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

July 8, 2020 updated by: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phase I, Randomized, Open-Label, Single-Dose, Three Period, Six-Sequence Crossover Study to Determine the Relative Bioavailability of the Evobrutinib Intended Commercial Tablet Formulation (TF2) Compared to the Clinical Tablet Formulation (TF1) and Evaluate the Effect of Food on TF2 Bioavailability in Healthy Participants

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Neu-Ulm, Germany
        • Nuvisan GmbH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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
  • Other protocol defined inclusion criteria could apply.

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
  • Other protocol defined exclusion criteria could apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • M2951
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • M2951
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • M2951
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • M2951
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • M2951
EXPERIMENTAL: 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.
Drug: 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.
Other Names:
  • M2951

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib Under Fasted Conditions
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Evobrutinib Under Fasted Conditions
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Under Fasted Conditions
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Evobrutinib Under Fed Conditions
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Evobrutinib Under Fed Conditions
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Under Fed Conditions
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment -Emergent Adverse Events (TEAEs) Based on Severity Under Fasted Conditions
Time Frame: Day 1 up to Day 6
Day 1 up to Day 6
Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings Under Fasted Conditions
Time Frame: Day 1 up to Day 6
Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported
Day 1 up to Day 6
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 24 Hours After Evobrutinib Administration (AUC0-24)
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Area Under The Plasma Concentration-Time Curve From Time Zero to Time 12 Hours After Evobrutinib Administration (AUC0-12)
Time Frame: Pre-dose up to 12 hours post-dose on Day 6
Pre-dose up to 12 hours post-dose on Day 6
Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Time Prior to the First Measurable (non-zero) Concentration (t lag) of Evobrutinib
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Terminal First Order (elimination) Rate Constant (λz) of Evobrutinib
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Apparent Elimination Half Life (t1/2) of Evobrutinib
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Apparent Total Body Clearance (CL/f) of Evobrutinib
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Apparent Volume of Distribution During Terminal Phase (VZ/f) of Evobrutinib
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6
Relative Bioavailability of Test Treatment in Relation to Reference Treatment (Frel)
Time Frame: Pre-dose up to 24 hours post-dose on Day 6
Pre-dose up to 24 hours post-dose on Day 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 25, 2020

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 23, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 23, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS200527_0077
  • 2019-004738-40 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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