A TQT Study to Investigate the Effect of Enpatoran on Cardiac Repolarization in Healthy Participants

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: Enpatoran low dose; Drug: Enpatoran high dose

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany
    • Nuvisan GmBH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• Participants are overtly healthy, as determined by medical evaluation, including no clinically significant abnormality identified on medical history, physical examination, vital signs, 12-lead ECG, 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 the range 50.0 to 100.0 kilograms (kg) (inclusive) and body mass index (BMI) within the range 19.0 to 30.0 kilograms per square meter (kg/m^2) (inclusive)
• Other protocol defined inclusion criteria could apply

Exclusion criteria:

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, 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
• Individuals with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease
• Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to the first administration of study intervention
• History of malignancy (e.g. hematologic, skin, solid tumor) less than or equal to (<=) 10 years prior to Screening
• History of chronic or recurrent acute infection or any bacterial, viral, parasitic, or fungal infections within 30 days prior to Screening and at any time between Screening and admission to CRU, or hospitalization due to infection within 6 months prior to the first administration of study intervention
• History of shingles within 12 months prior to Screening
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1: A-B-C-D; Participants will receive a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 1, followed by a single oral dose of moxifloxacin tablet (Treatment B) in treatment period 2, followed by a single oral low dose of enpatoran tablet (Treatment C) in treatment period 3, followed by a single oral high dose of enpatoran tablet (Treatment D) in treatment period 4. There will be a washout period of at least 10 days between each treatment period.	Drug: Placebo; Participants will receive a single oral dose of placebo matched to enpatoran in either of treatment period 1, 2, 3 and 4.; Drug: Moxifloxacin; Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in either of treatment period 1, 2, 3 and 4.; Drug: Enpatoran low dose; Participants will receive a single oral low dose of enpatoran tablet (Treatment C) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049; Drug: Enpatoran high dose; Participants will receive a single oral high dose of enpatoran tablet (Treatment D) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049
Experimental: Treatment Sequence 2: B-D-A-C; Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in treatment period 1, followed by a single oral high dose of enpatoran tablet (Treatment D) in treatment period 2, followed by a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 3, followed by a single oral low dose of enpatoran tablet (Treatment C) in treatment period 4. There will be a washout period of at least 10 days between each treatment period.	Drug: Placebo; Participants will receive a single oral dose of placebo matched to enpatoran in either of treatment period 1, 2, 3 and 4.; Drug: Moxifloxacin; Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in either of treatment period 1, 2, 3 and 4.; Drug: Enpatoran low dose; Participants will receive a single oral low dose of enpatoran tablet (Treatment C) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049; Drug: Enpatoran high dose; Participants will receive a single oral high dose of enpatoran tablet (Treatment D) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049
Experimental: Treatment Sequence 3: C-A-D-B; Participants will receive a single oral low dose of enpatoran tablet (Treatment C) in treatment period 1, followed by a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 2, followed by a single oral high dose of enpatoran tablet (Treatment D) in treatment period 3, followed a by single oral of moxifloxacin tablet (Treatment B) in treatment period 4. There will be a washout period of at least 10 days between each treatment period.	Drug: Placebo; Participants will receive a single oral dose of placebo matched to enpatoran in either of treatment period 1, 2, 3 and 4.; Drug: Moxifloxacin; Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in either of treatment period 1, 2, 3 and 4.; Drug: Enpatoran low dose; Participants will receive a single oral low dose of enpatoran tablet (Treatment C) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049; Drug: Enpatoran high dose; Participants will receive a single oral high dose of enpatoran tablet (Treatment D) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049
Experimental: Treatment Sequence 4: D-C-B-A; Participants will receive a single oral high dose of enpatoran tablet (Treatment D) in treatment period 1, followed by a single oral low dose of enpatoran (Treatment C) in treatment period 2, followed by a single oral dose of moxifloxacin tablet (Treatment B) in treatment period 3, followed by a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 4. There will be a washout period of at least 10 days between each treatment period.	Drug: Placebo; Participants will receive a single oral dose of placebo matched to enpatoran in either of treatment period 1, 2, 3 and 4.; Drug: Moxifloxacin; Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in either of treatment period 1, 2, 3 and 4.; Drug: Enpatoran low dose; Participants will receive a single oral low dose of enpatoran tablet (Treatment C) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049; Drug: Enpatoran high dose; Participants will receive a single oral high dose of enpatoran tablet (Treatment D) in either of treatment period 1, 2, 3 and 4.; Other Names: M5049

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-Corrected Change from Baseline in Heart Rate-Corrected QT Interval by Fridericia's Formula (QTcF) for Enpatoran	Pre-dose on Day 1 (baseline) up to 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Placebo-Corrected Change from Baseline in Heart Rate-Corrected QT Interval by Fridericia's Formula (QTcF) for Moxifloxacin	Pre-dose on Day 1 (baseline) up to 24 hours post-dose
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Up to approximately 72 days
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) by Severity	Up to approximately 72 days
Number of Participants with Abnormal Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Findings	Up to approximately 72 days
ECG Parameters: QT Interval, heart rate-corrected QT interval (QTc), individual corrected QT interval (QTcI), PR Interval, QRS interval and RR Interval	Pre-dose up to 24 hours post-dose
ECG Parameter: Heart Rate (HR)	Pre-dose up to 24 hours post-dose
Number of Participants with T-wave Morphology Changes and U-wave Presence	Pre-dose up to 24 hours post-dose
Pharmacokinetic (PK) Plasma Concentrations of Enpatoran	Pre-dose up to 24 hours post-dose
Pharmacokinetic (PK) Plasma Concentrations of Moxifloxacin	Pre-dose up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Actual): December 2, 2024
• Study Completion (Actual): December 2, 2024

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: September 6, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Moxifloxacin
• Other Study ID Numbers: MS200569_0065; 2024-512841-17-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website http://bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No