Healthy
Conditions
Keywords
M2951, Bruton's Tyrosine Kinase, Cardiac Repolarization
Brief summary
The purpose of this study is to assess potential effects of M2951 on cardiac repolarization (i.e. prolongation of QT interval).
Interventions
DRUGPlacebo matched to M2951
Participants will receive single oral dose of placebo matched to M2951 in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions.
DRUGMoxifloxacin
Participants will receive single oral dose of moxifloxacin in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions.
DRUGM2951 Low Dose
Participants will receive single oral low dose of M2951 in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions.
DRUGM2951 High Dose
Participants will receive single oral high dose of M2951 in either of study periods (period 1 or period 2 or period 3 or period 4) under fasted conditions.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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 (BMI) within the range 19.0 and 30.0 kilograms per square meter (kg/m\^2) (inclusive) * Participants are stable nonsmokers for at least 3 months preceding the first administration of study intervention
Exclusion criteria
* Participants with 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 * Participants 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 the first administration of study intervention * Participants with history of any malignancy * Participants with history of seizures * Participants with history of pharmacologically treated psychiatric disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib | Baseline and from 1 hour before any administration until 24 hours post-administration at the following timepoints: -1-hour, 5 min, 10 min, 20 min, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours | A linear mixed-effects model was used to analyze the relationship between evobrutinib and MSC2729909A concentrations and ΔQTc. Based on this model, drug-induced ΔΔQTc and its two-sided 90% CI was predicted over the clinical concentration range and at concentrations corresponding to the observed geometric mean Cmax following administration of 45 mg and 225 mg evobrutinib. The higher geometric mean Cmax calculated based on the PK and ECG Analysis Sets was considered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 3 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.Therefore, an AE can be any unfavorable and unintended sign (including an abnormallaboratory finding), symptom, or disease temporally associated with the use of amedicinal product, regardless if it is considered related to the medicinal product.Serious AE: AE that resulted in any of the following outcomes: death; life threatening;persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization;congenital anomaly/birth defect. TEAEs are defined as AEs that were reported orworsened on or after start of study drug dosing through the Safety Follow-up Visit.TEAEs included both serious TEAEs and non-serious TEAEs. Treatment related AEs:reasonably related to the study drug/study treatment. |
| Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last, as estimated using the linear regression from lambda (λ)z determination. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | Up to 3 months | Severity of adverse events (AE) were assessed by the investigator. The Investigator assessed the intensity of each AE and SAE reported during the study and assigned it to 1 of the following categories: 1\. Mild: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. 2. Moderate: A type of adverse event that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. 3. Severe: A type of adverse event that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Number of participants with severe adverse events were reported. |
| Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests | Up to Day 29 | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities from baseline were reported. Clinically Significance was decided by investigator. |
| Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs | Up to Day 29 | Vital sign assessment included blood pressure, pulse rate, body temperature and respiration (frequency per minute). Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator. |
| Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings | Up to Day 29 | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities were reported. Clinically significance was decided by investigator. |
| Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) of Evobrutinib | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval. |
| Maximum Observed Plasma Concentration (Cmax) of Evobrutinib | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | Cmax is the maximum observed plasma concentration. Cmax was obtained directly from the concentration versus time curve. |
| Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Apparent Terminal Half-life (t1/2) of Evobrutinib | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. |
| Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Moxifloxacin | From 1 hour before any administration until 24 hours post-administration at the following timepoints: -1-hour, 5 min, 10 min, 20 min, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours | A linear mixed-effects model was used to analyze the relationship between moxifloxacin concentrations and ΔQTc. Based on this model, drug-induced ΔΔQTc and its two-sided 90% CI was predicted. The higher geometric mean Cmax calculated based on the PK and ECG Analysis Sets was considered. |
| Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | Cmax is the maximum observed plasma concentration. Cmax was obtained directly from the concentration versus time curve. |
| Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Moxifloxacin | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last, as estimated using the linear regression from lambda (λ)z determination. |
| Time to Reach Maximum Blood Concentration (Tmax) of Moxifloxacin | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of Heart rate was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Effect of Evobrutinib on ECG Parameters: RR Interval | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of RR interval was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Effect of Evobrutinib on ECG Parameters: QT Interval | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of QT interval was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Effect of Evobrutinib on ECG Parameters: QTcF Interval | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of QTcF was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Effect of Evobrutinib on ECG Parameters: QTcP Interval | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of QTcP was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Effect of Evobrutinib on ECG Parameters: PR Interval | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of PR interval was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Effect of Evobrutinib on ECG Parameters: QRS Duration | Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours | The effect of evobrutinib on baseline-corrected measurements of QRS duration was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported. |
| Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) Of Moxifloxacin | Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22 | AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Participants received single oral dose of Placebo on Day 1 in fasted state in Period 1, followed by single oral dose of moxifloxacin 400 mg tablet on Day 8 in fasted state in Period 2, followed by 45 mg single dose of oral solution of evobrutinib in fasted state on Day 15 in Period 3, and 225mg single dose of oral solution of evobrutinib in fasted state on Day 22 in period 4. A washout period of 7 days was maintained between 4 treatment periods | 9 |
| Sequence 2 Participants received single oral dose of moxifloxacin 400 mg tablet on Day 1 in fasted state in Period 1, followed by single oral dose of Evobrutinib 225 mg solution on Day 8 in fasted state in Period 2, followed by single oral dose of Placebo in fasted state on Day 15 in Period 3, and 45 mg of dose of single oral solution of evobrutinib in fasted state on Day 22 in period 4. A washout period of 7 days was maintained between 4 treatment periods | 9 |
| Sequence 3 Participants received single oral dose of evobrutinib 45 mg solution on Day 1 in fasted state in Period 1, followed by single oral dose of Placebo on Day 8 in fasted state in Period 2, followed by single oral dose of 225 mg evobrutinib solution in fasted state on Day 15 in Period 3, and 400 mg of dose of single oral tablet of moxifloxacin in fasted state on Day 22 in period 4. A washout period of 7 days was maintained between 4 treatment periods | 9 |
| Sequence 4 Participants received single oral dose of evobrutinib 225 mg solution on Day 1 in fasted state in Period 1, followed by single oral dose of 45 mg evobrutinib solution on Day 8 in fasted state in Period 2, followed by single oral dose of 400 mg moxifloxacin tablet in fasted state on Day 15 in Period 3, and single oral dose of Placebo in fasted state on Day 22 in period 4. A washout period of 7 days was maintained between 4 treatment periods | 8 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Participant did not meet all eligibility criteria, ADMISSION DRUG SCREEN POSITIVE | 1 | 0 | 0 | 0 |
| Overall Study | Participant discontinued prior to first dosing | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Sequence 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45 Years STANDARD_DEVIATION 7.5 | 36 Years STANDARD_DEVIATION 10.4 | 41 Years STANDARD_DEVIATION 8.6 | 40 Years STANDARD_DEVIATION 11.3 | 41 Years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 9 Participants | 8 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 7 Participants | 7 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 32 |
| other Total, other adverse events | 8 / 32 | 5 / 32 | 8 / 31 | 5 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 32 |
Outcome results
Primary
Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib
A linear mixed-effects model was used to analyze the relationship between evobrutinib and MSC2729909A concentrations and ΔQTc. Based on this model, drug-induced ΔΔQTc and its two-sided 90% CI was predicted over the clinical concentration range and at concentrations corresponding to the observed geometric mean Cmax following administration of 45 mg and 225 mg evobrutinib. The higher geometric mean Cmax calculated based on the PK and ECG Analysis Sets was considered.
Time frame: Baseline and from 1 hour before any administration until 24 hours post-administration at the following timepoints: -1-hour, 5 min, 10 min, 20 min, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours
Population: The ECG analysis set includes all participants who had a baseline Holter ECG in triplicate and at least one post baseline Holter ECG in triplicate with a time-matched concentration
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Evobrutinib 45mg | Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib | -1.62 milliseconds |
| Evobrutinib 225mg | Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib | -2.28 milliseconds |
Secondary
Apparent Terminal Half-life (t1/2) of Evobrutinib
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Apparent Terminal Half-life (t1/2) of Evobrutinib | 1.32 hours | Geometric Coefficient of Variation 22.7 |
| Evobrutinib 225mg | Apparent Terminal Half-life (t1/2) of Evobrutinib | 2.09 hours | Geometric Coefficient of Variation 33.8 |
Secondary
Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) of Evobrutinib
AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) of Evobrutinib | 249 hour*nanogram/milliliter | Geometric Coefficient of Variation 38.4 |
| Evobrutinib 225mg | Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) of Evobrutinib | 1420 hour*nanogram/milliliter | Geometric Coefficient of Variation 37.5 |
Secondary
Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) Of Moxifloxacin
AUC from time zero to 24 hours post dose, calculated using the mixed log linear trapezoidal rule (linear up, log down) using the nominal dosing interval.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) Of Moxifloxacin | 19600 h*ng/mL | Geometric Coefficient of Variation 19.6 |
Secondary
Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last, as estimated using the linear regression from lambda (λ)z determination.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib | 248 h*ng/mL | Geometric Coefficient of Variation 38.4 |
| Evobrutinib 225mg | Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib | 1420 h*ng/mL | Geometric Coefficient of Variation 37.5 |
Secondary
Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Moxifloxacin
The AUC from time zero (= dosing time) extrapolated to infinity, based on the predicted value for the concentration at t last, as estimated using the linear regression from lambda (λ)z determination.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Moxifloxacin | 24900 h*ng/mL | Geometric Coefficient of Variation 19.8 |
Secondary
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
The effect of evobrutinib on baseline-corrected measurements of Heart rate was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 4 Hour Post-dose | 0.8 beats/min | Standard Deviation 3.67 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 3 Hour Post-dose | -0.4 beats/min | Standard Deviation 4.43 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1 Hour Post-dose | 1.7 beats/min | Standard Deviation 3.68 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 24 Hour Post-dose | 6.0 beats/min | Standard Deviation 7.88 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2.5 Hour Post-dose | 0.4 beats/min | Standard Deviation 4.04 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2 Hour Post-dose | 0.6 beats/min | Standard Deviation 3.1 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 12 Hour Post-dose | 1.3 beats/min | Standard Deviation 5.36 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1.5 Hour Post-dose | 1.7 beats/min | Standard Deviation 3.26 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 15 Minutes Post-dose | 0.6 beats/min | Standard Deviation 3.26 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 16 Hour Post-dose | 3.5 beats/min | Standard Deviation 5.91 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 8 Hour Post-dose | 4.2 beats/min | Standard Deviation 5.85 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 6 Hour Post-dose | 6.6 beats/min | Standard Deviation 6.42 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 30 Minutes Post-dose | 0.0 beats/min | Standard Deviation 3.43 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | Baseline | 58.1 beats/min | Standard Deviation 8.38 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 8 Hour Post-dose | 2.3 beats/min | Standard Deviation 5.29 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1.5 Hour Post-dose | 1.1 beats/min | Standard Deviation 3.6 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | Baseline | 58.6 beats/min | Standard Deviation 7.38 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 15 Minutes Post-dose | 1.3 beats/min | Standard Deviation 3.83 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 30 Minutes Post-dose | 0.2 beats/min | Standard Deviation 3.26 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1 Hour Post-dose | 1.0 beats/min | Standard Deviation 4 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2 Hour Post-dose | 1.4 beats/min | Standard Deviation 2.21 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2.5 Hour Post-dose | 0.7 beats/min | Standard Deviation 3.73 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 3 Hour Post-dose | -0.0 beats/min | Standard Deviation 3.28 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 4 Hour Post-dose | 0.8 beats/min | Standard Deviation 3.54 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 6 Hour Post-dose | 6.1 beats/min | Standard Deviation 4.85 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 12 Hour Post-dose | -0.1 beats/min | Standard Deviation 4.63 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 16 Hour Post-dose | 2.1 beats/min | Standard Deviation 5.73 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 24 Hour Post-dose | 2.6 beats/min | Standard Deviation 5.62 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 8 Hour Post-dose | 5.5 beats/min | Standard Deviation 4.24 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 16 Hour Post-dose | 4.6 beats/min | Standard Deviation 5.25 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | Baseline | 58.7 beats/min | Standard Deviation 7.9 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 30 Minutes Post-dose | 1.6 beats/min | Standard Deviation 3.57 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 12 Hour Post-dose | 2.6 beats/min | Standard Deviation 5.62 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1.5 Hour Post-dose | 3.0 beats/min | Standard Deviation 3.48 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 6 Hour Post-dose | 7.8 beats/min | Standard Deviation 4.84 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 3 Hour Post-dose | 2.4 beats/min | Standard Deviation 3.63 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2 Hour Post-dose | 3.6 beats/min | Standard Deviation 4.76 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 15 Minutes Post-dose | 0.0 beats/min | Standard Deviation 2.58 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1 Hour Post-dose | 2.6 beats/min | Standard Deviation 3.8 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 24 Hour Post-dose | 4.3 beats/min | Standard Deviation 5.38 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2.5 Hour Post-dose | 1.9 beats/min | Standard Deviation 4.22 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 4 Hour Post-dose | 2.7 beats/min | Standard Deviation 6.52 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2.5 Hour Post-dose | 1.2 beats/min | Standard Deviation 3.64 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 3 Hour Post-dose | 1.9 beats/min | Standard Deviation 4.13 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 16 Hour Post-dose | 5.6 beats/min | Standard Deviation 5.16 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 4 Hour Post-dose | 2.7 beats/min | Standard Deviation 4.03 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 15 Minutes Post-dose | 0.8 beats/min | Standard Deviation 2.65 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 6 Hour Post-dose | 9.3 beats/min | Standard Deviation 5.53 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | Baseline | 57.9 beats/min | Standard Deviation 7.61 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 8 Hour Post-dose | 5.2 beats/min | Standard Deviation 5.3 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 24 Hour Post-dose | 5.3 beats/min | Standard Deviation 5.69 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 12 Hour Post-dose | 0.7 beats/min | Standard Deviation 4.75 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1 Hour Post-dose | 3.2 beats/min | Standard Deviation 4.1 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 1.5 Hour Post-dose | 3.9 beats/min | Standard Deviation 4.03 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 2 Hour Post-dose | 2.8 beats/min | Standard Deviation 3.05 |
| Placebo | Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate | 30 Minutes Post-dose | 0.7 beats/min | Standard Deviation 2.98 |
Secondary
Effect of Evobrutinib on ECG Parameters: PR Interval
The effect of evobrutinib on baseline-corrected measurements of PR interval was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 6 Hour Post-dose | -9.3 milliseconds | Standard Deviation 7.52 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 1.5 Hour Post-dose | 1.9 milliseconds | Standard Deviation 5.11 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 2.5 Hour Post-dose | 0.6 milliseconds | Standard Deviation 4.64 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 16 Hour Post-dose | -2.6 milliseconds | Standard Deviation 8.7 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 3 Hour Post-dose | 0.1 milliseconds | Standard Deviation 5.69 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 4 Hour Post-dose | -0.5 milliseconds | Standard Deviation 7.11 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 8 Hour Post-dose | -8.3 milliseconds | Standard Deviation 6.98 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 24 Hour Post-dose | -1.0 milliseconds | Standard Deviation 7 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | Baseline | 166.7 milliseconds | Standard Deviation 16.59 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 15 Minutes Post-dose | -0.2 milliseconds | Standard Deviation 4.66 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 12 Hour Post-dose | -2.2 milliseconds | Standard Deviation 7.43 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 30 Minutes Post-dose | 0.5 milliseconds | Standard Deviation 3.72 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 1 Hour Post-dose | 1.1 milliseconds | Standard Deviation 4.13 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 2 Hour Post-dose | 0.9 milliseconds | Standard Deviation 4.91 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 24 Hour Post-dose | -2.6 milliseconds | Standard Deviation 6.14 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 1 Hour Post-dose | 1.2 milliseconds | Standard Deviation 4.04 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 2 Hour Post-dose | -0.5 milliseconds | Standard Deviation 3.59 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 3 Hour Post-dose | -1.5 milliseconds | Standard Deviation 5.45 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | Baseline | 170.4 milliseconds | Standard Deviation 17.93 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 2.5 Hour Post-dose | -1.8 milliseconds | Standard Deviation 5.2 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 12 Hour Post-dose | -3.9 milliseconds | Standard Deviation 8.28 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 16 Hour Post-dose | -5.2 milliseconds | Standard Deviation 7.2 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 15 Minutes Post-dose | -1.2 milliseconds | Standard Deviation 5.29 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 4 Hour Post-dose | -1.2 milliseconds | Standard Deviation 5.01 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 1.5 Hour Post-dose | 0.9 milliseconds | Standard Deviation 5.15 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 30 Minutes Post-dose | 2.6 milliseconds | Standard Deviation 4.37 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 8 Hour Post-dose | -9.3 milliseconds | Standard Deviation 6.53 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 6 Hour Post-dose | -9.4 milliseconds | Standard Deviation 4.73 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | Baseline | 167.7 milliseconds | Standard Deviation 17.73 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 1.5 Hour Post-dose | -1.9 milliseconds | Standard Deviation 7.41 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 4 Hour Post-dose | -3.6 milliseconds | Standard Deviation 7.77 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 15 Minutes Post-dose | -0.8 milliseconds | Standard Deviation 4.01 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 30 Minutes Post-dose | -1.2 milliseconds | Standard Deviation 5.27 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 1 Hour Post-dose | -1.5 milliseconds | Standard Deviation 7.52 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 2 Hour Post-dose | -2.5 milliseconds | Standard Deviation 8.15 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 2.5 Hour Post-dose | -3.5 milliseconds | Standard Deviation 6.49 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 3 Hour Post-dose | -3.7 milliseconds | Standard Deviation 7.42 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 6 Hour Post-dose | -10.6 milliseconds | Standard Deviation 8.22 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 8 Hour Post-dose | -9.3 milliseconds | Standard Deviation 7.3 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 12 Hour Post-dose | -3.6 milliseconds | Standard Deviation 8.03 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 16 Hour Post-dose | -3.1 milliseconds | Standard Deviation 7.95 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: PR Interval | 24 Hour Post-dose | -0.5 milliseconds | Standard Deviation 9.38 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 1.5 Hour Post-dose | -0.9 milliseconds | Standard Deviation 5.69 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 6 Hour Post-dose | -11.1 milliseconds | Standard Deviation 8.48 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 24 Hour Post-dose | -1.2 milliseconds | Standard Deviation 7.99 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 8 Hour Post-dose | -11.1 milliseconds | Standard Deviation 7.17 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 15 Minutes Post-dose | -1.3 milliseconds | Standard Deviation 4.36 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | Baseline | 167.1 milliseconds | Standard Deviation 17.99 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 16 Hour Post-dose | -4.1 milliseconds | Standard Deviation 6.25 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 12 Hour Post-dose | -2.8 milliseconds | Standard Deviation 6.28 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 2.5 Hour Post-dose | -1.4 milliseconds | Standard Deviation 6.69 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 2 Hour Post-dose | -0.3 milliseconds | Standard Deviation 5.24 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 3 Hour Post-dose | -3.0 milliseconds | Standard Deviation 5.16 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 4 Hour Post-dose | -4.2 milliseconds | Standard Deviation 4.16 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 1 Hour Post-dose | -0.8 milliseconds | Standard Deviation 5.11 |
| Placebo | Effect of Evobrutinib on ECG Parameters: PR Interval | 30 Minutes Post-dose | 0.1 milliseconds | Standard Deviation 5.14 |
Secondary
Effect of Evobrutinib on ECG Parameters: QRS Duration
The effect of evobrutinib on baseline-corrected measurements of QRS duration was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2 Hour Post-dose | -0.5 milliseconds | Standard Deviation 1.17 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1.5 Hour Post-dose | -0.4 milliseconds | Standard Deviation 1.3 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.2 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 16 Hour Post-dose | 0.0 milliseconds | Standard Deviation 1.91 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 15 Minutes Post-dose | 0.1 milliseconds | Standard Deviation 1.44 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 12 Hour Post-dose | -0.2 milliseconds | Standard Deviation 1.95 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 30 Minutes Post-dose | 0.4 milliseconds | Standard Deviation 1.25 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | Baseline | 91.7 milliseconds | Standard Deviation 8.28 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 6 Hour Post-dose | -0.6 milliseconds | Standard Deviation 2.26 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 4 Hour Post-dose | -0.7 milliseconds | Standard Deviation 1.41 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 3 Hour Post-dose | -0.5 milliseconds | Standard Deviation 1.35 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 8 Hour Post-dose | -0.8 milliseconds | Standard Deviation 1.99 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 24 Hour Post-dose | 0.5 milliseconds | Standard Deviation 1.93 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2.5 Hour Post-dose | -0.6 milliseconds | Standard Deviation 1.29 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 30 Minutes Post-dose | 0.4 milliseconds | Standard Deviation 1.41 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | Baseline | 91.8 milliseconds | Standard Deviation 8.24 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 12 Hour Post-dose | 0.2 milliseconds | Standard Deviation 2.14 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 15 Minutes Post-dose | 0.3 milliseconds | Standard Deviation 1.15 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1 Hour Post-dose | 0.4 milliseconds | Standard Deviation 1.02 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1.5 Hour Post-dose | -0.2 milliseconds | Standard Deviation 1.29 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2 Hour Post-dose | -0.6 milliseconds | Standard Deviation 1.47 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2.5 Hour Post-dose | -0.3 milliseconds | Standard Deviation 1.64 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 3 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.5 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 4 Hour Post-dose | -0.3 milliseconds | Standard Deviation 1.71 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 6 Hour Post-dose | -0.5 milliseconds | Standard Deviation 2.12 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 8 Hour Post-dose | -0.5 milliseconds | Standard Deviation 1.78 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 16 Hour Post-dose | 0.4 milliseconds | Standard Deviation 1.74 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 24 Hour Post-dose | 0.1 milliseconds | Standard Deviation 1.22 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2.5 Hour Post-dose | -0.2 milliseconds | Standard Deviation 1.27 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 30 Minutes Post-dose | -0.4 milliseconds | Standard Deviation 1.22 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 16 Hour Post-dose | 0.6 milliseconds | Standard Deviation 1.9 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 6 Hour Post-dose | -0.6 milliseconds | Standard Deviation 1.7 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 15 Minutes Post-dose | 0.1 milliseconds | Standard Deviation 1.31 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 3 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.03 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 12 Hour Post-dose | 0.2 milliseconds | Standard Deviation 1.45 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1 Hour Post-dose | 0.2 milliseconds | Standard Deviation 1.26 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.42 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 24 Hour Post-dose | 0.3 milliseconds | Standard Deviation 1.31 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 8 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.82 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1.5 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.16 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | Baseline | 91.7 milliseconds | Standard Deviation 8.11 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QRS Duration | 4 Hour Post-dose | -0.4 milliseconds | Standard Deviation 1.7 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 12 Hour Post-dose | 0.2 milliseconds | Standard Deviation 1.85 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2 Hour Post-dose | -0.5 milliseconds | Standard Deviation 1.6 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 15 Minutes Post-dose | 0.4 milliseconds | Standard Deviation 1.23 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 2.5 Hour Post-dose | -0.3 milliseconds | Standard Deviation 1.59 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 6 Hour Post-dose | -0.4 milliseconds | Standard Deviation 1.98 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | Baseline | 91.0 milliseconds | Standard Deviation 8.12 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 3 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.35 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 30 Minutes Post-dose | 0.7 milliseconds | Standard Deviation 1.44 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 4 Hour Post-dose | 0.0 milliseconds | Standard Deviation 1.53 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 24 Hour Post-dose | 0.5 milliseconds | Standard Deviation 1.43 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 16 Hour Post-dose | 0.8 milliseconds | Standard Deviation 2.08 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1 Hour Post-dose | 0.5 milliseconds | Standard Deviation 1.29 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 1.5 Hour Post-dose | -0.1 milliseconds | Standard Deviation 1.15 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QRS Duration | 8 Hour Post-dose | 0.4 milliseconds | Standard Deviation 1.97 |
Secondary
Effect of Evobrutinib on ECG Parameters: QTcF Interval
The effect of evobrutinib on baseline-corrected measurements of QTcF was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 8 Hour Post-dose | -4.5 milliseconds | Standard Deviation 5.64 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2.5 Hour Post-dose | -3.3 milliseconds | Standard Deviation 5.26 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 3 Hour Post-dose | -3.7 milliseconds | Standard Deviation 5.89 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | Baseline | 389.4 milliseconds | Standard Deviation 18.08 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 16 Hour Post-dose | 3.6 milliseconds | Standard Deviation 8.14 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 15 Minutes Post-dose | 1.6 milliseconds | Standard Deviation 4.5 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1 Hour Post-dose | -1.2 milliseconds | Standard Deviation 4.49 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 30 Minutes Post-dose | 0.8 milliseconds | Standard Deviation 5.08 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 24 Hour Post-dose | -3.8 milliseconds | Standard Deviation 8.18 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 4 Hour Post-dose | -3.3 milliseconds | Standard Deviation 5.34 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 12 Hour Post-dose | 0.2 milliseconds | Standard Deviation 6.32 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1.5 Hour Post-dose | -3.7 milliseconds | Standard Deviation 4.5 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 6 Hour Post-dose | -5.0 milliseconds | Standard Deviation 7.51 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2 Hour Post-dose | -2.7 milliseconds | Standard Deviation 3.77 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1.5 Hour Post-dose | -3.8 milliseconds | Standard Deviation 5.04 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 30 Minutes Post-dose | 0.0 milliseconds | Standard Deviation 3.77 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2.5 Hour Post-dose | -3.9 milliseconds | Standard Deviation 4.87 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 24 Hour Post-dose | -4.1 milliseconds | Standard Deviation 6.16 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 6 Hour Post-dose | -4.0 milliseconds | Standard Deviation 7.07 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | Baseline | 388.4 milliseconds | Standard Deviation 17.88 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 3 Hour Post-dose | -3.4 milliseconds | Standard Deviation 4.64 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1 Hour Post-dose | -0.7 milliseconds | Standard Deviation 4.62 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 4 Hour Post-dose | -2.4 milliseconds | Standard Deviation 5.8 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2 Hour Post-dose | -3.6 milliseconds | Standard Deviation 3.98 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 8 Hour Post-dose | -6.2 milliseconds | Standard Deviation 7.41 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 15 Minutes Post-dose | 1.6 milliseconds | Standard Deviation 4.66 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 16 Hour Post-dose | 3.8 milliseconds | Standard Deviation 7.79 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 12 Hour Post-dose | -0.8 milliseconds | Standard Deviation 5.88 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 3 Hour Post-dose | 10.8 milliseconds | Standard Deviation 5.78 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 8 Hour Post-dose | 4.2 milliseconds | Standard Deviation 8 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | Baseline | 389.8 milliseconds | Standard Deviation 17.28 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 15 Minutes Post-dose | -0.1 milliseconds | Standard Deviation 3.91 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 30 Minutes Post-dose | 1.8 milliseconds | Standard Deviation 5.9 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1 Hour Post-dose | 8.8 milliseconds | Standard Deviation 7.14 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1.5 Hour Post-dose | 9.8 milliseconds | Standard Deviation 8.09 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2 Hour Post-dose | 11.7 milliseconds | Standard Deviation 7.92 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2.5 Hour Post-dose | 10.0 milliseconds | Standard Deviation 6.33 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 4 Hour Post-dose | 8.4 milliseconds | Standard Deviation 7.03 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 6 Hour Post-dose | 3.0 milliseconds | Standard Deviation 8.24 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 12 Hour Post-dose | 7.2 milliseconds | Standard Deviation 8.94 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 16 Hour Post-dose | 9.6 milliseconds | Standard Deviation 6.99 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 24 Hour Post-dose | 0.9 milliseconds | Standard Deviation 6.97 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2 Hour Post-dose | -1.1 milliseconds | Standard Deviation 5.61 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1.5 Hour Post-dose | 0.2 milliseconds | Standard Deviation 5.46 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 8 Hour Post-dose | -3.4 milliseconds | Standard Deviation 7.85 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 1 Hour Post-dose | 1.3 milliseconds | Standard Deviation 5.16 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 15 Minutes Post-dose | 2.8 milliseconds | Standard Deviation 3.75 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 30 Minutes Post-dose | 1.6 milliseconds | Standard Deviation 4.26 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | Baseline | 390.0 milliseconds | Standard Deviation 17.58 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 12 Hour Post-dose | 0.1 milliseconds | Standard Deviation 4.51 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 24 Hour Post-dose | -4.9 milliseconds | Standard Deviation 6.05 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 16 Hour Post-dose | 3.7 milliseconds | Standard Deviation 6.89 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 4 Hour Post-dose | -2.0 milliseconds | Standard Deviation 5.54 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 2.5 Hour Post-dose | -1.7 milliseconds | Standard Deviation 4.52 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 3 Hour Post-dose | -1.9 milliseconds | Standard Deviation 5.29 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcF Interval | 6 Hour Post-dose | -3.4 milliseconds | Standard Deviation 7.51 |
Secondary
Effect of Evobrutinib on ECG Parameters: QTcP Interval
The effect of evobrutinib on baseline-corrected measurements of QTcP was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 3 Hour Post-dose | -3.7 milliseconds | Standard Deviation 6.33 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 6 Hour Post-dose | -2.6 milliseconds | Standard Deviation 7.96 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2.5 Hour Post-dose | -3.1 milliseconds | Standard Deviation 5.59 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2 Hour Post-dose | -2.4 milliseconds | Standard Deviation 4.06 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1.5 Hour Post-dose | -3.1 milliseconds | Standard Deviation 4.95 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 24 Hour Post-dose | -1.5 milliseconds | Standard Deviation 8.22 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | Baseline | 388.2 milliseconds | Standard Deviation 17.69 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 16 Hour Post-dose | 4.9 milliseconds | Standard Deviation 8.65 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 12 Hour Post-dose | 0.8 milliseconds | Standard Deviation 6.2 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 8 Hour Post-dose | -3.0 milliseconds | Standard Deviation 6.12 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 15 Minutes Post-dose | 1.9 milliseconds | Standard Deviation 5.21 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 30 Minutes Post-dose | 0.8 milliseconds | Standard Deviation 5.51 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1 Hour Post-dose | -0.6 milliseconds | Standard Deviation 4.91 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 4 Hour Post-dose | -2.9 milliseconds | Standard Deviation 5.43 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 15 Minutes Post-dose | 2.1 milliseconds | Standard Deviation 5.54 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 6 Hour Post-dose | -1.7 milliseconds | Standard Deviation 7.46 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | Baseline | 387.5 milliseconds | Standard Deviation 17.4 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 30 Minutes Post-dose | 0.1 milliseconds | Standard Deviation 4.57 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1 Hour Post-dose | -0.3 milliseconds | Standard Deviation 5.15 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1.5 Hour Post-dose | -3.4 milliseconds | Standard Deviation 5.18 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2 Hour Post-dose | -3.1 milliseconds | Standard Deviation 3.94 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2.5 Hour Post-dose | -3.7 milliseconds | Standard Deviation 5.2 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 3 Hour Post-dose | -3.5 milliseconds | Standard Deviation 4.6 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 4 Hour Post-dose | -2.0 milliseconds | Standard Deviation 5.71 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 8 Hour Post-dose | -5.2 milliseconds | Standard Deviation 7.82 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 12 Hour Post-dose | -0.9 milliseconds | Standard Deviation 5.9 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 16 Hour Post-dose | 4.5 milliseconds | Standard Deviation 8.1 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 24 Hour Post-dose | -3.2 milliseconds | Standard Deviation 6.86 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 24 Hour Post-dose | 2.5 milliseconds | Standard Deviation 7.33 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 16 Hour Post-dose | 11.3 milliseconds | Standard Deviation 7.53 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 3 Hour Post-dose | 11.7 milliseconds | Standard Deviation 5.43 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 30 Minutes Post-dose | 2.5 milliseconds | Standard Deviation 6.65 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 4 Hour Post-dose | 9.4 milliseconds | Standard Deviation 6.86 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 6 Hour Post-dose | 5.8 milliseconds | Standard Deviation 8.54 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 15 Minutes Post-dose | -0.1 milliseconds | Standard Deviation 4.06 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 8 Hour Post-dose | 6.3 milliseconds | Standard Deviation 8.36 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | Baseline | 389.1 milliseconds | Standard Deviation 17.18 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 12 Hour Post-dose | 8.2 milliseconds | Standard Deviation 9.62 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1.5 Hour Post-dose | 10.9 milliseconds | Standard Deviation 8.35 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2 Hour Post-dose | 13.0 milliseconds | Standard Deviation 8.26 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1 Hour Post-dose | 9.8 milliseconds | Standard Deviation 7.3 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2.5 Hour Post-dose | 10.7 milliseconds | Standard Deviation 6.57 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1.5 Hour Post-dose | 1.7 milliseconds | Standard Deviation 5.45 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2.5 Hour Post-dose | -1.3 milliseconds | Standard Deviation 4.45 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 30 Minutes Post-dose | 1.9 milliseconds | Standard Deviation 4.32 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 8 Hour Post-dose | -1.4 milliseconds | Standard Deviation 8.29 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 1 Hour Post-dose | 2.5 milliseconds | Standard Deviation 5.47 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 3 Hour Post-dose | -1.2 milliseconds | Standard Deviation 5.18 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 24 Hour Post-dose | -2.9 milliseconds | Standard Deviation 6.47 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 16 Hour Post-dose | 5.8 milliseconds | Standard Deviation 7.07 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 15 Minutes Post-dose | 3.2 milliseconds | Standard Deviation 3.71 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 4 Hour Post-dose | -1.0 milliseconds | Standard Deviation 5.65 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 12 Hour Post-dose | 0.3 milliseconds | Standard Deviation 4.98 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 6 Hour Post-dose | -0.0 milliseconds | Standard Deviation 7.63 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | Baseline | 388.9 milliseconds | Standard Deviation 17.08 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QTcP Interval | 2 Hour Post-dose | -0.1 milliseconds | Standard Deviation 5.33 |
Secondary
Effect of Evobrutinib on ECG Parameters: QT Interval
The effect of evobrutinib on baseline-corrected measurements of QT interval was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 1 Hour Post-dose | -5.2 milliseconds | Standard Deviation 8.86 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 3 Hour Post-dose | -3.5 milliseconds | Standard Deviation 10.58 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 2 Hour Post-dose | -4.3 milliseconds | Standard Deviation 7.63 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 1.5 Hour Post-dose | -8.0 milliseconds | Standard Deviation 8.12 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 24 Hour Post-dose | -16.3 milliseconds | Standard Deviation 18.95 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 16 Hour Post-dose | -4.1 milliseconds | Standard Deviation 14.04 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 15 Minutes Post-dose | -0.1 milliseconds | Standard Deviation 6.99 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 12 Hour Post-dose | -2.7 milliseconds | Standard Deviation 14.12 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 8 Hour Post-dose | -13.7 milliseconds | Standard Deviation 13.06 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 6 Hour Post-dose | -19.2 milliseconds | Standard Deviation 15.98 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 30 Minutes Post-dose | 0.6 milliseconds | Standard Deviation 8.71 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | Baseline | 395.8 milliseconds | Standard Deviation 28.44 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 4 Hour Post-dose | -5.7 milliseconds | Standard Deviation 9.95 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 2.5 Hour Post-dose | -4.5 milliseconds | Standard Deviation 9.55 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 15 Minutes Post-dose | -1.5 milliseconds | Standard Deviation 6.7 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | Baseline | 393.2 milliseconds | Standard Deviation 27.84 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 30 Minutes Post-dose | -0.5 milliseconds | Standard Deviation 5.61 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 1 Hour Post-dose | -2.8 milliseconds | Standard Deviation 7.99 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 1.5 Hour Post-dose | -6.0 milliseconds | Standard Deviation 8.93 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 2 Hour Post-dose | -6.9 milliseconds | Standard Deviation 6.62 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 2.5 Hour Post-dose | -5.4 milliseconds | Standard Deviation 9.46 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 3 Hour Post-dose | -3.6 milliseconds | Standard Deviation 9.31 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 4 Hour Post-dose | -4.4 milliseconds | Standard Deviation 10.67 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 6 Hour Post-dose | -16.9 milliseconds | Standard Deviation 13.1 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 8 Hour Post-dose | -11.3 milliseconds | Standard Deviation 13.33 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 12 Hour Post-dose | -0.7 milliseconds | Standard Deviation 13.23 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 16 Hour Post-dose | -0.8 milliseconds | Standard Deviation 15.15 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 24 Hour Post-dose | -9.5 milliseconds | Standard Deviation 13.66 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 2.5 Hour Post-dose | 5.5 milliseconds | Standard Deviation 11.71 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 24 Hour Post-dose | -8.5 milliseconds | Standard Deviation 13.92 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 3 Hour Post-dose | 5.3 milliseconds | Standard Deviation 12.19 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 30 Minutes Post-dose | -1.7 milliseconds | Standard Deviation 7.29 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 16 Hour Post-dose | -0.9 milliseconds | Standard Deviation 13.19 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 4 Hour Post-dose | 2.4 milliseconds | Standard Deviation 16.1 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 6 Hour Post-dose | -13.6 milliseconds | Standard Deviation 13.12 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 15 Minutes Post-dose | 0.1 milliseconds | Standard Deviation 6.34 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | Baseline | 394.5 milliseconds | Standard Deviation 26.29 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 8 Hour Post-dose | -8.2 milliseconds | Standard Deviation 12.25 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 12 Hour Post-dose | 1.4 milliseconds | Standard Deviation 14.28 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 1.5 Hour Post-dose | 3.2 milliseconds | Standard Deviation 10.41 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 1 Hour Post-dose | 3.6 milliseconds | Standard Deviation 10.74 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: QT Interval | 2 Hour Post-dose | 3.5 milliseconds | Standard Deviation 13.02 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 12 Hour Post-dose | -1.7 milliseconds | Standard Deviation 12.04 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 8 Hour Post-dose | -14.2 milliseconds | Standard Deviation 12.8 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 2.5 Hour Post-dose | -4.1 milliseconds | Standard Deviation 10.14 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 3 Hour Post-dose | -6.0 milliseconds | Standard Deviation 12.45 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 24 Hour Post-dose | -15.8 milliseconds | Standard Deviation 12.3 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 1 Hour Post-dose | -5.0 milliseconds | Standard Deviation 9.08 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | Baseline | 396.4 milliseconds | Standard Deviation 27.77 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 4 Hour Post-dose | -7.8 milliseconds | Standard Deviation 10.66 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 15 Minutes Post-dose | 1.2 milliseconds | Standard Deviation 8.39 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 16 Hour Post-dose | -8.5 milliseconds | Standard Deviation 13.26 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 2 Hour Post-dose | -7.4 milliseconds | Standard Deviation 10.21 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 6 Hour Post-dose | -22.3 milliseconds | Standard Deviation 14.43 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 1.5 Hour Post-dose | -8.2 milliseconds | Standard Deviation 11.75 |
| Placebo | Effect of Evobrutinib on ECG Parameters: QT Interval | 30 Minutes Post-dose | 0.1 milliseconds | Standard Deviation 7.44 |
Secondary
Effect of Evobrutinib on ECG Parameters: RR Interval
The effect of evobrutinib on baseline-corrected measurements of RR interval was summarized by treatment and time points using descriptive statistics. Absolute change from baseline values was reported.
Time frame: Baseline, and post-dose at 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, and 24 hours
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 2.5 Hour Post-dose | -10.8 milliseconds | Standard Deviation 69.18 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 15 Minutes Post-dose | -14.8 milliseconds | Standard Deviation 60.09 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 8 Hour Post-dose | -74.0 milliseconds | Standard Deviation 95.45 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 4 Hour Post-dose | -20.1 milliseconds | Standard Deviation 67.37 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 6 Hour Post-dose | -112.1 milliseconds | Standard Deviation 115.18 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 3 Hour Post-dose | 0.2 milliseconds | Standard Deviation 80.54 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 30 Minutes Post-dose | -4.2 milliseconds | Standard Deviation 65.1 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | Baseline | 1057.4 milliseconds | Standard Deviation 146.41 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 16 Hour Post-dose | -61.3 milliseconds | Standard Deviation 98.99 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 1 Hour Post-dose | -30.2 milliseconds | Standard Deviation 72.81 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 1.5 Hour Post-dose | -34.4 milliseconds | Standard Deviation 65.46 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 12 Hour Post-dose | -24.8 milliseconds | Standard Deviation 94.78 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 2 Hour Post-dose | -14.0 milliseconds | Standard Deviation 57.06 |
| Evobrutinib 45mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 24 Hour Post-dose | -98.8 milliseconds | Standard Deviation 127.77 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 2.5 Hour Post-dose | -10.6 milliseconds | Standard Deviation 70.27 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 3 Hour Post-dose | -1.8 milliseconds | Standard Deviation 65.55 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 8 Hour Post-dose | -38.8 milliseconds | Standard Deviation 95.45 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 1 Hour Post-dose | -17.0 milliseconds | Standard Deviation 60.28 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | Baseline | 1044.0 milliseconds | Standard Deviation 139.39 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 4 Hour Post-dose | -15.9 milliseconds | Standard Deviation 61.57 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 15 Minutes Post-dose | -24.4 milliseconds | Standard Deviation 63.48 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 6 Hour Post-dose | -101.1 milliseconds | Standard Deviation 94.08 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 12 Hour Post-dose | 1.4 milliseconds | Standard Deviation 89.18 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 2 Hour Post-dose | -26.2 milliseconds | Standard Deviation 40.34 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 16 Hour Post-dose | -39.9 milliseconds | Standard Deviation 105.2 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 1.5 Hour Post-dose | -17.2 milliseconds | Standard Deviation 59.43 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 30 Minutes Post-dose | -4.9 milliseconds | Standard Deviation 55.65 |
| Evobrutinib 225mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 24 Hour Post-dose | -42.6 milliseconds | Standard Deviation 106.76 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 1.5 Hour Post-dose | -52.5 milliseconds | Standard Deviation 59 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | Baseline | 1043.4 milliseconds | Standard Deviation 144.03 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 15 Minutes Post-dose | 0.6 milliseconds | Standard Deviation 45.64 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 30 Minutes Post-dose | -26.6 milliseconds | Standard Deviation 66.04 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 1 Hour Post-dose | -40.3 milliseconds | Standard Deviation 62.87 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 2.5 Hour Post-dose | -37.4 milliseconds | Standard Deviation 79.84 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 2 Hour Post-dose | -65.0 milliseconds | Standard Deviation 81.34 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 3 Hour Post-dose | -45.2 milliseconds | Standard Deviation 74.46 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 4 Hour Post-dose | -48.1 milliseconds | Standard Deviation 99.08 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 6 Hour Post-dose | -127.3 milliseconds | Standard Deviation 89.62 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 8 Hour Post-dose | -97.8 milliseconds | Standard Deviation 83.82 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 12 Hour Post-dose | -47.3 milliseconds | Standard Deviation 103.93 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 16 Hour Post-dose | -83.3 milliseconds | Standard Deviation 99.08 |
| Moxifloxacin 400mg | Effect of Evobrutinib on ECG Parameters: RR Interval | 24 Hour Post-dose | -74.0 milliseconds | Standard Deviation 101.4 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | Baseline | 1056.1 milliseconds | Standard Deviation 140.61 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 8 Hour Post-dose | -83.7 milliseconds | Standard Deviation 88.55 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 1.5 Hour Post-dose | -66.0 milliseconds | Standard Deviation 78.1 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 1 Hour Post-dose | -47.3 milliseconds | Standard Deviation 58.95 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 2.5 Hour Post-dose | -18.8 milliseconds | Standard Deviation 65.83 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 12 Hour Post-dose | -15.7 milliseconds | Standard Deviation 93.15 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 30 Minutes Post-dose | -11.3 milliseconds | Standard Deviation 48.52 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 15 Minutes Post-dose | -13.8 milliseconds | Standard Deviation 54.73 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 24 Hour Post-dose | -85.1 milliseconds | Standard Deviation 88.69 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 4 Hour Post-dose | -44.6 milliseconds | Standard Deviation 71.37 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 16 Hour Post-dose | -94.7 milliseconds | Standard Deviation 84.41 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 6 Hour Post-dose | -146.5 milliseconds | Standard Deviation 94.86 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 3 Hour Post-dose | -31.8 milliseconds | Standard Deviation 81.31 |
| Placebo | Effect of Evobrutinib on ECG Parameters: RR Interval | 2 Hour Post-dose | -49.9 milliseconds | Standard Deviation 57.51 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
Cmax is the maximum observed plasma concentration. Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Maximum Observed Plasma Concentration (Cmax) of Evobrutinib | 123 ng/mL | Geometric Coefficient of Variation 45.8 |
| Evobrutinib 225mg | Maximum Observed Plasma Concentration (Cmax) of Evobrutinib | 670 ng/mL | Geometric Coefficient of Variation 51.3 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin
Cmax is the maximum observed plasma concentration. Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evobrutinib 45mg | Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin | 2000 ng/mL | Geometric Coefficient of Variation 30.3 |
Secondary
Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests
The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities from baseline were reported. Clinically Significance was decided by investigator.
Time frame: Up to Day 29
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib 45mg | Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests | 0 Participants |
| Evobrutinib 225mg | Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests | 0 Participants |
| Moxifloxacin 400mg | Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs
Vital sign assessment included blood pressure, pulse rate, body temperature and respiration (frequency per minute). Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator.
Time frame: Up to Day 29
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib 45mg | Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs | 0 Participants |
| Evobrutinib 225mg | Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs | 0 Participants |
| Moxifloxacin 400mg | Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings
The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities were reported. Clinically significance was decided by investigator.
Time frame: Up to Day 29
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib 45mg | Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings | 0 Participants |
| Evobrutinib 225mg | Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings | 0 Participants |
| Moxifloxacin 400mg | Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.Therefore, an AE can be any unfavorable and unintended sign (including an abnormallaboratory finding), symptom, or disease temporally associated with the use of amedicinal product, regardless if it is considered related to the medicinal product.Serious AE: AE that resulted in any of the following outcomes: death; life threatening;persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization;congenital anomaly/birth defect. TEAEs are defined as AEs that were reported orworsened on or after start of study drug dosing through the Safety Follow-up Visit.TEAEs included both serious TEAEs and non-serious TEAEs. Treatment related AEs:reasonably related to the study drug/study treatment.
Time frame: Up to 3 months
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib 45mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 8 Participants |
| Evobrutinib 225mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| Moxifloxacin 400mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 8 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
Severity of adverse events (AE) were assessed by the investigator. The Investigator assessed the intensity of each AE and SAE reported during the study and assigned it to 1 of the following categories: 1\. Mild: A type of adverse event that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. 2. Moderate: A type of adverse event that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. 3. Severe: A type of adverse event that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Number of participants with severe adverse events were reported.
Time frame: Up to 3 months
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evobrutinib 45mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | 0 Participants |
| Evobrutinib 225mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | 0 Participants |
| Moxifloxacin 400mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity | 0 Participants |
Secondary
Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Moxifloxacin
A linear mixed-effects model was used to analyze the relationship between moxifloxacin concentrations and ΔQTc. Based on this model, drug-induced ΔΔQTc and its two-sided 90% CI was predicted. The higher geometric mean Cmax calculated based on the PK and ECG Analysis Sets was considered.
Time frame: From 1 hour before any administration until 24 hours post-administration at the following timepoints: -1-hour, 5 min, 10 min, 20 min, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours
Population: All participants who had a baseline Holter ECG in triplicate and at least one post baseline Holter ECG in triplicate with a time-matched concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Evobrutinib 45mg | Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Moxifloxacin | 12.2 milliseconds |
Secondary
Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib
Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evobrutinib 45mg | Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib | 0.500 hours |
| Evobrutinib 225mg | Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib | 0.500 hours |
Secondary
Time to Reach Maximum Blood Concentration (Tmax) of Moxifloxacin
Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22
Population: The PK Analysis Set was a subset of the SAF, and the PK population included all participants: who had completed the study without any relevant protocol deviations and factors likely to affect the comparability of PK results and with adequate study intervention compliance and with evaluable PK data, i.e. no missing values for primary endpoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evobrutinib 45mg | Time to Reach Maximum Blood Concentration (Tmax) of Moxifloxacin | 1.50 hours |