MedPath

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

Registration Number
NCT02236988
Lead Sponsor
Amgen
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
80
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Group 1Apremilast Immediate ReleaseParticipants 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
Group 1Apremilast Modified Release 1Participants 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
Group 3Apremilast Immediate ReleaseParticipants 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
Group 2Apremilast Modified Release 5Participants 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
Group 2Apremilast Modified Release 4Participants 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
Group 4Apremilast Modified Release 12Participants 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
Group 3Apremilast Modified Release 9Participants 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
Group 4Apremilast Immediate ReleaseParticipants 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
Group 4Apremilast Modified Release 13Participants 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
Group 4Apremilast Modified Release 14Participants 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
Group 1Apremilast Modified Release 3Participants 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
Group 2Apremilast Immediate ReleaseParticipants 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
Group 1Apremilast Modified Release 2Participants 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
Group 2Apremilast Modified Release 6Participants 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
Group 3Apremilast Modified Release 8Participants 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
Group 4Apremilast Modified Release 11Participants 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
Primary Outcome Measures
NameTimeMethod
Group 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Apparent Total Plasma Clearance (CL/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by DoseIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞/Dose\[test\]) / (AUC0-∞/Dose\[reference\]) \* 100%.

Group 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by DoseIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞/Dose\[test\]) / (AUC0-∞/Dose\[reference\]) \* 100%.

Group 3: Half-life of Apremilast in Terminal Phase (T1/2)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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Observed Maximum Plasma Concentration (Cmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Time to Observed Maximum Plasma Concentration (Tmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Apparent Total Volume of Distribution (Vz/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Time to Observed Maximum Plasma Concentration (Tmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Apparent Total Plasma Clearance (CL/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Apparent Total Volume of Distribution (Vz/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 3: Apparent Total Plasma Clearance (CL/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 4: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 4: Time to Observed Maximum Plasma Concentration (Tmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 4: Apparent Total Plasma Clearance (CL/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Half-life of Apremilast in Terminal Phase (T1/2)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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to ReferenceIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞\[test\]) / (AUC0-∞\[reference\]) \* 100%.

Group 2: Observed Maximum Plasma Concentration (Cmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Half-life of Apremilast in Terminal Phase (T1/2)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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to ReferenceIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞\[test\]) / (AUC0-∞\[reference\]) \* 100%.

Group 3: Observed Maximum Plasma Concentration (Cmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 3: Time to Observed Maximum Plasma Concentration (Tmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to ReferenceIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞\[test\]) / (AUC0-∞\[reference\]) \* 100%.

Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by DoseIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞/Dose\[test\]) / (AUC0-∞/Dose\[reference\]) \* 100%.

Group 3: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 3: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 4: Half-life of Apremilast in Terminal Phase (T1/2)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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by DoseIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞/Dose\[test\]) / (AUC0-∞/Dose\[reference\]) \* 100%.

Group 4: Observed Maximum Plasma Concentration (Cmax) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 4: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to ReferenceIR 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.

Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:

(AUC0-∞\[test\]) / (AUC0-∞\[reference\]) \* 100%.

Group 4: Apparent Total Volume of Distribution (Vz/F) of ApremilastIR 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.

Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.

Secondary Outcome Measures
NameTimeMethod
Group 1: Number of Participants With Treatment-emergent Adverse EventsAdverse events were collected for 7 to 10 days after each treatment.

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.

Group 2: Number of Participants With Treatment-emergent Adverse EventsAdverse events were collected for 7 to 10 days after each treatment.

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.

Group 4: Number of Participants With Treatment-emergent Adverse EventsAdverse events were collected for 7 to 10 days after each treatment.

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.

Group 3: Number of Participants With Treatment-emergent Adverse EventsAdverse events were collected for 7 to 10 days after each treatment.

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.

Trial Locations

Locations (1)

Covance Clinical Research Unit Inc.

🇺🇸

Madison, Wisconsin, United States

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