Relative Bioavailability (rBA) of Evobrutinib Intended Commercial and Clinical Tablets, and Effect of Food on Intended Commercial Tablets

NCT ID: NCT04314024

Last Updated: 2020-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-25
• Study Completion Date: 2020-06-23

Brief Summary

The study will evaluate the relative bioavailability (rBA) of the intended commercial tablet formulation (Test Treatment, TF2) of Evobrutinib compared to the clinical tablet formulation (Reference Treatment, TF1) of Evobrutinib and to assess the effect of food on the bioavailability of the intended commercial tablet formulation of Evobrutinib.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Evobrutinib: Treatment Sequence 1: A-B-C

Participants will receive single oral dose of TF1 (Treatment A) evobrutinib on Day 1 under fasted condition in period 1, followed by single oral dose of TF2 (Treatment B) on Day 3 under fasted condition in period 2, followed by TF2 (Treatment C) on Day 5 under fed condition in period 3. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Evobrutinib

Intervention Type: DRUG

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Evobrutinib: Treatment Sequence 2: A-C-B

Participants will receive single oral dose of TF1 (Treatment A) evobrutinib on Day 1 under fasted condition in period 1, followed by TF2 (Treatment C) on Day 3 under fed condition in period 2, followed by single oral dose of TF2 (Treatment B) on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Evobrutinib

Intervention Type: DRUG

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Evobrutinib: Treatment Sequence 3: B-A-C

Participants will receive single oral dose of TF2 (Treatment B) on Day 1 under fasted condition in period 1, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 3 under fasted condition in period 2, followed by TF2 (Treatment C) on Day 5 under fed condition in period 3. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Evobrutinib

Intervention Type: DRUG

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Evobrutinib: Treatment Sequence 4: B-C-A

Participants will receive single oral dose of TF2 (Treatment B) on Day 1 under fasted condition in period 1, followed by TF2 (Treatment C) on Day 3 under fed condition in period 2, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Evobrutinib

Intervention Type: DRUG

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Evobrutinib: Treatment Sequence 5: C-A-B

Participants will receive single oral dose of TF2 (Treatment C) on Day 1 under fed condition in period 1, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 3 under fasted condition in period 2, followed by single oral dose of TF2 (Treatment B) on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Evobrutinib

Intervention Type: DRUG

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Evobrutinib: Treatment Sequence 6: C-B-A

Participants will receive single oral dose of TF2 (Treatment C) on Day 1 under fed condition in period 1, followed by single oral dose of TF2 (Treatment B) on Day 3 under fasted condition in period 2, followed by single oral dose of TF1 (Treatment A) evobrutinib on Day 5 under fasted condition in period 3. There will be 48 hours washout period between each treatment period.

Group Type: EXPERIMENTAL

Evobrutinib

Intervention Type: DRUG

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Interventions

Evobrutinib

Participants will receive single oral dose of evobrutinib either after an overnight fast of at least 10 hours (Treatment A and Treatment B), or under fed conditions that is within 30 minutes after start of high-fat meal (Treatment C) in period 1, 2 and 3.

Intervention Type: DRUG

Other Intervention Names

M2951

Eligibility Criteria

Inclusion Criteria

• Participants are overtly healthy as medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
• Male or female participants agree to be consistent with local regulations on contraception methods
• Female participants are not pregnant or breastfeeding, and at least one of the following condition applies:
• Not a WOCBP or
• If a WOCBP, use a highly effective contraceptive method (that is, with a failure rate of <1 percent per year, preferably with low user dependency for the following time period:
• Before the first dose of the study intervention, if using hormonal contraception:
• Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses or
• Has used a depot contraceptive or extended-cycle oral contraceptive for least 28 days and has a documented negative pregnancy test using a highly sensitive assay and
• A barrier method
• During the intervention period
• After the study intervention period (that is after the last dose of study intervention is administered) for at least 90 days, plus 30 days (a menstrual cycle) after the last dose of study intervention and agree not to donate eggs (ova, oocytes) for reproduction during this period. The Investigator evaluates the effectiveness of the contraceptive method in relationship to the first dose of study intervention
• Females have a negative serum pregnancy test at the Screening Visit and within 24 hours before the first dose of study intervention
• The Investigator reviews the medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy
• Participants are stable non-smokers for at least 3 months preceding screening

Exclusion Criteria

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
• Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to screening
• History of any malignancy
• History of chronic or recurrent acute infection or any bacterial, viral, parasitic or fungal infections within 30 days prior to screening and at any time between screening and admission, or hospitalization due to infection within 6 months prior to screening
• History of shingles within 12 months prior to screening
• History of drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients
• History of alcoholism or drug abuse within 2 years prior to screening, or evidence of such abuse as indicated by the laboratory assays conducted during screening
• History of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to screening
• Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to screening
• Any condition, including findings in the laboratory tests, medical history, or other screening assessments, that in the opinion of the Investigator constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study's objectives, conduct, or evaluation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

Nuvisan GmbH

Neu-Ulm, , Germany

Countries

Germany

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200527_0077

Trial Awareness and Transparency website

https://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html

Medical Information Location Map - Med Info Contacts

Other Identifiers

2019-004738-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200527_0077

Identifier Type: -

Identifier Source: org_study_id