Study to Evaluate Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast in Healthy Men

A Phase 1, Open-Label, Single Center Study to Evaluate the Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast (CC-10004) in Healthy Male Subjects

This study will assess up to 12 different oral formulations of apremilast to determine how much apremilast is absorbed by the body compared to a reference formulation.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Apremilast Immediate Release; Drug: Apremilast Modified Release 1; Drug: Apremilast Modified Release 2; Drug: Apremilast Modified Release 3; Drug: Apremilast Modified Release 4; Drug: Apremilast Modified Release 5; Drug: Apremilast Modified Release 6; Drug: Apremilast Modified Release 8; Drug: Apremilast Modified Release 9; Drug: Apremilast Modified Release 11; Drug: Apremilast Modified Release 12; Drug: Apremilast Modified Release 13; Drug: Apremilast Modified Release 14

Detailed Description

This will be a single-center, open-label, crossover, single modified-release-dose study in adult males to evaluate the pharmacokinetics (PK) of prototype modified-release (MR) formulations compared to the reference immediate-release (IR) apremilast formulation. Within 4 separate groups, participants will be randomly assigned to a treatment sequence. A total of up to 12 test MR formulations may be evaluated.

Group 1: A 4-sequence, 4-period design to compare three modified-release prototypes with the reference immediate-release formulation. A total of 16 participants will be enrolled to obtain at least 12 participants who complete all 4 periods.

Group 2: A 4-sequence, 4-period design to compare three MR prototypes with the reference IR formulation. Sixteen participants will be enrolled to obtain at least 12 participants who complete all four periods.

Group 3: A six-sequence, three-period design to compare two MR prototypes with the reference IR formulation. Eighteen participants will be enrolled to obtain at least 12 participants who complete all three periods.

Group 4: A 10-sequence, 5-period design to compare four MR prototypes with the reference IR formulation. Thirty participants will be enrolled to obtain at least 20 participants who complete all five periods.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704-2526
      • Covance Clinical Research Unit Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subjects must satisfy ALL of the following criteria to be eligible for enrollment into the study:

1. Must understand and voluntarily sign a written informed consent form prior to any study-related procedures being performed.
2. Must be able to communicate with the investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.
3. Male subjects of any race between 18 to 55 years of age (inclusive), and in good health as determined by the Investigator.
4. Has a body mass index between 18 and 33 kg/m^2 (inclusive).
5. No clinically significant laboratory tests as determined by the investigator.
6. Must not have a fever, with systolic blood pressure: 90 to 140 mmHg and diastolic blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm (measurements taken while lying down).
7. Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG).
8. Subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or non-latex condom not made out of natural [animal] membrane [eg, polyurethane]) while on study medication, and for 28 days after the last dose of study medication.
9. 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 study drug.

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, 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, unless Sponsor agreement is obtained.
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, unless Sponsor agreement is obtained.
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 cholecytectomy 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 8 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 serum hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody, or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment: A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3	Drug: Apremilast Immediate Release; 30 mg immediate release tablets; Other Names: CC-10004; Otezla; Drug: Apremilast Modified Release 1; 75 mg oral tablet of prototype modified release (MR) 1; Drug: Apremilast Modified Release 2; 75 mg oral tablet of prototype MR 2; Drug: Apremilast Modified Release 3; 75 mg oral capsule of prototype MR 3
Experimental: Group 2; Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment: A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6	Drug: Apremilast Immediate Release; 30 mg immediate release tablets; Other Names: CC-10004; Otezla; Drug: Apremilast Modified Release 4; 75 mg oral capsule of prototype MR 4; Drug: Apremilast Modified Release 5; 75 mg oral capsule of prototype MR 5; Drug: Apremilast Modified Release 6; 75 mg oral capsule of prototype MR 6
Experimental: Group 3; Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment: A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9	Drug: Apremilast Immediate Release; 30 mg immediate release tablets; Other Names: CC-10004; Otezla; Drug: Apremilast Modified Release 8; 80 mg oral capsule of prototype MR 8; Drug: Apremilast Modified Release 9; 80 mg oral capsule of prototype MR 9
Experimental: Group 4; Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment: A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14	Drug: Apremilast Immediate Release; 30 mg immediate release tablets; Other Names: CC-10004; Otezla; Drug: Apremilast Modified Release 11; 80 mg oral capsule of prototype MR 11; Drug: Apremilast Modified Release 12; 80 mg oral capsule of prototype MR 12; Drug: Apremilast Modified Release 13; 80 mg oral capsule of prototype MR 13; Drug: Apremilast Modified Release 14; 80 mg oral capsule of prototype MR 14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group 1: Observed Maximum Plasma Concentration (Cmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Half-life of Apremilast in Terminal Phase (T1/2)	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Apparent Total Plasma Clearance (CL/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Apparent Total Volume of Distribution (Vz/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Observed Maximum Plasma Concentration (Cmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Half-life of Apremilast in Terminal Phase (T1/2)	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Apparent Total Plasma Clearance (CL/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Observed Maximum Plasma Concentration (Cmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Half-life of Apremilast in Terminal Phase (T1/2)	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Apparent Total Plasma Clearance (CL/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Observed Maximum Plasma Concentration (Cmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Half-life of Apremilast in Terminal Phase (T1/2)	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Apparent Total Plasma Clearance (CL/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Apparent Total Volume of Distribution (Vz/F) of Apremilast	Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference	Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as: (AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.	IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group 1: 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.	Adverse events were collected for 7 to 10 days after each treatment.
Group 2: 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.	Adverse events were collected for 7 to 10 days after each treatment.
Group 3: 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.	Adverse events were collected for 7 to 10 days after each treatment.
Group 4: 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.	Adverse events were collected for 7 to 10 days after each treatment.

Collaborators and Investigators

• Sponsor: Amgen

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2014
• Primary Completion (Actual): September 11, 2014
• Study Completion (Actual): September 11, 2014

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 9, 2014
• First Posted (Estimate): September 11, 2014

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Apremilast; Healthy male subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Thalidomide; Apremilast
• Other Study ID Numbers: CC-10004-CP-027

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)