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

This two-part study was designed to evaluate the pharmacokinetics (PK) of single and multiple doses of apremilast in healthy adult Korean males.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Placebo; Drug: Apremilast

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: Apremilast 20 mg; A single oral dose of 20 mg apremilast.	Drug: Apremilast; Tablet for oral administration; Other Names: CC-10004; OTEZLA®
EXPERIMENTAL: Part 1: Apremilast 30 mg; A single oral dose of 30 mg apremilast.	Drug: Apremilast; Tablet for oral administration; Other Names: CC-10004; OTEZLA®
EXPERIMENTAL: Part 1: Apremilast 40 mg; A single oral dose of 40 mg apremilast.	Drug: Apremilast; Tablet for oral administration; Other Names: CC-10004; OTEZLA®
EXPERIMENTAL: Part 2: Apremilast 30 mg BID; 30 mg apremilast orally twice a day (BID) for 14 days.	Drug: Apremilast; Tablet for oral administration; Other Names: CC-10004; OTEZLA®
PLACEBO_COMPARATOR: Part 2: Placebo; Matching placebo orally twice a day for 14 days.	Drug: Placebo; Tablet for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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		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: 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: 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	Area under the plasma concentration-time curve during a dosage interval (tau) at steady state, where tau is 12 hours.	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		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
Part 2: Ratio of Accumulation	Ratio of accumulation calculated as Day 14 AUC0-τ / Day 1 AUC0-τ	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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• Expanded Access for CC-10004

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 22, 2016
• Primary Completion (ACTUAL): August 5, 2016
• Study Completion (ACTUAL): August 5, 2016

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 14, 2016
• First Posted (ESTIMATE): June 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 6, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Apremilast; Healthy Adult Male; Korean Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: CC-10004-CP-033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR