Healthy
Conditions
Brief summary
The aim of this trial is to establish bioequivalence between EU-, US- and Japan-sourced Otezla® tablet formulations to assure comparability of results from Phase III trials of BI 730357 (new oral agent for treatment of psoriasis as well as other T helper 17 cells (Th17)-mediated diseases) regardless of whether only the EU-sourced Otezla® or EU and US-sourced Otezla®/Japan-sourced Otezla® have been used as an active comparator.
Interventions
DRUGEU-sourced Otezla®
Test product
DRUGUS-sourced Otezla®
Reference product 1
DRUGJapan-sourced Otezla®
Reference product 2
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Five-period, ten-sequence crossover trial. Periods: (A): EU-sourced Otezla - fasted condition (B): US-sourced Otezla - fasted condition (C): EU-sourced Otezla - fed condition (C): US-sourced Otezla - fed condition (E): Japan-sourced Otezla - fasted condition Sequences: see Arms
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests * Age of 18 to 55 years (inclusive) * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) * Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation * Male subjects, or female subjects who meet any of the following criteria for a highly effective contraception from at least 30 days before the first administration of trial medication until 30 days after trial completion: * Use of combined (estrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal or transdermal), plus condom * Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom * Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) * A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment) * Surgically sterilised (including hysterectomy or bilateral occlusion) * Postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of Follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory)
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator * Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease assessed as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair) * Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders * History of relevant orthostatic hypotension, fainting spells, or blackouts Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration. | The area under the concentration-time curve of apremilast in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. |
| Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration. | The area under the concentration-time curve of apremilast in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. |
| Maximum Measured Concentration of Apremilast in Plasma (Cmax) | 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration. | The maximum measured concentration of apremilast in plasma (Cmax) is reported. |
Countries
Germany
Participant flow
Recruitment details
This open-label, randomised, single-dose, five-period, ten-sequence crossover study was to compare the test treatment (EU-sourced Otezla) to the reference treatments US-sourced Otezla and Japan-sourced Otezla) under fasting and fed conditions.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| EU-Otezla Fasted(A)/ Japan-Otezla Fasted(E)/ US-Otezla Fasted(B)/ US-Otezla Fed(D)/ EU-Otezla Fed(C) Treatment sequence AEBDC was applied:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| US-Otezla Fasted(B)/ EU-Otezla Fasted(A)/ EU-Otezla Fed(C)/ Japan-Otezla Fasted(E)/ US-Otezla Fed(D) Treatment sequence BACED was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| EU-Otezla Fed(C)/US-Otezla Fasted(B)/US-Otezla Fed(D)/EU-Otezla Fasted(A)/ Japan-Otezla Fasted(E) Treatment sequence CBDAE was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| US-Otezla Fed(D)/ EU-Otezla Fed(C)/ Japan-Otezla Fasted(E)/ US-Otezla Fasted(B)/ EU-Otezla Fasted(A) Treatment sequence DCEAB was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| Japan-Otezla Fasted(E)/ US-Otezla Fed(D)/ EU-Otezla Fasted(A)/EU-Otezla Fed(C)/ US-Otezla Fasted(B) Treatment sequence EDACB was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| EU-Otezla Fasted(A)/ US-Otezla Fasted(B)/ Japan-Otezla Fasted(E)/ EU-Otezla Fed(C)/ US-Otezla Fed(D) Treatment sequence ABECD was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| US-Otezla Fasted(B)/ EU-Otezla Fed(C)/ EU-Otezla Fasted(A)/ US-Otezla Fed(D)/ Japan-Otezla Fasted(E) Treatment sequence BCADE was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| EU-Otezla Fed(C)/ US-Otezla Fed(D)/ US-Otezla Fasted(B)/ Japan-Otezla Fasted(E)/ EU-Otezla Fasted(A) Treatment sequence CDBEA was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| US-Otezla Fed(D)/ Japan-Otezla Fasted(E)/ EU-Otezla Fed(C)/ EU-Otezla Fasted(A)/ US-Otezla Fasted(B) Treatment sequence DECAB was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| Japan-Otezla Fasted(E)/ EU-Otezla Fasted(A)/ US-Otezla Fed(D)/ US-Otezla Fasted(B)/ EU-Otezla Fed(C) Treatment sequence EADBC was applied with the following treatments:
EU-Otezla fasted(A): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
US-Otezla fasted(B): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
EU-Otezla fed(C): One EU-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
US-Otezla fed(D): One US-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fed state (after a high-fat, high-calorie meal).
Japan-Otezla fasted(E): One Japan-sourced Otezla® film-coated tablet of 30 milligrams (mg) apremilast was administered orally with 240 milliliter (mL) water as a single dose in the fasted state (after an overnight fasting period of at least 10 hours (h)).
The 5 treatments were separated by a washout period of at least 5 days. | 2 |
| Total | 20 |
Baseline characteristics
| Characteristic | EU-Otezla Fasted(A)/ Japan-Otezla Fasted(E)/ US-Otezla Fasted(B)/ US-Otezla Fed(D)/ EU-Otezla Fed(C) | US-Otezla Fasted(B)/ EU-Otezla Fasted(A)/ EU-Otezla Fed(C)/ Japan-Otezla Fasted(E)/ US-Otezla Fed(D) | EU-Otezla Fed(C)/US-Otezla Fasted(B)/US-Otezla Fed(D)/EU-Otezla Fasted(A)/ Japan-Otezla Fasted(E) | US-Otezla Fed(D)/ EU-Otezla Fed(C)/ Japan-Otezla Fasted(E)/ US-Otezla Fasted(B)/ EU-Otezla Fasted(A) | Japan-Otezla Fasted(E)/ US-Otezla Fed(D)/ EU-Otezla Fasted(A)/EU-Otezla Fed(C)/ US-Otezla Fasted(B) | EU-Otezla Fasted(A)/ US-Otezla Fasted(B)/ Japan-Otezla Fasted(E)/ EU-Otezla Fed(C)/ US-Otezla Fed(D) | US-Otezla Fasted(B)/ EU-Otezla Fed(C)/ EU-Otezla Fasted(A)/ US-Otezla Fed(D)/ Japan-Otezla Fasted(E) | EU-Otezla Fed(C)/ US-Otezla Fed(D)/ US-Otezla Fasted(B)/ Japan-Otezla Fasted(E)/ EU-Otezla Fasted(A) | US-Otezla Fed(D)/ Japan-Otezla Fasted(E)/ EU-Otezla Fed(C)/ EU-Otezla Fasted(A)/ US-Otezla Fasted(B) | Japan-Otezla Fasted(E)/ EU-Otezla Fasted(A)/ US-Otezla Fed(D)/ US-Otezla Fasted(B)/ EU-Otezla Fed(C) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 44.5 Years STANDARD_DEVIATION 13.4 | 43.5 Years STANDARD_DEVIATION 13.4 | 40.5 Years STANDARD_DEVIATION 7.8 | 30.5 Years STANDARD_DEVIATION 14.8 | 38.0 Years STANDARD_DEVIATION 18.4 | 39.5 Years STANDARD_DEVIATION 3.5 | 25.0 Years STANDARD_DEVIATION 2.8 | 48.5 Years STANDARD_DEVIATION 7.8 | 30.5 Years STANDARD_DEVIATION 4.9 | 43.5 Years STANDARD_DEVIATION 2.1 | 38.4 Years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 20 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 13 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 2 / 20 | 1 / 20 | 3 / 20 | 5 / 20 | 5 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
The area under the concentration-time curve of apremilast in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Time frame: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
Population: Pharmacokinetic (PK) set: This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| EU-Otezla Fasted (A; Tfasted) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2420 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.3 |
| US-Otezla Fasted (B; R1fasted) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2460 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.4 |
| EU-Otezla Fed (C; Tfed) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2600 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.6 |
| US-Otezla Fed (D; R1fed) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2600 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.6 |
| Japan-Otezla Fasted (E; R2fasted) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2370 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 36.9 |
Primary
Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
The area under the concentration-time curve of apremilast in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Time frame: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
Population: Pharmacokinetic (PK) set: This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| EU-Otezla Fasted (A; Tfasted) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2390 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.5 |
| US-Otezla Fasted (B; R1fasted) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2430 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.5 |
| EU-Otezla Fed (C; Tfed) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2580 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.6 |
| US-Otezla Fed (D; R1fed) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2580 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.6 |
| Japan-Otezla Fasted (E; R2fasted) | Area Under the Concentration-time Curve of Apremilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 2350 hour * nanogram / milliliter (h*ng/mL) | Geometric Coefficient of Variation 36.9 |
Primary
Maximum Measured Concentration of Apremilast in Plasma (Cmax)
The maximum measured concentration of apremilast in plasma (Cmax) is reported.
Time frame: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
Population: Pharmacokinetic (PK) set: This set includes all subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| EU-Otezla Fasted (A; Tfasted) | Maximum Measured Concentration of Apremilast in Plasma (Cmax) | 298 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 36.1 |
| US-Otezla Fasted (B; R1fasted) | Maximum Measured Concentration of Apremilast in Plasma (Cmax) | 301 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 35.6 |
| EU-Otezla Fed (C; Tfed) | Maximum Measured Concentration of Apremilast in Plasma (Cmax) | 303 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 27.8 |
| US-Otezla Fed (D; R1fed) | Maximum Measured Concentration of Apremilast in Plasma (Cmax) | 271 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| Japan-Otezla Fasted (E; R2fasted) | Maximum Measured Concentration of Apremilast in Plasma (Cmax) | 299 nanogram / milliliter (ng/mL) | Geometric Coefficient of Variation 33 |