Trial Outcomes & Findings for A Study in Healthy People to Compare 3 Different Formulations of Apremilast Tablets Taken With or Without Food (NCT NCT04811573)

Last Updated: 2023-08-31

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

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.

Results posted on

2023-08-31

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.
Overall Study STARTED	2	2	2	2	2	2	2	2	2	2
Overall Study COMPLETED	2	2	2	2	2	2	2	2	2	2
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study in Healthy People to Compare 3 Different Formulations of Apremilast Tablets Taken With or Without Food

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EU-Otezla Fasted(A)/ Japan-Otezla Fasted(E)/ US-Otezla Fasted(B)/ US-Otezla Fed(D)/ EU-Otezla Fed(C) n=2 Participants 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.	US-Otezla Fasted(B)/ EU-Otezla Fasted(A)/ EU-Otezla Fed(C)/ Japan-Otezla Fasted(E)/ US-Otezla Fed(D) n=2 Participants 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.	EU-Otezla Fed(C)/US-Otezla Fasted(B)/US-Otezla Fed(D)/EU-Otezla Fasted(A)/ Japan-Otezla Fasted(E) n=2 Participants 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.	US-Otezla Fed(D)/ EU-Otezla Fed(C)/ Japan-Otezla Fasted(E)/ US-Otezla Fasted(B)/ EU-Otezla Fasted(A) n=2 Participants 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.	Japan-Otezla Fasted(E)/ US-Otezla Fed(D)/ EU-Otezla Fasted(A)/EU-Otezla Fed(C)/ US-Otezla Fasted(B) n=2 Participants 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.	EU-Otezla Fasted(A)/ US-Otezla Fasted(B)/ Japan-Otezla Fasted(E)/ EU-Otezla Fed(C)/ US-Otezla Fed(D) n=2 Participants 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.	US-Otezla Fasted(B)/ EU-Otezla Fed(C)/ EU-Otezla Fasted(A)/ US-Otezla Fed(D)/ Japan-Otezla Fasted(E) n=2 Participants 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.	EU-Otezla Fed(C)/ US-Otezla Fed(D)/ US-Otezla Fasted(B)/ Japan-Otezla Fasted(E)/ EU-Otezla Fasted(A) n=2 Participants 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.	US-Otezla Fed(D)/ Japan-Otezla Fasted(E)/ EU-Otezla Fed(C)/ EU-Otezla Fasted(A)/ US-Otezla Fasted(B) n=2 Participants 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.	Japan-Otezla Fasted(E)/ EU-Otezla Fasted(A)/ US-Otezla Fed(D)/ US-Otezla Fasted(B)/ EU-Otezla Fed(C) n=2 Participants 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.	Total n=20 Participants Total of all reporting groups
Age, Continuous	44.5 Years STANDARD_DEVIATION 13.4 • n=5 Participants	43.5 Years STANDARD_DEVIATION 13.4 • n=7 Participants	40.5 Years STANDARD_DEVIATION 7.8 • n=5 Participants	30.5 Years STANDARD_DEVIATION 14.8 • n=4 Participants	38.0 Years STANDARD_DEVIATION 18.4 • n=21 Participants	39.5 Years STANDARD_DEVIATION 3.5 • n=8 Participants	25.0 Years STANDARD_DEVIATION 2.8 • n=8 Participants	48.5 Years STANDARD_DEVIATION 7.8 • n=24 Participants	30.5 Years STANDARD_DEVIATION 4.9 • n=42 Participants	43.5 Years STANDARD_DEVIATION 2.1 • n=42 Participants	38.4 Years STANDARD_DEVIATION 10.5 • n=42 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants	7 Participants n=42 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	1 Participants n=24 Participants	2 Participants n=42 Participants	0 Participants n=42 Participants	13 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	2 Participants n=24 Participants	2 Participants n=42 Participants	2 Participants n=42 Participants	20 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	2 Participants n=24 Participants	2 Participants n=42 Participants	2 Participants n=42 Participants	20 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	EU-Otezla Fasted (A; Tfasted) n=20 Participants 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; R1fasted) n=20 Participants 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; Tfed) n=20 Participants 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; R1fed) n=20 Participants 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; R2fasted) n=20 Participants 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)).
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	2430 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 35.5	2580 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 35.6	2580 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 39.6	2350 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 36.9

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	EU-Otezla Fasted (A; Tfasted) n=20 Participants 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; R1fasted) n=20 Participants 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; Tfed) n=20 Participants 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; R1fed) n=20 Participants 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; R2fasted) n=20 Participants 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)).
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	2460 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 35.4	2600 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 35.6	2600 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 39.6	2370 hour * nanogram / milliliter (h*ng/mL) Geometric Coefficient of Variation 36.9

PRIMARY outcome

Timeframe: 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.