Study to Evaluate the Pharmacokinetics of Single and Multiple Doses of Apremilast in Healthy Adult Male Korean Subjects

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02802735

Enrollment

Registered

2016-06-16

Start date

2016-06-22

Completion date

2016-08-05

Last updated

2021-07-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pharmacokinetics

Keywords

Pharmacokinetics, Apremilast, Healthy Adult Male, Korean Subjects

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.

Interventions

DRUGApremilast

Tablet for oral administration

DRUGPlacebo

Tablet for oral administration

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Masking description

Part 1 was a randomized open-label crossover study. Part 2 was a randomized, double-blind study.

Intervention model description

Part 1 of the study was a 3-treatment period, 3-sequence crossover study. Part 2 was a parallel-group, placebo-controlled, single-period study.

Eligibility

Sex/Gender

MALE

Age

18 Years to 45 Years

Healthy volunteers

Yes

Inclusion criteria

\- Subjects must satisfy the following criteria to be enrolled in the study: 1. Healthy adult male Korean subjects between 18 and 45 years of age (inclusive) at the time of signing the informed consent form (ICF). 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 4. Must be able to communicate with the Investigator and understand and comply with the requirements of the study. 5. 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. 6. Must have a body mass index (BMI) between 18 and 30 kg/m\^2 (inclusive). 7. Clinical laboratory tests must be within normal limits or considered by the Investigator to be not clinically significant. 8. 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; * Diastolic blood pressure: 50 to 90 mm Hg; * Pulse rate: 40 to 110 bpm. 9. Must have a normal or clinically acceptable 12-lead ECG. Subjects must have a QTc value ≤ 450 msec. 10. Must have a normal or clinically acceptable physical examination. 11. Contraception Requirements: \- Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex or non-latex condoms NOT made out of natural \[animal\] membrane \[for example, polyurethane\]) while on Investigational Product (IP) and for at least 28 days after the last dose of investigational product (IP). 12. Must agree to refrain from donating sperm, blood or plasma (other than for this study) while participating in this study, and for at least 28 days after the last dose of IP.

Exclusion criteria

* The presence of any of the following will exclude any healthy subject from enrollment into the study: 1. 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. 2. 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. 3. Use of any prescribed systemic or topical medication within 30 days of the first dose administration. 4. Use of any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration. 5. 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. 6. 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). 7. Donated blood or plasma within eight weeks before the first dose administration to a blood bank or blood donation center. 8. 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. 9. History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or a positive alcohol screen. 10. Known to have hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies, or have a positive result to the test for HBsAg, HCV antibodies or human immunodeficiency virus (HIV) antibodies at Screening.

Design outcomes

Primary

Measure	Time frame	Description
Part 2: Ratio of Accumulation	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: Terminal Elimination Half-life (T1/2) for Apremilast	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: Maximum Observed Plasma Concentration (Cmax) of Apremilast	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	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	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	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)	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)	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	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	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	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	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)	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)	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

Measure	Time frame
Number of Participants With Treatment-emergent Adverse Events (AEs)	Part 1, up to 40 days; Part 2, up to 24 days

Countries

South Korea

Participant flow

Recruitment details

This was a two-part study in healthy Korean men. The study was conducted at 1 clinic in Korea.

Pre-assignment details

In Part 1 participants were randomized to 1 of 3 treatment sequences consisting of 3 treatment periods. In Part 2 participants were randomized in a 3:1 ratio to receive apremilast or matching placebo twice a day (BID) for 14 days.

Participants by arm

Arm	Count
Part 1: Apremilast Participants received a single oral dose of 20 mg apremilast, 30 mg apremilast, and 40 mg apremilast across 3 treatment periods separated by a washout period of 7-10 days.	12
Part 2: Apremilast 30 mg BID Participants received 30 mg apremilast orally twice a day for 14 days.	12
Part 2: Placebo BID Participants received matching placebo orally twice a day for 14 days.	4
Total	28

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Withdrawal by Subject	0	1	0	0	0

Baseline characteristics

Characteristic	Part 2: Placebo BID	Total	Part 1: Apremilast	Part 2: Apremilast 30 mg BID
Age, Continuous	25.5 years	29.6 years	29.8 years	30.8 years
Race/Ethnicity, Customized Asian	4 Participants	28 Participants	12 Participants	12 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	4 Participants	28 Participants	12 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	2 / 11	1 / 12	3 / 12	4 / 12	7 / 12	3 / 4	10 / 16
serious Total, serious adverse events	0 / 11	0 / 12	0 / 12	0 / 12	0 / 12	0 / 4	0 / 16

Outcome results

Primary

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.