -1 of study Period 1 for baseline measurements. During each study period, participants will receive a single 30 mg oral dose of apremilast on Day 1 according to the assigned treatment sequence. Participants will be confined at the study center from Day 1 of study Period 1 through Day 4 of study Period 3, including the 5 day washout between doses. All participants will be discharged from the study center on Day 4 of study Period 3 following completion of required study procedures. A follow-up phone call will occur approximately four days after the discharge from the study center. The study will be conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practices (GCPs).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
34
30 mg tablet
30 mg oral suspension
Covance Clinical Research Unit Inc
Madison, Wisconsin, United States
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: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) for Apremilast
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to the last measured time point was calculated by the linear trapezoidal method.
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-∞) for Apremilast
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to infinity was calculated as (AUC0-t + Ct/λz), where Ct is the last quantifiable concentration, and λz is the apparent terminal rate constant.
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Time to Maximum Observed Plasma Concentration (Tmax) of Apremilast
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Terminal Elimination Half-life (T1/2) of Apremilast
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Apparent Clearance of Apremilast From Plasma After Extravascular Administration (CL/F)
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Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Apparent Volume of Distribution of Apremilast During the Terminal Phase (Vz/F)
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Lag Time (Tlag) of Apremilast
Lag time is the delay between the time of administration and start of absorption.
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Relative Bioavailability (F) of Apremilast Oral Suspension Formulation
Relative bioavailability of the oral suspension formulation compared to the tablet formulation, calculated as (AUC0-∞/Dose\[oral suspension\]) / (AUC0-∞/Dose\[tablet\]) \* 100%.
Time frame: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
Number of Participants With Treatment-emergent Adverse Events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug. A serious adverse event (SAE) is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event.
Time frame: From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.