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

NCT04811573 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 1407-00412019-005037-37
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

• 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.

  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.

• Maximum Measured Concentration of Apremilast in Plasma (Cmax)

  The maximum measured concentration of apremilast in plasma (Cmax) is reported.

  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.

Study Arms (10)

EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C)

EXPERIMENTAL

Treatment sequence AEBDC is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D)

EXPERIMENTAL

Treatment sequence BACED is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E)

EXPERIMENTAL

Treatment sequence CBDAE is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ EU-Otezla fasted(A)

EXPERIMENTAL

Treatment sequence DCEAB is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B)

EXPERIMENTAL

Treatment sequence EDACB is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D)

EXPERIMENTAL

Treatment sequence ABECD is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E)

EXPERIMENTAL

Treatment sequence BCADE is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A)

EXPERIMENTAL

Treatment sequence CDBEA is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

US-Otezla fed(D)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fasted(B)

EXPERIMENTAL

Treatment sequence DECAB is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C)

EXPERIMENTAL

Treatment sequence EADBC is applied. The 5 treatments were separated by a washout period of at least 5 days.

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

Interventions

EU-sourced Otezla® DRUG

Test product

Also known as: Apremilast

EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C); EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D); EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A); EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E); Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C); Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B); US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D); US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E); US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ EU-Otezla fasted(A); US-Otezla fed(D)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fasted(B)

US-sourced Otezla® DRUG

Reference product 1

Also known as: Apremilast

EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C); EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D); EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A); EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E); Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C); Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B); US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D); US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E); US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ 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-sourced Otezla® DRUG

Reference product 2

Also known as: Apremilast

EU-Otezla fasted(A)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ US-Otezla fed(D)/ EU-Otezla fed(C); EU-Otezla fasted(A)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ US-Otezla fed(D); EU-Otezla fed(C)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ Japan-Otezla fasted(E)/ EU-Otezla fasted(A); EU-Otezla fed(C)/US-Otezla fasted(B)/US-Otezla fasted(D)/EU-Otezla fasted(A)/ Japan-Otezla fasted(E); Japan-Otezla fasted(E)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ US-Otezla fasted(B)/ EU-Otezla fed(C); Japan-Otezla fasted(E)/ US-Otezla fed(D)/ EU-Otezla fasted(A)/EU-Otezla fed(C)/ US-Otezla fasted(B); US-Otezla fasted(B)/ EU-Otezla fasted(A)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fed(D); US-Otezla fasted(B)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fed(D)/ Japan-Otezla fasted(E); US-Otezla fed(D)/ EU-Otezla fed(C)/ Japan-Otezla fasted(E)/ US-Otezla fasted(B)/ EU-Otezla fasted(A); US-Otezla fed(D)/ Japan-Otezla fasted(E)/ EU-Otezla fed(C)/ EU-Otezla fasted(A)/ US-Otezla fasted(B)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Location

Related Links

• Related Info

MeSH Terms

Interventions

apremilast

Limitations and Caveats

This trial was prematurely discontinued due to sponsor decision. The planned recruitment amount was not reached. The planned statistical analyses of the pharmacokinetic parameters were not performed.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

18002430127

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 23, 2021
• Study Start: March 31, 2021
• Primary Completion: August 18, 2021
• Study Completion: August 18, 2021
• Last Updated: August 31, 2023
• Results First Posted: August 31, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)