Healthy Volunteers
Conditions
Keywords
Healthy Subjects, Apremilast, Pharmacokinetic
Brief summary
The purpose of this study is to evaluate the relative bioavailability of apremilast once-daily formulation relative to a twice daily formulation when administered as multiple doses (Part 1), and when administered as a single dose under fasting and fed conditions (Part 2). Information on safety and tolerability will also be obtained.
Detailed description
Part 1: This is an open-label, randomized, two-period, two-sequence, crossover study in healthy subjects. The study will consist of a screening phase, a baseline phase, two treatment periods, and a follow-up phone call. Each period will be ten days in duration including 7 days of dosing and sample collection for up to 72 hours post Day 7 morning dose. There will be a washout between period 1 and period 2. Part 2: This is an open-label, randomized, four-period, four-sequence crossover study to evaluate the PK and exposure of apremilast following single dose administration of different formulations of apremilast. Part 2 will consist of a screening phase, baseline, four treatment periods, and a follow-up phone call. Each period will be four days in duration for dosing (Day 1) and sample collection for up to 72 hours post Day 1.
Interventions
DRUGApremilast IR
Apremilast immediate release tablet
DRUGApremilast XL
Apremilast extended release formulation tablet
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must satisfy the following criteria to be enrolled in the study (Part 1 and Part 2): 1. Must understand and voluntarily sign a written Informed consent form (ICF) 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 and female subjects of any race between 18 to 55 years of age (inclusive), and in good health as determined by the Investigator at the time of signing the informed consent document. 4. Have a body mass index (BMI) between 18 and 33 kg/m\^2 (inclusive). 5. No clinically significant laboratory test results as determined by the investigator. 6. At the screening visit, must be afebrile, with supine systolic blood pressure (BP): 90 to 140 mmHg, supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm. Eligibility criteria for vital signs performed during check-in and/or predose on Day 1 will be at the discretion of the Investigator. 7. Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG). Subjects must have a QT interval corrected using the Fridericia formula (QTcF) value ≤ 450 msec. 8. Female subjects 1. Must have a negative pregnancy test 2. If postmenopausal: must have follicular stimulating hormone (FSH) test result \> 40 IU/L and a negative pregnancy test 9. Contraception Requirements: Must comply with the following acceptable forms of contraception. All Female of child bearing potential (FCBP)1 must use one of the approved contraceptive options as described below while taking apremilast and for at least 28 days after administration of the last dose of the apremilast. At the time of study entry, and at any time during the study when a FCBP's contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy. All FCBP must have a negative pregnancy test at Screening and Day -1 of each Treatment Period. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below: Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]); Plus one additional barrier(c) contraceptive sponge with spermicide. 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 IP. 10. 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 investigational product. 11. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion criteria
The presence of any of the following will exclude a subject from enrollment: 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. 1 A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months). 3\. Use of any prescribed systemic or topical medication within 30 days of the first dose administration (exception, FCBP may use hormonal contraception). 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 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 hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV Ab), or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Peak Maximum Plasma Concentration (Cmax) of Apremilast | Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose. |
| Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Apremilast | Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose. |
| Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast | Apremilast IR: 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 morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose. |
| Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast | Apremilast IR: 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 morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose. |
| Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast | Apremilast IR: 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 morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | Part 1: Up to 7 days after last dose in each treatment period (14 days); Part 2: Up to 7 days after each dose. | 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 subject's health, including laboratory test values, regardless of etiology. A serious AE 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. The Investigator determined the relationship between the administration of study drug and the occurrence of each AE as Not Suspected or Suspected as defined in the Protocol. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 2 clinical sites in the United States. The study consisted of 2 parts. Part 1 was a multiple-dose two-period, two-sequence, crossover study. Part 2 was a four-period, four-sequence crossover study. Both parts enrolled healthy volunteers.
Pre-assignment details
In Part 1 participants were randomly assigned to 1 of 2 treatment sequences. In Part 2 participants were randomly assigned to 1 of 4 treatment sequences.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Participants in Part 1 received apremilast 30 mg IR tablet BID for 7 days and apremilast 75 mg XL formulation QD for 7 days in each treatment period depending on sequence assignment. | 124 |
| Part 2 Participants in Part 2 received a single dose of the following treatments in 4 treatment periods according to sequence assignment:
* Apremilast 30 mg IR tablet in the morning and evening under fasted conditions;
* Apremilast 75 mg XL formulation after a high-fat meal;
* Apremilast 75 mg XL formulation under fasted conditions;
* Apremilast 75 mg XL formulation after a standard meal. | 20 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 0 | 1 | 0 | 0 |
| Overall Study | Discharged early due to hurricane | 22 | 20 | 0 | 0 | 0 | 0 |
| Overall Study | Other - Miscellaneous | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 | Part 2 | Total |
|---|---|---|---|
| Age, Continuous | 37.8 years | 34.7 years | 37.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 8 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 12 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 47 Participants | 10 Participants | 57 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 70 Participants | 10 Participants | 80 Participants |
| Sex: Female, Male Female | 46 Participants | 7 Participants | 53 Participants |
| Sex: Female, Male Male | 78 Participants | 13 Participants | 91 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 | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 108 | 35 / 107 | 59 / 124 | 2 / 20 | 4 / 19 | 3 / 18 | 2 / 19 | 8 / 20 |
| serious Total, serious adverse events | 0 / 108 | 0 / 107 | 0 / 124 | 0 / 20 | 0 / 19 | 0 / 18 | 0 / 19 | 0 / 20 |
Outcome results
Primary
Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Apremilast
Time frame: Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose.
Population: The PK population with available data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Apremilast 30 mg IR BID | Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Apremilast | 6370 ng*hr/mL | Geometric Coefficient of Variation 51.2 |
| Part 1: Apremilast 75 mg XL QD | Part 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Apremilast | 6090 ng*hr/mL | Geometric Coefficient of Variation 46.1 |
Comparison: To assess the exposure between the extended release apremilast formulation, and Reference IR (30 mg reference IR BID) tablet following multiple oral doses, an ANOVA model, with sequence, period, and treatment as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed Day 7 AUC0-24.90% CI: [88.9, 102.2]
Primary
Part 1: Peak Maximum Plasma Concentration (Cmax) of Apremilast
Time frame: Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose.
Population: The pharmacokinetic (PK) population (all participants who received at least one dose of apremilast and had at least one measurable concentration datum) with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Apremilast 30 mg IR BID | Part 1: Peak Maximum Plasma Concentration (Cmax) of Apremilast | 451 ng/mL | Geometric Coefficient of Variation 49 |
| Part 1: Apremilast 75 mg XL QD | Part 1: Peak Maximum Plasma Concentration (Cmax) of Apremilast | 459 ng/mL | Geometric Coefficient of Variation 35 |
Comparison: To assess the exposure between the extended release apremilast formulation, and Reference IR (30 mg reference IR BID) tablet following multiple oral doses, an analysis of variance (ANOVA) model, with sequence, period, and treatment as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed Day 7 Cmax.90% CI: [95.1, 108.5]
Primary
Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
Time frame: Apremilast IR: 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 morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.
Population: PK population; two participants were excluded from PK analyses due to predose concentrations \> 5% than their Cmax values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Apremilast 30 mg IR BID | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast | 7100 ng*h/mL | Geometric Coefficient of Variation 31.4 |
| Part 1: Apremilast 75 mg XL QD | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast | 6680 ng*h/mL | Geometric Coefficient of Variation 42.4 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast | 7600 ng*h/mL | Geometric Coefficient of Variation 31.1 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast | 7450 ng*h/mL | Geometric Coefficient of Variation 31.1 |
Comparison: To estimate the exposure of apremilast following single dose administration of extended release (QD) relative to the Reference IR (BID) tablet under fasted conditions, an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-∞ of apremilast.90% CI: [81.1, 105.9]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-∞ of apremilast.90% CI: [75, 98.8]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-∞ of apremilast.90% CI: [85, 111.8]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-∞ of apremilast.90% CI: [98.8, 129.7]
Primary
Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast
Time frame: Apremilast IR: 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 morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.
Population: PK population; two participants were excluded from PK analyses due to predose concentrations \> 5% than their Cmax values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Apremilast 30 mg IR BID | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast | 7030 ng*h/mL | Geometric Coefficient of Variation 31.5 |
| Part 1: Apremilast 75 mg XL QD | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast | 6650 ng*h/mL | Geometric Coefficient of Variation 42.5 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast | 7580 ng*h/mL | Geometric Coefficient of Variation 31.1 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Observable Concentration (AUC0-t) of Apremilast | 7400 ng*h/mL | Geometric Coefficient of Variation 31.1 |
Comparison: To estimate the exposure of apremilast following single dose administration of extended release (QD) relative to the Reference IR (BID) tablet under fasted conditions, an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-t of apremilast.90% CI: [81.3, 106.2]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-t of apremilast.90% CI: [74.9, 98.7]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-t of apremilast.90% CI: [84.9, 111.6]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed AUC0-t of apremilast.90% CI: [98.8, 129.7]
Primary
Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast
Time frame: Apremilast IR: 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 morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.
Population: PK population; two participants were excluded from PK analyses due to predose concentrations \> 5% than their Cmax values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Apremilast 30 mg IR BID | Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast | 379 ng/mL | Geometric Coefficient of Variation 29.9 |
| Part 1: Apremilast 75 mg XL QD | Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast | 402 ng/mL | Geometric Coefficient of Variation 32.5 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast | 436 ng/mL | Geometric Coefficient of Variation 33.2 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Part 2: Peak Maximum Plasma Concentration (Cmax) of Apremilast | 496 ng/mL | Geometric Coefficient of Variation 25.2 |
Comparison: To estimate the exposure of apremilast following single dose administration of extended release (QD) relative to the Reference IR (BID) tablet under fasted conditions, an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed Cmax of apremilast.90% CI: [93.6, 115.4]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed Cmax of apremilast.90% CI: [81.6, 101.3]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed Cmax of apremilast.90% CI: [103.3, 128.1]
Comparison: To estimate the effect of food on the PK of a single oral dose of extended release apremilast (QD), an ANOVA model with treatment, sequence, and period as fixed effects, and subject nested within sequence as a random effect, was performed on the natural log-transformed Cmax of apremilast.90% CI: [113.7, 140.8]
Secondary
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 subject's health, including laboratory test values, regardless of etiology. A serious AE 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. The Investigator determined the relationship between the administration of study drug and the occurrence of each AE as Not Suspected or Suspected as defined in the Protocol.
Time frame: Part 1: Up to 7 days after last dose in each treatment period (14 days); Part 2: Up to 7 days after each dose.
Population: All participants who received at least one dose of apremilast
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 50 Participants |
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation | 3 Participants |
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug | 45 Participants |
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | Deaths | 0 Participants |
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug leading to discontinuation | 3 Participants |
| Part 1: Apremilast 30 mg IR BID | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events related to study drug | 0 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug | 41 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events related to study drug | 0 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation | 5 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 47 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | Deaths | 0 Participants |
| Part 1: Apremilast 75 mg XL QD | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug leading to discontinuation | 5 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug | 2 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 2 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation | 1 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug leading to discontinuation | 1 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events related to study drug | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Deaths | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events related to study drug | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 4 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug | 3 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug leading to discontinuation | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Deaths | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug | 2 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Deaths | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 3 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug leading to discontinuation | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events related to study drug | 0 Participants |
| Part 2: Apremilast 75 mg XL (Standard Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Deaths | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug | 2 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | TEAE related to study drug leading to discontinuation | 0 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Any treatment-emergent adverse event (TEAE) | 2 Participants |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events related to study drug | 0 Participants |