Phase 1
N=14
DDI Study of Evobrutinib and Carbamazepine
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT05248945 ↗Enrolled (actual)
14
Serious AEs
0.0%
Results posted
Jan 2026
Primary outcome: Primary: Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib — 310; 49.2 Hour*nanograms per milliliter (h*ng/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Evobrutinib (Drug); Carbamazepine (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Primary completion
- Jul 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib |
310; 49.2 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Evobrutinib |
132; 22.4 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Serious TEAEs |
14; 0 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes Values |
11; -0.23; -0.18; 0.04; 0.03; -0.00 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Hemoglobin Levels |
-5.178 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Hematocrit Values |
-0.014 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Activated Partial Thromboplastin Time |
-0.6 | — |
| SECONDARY Change From Baseline in Hematology Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/ Leukocytes, and Neutrophils/Leukocytes |
0.5; 0.7; 0.1; 0.3; -1.6 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin |
0.35557 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume |
1.4 | — |
| SECONDARY Absolute Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio |
-0.04 | — |
| SECONDARY Absolute Change From Baseline in Biochemistry Parameter: Bilirubin, Creatinine and Urate |
-4.9; -1; -34.6 | — |
| SECONDARY Absolute Change From Baseline in Biochemistry Parameter: Sodium, Potassium, Calcium, Magnesium and Phosphate Levels |
1; 0.49; 0.02; 0.05; 0.04 | — |
| SECONDARY Absolute Change From Baseline in Biochemistry Parameter: Protein and Albumin Levels |
-4; 2.3 | — |
| SECONDARY Absolute Change From Baseline in Biochemistry Parameter: Alkaline Phosphatase, Amylase, Lipase, Creatinine Kinase, Gamma Glutamyl Transferase Levels, Lactate Dehydrogenase, Aspartate Aminotransferase |
8; 1; 2; -33; 56; -1 | — |
| SECONDARY Absolute Change From Baseline in Biochemistry Parameter: Glucose, Chloride, Cholesterol, Triglycerides, Phosphate Levels |
0.01; 2; 0.4; 0.2; 0.04 | — |
| SECONDARY Absolute Change From Baseline in 12-Lead ECG Parameter: Heart Rate |
2 | — |
| SECONDARY Absolute Change From Baseline in 12-Lead ECG Parameter: RR Duration, QT Duration, Fridericia's Formula (QTcF), PR Duration and QRS Duration |
-29; -1; 2; -2; -1 | — |
| SECONDARY Absolute Change From Baseline in Vital Sign: Blood Pressure |
-2; -2 | — |
| SECONDARY Absolute Change From Baseline in Vital Sign: Pulse Rate |
2 | — |
| SECONDARY Absolute Change From Baseline in Vital Sign: Respiratory Rate |
-1 | — |
| SECONDARY Absolute Change From Baseline in Vital Sign: Body Temperature |
0.1 | — |
| SECONDARY Total Body Clearance of Evobrutinib From Plasma (CL/f) |
145; 914 | — |
| SECONDARY Apparent Volume of Distribution (Vz/f) of Evobrutinib |
373; 1218 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-tlast) of Evobrutinib |
308; 46.1 | — |
| SECONDARY Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib |
2.00; 2.00 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Evobrutinib in Plasma |
1.64; 0.961 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A) |
115; 57.1 | — |
| SECONDARY 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) |
113; 55.7 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A) |
30.2; 21.0 | — |
| SECONDARY Time to Reach the Maximum Plasma Concentration (Tmax) of Evobrutinib Metabolite (MSC2729909A) |
2.50; 2.50 | — |
| SECONDARY Time Prior to the First Quantifiable (Non-zero) Concentration (Tlag) of Evobrutinib Metabolite (MSC2729909A) in Plasma |
0.500; 0.500 | — |
| SECONDARY Metabolite to Parent Ratios for Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Evobrutinib Metabolite (MSC2729909A) |
0.344; 1.11 | — |
| SECONDARY Metabolite to Parent Ratios for Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Metabolite (MSC2729909A) |
0.213; 0.870 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity |
14; 7; 0 | — |
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. 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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT05248945). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.