Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT05064488
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Brief Summary
This study consists of 2 parts: Part 1 and 2. The purpose of this study is 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Inclusion Criteria
- Participants are 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 have 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 will be 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part-1: Evobrutinib + Digoxin + Metformin + Rosuvastatin Rosuvastatin - Part-1: Evobrutinib + Digoxin + Metformin + Rosuvastatin Digoxin - Part-1: Evobrutinib + Digoxin + Metformin + Rosuvastatin Metformin - Part-2: Evobrutinib + Sumatriptan Sumatriptan - Part-1: Evobrutinib + Digoxin + Metformin + Rosuvastatin Evobrutinib - Part-2: Evobrutinib + Sumatriptan Evobrutinib -
- Primary Outcome Measures
Name Time Method Part 2: Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 The transporter cocktail includes digoxin, metformin, and rosuvastatin.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib Day 10, 11 and 12: 1 hours post-dose Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9 Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1: Maximum Observed Plasma Concentration (Cmax) of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 Part 1: Maximum Observed Plasma Concentration (Cmax) of Evobrutinib Day 10, 11 and 12: 1 hours post-dose Part 2: Maximum Observed Plasma Concentration (Cmax) of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9
- Secondary Outcome Measures
Name Time Method Part 1 and Part 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs) by Severity Part 1: Up to Day 13; Part 2: Up to Day 9 Part 1 and Part 2: Number of Participants With Abnormal Changes From Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Findings Part 1: Baseline up to Day 13; Part 2: Baseline up to Day 9 Number of participants with abnormal changes from baseline in laboratory parameters, vital signs and 12-Lead electrocardiogram (ECG) findings will be reported.
Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1 and Part 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs) Part 1: Up to Day 13; Part 2: Up to Day 9 Part 1: Time to Reach Maximum Plasma Concentration (Tmax) of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 Part 1: Time to Reach Maximum Plasma Concentration (Tmax) of Evobrutinib Day 10, 11 and 12: 1 hours post-dose Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9 Part 1: Apparent Terminal Half-Life (t1/2) of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 Part 1: Apparent Terminal Half-Life (t1/2) of Evobrutinib Day 10, 11 and 12: 1 hours post-dose Part 2: Apparent Terminal Half-Life (t1/2) of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9 Part 2: Apparent Terminal Half-Life (t1/2) of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Evobrutinib Day 10, 11 and 12: 1 hours post-dose Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9 Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Evobrutinib Day 10, 11 and 12: 1 hours post-dose Part 2: Apparent Total Body Clearance From Plasma (CL/F) of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9 Part 2: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Sumatriptan Pre-dose through 16 hours post-dose on Days 1 and Day 8; 24 hours post-dose on Day 2 and Day 9 Part 2: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1: Cumulative Amount Excreted From Time Zero to the End of the Collection Interval After Dosing Dosing (Ae0-36) of Merformin Pre-dose, 0 to 4, 4 to 8, 8 to 12 hours post-dose on Day 1 and Day 10; 12 to 24, 24 to 36 hours post-dose on Day 2 and Day 11 Part 1: Renal Clearance (CLR) of Metformin Pre-dose, 0 to 4, 4 to 8, 8 to 12 hours post-dose on Day 1 and Day 10; 12 to 24, 24 to 36 hours post-dose on Day 2 and Day 11 Part 2: Apparent Total Body Clearance From Plasma (CL/F) of Evobrutinib Day 6, 7 and 8: 1 hours post-dose Part 1: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Transporter Cocktail Pre-dose through 16 hours post-dose on Days 1 and 10; 24, 36 hours post-dose on Day 2 and Day 11; 48, 60 hours post-dose on Day 3 and Day 12; 72 hours post-dose on Day 4 and Day 13 Part 1: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Evobrutinib Day 10, 11 and 12: 1 hours post-dose
Trial Locations
- Locations (1)
Nuvisan GmbH
🇩🇪Neu-Ulm, Germany