Trial Outcomes & Findings for A TQT Study of Effect of M2951 on Cardiac Repolarization (NCT NCT07214935)
NCT ID: NCT07214935
Last Updated: 2025-11-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
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
Results posted on
2025-11-13
Participant Flow
Participant milestones
| Measure |
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
|
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
|
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
|
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
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
9
|
9
|
|
Overall Study
COMPLETED
|
7
|
7
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
1
|
1
|
Reasons for withdrawal
| Measure |
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
|
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
|
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
|
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
|
|---|---|---|---|---|
|
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
A TQT Study of Effect of M2951 on Cardiac Repolarization
Baseline characteristics by cohort
| Measure |
Sequence 1
n=9 Participants
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
|
Sequence 2
n=9 Participants
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
|
Sequence 3
n=9 Participants
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
|
Sequence 4
n=8 Participants
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
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Sex: Female, Male
Female
|
3 Participants
n=10 Participants
|
2 Participants
n=10 Participants
|
2 Participants
n=20 Participants
|
1 Participants
n=45 Participants
|
8 Participants
n=44 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=10 Participants
|
7 Participants
n=10 Participants
|
7 Participants
n=20 Participants
|
7 Participants
n=45 Participants
|
27 Participants
n=44 Participants
|
|
Age, Continuous
|
45 Years
STANDARD_DEVIATION 7.5 • n=10 Participants
|
36 Years
STANDARD_DEVIATION 10.4 • n=10 Participants
|
41 Years
STANDARD_DEVIATION 8.6 • n=20 Participants
|
40 Years
STANDARD_DEVIATION 11.3 • n=45 Participants
|
41 Years
STANDARD_DEVIATION 9.6 • n=44 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=10 Participants
|
9 Participants
n=10 Participants
|
9 Participants
n=20 Participants
|
8 Participants
n=45 Participants
|
35 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
1 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=10 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
2 Participants
n=44 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=10 Participants
|
8 Participants
n=10 Participants
|
8 Participants
n=20 Participants
|
8 Participants
n=45 Participants
|
32 Participants
n=44 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=44 Participants
|
PRIMARY outcome
Timeframe: 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 hoursPopulation: 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
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib
|
-1.62 milliseconds
Interval -2.15 to -1.09
|
-2.28 milliseconds
Interval -3.63 to -0.93
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: 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.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=32 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Moxifloxacin
|
12.2 milliseconds
Interval 10.3 to 14.1
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 3 monthsPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
8 Participants
|
5 Participants
|
5 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Up to 3 monthsPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 29Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 29Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 29Population: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=30 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
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
|
1420 hour*nanogram/milliliter
Geometric Coefficient of Variation 37.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=30 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
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
|
1420 h*ng/mL
Geometric Coefficient of Variation 37.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
Cmax is the maximum observed plasma concentration. Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=30 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Evobrutinib
|
123 ng/mL
Geometric Coefficient of Variation 45.8
|
670 ng/mL
Geometric Coefficient of Variation 51.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=30 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib
|
0.500 hours
Interval 0.267 to 2.02
|
0.500 hours
Interval 0.25 to 2.03
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=30 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Apparent Terminal Half-life (t1/2) of Evobrutinib
|
1.32 hours
Geometric Coefficient of Variation 22.7
|
2.09 hours
Geometric Coefficient of Variation 33.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
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 outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
Cmax is the maximum observed plasma concentration. Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin
|
2000 ng/mL
Geometric Coefficient of Variation 30.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
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 outcome
Timeframe: Pre-dose up to 24 hours post-dose on Days 1, 8, 15, and 22Population: 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.
Time to reach the maximum blood concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Evobrutinib 45mg
n=30 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Time to Reach Maximum Blood Concentration (Tmax) of Moxifloxacin
|
1.50 hours
Interval 0.25 to 4.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
Baseline
|
58.1 beats/min
Standard Deviation 8.38
|
58.6 beats/min
Standard Deviation 7.38
|
58.7 beats/min
Standard Deviation 7.90
|
57.9 beats/min
Standard Deviation 7.61
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
15 Minutes Post-dose
|
0.6 beats/min
Standard Deviation 3.26
|
1.3 beats/min
Standard Deviation 3.83
|
0.0 beats/min
Standard Deviation 2.58
|
0.8 beats/min
Standard Deviation 2.65
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
30 Minutes Post-dose
|
0.0 beats/min
Standard Deviation 3.43
|
0.2 beats/min
Standard Deviation 3.26
|
1.6 beats/min
Standard Deviation 3.57
|
0.7 beats/min
Standard Deviation 2.98
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
1 Hour Post-dose
|
1.7 beats/min
Standard Deviation 3.68
|
1.0 beats/min
Standard Deviation 4.00
|
2.6 beats/min
Standard Deviation 3.80
|
3.2 beats/min
Standard Deviation 4.10
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
1.5 Hour Post-dose
|
1.7 beats/min
Standard Deviation 3.26
|
1.1 beats/min
Standard Deviation 3.60
|
3.0 beats/min
Standard Deviation 3.48
|
3.9 beats/min
Standard Deviation 4.03
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
2 Hour Post-dose
|
0.6 beats/min
Standard Deviation 3.10
|
1.4 beats/min
Standard Deviation 2.21
|
3.6 beats/min
Standard Deviation 4.76
|
2.8 beats/min
Standard Deviation 3.05
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
2.5 Hour Post-dose
|
0.4 beats/min
Standard Deviation 4.04
|
0.7 beats/min
Standard Deviation 3.73
|
1.9 beats/min
Standard Deviation 4.22
|
1.2 beats/min
Standard Deviation 3.64
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
3 Hour Post-dose
|
-0.4 beats/min
Standard Deviation 4.43
|
-0.0 beats/min
Standard Deviation 3.28
|
2.4 beats/min
Standard Deviation 3.63
|
1.9 beats/min
Standard Deviation 4.13
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
4 Hour Post-dose
|
0.8 beats/min
Standard Deviation 3.67
|
0.8 beats/min
Standard Deviation 3.54
|
2.7 beats/min
Standard Deviation 6.52
|
2.7 beats/min
Standard Deviation 4.03
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
6 Hour Post-dose
|
6.6 beats/min
Standard Deviation 6.42
|
6.1 beats/min
Standard Deviation 4.85
|
7.8 beats/min
Standard Deviation 4.84
|
9.3 beats/min
Standard Deviation 5.53
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
8 Hour Post-dose
|
4.2 beats/min
Standard Deviation 5.85
|
2.3 beats/min
Standard Deviation 5.29
|
5.5 beats/min
Standard Deviation 4.24
|
5.2 beats/min
Standard Deviation 5.30
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
12 Hour Post-dose
|
1.3 beats/min
Standard Deviation 5.36
|
-0.1 beats/min
Standard Deviation 4.63
|
2.6 beats/min
Standard Deviation 5.62
|
0.7 beats/min
Standard Deviation 4.75
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
16 Hour Post-dose
|
3.5 beats/min
Standard Deviation 5.91
|
2.1 beats/min
Standard Deviation 5.73
|
4.6 beats/min
Standard Deviation 5.25
|
5.6 beats/min
Standard Deviation 5.16
|
|
Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate
24 Hour Post-dose
|
6.0 beats/min
Standard Deviation 7.88
|
2.6 beats/min
Standard Deviation 5.62
|
4.3 beats/min
Standard Deviation 5.38
|
5.3 beats/min
Standard Deviation 5.69
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
Baseline
|
1057.4 milliseconds
Standard Deviation 146.41
|
1044.0 milliseconds
Standard Deviation 139.39
|
1043.4 milliseconds
Standard Deviation 144.03
|
1056.1 milliseconds
Standard Deviation 140.61
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
15 Minutes Post-dose
|
-14.8 milliseconds
Standard Deviation 60.09
|
-24.4 milliseconds
Standard Deviation 63.48
|
0.6 milliseconds
Standard Deviation 45.64
|
-13.8 milliseconds
Standard Deviation 54.73
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
30 Minutes Post-dose
|
-4.2 milliseconds
Standard Deviation 65.10
|
-4.9 milliseconds
Standard Deviation 55.65
|
-26.6 milliseconds
Standard Deviation 66.04
|
-11.3 milliseconds
Standard Deviation 48.52
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
1 Hour Post-dose
|
-30.2 milliseconds
Standard Deviation 72.81
|
-17.0 milliseconds
Standard Deviation 60.28
|
-40.3 milliseconds
Standard Deviation 62.87
|
-47.3 milliseconds
Standard Deviation 58.95
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
1.5 Hour Post-dose
|
-34.4 milliseconds
Standard Deviation 65.46
|
-17.2 milliseconds
Standard Deviation 59.43
|
-52.5 milliseconds
Standard Deviation 59.00
|
-66.0 milliseconds
Standard Deviation 78.10
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
2 Hour Post-dose
|
-14.0 milliseconds
Standard Deviation 57.06
|
-26.2 milliseconds
Standard Deviation 40.34
|
-65.0 milliseconds
Standard Deviation 81.34
|
-49.9 milliseconds
Standard Deviation 57.51
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
2.5 Hour Post-dose
|
-10.8 milliseconds
Standard Deviation 69.18
|
-10.6 milliseconds
Standard Deviation 70.27
|
-37.4 milliseconds
Standard Deviation 79.84
|
-18.8 milliseconds
Standard Deviation 65.83
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
3 Hour Post-dose
|
0.2 milliseconds
Standard Deviation 80.54
|
-1.8 milliseconds
Standard Deviation 65.55
|
-45.2 milliseconds
Standard Deviation 74.46
|
-31.8 milliseconds
Standard Deviation 81.31
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
4 Hour Post-dose
|
-20.1 milliseconds
Standard Deviation 67.37
|
-15.9 milliseconds
Standard Deviation 61.57
|
-48.1 milliseconds
Standard Deviation 99.08
|
-44.6 milliseconds
Standard Deviation 71.37
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
6 Hour Post-dose
|
-112.1 milliseconds
Standard Deviation 115.18
|
-101.1 milliseconds
Standard Deviation 94.08
|
-127.3 milliseconds
Standard Deviation 89.62
|
-146.5 milliseconds
Standard Deviation 94.86
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
8 Hour Post-dose
|
-74.0 milliseconds
Standard Deviation 95.45
|
-38.8 milliseconds
Standard Deviation 95.45
|
-97.8 milliseconds
Standard Deviation 83.82
|
-83.7 milliseconds
Standard Deviation 88.55
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
12 Hour Post-dose
|
-24.8 milliseconds
Standard Deviation 94.78
|
1.4 milliseconds
Standard Deviation 89.18
|
-47.3 milliseconds
Standard Deviation 103.93
|
-15.7 milliseconds
Standard Deviation 93.15
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
16 Hour Post-dose
|
-61.3 milliseconds
Standard Deviation 98.99
|
-39.9 milliseconds
Standard Deviation 105.20
|
-83.3 milliseconds
Standard Deviation 99.08
|
-94.7 milliseconds
Standard Deviation 84.41
|
|
Effect of Evobrutinib on ECG Parameters: RR Interval
24 Hour Post-dose
|
-98.8 milliseconds
Standard Deviation 127.77
|
-42.6 milliseconds
Standard Deviation 106.76
|
-74.0 milliseconds
Standard Deviation 101.40
|
-85.1 milliseconds
Standard Deviation 88.69
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
3 Hour Post-dose
|
-3.5 milliseconds
Standard Deviation 10.58
|
-3.6 milliseconds
Standard Deviation 9.31
|
5.3 milliseconds
Standard Deviation 12.19
|
-6.0 milliseconds
Standard Deviation 12.45
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
24 Hour Post-dose
|
-16.3 milliseconds
Standard Deviation 18.95
|
-9.5 milliseconds
Standard Deviation 13.66
|
-8.5 milliseconds
Standard Deviation 13.92
|
-15.8 milliseconds
Standard Deviation 12.30
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
Baseline
|
395.8 milliseconds
Standard Deviation 28.44
|
393.2 milliseconds
Standard Deviation 27.84
|
394.5 milliseconds
Standard Deviation 26.29
|
396.4 milliseconds
Standard Deviation 27.77
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
15 Minutes Post-dose
|
-0.1 milliseconds
Standard Deviation 6.99
|
-1.5 milliseconds
Standard Deviation 6.70
|
0.1 milliseconds
Standard Deviation 6.34
|
1.2 milliseconds
Standard Deviation 8.39
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
30 Minutes Post-dose
|
0.6 milliseconds
Standard Deviation 8.71
|
-0.5 milliseconds
Standard Deviation 5.61
|
-1.7 milliseconds
Standard Deviation 7.29
|
0.1 milliseconds
Standard Deviation 7.44
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
1 Hour Post-dose
|
-5.2 milliseconds
Standard Deviation 8.86
|
-2.8 milliseconds
Standard Deviation 7.99
|
3.6 milliseconds
Standard Deviation 10.74
|
-5.0 milliseconds
Standard Deviation 9.08
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
1.5 Hour Post-dose
|
-8.0 milliseconds
Standard Deviation 8.12
|
-6.0 milliseconds
Standard Deviation 8.93
|
3.2 milliseconds
Standard Deviation 10.41
|
-8.2 milliseconds
Standard Deviation 11.75
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
2 Hour Post-dose
|
-4.3 milliseconds
Standard Deviation 7.63
|
-6.9 milliseconds
Standard Deviation 6.62
|
3.5 milliseconds
Standard Deviation 13.02
|
-7.4 milliseconds
Standard Deviation 10.21
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
2.5 Hour Post-dose
|
-4.5 milliseconds
Standard Deviation 9.55
|
-5.4 milliseconds
Standard Deviation 9.46
|
5.5 milliseconds
Standard Deviation 11.71
|
-4.1 milliseconds
Standard Deviation 10.14
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
4 Hour Post-dose
|
-5.7 milliseconds
Standard Deviation 9.95
|
-4.4 milliseconds
Standard Deviation 10.67
|
2.4 milliseconds
Standard Deviation 16.10
|
-7.8 milliseconds
Standard Deviation 10.66
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
6 Hour Post-dose
|
-19.2 milliseconds
Standard Deviation 15.98
|
-16.9 milliseconds
Standard Deviation 13.10
|
-13.6 milliseconds
Standard Deviation 13.12
|
-22.3 milliseconds
Standard Deviation 14.43
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
8 Hour Post-dose
|
-13.7 milliseconds
Standard Deviation 13.06
|
-11.3 milliseconds
Standard Deviation 13.33
|
-8.2 milliseconds
Standard Deviation 12.25
|
-14.2 milliseconds
Standard Deviation 12.80
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
12 Hour Post-dose
|
-2.7 milliseconds
Standard Deviation 14.12
|
-0.7 milliseconds
Standard Deviation 13.23
|
1.4 milliseconds
Standard Deviation 14.28
|
-1.7 milliseconds
Standard Deviation 12.04
|
|
Effect of Evobrutinib on ECG Parameters: QT Interval
16 Hour Post-dose
|
-4.1 milliseconds
Standard Deviation 14.04
|
-0.8 milliseconds
Standard Deviation 15.15
|
-0.9 milliseconds
Standard Deviation 13.19
|
-8.5 milliseconds
Standard Deviation 13.26
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
2.5 Hour Post-dose
|
-3.3 milliseconds
Standard Deviation 5.26
|
-3.9 milliseconds
Standard Deviation 4.87
|
10.0 milliseconds
Standard Deviation 6.33
|
-1.7 milliseconds
Standard Deviation 4.52
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
Baseline
|
389.4 milliseconds
Standard Deviation 18.08
|
388.4 milliseconds
Standard Deviation 17.88
|
389.8 milliseconds
Standard Deviation 17.28
|
390.0 milliseconds
Standard Deviation 17.58
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
15 Minutes Post-dose
|
1.6 milliseconds
Standard Deviation 4.50
|
1.6 milliseconds
Standard Deviation 4.66
|
-0.1 milliseconds
Standard Deviation 3.91
|
2.8 milliseconds
Standard Deviation 3.75
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
30 Minutes Post-dose
|
0.8 milliseconds
Standard Deviation 5.08
|
0.0 milliseconds
Standard Deviation 3.77
|
1.8 milliseconds
Standard Deviation 5.90
|
1.6 milliseconds
Standard Deviation 4.26
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
1 Hour Post-dose
|
-1.2 milliseconds
Standard Deviation 4.49
|
-0.7 milliseconds
Standard Deviation 4.62
|
8.8 milliseconds
Standard Deviation 7.14
|
1.3 milliseconds
Standard Deviation 5.16
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
1.5 Hour Post-dose
|
-3.7 milliseconds
Standard Deviation 4.50
|
-3.8 milliseconds
Standard Deviation 5.04
|
9.8 milliseconds
Standard Deviation 8.09
|
0.2 milliseconds
Standard Deviation 5.46
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
2 Hour Post-dose
|
-2.7 milliseconds
Standard Deviation 3.77
|
-3.6 milliseconds
Standard Deviation 3.98
|
11.7 milliseconds
Standard Deviation 7.92
|
-1.1 milliseconds
Standard Deviation 5.61
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
3 Hour Post-dose
|
-3.7 milliseconds
Standard Deviation 5.89
|
-3.4 milliseconds
Standard Deviation 4.64
|
10.8 milliseconds
Standard Deviation 5.78
|
-1.9 milliseconds
Standard Deviation 5.29
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
4 Hour Post-dose
|
-3.3 milliseconds
Standard Deviation 5.34
|
-2.4 milliseconds
Standard Deviation 5.80
|
8.4 milliseconds
Standard Deviation 7.03
|
-2.0 milliseconds
Standard Deviation 5.54
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
6 Hour Post-dose
|
-5.0 milliseconds
Standard Deviation 7.51
|
-4.0 milliseconds
Standard Deviation 7.07
|
3.0 milliseconds
Standard Deviation 8.24
|
-3.4 milliseconds
Standard Deviation 7.51
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
8 Hour Post-dose
|
-4.5 milliseconds
Standard Deviation 5.64
|
-6.2 milliseconds
Standard Deviation 7.41
|
4.2 milliseconds
Standard Deviation 8.00
|
-3.4 milliseconds
Standard Deviation 7.85
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
12 Hour Post-dose
|
0.2 milliseconds
Standard Deviation 6.32
|
-0.8 milliseconds
Standard Deviation 5.88
|
7.2 milliseconds
Standard Deviation 8.94
|
0.1 milliseconds
Standard Deviation 4.51
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
16 Hour Post-dose
|
3.6 milliseconds
Standard Deviation 8.14
|
3.8 milliseconds
Standard Deviation 7.79
|
9.6 milliseconds
Standard Deviation 6.99
|
3.7 milliseconds
Standard Deviation 6.89
|
|
Effect of Evobrutinib on ECG Parameters: QTcF Interval
24 Hour Post-dose
|
-3.8 milliseconds
Standard Deviation 8.18
|
-4.1 milliseconds
Standard Deviation 6.16
|
0.9 milliseconds
Standard Deviation 6.97
|
-4.9 milliseconds
Standard Deviation 6.05
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
3 Hour Post-dose
|
-3.7 milliseconds
Standard Deviation 6.33
|
-3.5 milliseconds
Standard Deviation 4.60
|
11.7 milliseconds
Standard Deviation 5.43
|
-1.2 milliseconds
Standard Deviation 5.18
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
4 Hour Post-dose
|
-2.9 milliseconds
Standard Deviation 5.43
|
-2.0 milliseconds
Standard Deviation 5.71
|
9.4 milliseconds
Standard Deviation 6.86
|
-1.0 milliseconds
Standard Deviation 5.65
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
6 Hour Post-dose
|
-2.6 milliseconds
Standard Deviation 7.96
|
-1.7 milliseconds
Standard Deviation 7.46
|
5.8 milliseconds
Standard Deviation 8.54
|
-0.0 milliseconds
Standard Deviation 7.63
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
8 Hour Post-dose
|
-3.0 milliseconds
Standard Deviation 6.12
|
-5.2 milliseconds
Standard Deviation 7.82
|
6.3 milliseconds
Standard Deviation 8.36
|
-1.4 milliseconds
Standard Deviation 8.29
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
12 Hour Post-dose
|
0.8 milliseconds
Standard Deviation 6.20
|
-0.9 milliseconds
Standard Deviation 5.90
|
8.2 milliseconds
Standard Deviation 9.62
|
0.3 milliseconds
Standard Deviation 4.98
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
16 Hour Post-dose
|
4.9 milliseconds
Standard Deviation 8.65
|
4.5 milliseconds
Standard Deviation 8.10
|
11.3 milliseconds
Standard Deviation 7.53
|
5.8 milliseconds
Standard Deviation 7.07
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
24 Hour Post-dose
|
-1.5 milliseconds
Standard Deviation 8.22
|
-3.2 milliseconds
Standard Deviation 6.86
|
2.5 milliseconds
Standard Deviation 7.33
|
-2.9 milliseconds
Standard Deviation 6.47
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
Baseline
|
388.2 milliseconds
Standard Deviation 17.69
|
387.5 milliseconds
Standard Deviation 17.40
|
389.1 milliseconds
Standard Deviation 17.18
|
388.9 milliseconds
Standard Deviation 17.08
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
15 Minutes Post-dose
|
1.9 milliseconds
Standard Deviation 5.21
|
2.1 milliseconds
Standard Deviation 5.54
|
-0.1 milliseconds
Standard Deviation 4.06
|
3.2 milliseconds
Standard Deviation 3.71
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
30 Minutes Post-dose
|
0.8 milliseconds
Standard Deviation 5.51
|
0.1 milliseconds
Standard Deviation 4.57
|
2.5 milliseconds
Standard Deviation 6.65
|
1.9 milliseconds
Standard Deviation 4.32
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
1 Hour Post-dose
|
-0.6 milliseconds
Standard Deviation 4.91
|
-0.3 milliseconds
Standard Deviation 5.15
|
9.8 milliseconds
Standard Deviation 7.30
|
2.5 milliseconds
Standard Deviation 5.47
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
1.5 Hour Post-dose
|
-3.1 milliseconds
Standard Deviation 4.95
|
-3.4 milliseconds
Standard Deviation 5.18
|
10.9 milliseconds
Standard Deviation 8.35
|
1.7 milliseconds
Standard Deviation 5.45
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
2 Hour Post-dose
|
-2.4 milliseconds
Standard Deviation 4.06
|
-3.1 milliseconds
Standard Deviation 3.94
|
13.0 milliseconds
Standard Deviation 8.26
|
-0.1 milliseconds
Standard Deviation 5.33
|
|
Effect of Evobrutinib on ECG Parameters: QTcP Interval
2.5 Hour Post-dose
|
-3.1 milliseconds
Standard Deviation 5.59
|
-3.7 milliseconds
Standard Deviation 5.20
|
10.7 milliseconds
Standard Deviation 6.57
|
-1.3 milliseconds
Standard Deviation 4.45
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
Baseline
|
166.7 milliseconds
Standard Deviation 16.59
|
170.4 milliseconds
Standard Deviation 17.93
|
167.7 milliseconds
Standard Deviation 17.73
|
167.1 milliseconds
Standard Deviation 17.99
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
15 Minutes Post-dose
|
-0.2 milliseconds
Standard Deviation 4.66
|
-1.2 milliseconds
Standard Deviation 5.29
|
-0.8 milliseconds
Standard Deviation 4.01
|
-1.3 milliseconds
Standard Deviation 4.36
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
30 Minutes Post-dose
|
0.5 milliseconds
Standard Deviation 3.72
|
2.6 milliseconds
Standard Deviation 4.37
|
-1.2 milliseconds
Standard Deviation 5.27
|
0.1 milliseconds
Standard Deviation 5.14
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
1 Hour Post-dose
|
1.1 milliseconds
Standard Deviation 4.13
|
1.2 milliseconds
Standard Deviation 4.04
|
-1.5 milliseconds
Standard Deviation 7.52
|
-0.8 milliseconds
Standard Deviation 5.11
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
1.5 Hour Post-dose
|
1.9 milliseconds
Standard Deviation 5.11
|
0.9 milliseconds
Standard Deviation 5.15
|
-1.9 milliseconds
Standard Deviation 7.41
|
-0.9 milliseconds
Standard Deviation 5.69
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
2 Hour Post-dose
|
0.9 milliseconds
Standard Deviation 4.91
|
-0.5 milliseconds
Standard Deviation 3.59
|
-2.5 milliseconds
Standard Deviation 8.15
|
-0.3 milliseconds
Standard Deviation 5.24
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
2.5 Hour Post-dose
|
0.6 milliseconds
Standard Deviation 4.64
|
-1.8 milliseconds
Standard Deviation 5.20
|
-3.5 milliseconds
Standard Deviation 6.49
|
-1.4 milliseconds
Standard Deviation 6.69
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
3 Hour Post-dose
|
0.1 milliseconds
Standard Deviation 5.69
|
-1.5 milliseconds
Standard Deviation 5.45
|
-3.7 milliseconds
Standard Deviation 7.42
|
-3.0 milliseconds
Standard Deviation 5.16
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
4 Hour Post-dose
|
-0.5 milliseconds
Standard Deviation 7.11
|
-1.2 milliseconds
Standard Deviation 5.01
|
-3.6 milliseconds
Standard Deviation 7.77
|
-4.2 milliseconds
Standard Deviation 4.16
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
6 Hour Post-dose
|
-9.3 milliseconds
Standard Deviation 7.52
|
-9.4 milliseconds
Standard Deviation 4.73
|
-10.6 milliseconds
Standard Deviation 8.22
|
-11.1 milliseconds
Standard Deviation 8.48
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
8 Hour Post-dose
|
-8.3 milliseconds
Standard Deviation 6.98
|
-9.3 milliseconds
Standard Deviation 6.53
|
-9.3 milliseconds
Standard Deviation 7.30
|
-11.1 milliseconds
Standard Deviation 7.17
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
12 Hour Post-dose
|
-2.2 milliseconds
Standard Deviation 7.43
|
-3.9 milliseconds
Standard Deviation 8.28
|
-3.6 milliseconds
Standard Deviation 8.03
|
-2.8 milliseconds
Standard Deviation 6.28
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
16 Hour Post-dose
|
-2.6 milliseconds
Standard Deviation 8.70
|
-5.2 milliseconds
Standard Deviation 7.20
|
-3.1 milliseconds
Standard Deviation 7.95
|
-4.1 milliseconds
Standard Deviation 6.25
|
|
Effect of Evobrutinib on ECG Parameters: PR Interval
24 Hour Post-dose
|
-1.0 milliseconds
Standard Deviation 7.00
|
-2.6 milliseconds
Standard Deviation 6.14
|
-0.5 milliseconds
Standard Deviation 9.38
|
-1.2 milliseconds
Standard Deviation 7.99
|
SECONDARY outcome
Timeframe: 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 hoursPopulation: The safety analysis set included all participants who were administered any dose of any study intervention.
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.
Outcome measures
| Measure |
Evobrutinib 45mg
n=31 Participants
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
Evobrutinib 225mg
n=32 Participants
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Moxifloxacin 400mg
n=32 Participants
Participants received single oral dose of Moxifloxacin 400 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
Placebo
n=32 Participants
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
Baseline
|
91.7 milliseconds
Standard Deviation 8.28
|
91.8 milliseconds
Standard Deviation 8.24
|
91.7 milliseconds
Standard Deviation 8.11
|
91.0 milliseconds
Standard Deviation 8.12
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
15 Minutes Post-dose
|
0.1 milliseconds
Standard Deviation 1.44
|
0.3 milliseconds
Standard Deviation 1.15
|
0.1 milliseconds
Standard Deviation 1.31
|
0.4 milliseconds
Standard Deviation 1.23
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
30 Minutes Post-dose
|
0.4 milliseconds
Standard Deviation 1.25
|
0.4 milliseconds
Standard Deviation 1.41
|
-0.4 milliseconds
Standard Deviation 1.22
|
0.7 milliseconds
Standard Deviation 1.44
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
1 Hour Post-dose
|
-0.1 milliseconds
Standard Deviation 1.20
|
0.4 milliseconds
Standard Deviation 1.02
|
0.2 milliseconds
Standard Deviation 1.26
|
0.5 milliseconds
Standard Deviation 1.29
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
1.5 Hour Post-dose
|
-0.4 milliseconds
Standard Deviation 1.30
|
-0.2 milliseconds
Standard Deviation 1.29
|
-0.1 milliseconds
Standard Deviation 1.16
|
-0.1 milliseconds
Standard Deviation 1.15
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
2 Hour Post-dose
|
-0.5 milliseconds
Standard Deviation 1.17
|
-0.6 milliseconds
Standard Deviation 1.47
|
-0.1 milliseconds
Standard Deviation 1.42
|
-0.5 milliseconds
Standard Deviation 1.60
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
2.5 Hour Post-dose
|
-0.6 milliseconds
Standard Deviation 1.29
|
-0.3 milliseconds
Standard Deviation 1.64
|
-0.2 milliseconds
Standard Deviation 1.27
|
-0.3 milliseconds
Standard Deviation 1.59
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
3 Hour Post-dose
|
-0.5 milliseconds
Standard Deviation 1.35
|
-0.1 milliseconds
Standard Deviation 1.50
|
-0.1 milliseconds
Standard Deviation 1.03
|
-0.1 milliseconds
Standard Deviation 1.35
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
6 Hour Post-dose
|
-0.6 milliseconds
Standard Deviation 2.26
|
-0.5 milliseconds
Standard Deviation 2.12
|
-0.6 milliseconds
Standard Deviation 1.70
|
-0.4 milliseconds
Standard Deviation 1.98
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
8 Hour Post-dose
|
-0.8 milliseconds
Standard Deviation 1.99
|
-0.5 milliseconds
Standard Deviation 1.78
|
-0.1 milliseconds
Standard Deviation 1.82
|
0.4 milliseconds
Standard Deviation 1.97
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
12 Hour Post-dose
|
-0.2 milliseconds
Standard Deviation 1.95
|
0.2 milliseconds
Standard Deviation 2.14
|
0.2 milliseconds
Standard Deviation 1.45
|
0.2 milliseconds
Standard Deviation 1.85
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
16 Hour Post-dose
|
0.0 milliseconds
Standard Deviation 1.91
|
0.4 milliseconds
Standard Deviation 1.74
|
0.6 milliseconds
Standard Deviation 1.90
|
0.8 milliseconds
Standard Deviation 2.08
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
24 Hour Post-dose
|
0.5 milliseconds
Standard Deviation 1.93
|
0.1 milliseconds
Standard Deviation 1.22
|
0.3 milliseconds
Standard Deviation 1.31
|
0.5 milliseconds
Standard Deviation 1.43
|
|
Effect of Evobrutinib on ECG Parameters: QRS Duration
4 Hour Post-dose
|
-0.7 milliseconds
Standard Deviation 1.41
|
-0.3 milliseconds
Standard Deviation 1.71
|
-0.4 milliseconds
Standard Deviation 1.70
|
0.0 milliseconds
Standard Deviation 1.53
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
400 mg Moxifloxacin
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
45 mg Evobrutinib
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
225 mg Evobrutinib
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=32 participants at risk
Participants received single oral solution of placebo in treatment period 1, 2, 3 or 4 under fasted condition
|
400 mg Moxifloxacin
n=32 participants at risk
Participants received single oral dose of Moxifloxacin 400mg in treatment period 1, 2, 3 or 4under fasted condition
|
45 mg Evobrutinib
n=31 participants at risk
Participants received single oral dose of Evobrutinib 45 milligram (mg) in treatment period 1, 2, 3 or 4 under fasted condition
|
225 mg Evobrutinib
n=32 participants at risk
Participants received single oral dose of Evobrutinib 225 mg in treatment period 1, 2, 3 or 4 under fasted condition
|
|---|---|---|---|---|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
|
Gastrointestinal disorders
Diarrhoea
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Injury, poisoning and procedural complications
Periorbital haematoma
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
|
Investigations
Blood pressure increased
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Investigations
Lipase increased
|
0.00%
0/32 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/32 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Nervous system disorders
Headache
|
12.5%
4/32 • Up to 3 months
|
9.4%
3/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Nervous system disorders
Paraesthesia
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
|
Cardiac disorders
Ventricular extrasystoles
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
0.00%
0/31 • Up to 3 months
|
3.1%
1/32 • Up to 3 months
|
|
Cardiac disorders
Atrioventricular block second degree
|
3.1%
1/32 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
3.2%
1/31 • Up to 3 months
|
0.00%
0/32 • Up to 3 months
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place