Relative Bioavailability of Evobrutinib Tablet Batches
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT07214922
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Brief Summary
The main purpose of the study is to compare the Pharmacokinetics (PK), safety and tolerability of different manufacturing batches of M2951 tablet formulation relative to a reference batch under fasted conditions in healthy participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
- Participants who are overtly healthy as determined by 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
- Participants who have a body weight within 50.0 and 100.0 kilogram (kg) (inclusive) and Body Mass Index within the range 19.0 and 30.0 kg/ meter square (m2) (inclusive)
- Female participant who agrees to use appropriate contraception and barrier methods.
- Male participants: No contraception needed
- Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and this protocol
- Participants who are stable non-smokers for at least 3 months preceding Screening
- Other protocol defined inclusion criteria could apply
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Participants with history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, musculoskeletal, genitourinary, immunological, dermatological, connective tissue, psychiatric (due to rare risk of hallucinations, agitation and activation of psychosis), and other diseases or disorders, and epilepsy, as determined by medical evaluation
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Participants with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study
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Participants with prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to the first administration of study intervention
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Participants with history of any malignancy
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Participants with history of seizures
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Participants with history of pharmacologically treated psychiatric disease
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Participants with 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 the first administration of study intervention
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Participants with history of shingles within 12 months prior to Screening
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Participants with history of drug hypersensitivity
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Participants with history of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to or at the time of Screening
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Participants positive for
- hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or Human Immunodeficiency Virus (HIV) I and II tests at Screening
- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening and Day -1
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Participants with any condition, including findings in the laboratory tests, medical history (example heart failure, hypokalemia, family history of Long QT Syndrome), 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
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Participants with history of administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Day 1.
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Participants with history of administration of other types of vaccines is allowed until 14 days before the first administration of study intervention, thereafter it is prohibited until the end of the study.
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Participants with Moderate or strong inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4)/5 or Pgp within 4 weeks prior to the first administration of study intervention
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Participants with use of any prescribed medicine or over-the-counter drug or dietary supplement, including herbal remedies, vitamins, and minerals, antacids and dietary supplements such as fish oils within 2 weeks or 5 times the half-life of the respective drug, whichever is longer, prior to the first administration of study intervention
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Participants with use of any investigational drug in any clinical study within 60 days prior to Day 1 administration, or have used an experimental monoclonal antibody within the past 1 year prior to Day 1, or have participated in a study evaluating a Bruton Tyrosine Kinase (BTK) inhibitor within 60 days, or are on extended follow-up in a clinical study, even if last administration of a study intervention was more than 60 days ago, or 5 half-lives of the investigational drug, whichever is longer, prior to the first administration of study intervention
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Participants with a medical history and physical examination results that include any ongoing clinically relevant findings as judged by the Investigator
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Participants with clinically relevant findings (excluding minor, not clinically relevant excursions from normal ranges, as judged by the Investigator) at Screening in biochemistry, hematology, coagulation, and urinalysis examinations for the age of the participant, as judged by the Investigator:
- Alanine aminotransferase, aspartate aminotransferase: above upper limit of normal (ULN)
- Creatinine: above normal limits
- Absolute lymphocyte count, absolute neutrophil count: below limit of reference range.
- Amylase and lipase above normal ranges; minor deviations are allowed, if not clinically relevant.
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Participants with estimated glomerular rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation (2009) < 90 milliliters/minute(mL/min) at Screening. In case of a borderline result between ≥ 80 and < 90 mL/min, Cystatin C will be determined in addition, and the participant will only be included if the Cystatin C value is below the upper limit of normal
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Participants with semi-supine systolic blood pressure > 140 mmHg or < 90 millimeters of mercury (mmHg), diastolic blood pressure > 90 mmHg or < 50 mmHg, and pulse rate > 90 or < 50 beats per minute (bpm) at Screening.
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Participants with consumption of alcohol from 48 hours prior to first administration of study intervention.
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Other protocol defined exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Evobrutinib: Treatment Sequence 2: BDAC Treatment B Participants will receive single oral dose of Treatment B on Day 1 in period 1, followed by single oral dose of Treatment D on Day 3 in period 2, followed by Treatment A on Day 5 in period 3 and followed by single oral dose of Treatment C on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 2: BDAC Treatment C Participants will receive single oral dose of Treatment B on Day 1 in period 1, followed by single oral dose of Treatment D on Day 3 in period 2, followed by Treatment A on Day 5 in period 3 and followed by single oral dose of Treatment C on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 2: BDAC Treatment D Participants will receive single oral dose of Treatment B on Day 1 in period 1, followed by single oral dose of Treatment D on Day 3 in period 2, followed by Treatment A on Day 5 in period 3 and followed by single oral dose of Treatment C on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 3: CADB Treatment A Participants will receive single oral dose of Treatment C on Day 1 in period 1, followed by single oral dose of Treatment A on Day 3 in period 2, followed by Treatment D on Day 5 in period 3 and followed by single oral dose of Treatment B on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 3: CADB Treatment C Participants will receive single oral dose of Treatment C on Day 1 in period 1, followed by single oral dose of Treatment A on Day 3 in period 2, followed by Treatment D on Day 5 in period 3 and followed by single oral dose of Treatment B on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 3: CADB Treatment B Participants will receive single oral dose of Treatment C on Day 1 in period 1, followed by single oral dose of Treatment A on Day 3 in period 2, followed by Treatment D on Day 5 in period 3 and followed by single oral dose of Treatment B on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 3: CADB Treatment D Participants will receive single oral dose of Treatment C on Day 1 in period 1, followed by single oral dose of Treatment A on Day 3 in period 2, followed by Treatment D on Day 5 in period 3 and followed by single oral dose of Treatment B on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 4: DCBA Treatment A Participants will receive single oral dose of Treatment D on Day 1 in period 1, followed by single oral dose of Treatment C on Day 3 in period 2, followed by Treatment B on Day 5 in period 3 and followed by single oral dose of Treatment A on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 4: DCBA Treatment B Participants will receive single oral dose of Treatment D on Day 1 in period 1, followed by single oral dose of Treatment C on Day 3 in period 2, followed by Treatment B on Day 5 in period 3 and followed by single oral dose of Treatment A on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 4: DCBA Treatment C Participants will receive single oral dose of Treatment D on Day 1 in period 1, followed by single oral dose of Treatment C on Day 3 in period 2, followed by Treatment B on Day 5 in period 3 and followed by single oral dose of Treatment A on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 4: DCBA Treatment D Participants will receive single oral dose of Treatment D on Day 1 in period 1, followed by single oral dose of Treatment C on Day 3 in period 2, followed by Treatment B on Day 5 in period 3 and followed by single oral dose of Treatment A on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 1: ABCD Treatment A Participants will receive single oral dose of Treatment A on Day 1 in period 1, followed by single oral dose of Treatment B on Day 3 in period 2, followed by Treatment C on Day 5 in period 3 and followed by single oral dose of Treatment D on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 1: ABCD Treatment B Participants will receive single oral dose of Treatment A on Day 1 in period 1, followed by single oral dose of Treatment B on Day 3 in period 2, followed by Treatment C on Day 5 in period 3 and followed by single oral dose of Treatment D on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 1: ABCD Treatment C Participants will receive single oral dose of Treatment A on Day 1 in period 1, followed by single oral dose of Treatment B on Day 3 in period 2, followed by Treatment C on Day 5 in period 3 and followed by single oral dose of Treatment D on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 1: ABCD Treatment D Participants will receive single oral dose of Treatment A on Day 1 in period 1, followed by single oral dose of Treatment B on Day 3 in period 2, followed by Treatment C on Day 5 in period 3 and followed by single oral dose of Treatment D on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period. Evobrutinib: Treatment Sequence 2: BDAC Treatment A Participants will receive single oral dose of Treatment B on Day 1 in period 1, followed by single oral dose of Treatment D on Day 3 in period 2, followed by Treatment A on Day 5 in period 3 and followed by single oral dose of Treatment C on Day 7 under fasted condition in period 4. There will be 48 hours washout period between each treatment period.
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Evobrutinib Pre-dose up to 24 hours post-dose on Day 1, 3, 5 and 7 Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Pre-dose up to 24 hours post-dose on Day 1, 3, 5 and 7
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment -Emergent Adverse Events (TEAEs) Based on Severity Baseline up to Day 18 Number of Participants with Abnormal/Clinically Significant Changes From Baseline Laboratory Variables, Vital Signs and 12-Lead Electrocardiogram (ECG) Baseline up to Day 18 Pharmacokinetic (PK) Plasma Concentrations of Evobrutinib Pre-dose up to 24 hours post-dose on Day 1, 3, 5 and 7
Trial Locations
- Locations (1)
Nuvisan GmbH
🇩🇪Neu-Ulm, Germany
Nuvisan GmbH🇩🇪Neu-Ulm, Germany