A Phase 1, Open-label, Two Part Study to Evaluate the Pharmacokinetics of Single and Multiple Doses of Apremilast in Healthy Adult Male Korean Subjects
Overview
- Phase
- Phase 1
- Intervention
- Apremilast
- Conditions
- Pharmacokinetics
- Sponsor
- Amgen
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Part 1: Maximum Observed Plasma Concentration (Cmax) of Apremilast
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This two-part study was designed to evaluate the pharmacokinetics (PK) of single and multiple doses of apremilast in healthy adult Korean males.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Healthy adult male Korean subjects between 18 and 45 years of age (inclusive) at the time of signing the informed consent form (ICF).
- •Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- •Must be able to communicate with the Investigator and understand and comply with the requirements of the study.
- •Must be in good health as determined by the Investigator according to past medical history, physical examination (PE), vital signs, 12-lead electrocardiogram (ECG), and laboratory tests.
- •Must have a body mass index (BMI) between 18 and 30 kg/m\^2 (inclusive).
- •Clinical laboratory tests must be within normal limits or considered by the Investigator to be not clinically significant.
- •Vital signs (systolic and diastolic blood pressure, pulse rate, and oral \[or tympanic\] body temperature) will be assessed in the supine position after the subject has rested for at least five minutes. Subject must be afebrile (febrile \[oral or tympanic\] is defined as ≥ 38°C or 100.3°F) with vital signs within the following ranges:
- •Systolic blood pressure: 90 to 140 mm Hg;
Exclusion Criteria
- •The presence of any of the following will exclude any healthy subject from enrollment into the study:
- •History of any clinically significant and relevant neurological, psychiatric, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders.
- •Any condition which places the subject at unacceptable risk if he were to participate in the study, or confounds the ability to interpret data from the study.
- •Use of any prescribed systemic or topical medication within 30 days of the first dose administration.
- •Use of any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration.
- •Any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion, eg, bariatric procedure, colon resection, irritable bowel syndrome, Crohn's disease, etc. Subjects with cholecystectomy and appendectomy may be included.
- •Exposure to an investigational drug (new chemical entity) within 30 days prior to the first dose administration or 5 half-lives of that investigational drug, if known (whichever is longer).
- •Donated blood or plasma within eight weeks before the first dose administration to a blood bank or blood donation center.
- •History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
- •History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or a positive alcohol screen.
Arms & Interventions
Part 1: Apremilast 20 mg
A single oral dose of 20 mg apremilast.
Intervention: Apremilast
Part 1: Apremilast 30 mg
A single oral dose of 30 mg apremilast.
Intervention: Apremilast
Part 1: Apremilast 40 mg
A single oral dose of 40 mg apremilast.
Intervention: Apremilast
Part 2: Apremilast 30 mg BID
30 mg apremilast orally twice a day (BID) for 14 days.
Intervention: Apremilast
Part 2: Placebo
Matching placebo orally twice a day for 14 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1: Maximum Observed Plasma Concentration (Cmax) 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.
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
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: 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 2: Area Under the Plasma Concentration-time Curve During a Dosage Interval (AUCτ) for 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
Area under the plasma concentration-time curve during a dosage interval (tau) at steady state, where tau is 12 hours.
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: 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: Ratio of Accumulation
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
Ratio of accumulation calculated as Day 14 AUC0-τ / Day 1 AUC0-τ
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 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: 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 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.
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
Secondary Outcomes
- Number of Participants With Treatment-emergent Adverse Events (AEs)(Part 1, up to 40 days; Part 2, up to 24 days)