DDI Study of Evobrutinib and Carbamazepine

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05248945
• Other study ID #: MS200527_0108
• Secondary ID: 2021-003381-13
• Status: Completed
• Phase: Phase 1
• Start date: January 13, 2022
• Est. completion date: July 18, 2022

Study information

• Verified date: August 2022
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 18, 2022
• Est. primary completion date: July 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Evobrutinib
Participants will receive a single dose of film-coated evobrutinib tablet (TF2) on Day 1 and Day 19.
• Carbamazepine
Participants will receive carbamazepine tablet twice daily from Days 2 to 25.

Locations

Country	Name	City	State
Germany	Nuvisan GmbH	Neu-Ulm	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-Time Curve (AUC) from Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib		Pre-dose up to 24 hours post-dose on Day 1 and 19
Primary	Maximum Observed Plasma Concentration (Cmax) of Evobrutinib		Pre-dose up to 24 hours post-dose on Day 1 and 19
Secondary	Number of Participants with Treatment-emergent Adverse Events (TEAEs) Based on Severity		Baseline up to Day 26
Secondary	Number of Participants with Abnormal Laboratory Variables, Vital Signs and 12-Lead Electrocardiogram (ECG) Measurements		Baseline up to Day 26
Secondary	Pharmacokinetic Plasma Concentrations of Evobrutinib and MSC2729909A		Pre-dose up to 24 hours post-dose on Day 1 and 19

External Links

•   Trial Awareness and Transparency website