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

Phase 1

Terminated

Conditions: Healthy

Interventions: Drug: EU-sourced Otezla®
Drug: US-sourced Otezla®
Drug: Japan-sourced Otezla®

Registration Number: NCT04811573

Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

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 exclusion criteria apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)	EU-sourced Otezla®	Treatment sequence CBDAE is applied. 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)	Japan-sourced Otezla®	Treatment sequence CDBEA is applied. 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)	Japan-sourced Otezla®	Treatment sequence EDACB is applied. 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)	EU-sourced Otezla®	Treatment sequence BCADE is applied. 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)	Japan-sourced Otezla®	Treatment sequence BCADE is applied. 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)	US-sourced Otezla®	Treatment sequence DECAB is applied. 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)	EU-sourced Otezla®	Treatment sequence CDBEA is applied. 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)	US-sourced Otezla®	Treatment sequence CDBEA is applied. 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)	Japan-sourced Otezla®	Treatment sequence DECAB is applied. 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)	EU-sourced Otezla®	Treatment sequence EADBC is applied. 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)	US-sourced Otezla®	Treatment sequence EADBC is applied. 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)	Japan-sourced Otezla®	Treatment sequence EADBC is applied. The 5 treatments were separated by a washout period of at least 5 days.
EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)	EU-sourced Otezla®	Treatment sequence AEBDC is applied. The 5 treatments were separated by a washout period of at least 5 days.
EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)	Japan-sourced Otezla®	Treatment sequence AEBDC is applied. The 5 treatments were separated by a washout period of at least 5 days.
EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)	US-sourced Otezla®	Treatment sequence CBDAE is applied. 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)	EU-sourced Otezla®	Treatment sequence EDACB is applied. The 5 treatments were separated by a washout period of at least 5 days.
EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)	Japan-sourced Otezla®	Treatment sequence CBDAE is applied. 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)	Japan-sourced Otezla®	Treatment sequence DCEAB is applied. 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)	US-sourced Otezla®	Treatment sequence EDACB is applied. 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)	EU-sourced Otezla®	Treatment sequence DCEAB is applied. 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)	US-sourced Otezla®	Treatment sequence DCEAB is applied. 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)	Japan-sourced Otezla®	Treatment sequence ABECD is applied. 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)	EU-sourced Otezla®	Treatment sequence ABECD is applied. 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)	US-sourced Otezla®	Treatment sequence ABECD is applied. 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)	EU-sourced Otezla®	Treatment sequence DECAB is applied. 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)	EU-sourced Otezla®	Treatment sequence BACED is applied. The 5 treatments were separated by a washout period of at least 5 days.
EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)	US-sourced Otezla®	Treatment sequence AEBDC is applied. 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)	US-sourced Otezla®	Treatment sequence BACED is applied. 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)	Japan-sourced Otezla®	Treatment sequence BACED is applied. 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)	US-sourced Otezla®	Treatment sequence BCADE is applied. The 5 treatments were separated by a washout period of at least 5 days.

Primary Outcome Measures

Name	Time	Method
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.