Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Sumatriptan (25mg); Drug: Digoxin (0.25mg); Drug: Evobrutinib (45mg); Drug: Metformin (10mg); Drug: Rosuvastatin (10mg)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05064488

MS200527_0078

2021-001923-42 (EudraCT Number)

Details and patient eligibility

About

This study consisted of 2 parts: Part 1 and 2. The purpose of this study was to evaluate the pharmacokinetic, safety and tolerability of multiple doses of evobrutinib on single doses of digoxin, metformin and rosuvastatin in Part-1 and sumatriptan in Part-2 of the study.

Enrollment: 40 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants were 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 had a body weight within 50.0 and 100.0 kilograms [kg] (inclusive) and body mass index within the range of 19.0 and 30.0 kilograms per square meter [kg/m^2] (inclusive)
• Other protocol defined inclusion criteria could apply

Exclusion criteria

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
• Individuals with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease were excluded from the study
• Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening
• History of any malignancy
• 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 Screening
• History of shingles within 12 months prior to Screening
• 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, which may affect the safety of the participant and/or outcome of the study per the Investigator's discretion
• History of alcoholism or drug abuse within 2 years prior to Screening, or positive for drugs of abuse, nicotine/cotinine or alcohol by the laboratory assays conducted during Screening and Day -1
• History of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to or at the time of Screening
• Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening
• Moderate or strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A4/5) within 4 weeks prior to the first administration of study intervention
• Other protocol defined exclusion criteria could apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

40 participants in 6 patient groups

Part 1: Cocktail (Day 1)

Experimental group

Description:

Participants received single oral dose of Cocktail (digoxin 0.25 mg tablet, metformin 10 mg solution, rosuvastatin 10 mg tablet) on Day 1 in Part 1 under fed conditions.

Treatment:

Drug: Rosuvastatin (10mg)

Drug: Metformin (10mg)

Drug: Digoxin (0.25mg)

Part 1: Evobrutinib (Days 4 to 12)

Experimental group

Description:

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day on Days 4 to 12 in Part 1 under fed conditions.

Treatment:

Drug: Evobrutinib (45mg)

Part 1: Evobrutinib + Cocktail (Day 10)

Experimental group

Description:

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and cocktail (digoxin 0.25 mg tablet, metformin 10 mg solution, rosuvastatin 10 mg tablet) on Day 10 in Part 1 under fed conditions.

Treatment:

Drug: Rosuvastatin (10mg)

Drug: Metformin (10mg)

Drug: Digoxin (0.25mg)

Drug: Evobrutinib (45mg)

Part 2: Sumatriptan (Day 1)

Experimental group

Description:

Participants received single oral dose of Sumatriptan 25 mg tablet on Day 1 in Part 2 under fed conditions.

Treatment:

Drug: Sumatriptan (25mg)

Part 2: Evobrutinib (Days 2 to 8)

Experimental group

Description:

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day on Days 2 to 8 in Part 2 under fed conditions.

Treatment:

Drug: Evobrutinib (45mg)

Part 2: Evobrutinib + Sumatriptan (Day 8)

Experimental group

Description:

Participants received Evobrutinib film-coated tablets, at a dose of 45 mg, orally, twice a day and single oral dose of Sumatriptan 25 mg tablet on Day 8 in Part 2 under fed conditions.

Treatment:

Drug: Sumatriptan (25mg)

Drug: Evobrutinib (45mg)