Clinical trial NCT05248945: DDI Study of Evobrutinib and Carbamazepine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Clinical Pharmacology
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2022-02-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details include:

Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants will be resident in the Clinical Research Unit from Day 1 to Day 20 and return on Day 26 for a Safety Follow-Up visit.


Eligibility criteria: Inclusion Criteria:

* Type of Participant and Disease Characteristics
* Have 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 needed. Female: Is not a woman of childbearing potential
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and this protocol
* Are stable nonsmokers for at least 3 months preceding Screening

Exclusion Criteria:

* 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
* Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening. Administration of other types of vaccines (e.g., SARSCoV2 vaccines) is allowed until 2 weeks before admission to Clinical Research Unit (CRU), thereafter it is prohibited until the end of the study
* 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
* Contraindication to carbamazepine (carbamazepine SmPC)
* History of any malignancy
* 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 affect the safety of the participant and/or outcome of the study per the Investigator's discretion.
* Other protocol defined exclusion criteria could apply.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) from Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose on Day 1 and 19
measure: Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
timeFrame: Pre-dose up to 24 hours post-dose on Day 1 and 19
Secondary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs) Based on Severity
timeFrame: Baseline up to Day 26
measure: Number of Participants with Abnormal Laboratory Variables, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements
timeFrame: Baseline up to Day 26
measure: Pharmacokinetic Plasma Concentrations of Evobrutinib and MSC2729909A
timeFrame: Pre-dose up to 24 hours post-dose on Day 1 and 19
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
state: Bavaria
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: