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Phase 1 N=40 Treatment

Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates

Healthy

Enrolled (actual)
40
Serious AEs
0.0%
Results posted
Dec 2025
Primary outcome: Primary: Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Digoxin — 15.8; 18.7 Hour*nanogram per milliliter (h*ng/mL)

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Evobrutinib (45mg) (Drug); Digoxin (0.25mg) (Drug); Metformin (10mg) (Drug); Rosuvastatin (10mg) (Drug); Sumatriptan (25mg) (Drug)
Age
Adult · 18+ yrs
Sex
All
Sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Primary completion
Dec 2021

Outcome Measures

OutcomeResultp-value
PRIMARY
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Digoxin
15.8; 18.7
PRIMARY
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
20.2; 42.2
PRIMARY
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Rosuvastatin
34.6; 34.3
PRIMARY
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Sumatriptan
52.5; 46.9
PRIMARY
Part 1: Maximum Observed Plasma Concentration (Cmax) of Digoxin
1.15; 1.15
PRIMARY
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metformin
3.24; 6.58
PRIMARY
Part 1: Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin
2.35; 2.16
PRIMARY
Part 2: Maximum Observed Plasma Concentration (Cmax) of Sumatriptan
13.4; 10.9
SECONDARY
Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
7; 9; 6; 6; 10; 8
SECONDARY
Part 1 and Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
5; 9; 6; 4; 10; 7
SECONDARY
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters
0; 0; 0; 0; 0; 0
SECONDARY
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
0; 0; 0; 0; 0; 0
SECONDARY
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
0; 0; 0; 0; 0; 0
SECONDARY
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Digoxin
1.50; 2.00
SECONDARY
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
3.00; 4.00
SECONDARY
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Rosuvastatin
4.00; 4.00
SECONDARY
Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of Sumatriptan
2.00; 2.00
SECONDARY
Part 1: Apparent Terminal Half-Life (t1/2) of Digoxin
31.0; 46.9
SECONDARY
Part 1: Apparent Terminal Half-Life (t1/2) of Metformin
3.02; 3.50
SECONDARY
Part 1: Apparent Terminal Half-Life (t1/2) of Rosuvastatin
15.5; 15.5
SECONDARY
Part 2: Apparent Terminal Half-Life (t1/2) of Sumatriptan
3.16; 3.56
SECONDARY
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Digoxin
12.1; 12.9
SECONDARY
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Metformin
19.5; 41.3
SECONDARY
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Rosuvastatin
31.0; 30.9
SECONDARY
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Sumatriptan
51.2; 45.5
SECONDARY
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Digoxin
15.9; 13.4
SECONDARY
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Metformin
495; 237
SECONDARY
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Rosuvastatin
289; 292
SECONDARY
Part 2: Apparent Total Body Clearance From Plasma (CL/F) of Sumatriptan
476; 533
SECONDARY
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Digoxin
787; 861
SECONDARY
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Metformin
2206; 1389
SECONDARY
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Rosuvastatin
6712; 5789
SECONDARY
Part 2: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Sumatriptan
2193; 3007
SECONDARY
Part 1: Cumulative Amount Excreted (CAE) From Time Zero to the End of the Collection Interval After Dosing Dosing (Ae0-36) of Metformin
0.574; 1.24
SECONDARY
Part 1: Renal Clearance (CLr) of Metformin
28.5; 29.7

Summary

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.

Eligibility Criteria

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05064488). 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.

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