HealthyPhase 1NCT05064488
Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates
A Phase 1 study testing Evobrutinib (45mg), Digoxin (0.25mg) and Metformin (10mg) in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Evobrutinib (45mg), Digoxin (0.25mg) and Metformin (10mg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteGermany
- Study dates
- 4 Oct 2021to 10 Dec 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-Label, Two-Part Study of the Effect of Multiple-Dose Evobrutinib on Transporter Substrates Digoxin, Metformin, Rosuvastatin, and Sumatriptan Pharmacokinetics in Healthy Participants
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.
- Conditions
- Healthy
- Being tested
- Evobrutinib (45mg), Digoxin (0.25mg), Metformin (10mg), Rosuvastatin (10mg), Sumatriptan (25mg)
- Keywords
- Clinical Pharmacology, Drug interaction, Evobrutinib, Digoxin, Metformin, Rosuvastatin, Sumatriptan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evobrutinib (45mg)Drug
Also called M2951
Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions.
Digoxin (0.25mg)Drug
Participants received single oral dose of digoxin tablet (0.25 mg) on Day 1 and Day 10 in Part 1 under fed conditions.
Metformin (10mg)Drug
Participants received single oral dose of metformin 10 mg solution on Day 1 and Day 10 in Part 1 under fed conditions.
Rosuvastatin (10mg)Drug
Participants received single oral dose of rosuvastatin tablet (10 mg) on Day 1 and Day 10 in Part 1 under fed conditions.
Sumatriptan (25mg)Drug
Participants received single dose of sumatriptan tablet (25 mg) on Day 1 and Day 8 in Part 2 under fed conditions.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Cocktail (Day 1) | Experimental | 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. Receives: Drug: Digoxin (0.25mg); Drug: Metformin (10mg); Drug: Rosuvastatin (10mg) |
| Part 1: Evobrutinib (Days 4 to 12) | Experimental | 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. Receives: Drug: Evobrutinib (45mg) |
| Part 1: Evobrutinib + Cocktail (Day 10) | Experimental | 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. Receives: Drug: Evobrutinib (45mg); Drug: Digoxin (0.25mg); Drug: Metformin (10mg); Drug: Rosuvastatin (10mg) |
| Part 2: Sumatriptan (Day 1) | Experimental | Participants received single oral dose of Sumatriptan 25 mg tablet on Day 1 in Part 2 under fed conditions. Receives: Drug: Sumatriptan (25mg) |
| Part 2: Evobrutinib (Days 2 to 8) | Experimental | 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. Receives: Drug: Evobrutinib (45mg) |
| Part 2: Evobrutinib + Sumatriptan (Day 8) | Experimental | 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. Receives: Drug: Evobrutinib (45mg); Drug: Sumatriptan (25mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Digoxin
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Rosuvastatin
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Sumatriptan
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Maximum Observed Plasma Concentration (Cmax) of Digoxin
Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metformin
Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin
Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Maximum Observed Plasma Concentration (Cmax) of Sumatriptan
Cmax was obtained directly from the concentration versus time curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Secondary outcomes (27)
Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.
Measured: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.
Measured: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters
Laboratory investigation included hematology, biochemistry and urinalysis. Clinical meaningful changes were determined by the investigator. The number of participants with clinically relevant changes from baseline in laboratory parameters were reported.
Measured: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
Vital signs included body temperature, systolic and diastolic blood pressure and pulse rate. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in vital signs were reported.
Measured: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in 12-Lead ECG findings were reported.
Measured: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Digoxin
Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Rosuvastatin
Tmax was the time to reach the maximum observed concentration collected during a dosing interval. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of Sumatriptan
Tmax was the time to reach the maximum observed concentration collected during a dosing interval. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Apparent Terminal Half-Life (t1/2) of Digoxin
T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Terminal Half-Life (t1/2) of Metformin
T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin.
As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Terminal Half-Life (t1/2) of Rosuvastatin
T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. The transporter cocktail included digoxin, metformin, and rosuvastatin.
As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Apparent Terminal Half-Life (t1/2) of Sumatriptan
T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Digoxin
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Metformin
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Rosuvastatin
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification was calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Sumatriptan
The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification was calculated using the mixed log-linear trapezoidal rule (linear up, log down). As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Digoxin
CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification; Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Metformin
CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Rosuvastatin
CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Apparent Total Body Clearance From Plasma (CL/F) of Sumatriptan
CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-tlast + Clast pred/Lambda Z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Digoxin
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Metformin
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Rosuvastatin
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Sumatriptan
Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-tlast + Clast pred/Lambda Z), where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Measured: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Cumulative Amount Excreted (CAE) From Time Zero to the End of the Collection Interval After Dosing Dosing (Ae0-36) of Metformin
Ae0-36 was calculated as the cumulative amount excreted from time zero (= dosing time) to the end of the collection interval after dosing, for metformin only. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0 to 4, 4 to 8, 8 to 12; 12 to 24 hours post-dose on Days 1 and 10
Part 1: Renal Clearance (CLr) of Metformin
CLr was calculated as Ae0-36 divided by AUC0-36, for metformin only. AUC0-36: AUC from time zero (= dosing time) to 36 hours post-dose (metformin only) calculated using the mixed log-linear trapezoidal rule (linear up, log down). The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Measured: Pre-dose, 0 to 4, 4 to 8, 8 to 12; 12 to 24 hours post-dose on Days 1 and 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2021
- Study start4 Oct 2021
- Primary completion10 Dec 2021
- Study completion10 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- single-sequence study (each part)
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05064488
- Sponsor's protocol ID
- MS200527_0078
- Other IDs
- 2021-001923-42
- Status last verified
- Nov 2025
- First submitted
- 23 Sep 2021
- Last updated
- 5 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Two-Part Study of the Effect of Multiple-Dose Evobrutinib on Transporter Substrates Digoxin, Metformin, Rosuvastatin, and Sumatriptan Pharmacokinetics in Healthy Participants
- ClinicalTrials.gov ID
- NCT05064488
- Acronym / sponsor ID
- MS200527_0078
- Conditions
- Healthy
- Keywords
- Clinical Pharmacology, Drug interaction, Evobrutinib, Digoxin, Metformin, Rosuvastatin, Sumatriptan
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 4 Oct 2021 (actual)
- Primary completion
- 10 Dec 2021 (actual)
- Study completion
- 10 Dec 2021 (actual)
- First posted
- 1 Oct 2021 (actual)
- Results
- Posted 5 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- single-sequence study (each part)
| Arm | Type | Receives |
|---|---|---|
| Part 1: Cocktail (Day 1) | Experimental | Drug: Digoxin (0.25mg), Drug: Metformin (10mg), Drug: Rosuvastatin (10mg)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. |
| Part 1: Evobrutinib (Days 4 to 12) | Experimental | Drug: Evobrutinib (45mg)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. |
| Part 1: Evobrutinib + Cocktail (Day 10) | Experimental | Drug: Evobrutinib (45mg), Drug: Digoxin (0.25mg), Drug: Metformin (10mg), Drug: Rosuvastatin (10mg)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. |
| Part 2: Sumatriptan (Day 1) | Experimental | Drug: Sumatriptan (25mg)Participants received single oral dose of Sumatriptan 25 mg tablet on Day 1 in Part 2 under fed conditions. |
| Part 2: Evobrutinib (Days 2 to 8) | Experimental | Drug: Evobrutinib (45mg)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. |
| Part 2: Evobrutinib + Sumatriptan (Day 8) | Experimental | Drug: Evobrutinib (45mg), Drug: Sumatriptan (25mg)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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Evobrutinib (45mg)Also: M2951Participants received film-coated Evobrutinib tablet at a dose of 45 milligrams (mg), orally twice daily on Days 4 to 12 in Part 1 and Days 2 to 8 in Part 2 under fed conditions. | Drug | Part 1: Evobrutinib (Days 4 to 12), Part 1: Evobrutinib + Cocktail (Day 10), Part 2: Evobrutinib (Days 2 to 8), Part 2: Evobrutinib + Sumatriptan (Day 8) |
| Digoxin (0.25mg)Participants received single oral dose of digoxin tablet (0.25 mg) on Day 1 and Day 10 in Part 1 under fed conditions. | Drug | Part 1: Cocktail (Day 1), Part 1: Evobrutinib + Cocktail (Day 10) |
| Metformin (10mg)Participants received single oral dose of metformin 10 mg solution on Day 1 and Day 10 in Part 1 under fed conditions. | Drug | Part 1: Cocktail (Day 1), Part 1: Evobrutinib + Cocktail (Day 10) |
| Rosuvastatin (10mg)Participants received single oral dose of rosuvastatin tablet (10 mg) on Day 1 and Day 10 in Part 1 under fed conditions. | Drug | Part 1: Cocktail (Day 1), Part 1: Evobrutinib + Cocktail (Day 10) |
| Sumatriptan (25mg)Participants received single dose of sumatriptan tablet (25 mg) on Day 1 and Day 8 in Part 2 under fed conditions. | Drug | Part 2: Evobrutinib + Sumatriptan (Day 8), Part 2: Sumatriptan (Day 1) |
Primary outcome
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination: AUC0-inf= AUC0-tlast + Clast pred/lambda z, where AUC0-tlast was the AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down); Clast pred was defined as the predicted concentration at the last sampling time, calculated from the log-linear regression line for lambda z determination and Lambda z was the apparent terminal rate constant. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
Part 1: Maximum Observed Plasma Concentration (Cmax) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on digoxin in this outcome measure.
Part 1: Maximum Observed Plasma Concentration (Cmax) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on metformin in this outcome measure.
Part 1: Maximum Observed Plasma Concentration (Cmax) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Cmax was obtained directly from the concentration versus time curve. The transporter cocktail included digoxin, metformin, and rosuvastatin. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on rosuvastatin in this outcome measure.
Part 2: Maximum Observed Plasma Concentration (Cmax) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Cmax was obtained directly from the concentration versus time curve. As pre-specified in protocol, data was analyzed and reported to characterize the effect of evobrutinib on sumatriptan in this outcome measure.
27 secondary outcomes
Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Time frame: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters
Time frame: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
Time frame: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1 and Part 2: Number of Participants With Clinically Relevant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
Time frame: Part 1: Cocktail Alone - Day 1 to Day 3; Evobrutinib Alone - Day 4 to Day 9; Evobrutinib + Cocktail - Day 10 to Day 12; Part 2: Sumatriptan Alone - Day 1; Evobrutinib Alone - Day 2 to Day 7; Evobrutinib + Sumatriptan - Day 8
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Time to Reach Maximum Plasma Concentration (Tmax) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Apparent Terminal Half-Life (t1/2) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Terminal Half-Life (t1/2) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Terminal Half-Life (t1/2) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Apparent Terminal Half-Life (t1/2) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-tlast) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Total Body Clearance From Plasma (CL/F) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Apparent Total Body Clearance From Plasma (CL/F) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Digoxin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Metformin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 1: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Rosuvastatin
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10
Part 2: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Sumatriptan
Time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 8
Part 1: Cumulative Amount Excreted (CAE) From Time Zero to the End of the Collection Interval After Dosing Dosing (Ae0-36) of Metformin
Time frame: Pre-dose, 0 to 4, 4 to 8, 8 to 12; 12 to 24 hours post-dose on Days 1 and 10
Part 1: Renal Clearance (CLr) of Metformin
Time frame: Pre-dose, 0 to 4, 4 to 8, 8 to 12; 12 to 24 hours post-dose on Days 1 and 10
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
- Individual participant dataSharing planned: No. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Evobrutinib (45mg), Digoxin (0.25mg) and Metformin (10mg) in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Digoxin (time frame: Pre-dose, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Days 1 and 10). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.