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Completed

NCT Number: NCT07214935

A TQT Study of Effect of M2951 on Cardiac Repolarization

The purpose of this study is to assess potential effects of M2951 on cardiac repolarization (i.e. prolongation of QT interval).

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Key information

Conditions

Healthy

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Nuvisan GmbH

Neu-Ulm, Germany

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo matched to M2951

Drug

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.

moxifloxacin

Drug

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.

M2951 Low Dose

Drug

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.

Other names: Evobrutinib, MSC2364447C

M2951 High Dose

Drug

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.

Other names: Evobrutinib, MSC2364447C

Primary outcomes

  1. Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Evobrutinib

    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

    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 outcomes

  1. Placebo-corrected Change From Baseline in Corrected QT Interval by Fridericia' Formula (QTcF) for Moxifloxacin

    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

    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.

  2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame: 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.

  3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on Severity

    Time frame: 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:

    • 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.

  4. Number of Participants With Clinically Significant Abnormalities From Baseline in Safety Laboratory Tests

    Time frame: 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.

  5. Number of Participants With Clinically Significant Abnormalities From Baseline in Vital Signs

    Time frame: 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.

  6. Number of Participants With Clinically Significant Changes From Baseline in Electroencephalogram (EEG) and Electrocardiogram (ECG) Findings

    Time frame: 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.

  7. Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) of Evobrutinib

    Time frame: 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.

  8. Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Evobrutinib

    Time frame: 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.

  9. Maximum Observed Plasma Concentration (Cmax) of Evobrutinib

    Time frame: 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.

  10. Time to Reach Maximum Blood Concentration (Tmax) of Evobrutinib

    Time frame: 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.

  11. Apparent Terminal Half-life (t1/2) of Evobrutinib

    Time frame: 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.

  12. Area Under the Blood-Concentration Time Curve From Time Zero to 24 Hours Post-Dose (AUC 0-24) Of Moxifloxacin

    Time frame: 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.

  13. Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin

    Time frame: 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.

  14. Area Under the Plasma-Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Moxifloxacin

    Time frame: 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.

  15. Time to Reach Maximum Blood Concentration (Tmax) of Moxifloxacin

    Time frame: 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.

  16. Effect of Evobrutinib on ECG Parameters: ECG Mean Heart Rate

    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

    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.

  17. Effect of Evobrutinib on ECG Parameters: RR Interval

    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

    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.

  18. Effect of Evobrutinib on ECG Parameters: QT Interval

    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

    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.

  19. Effect of Evobrutinib on ECG Parameters: QTcF Interval

    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

    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.

  20. Effect of Evobrutinib on ECG Parameters: QTcP Interval

    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

    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.

  21. Effect of Evobrutinib on ECG Parameters: PR Interval

    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

    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.

  22. Effect of Evobrutinib on ECG Parameters: QRS Duration

    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

    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.

Sponsors and collaborators

Lead sponsor

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

A Single-Dose, Randomized, Double-Blind, Placebo- and Positive-Controlled, 4-Way Crossover Study to Evaluate the Effect of Evobrutinib on the QTc (Corrected QT) Interval in Healthy Adult Participants

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Oct 9, 2025
Registry last updated
Nov 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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