HealthyPhase 1NCT05248945
DDI Study of Evobrutinib and Carbamazepine
A Phase 1 study testing Evobrutinib and Carbamazepine in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial summary
The purpose of this study was to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details included: Study Duration: up to 54 days. Treatment Duration: 25 days. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Evobrutinib and Carbamazepine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteGermany
- Study dates
- 13 Jan 2022to 18 Jul 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Type of Participant and Disease Characteristics
- Had a body weight within 50.0 and 100.0 kg (kilogram) (inclusive) and Body Mass Index (BMI) within the range 19.0 and 30.0 kilogram per meter square (kg/m^2) (inclusive)
- Male: No contraception and barrier requirements were needed. Female: Was not a woman of childbearing potential
- Were capable of giving signed informed consent, which included compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol
- Were stable nonsmokers for at least 3 months preceding Screening
Who cannot join
- Had a 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
- Had been administered live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g., SARSCoV2 vaccines) was allowed until 2 weeks before admission to Clinical Research Unit (CRU), thereafter it was prohibited until the end of the study
- Had been administered moderate or strong inhibitors or inducers of Cytochrome P450 (CYP)3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention
- Had a contraindication to carbamazepine (carbamazepine SmPC)
- Had a history of any malignancy
- Had a history of drug hypersensitivity ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other hypersensitivity reaction in general, including contact hypersensitivity to Electrocardiogram (ECG) electrodes, which may have affected the safety of the participant and/or outcome of the study per the Investigator's discretion.
- Other protocol defined exclusion criteria could have applied.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I, Open-Label, Single-Sequence Study of the Effect of Multiple Doses of Carbamazepine on Single-Dose Evobrutinib Pharmacokinetics in Healthy Participants
The purpose of this study was to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details included:
Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants were residents in the Clinical Research Unit from Day 1 to Day 20 and returned on Day 26 for a Safety Follow-Up visit.
- Conditions
- Healthy
- Being tested
- Evobrutinib, Carbamazepine
- Keywords
- Clinical Pharmacology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvobrutinibDrug
Also called M2951
Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19
CarbamazepineDrug
Participants received Carbamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Evobrutinib plus Carbamazepine | Experimental | Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19 under fed condition followed by Cabamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily. Receives: Drug: Evobrutinib; Drug: Carbamazepine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
Cmax was obtained from plasma concentration time curve.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 16 and 24 hours post dose on Day 1 and Day 19.
Secondary outcomes (33)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a study intervention. A serious adverse event (SAE) was any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE's were those events with onset dates on or after the first administration of study intervention. TEAEs include both Serious TEAEs and non-serious TEAEs."
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes Values
Blood samples were collected to analyze the hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes Values. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline was calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Hemoglobin Levels
Blood samples were collected to analyze the hematology parameter: Hemoglobin levels. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Hematocrit Values
Blood samples were collected to analyze the hematology parameter: Hematocrit Value. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Activated Partial Thromboplastin Time
Blood samples were collected to analyze the hematology parameter: Activated Partial Thromboplastin Time. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/ Leukocytes, and Neutrophils/Leukocytes
Blood samples were collected to analyze the hematology parameter: basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/ leukocytes, and neutrophils/leukocytes. The data in terms of 'percentage of cells' was calculated as: Count of Basophils (10^9 cells/L) (or any other defined hematology parameter e.g. Neutrophils, Eosinophils etc.) divided by the total count of Leukocytes (10^9 cells/L) in the blood multiplied by 100."
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio
Blood samples were collected to analyze the hematology parameter: Prothrombin International Normalized Ratio. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value. Percent=Fraction×100
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Bilirubin, Creatinine and Urate
Blood samples were collected to analyze the Biochemistry Parameter: Bilirubin, Creatinine and Urate. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Sodium, Potassium, Calcium, Magnesium and Phosphate Levels
Blood samples were collected to analyze the Biochemistry Parameter: Sodium, Potassium, Calcium, Magnesium and Phosphate Levels. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Protein and Albumin Levels
Blood samples were collected to analyze the Biochemistry Parameter: Protein and Albumin Levels. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase, Amylase, Lipase, Creatinine Kinase, Gamma Glutamyl Transferase Levels, Lactate Dehydrogenase, Aspartate Aminotransferase
Biochemistry Parameter: Alkaline Phosphatase, Amylase, Lipase, Creatinine Kinase, Gamma Glutamyl Transferase Levels, Lactate Dehydrogenase, Aspartate Aminotransferase. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Glucose, Chloride, Cholesterol, Triglycerides, Phosphate Levels
Biochemistry Parameter: Glucose, Chloride, Cholesterol, Triglycerides, Phosphate levels. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in 12-Lead ECG Parameter: Heart Rate
12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. 12-Lead ECG Parameter: Heart Rate. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in 12-Lead ECG Parameter: RR Duration, QT Duration, Fridericia's Formula (QTcF), PR Duration and QRS Duration
12-Lead ECGs were collected after the participants rested quietly for at least 10 minutes in a supine position. 12-Lead ECG Parameter: RR Duration. Baseline was the last scheduled measurement before administration of study intervention. Absolute changes from baseline were calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Blood Pressure
Blood pressure (systolic and diastolic) was measured after at least 5 minutes resting, with the participant in the seated position without distractions.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Pulse Rate
Pulse rate was measured after at least 5 minutes resting, with the subject in the seated position without distractions.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Respiratory Rate
Respiratory Rate was measured after at least 5 minutes resting, with the participant in the seated position without distractions.
Measured: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Body Temperature
The absolute changes from baseline in Body Temperature (degree Celsius [°C]) were reported.
Measured: Baseline Day 1 and Day 26
Total Body Clearance of Evobrutinib From Plasma (CL/f)
CL/f was defined as the apparent total clearance of the drug from plasma after extravascular administration.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Apparent Volume of Distribution (Vz/f) of Evobrutinib
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. The apparent volume of distribution during the terminal phase following extravascular administration and was calculated by using the formula=Dose/ (AUC0-inf* λz).
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Evobrutinib
The AUC from time zero (= dosing time) to the time of the last quantifiable concentration (tlast).
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib
Tmax was obtained directly from the concentration versus time curve.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Apparent Terminal Half-Life (t1/2) of Evobrutinib in Plasma
t1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half. Terminal half-life calculated by natural log 2 divided by lambda z.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A)
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (LOQ) (AUC0-tlast) of Evobrutinib Metabolite (MSC2729909A)
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration was at or above LOQ. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A)
Cmax was obtained from plasma concentration time curve.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib Metabolite (MSC2729909A)
Tmax was obtained directly from the concentration versus time curve.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Time Prior to the First Quantifiable (Non-zero) Concentration (Tlag) of Evobrutinib Metabolite (MSC2729909A) in Plasma
The time prior to the first concentration at or above limit of quantification. It is calculated as last time point at which the concentration is less than (<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration.
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Metabolite to Parent Ratios for Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A)
Molecular weight-corrected ratio of metabolite (M) AUC0-inf to parent (P) AUC0-inf: M/P(AUC0-inf) = (AUC0-inf metabolite (MSC2729909A) *molecular weight (MW) parent) / (AUC0-inf parent*MW metabolite (MSC2729909A)).
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Metabolite to Parent Ratios for Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A)
Molecular weight-corrected ratio of metabolite Cmax to parent Cmax: M/P(Cmax) = (Cmaxmetabolite (MSC2729909A) * MWparent) / (Cmax parent * MW metabolite (MSC2729909A)).
Measured: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
AE was defined as any untoward medical occurrence in a subject. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a study intervention. SAE was any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE's were those events with onset dates on or after the first administration of study intervention. TEAEs include both Serious TEAEs and non-serious TEAEs. Severity of AE were assessed by the investigator as Mild, Moderate, and Severe: An event that prevents normal everyday activities. Severe is a category used to rate the intensity of an event; both AEs and SAEs can be assessed as severe. SAS is used.
Measured: Baseline (Day 1) and Day 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2022
- Study start13 Jan 2022
- Primary completion18 Jul 2022
- Study completion18 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05248945
- Sponsor's protocol ID
- MS200527_0108
- Other IDs
- 2021-003381-13
- Status last verified
- Dec 2025
- First submitted
- 13 Jan 2022
- Last updated
- 15 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports 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 bit.ly/IPD21
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open-Label, Single-Sequence Study of the Effect of Multiple Doses of Carbamazepine on Single-Dose Evobrutinib Pharmacokinetics in Healthy Participants
- ClinicalTrials.gov ID
- NCT05248945
- Acronym / sponsor ID
- MS200527_0108
- Conditions
- Healthy
- Keywords
- Clinical Pharmacology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 13 Jan 2022 (actual)
- Primary completion
- 18 Jul 2022 (actual)
- Study completion
- 18 Jul 2022 (actual)
- First posted
- 21 Feb 2022 (actual)
- Results
- Posted 15 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details included:
Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants were residents in the Clinical Research Unit from Day 1 to Day 20 and returned on Day 26 for a Safety Follow-Up visit.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evobrutinib plus Carbamazepine | Experimental | Drug: Evobrutinib, Drug: CarbamazepineParticipants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19 under fed condition followed by Cabamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Type of Participant and Disease Characteristics
- Had a body weight within 50.0 and 100.0 kg (kilogram) (inclusive) and Body Mass Index (BMI) within the range 19.0 and 30.0 kilogram per meter square (kg/m^2) (inclusive)
- Male: No contraception and barrier requirements were needed. Female: Was not a woman of childbearing potential
- Were capable of giving signed informed consent, which included compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol
- Were stable nonsmokers for at least 3 months preceding Screening
Key exclusion criteria (7 listed)
- Had a 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
- Had been administered live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g., SARSCoV2 vaccines) was allowed until 2 weeks before admission to Clinical Research Unit (CRU), thereafter it was prohibited until the end of the study
- Had been administered moderate or strong inhibitors or inducers of Cytochrome P450 (CYP)3A4/5 or Pgp within 4 weeks prior to the first administration of study intervention
- Had a contraindication to carbamazepine (carbamazepine SmPC)
- Had a history of any malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvobrutinibAlso: M2951Participants received a single oral dose of Evobrutinib 45 mg on Day 1 and Day 19 | Drug | Evobrutinib plus Carbamazepine |
| CarbamazepineParticipants received Carbamazepine 100 mg on Days 2 and 3, 200 mg on Days 4 and 5 and then 300 mg from Days 6 to 19 and were titrated back to 200 mg from Days 20 to 22 and 100 mg on Days 23 to 25 twice daily. | Drug | Evobrutinib plus Carbamazepine |
Primary outcome
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12, 16 and 24 hours post dose on Day 1 and Day 19.
Cmax was obtained from plasma concentration time curve.
33 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Serious TEAEs
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes Values
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Hemoglobin Levels
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Hematocrit Values
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Activated Partial Thromboplastin Time
Time frame: Baseline (Day 1) and Day 26
Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/ Leukocytes, and Neutrophils/Leukocytes
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Bilirubin, Creatinine and Urate
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Sodium, Potassium, Calcium, Magnesium and Phosphate Levels
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Protein and Albumin Levels
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase, Amylase, Lipase, Creatinine Kinase, Gamma Glutamyl Transferase Levels, Lactate Dehydrogenase, Aspartate Aminotransferase
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Biochemistry Parameter: Glucose, Chloride, Cholesterol, Triglycerides, Phosphate Levels
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in 12-Lead ECG Parameter: Heart Rate
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in 12-Lead ECG Parameter: RR Duration, QT Duration, Fridericia's Formula (QTcF), PR Duration and QRS Duration
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Blood Pressure
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Pulse Rate
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Respiratory Rate
Time frame: Baseline (Day 1) and Day 26
Absolute Change From Baseline in Vital Sign: Body Temperature
Time frame: Baseline Day 1 and Day 26
Total Body Clearance of Evobrutinib From Plasma (CL/f)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Apparent Volume of Distribution (Vz/f) of Evobrutinib
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Evobrutinib
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Apparent Terminal Half-Life (t1/2) of Evobrutinib in Plasma
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (LOQ) (AUC0-tlast) of Evobrutinib Metabolite (MSC2729909A)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib Metabolite (MSC2729909A)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Time Prior to the First Quantifiable (Non-zero) Concentration (Tlag) of Evobrutinib Metabolite (MSC2729909A) in Plasma
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Metabolite to Parent Ratios for Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12,16 and 24 hours post dose on Day 1 and Day 19.
Metabolite to Parent Ratios for Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A)
Time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
Time frame: Baseline (Day 1) and Day 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
- Individual participant dataSharing planned: No. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports 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 bit.ly/IPD21
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Evobrutinib and Carbamazepine in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib (time frame: Evobrutinib: Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,16 and 24 hours post dose on Day 1 and Day 19.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2026.