Study to Gather Information on the Influence of BAY1817080 on the Electrical Activity of the Heart Recorded by an Electrocardiogram in Healthy Male and Female Participants

Randomized, Single-blind, Double-dummy, 4-fold Cross-over, Placebo- and Active-controlled Study to Investigate the Influence of BAY 1817080 on the QTc Interval in Healthy Male and Female Participants (TQT Study)

In this study, researchers want to find whether the study drug BAY1817080 has an effect on the electrocardiogram (ECG). 40 healthy male or female participants with the age of 18 to 65 years will be enrolled into this study. The ECG of the participants will be monitored closely by the researchers to detect any change after intake of the study medication.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder; Cough; Endometriosis
• Intervention / Treatment: Drug: BAY1817080; Drug: Moxifloxacin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167
      • CRS Clinical Research Services Mannheim GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men must be 18 to 65 years of age inclusive, women must be 40 to 65 years of age inclusive at the time of signing the informed consent
• Female participants have to be in postmenopausal state
• Body mass index (BMI) within the range 18.0-32.0 kg/m^2 (inclusive)
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, ECG, and vital signs
• 12-lead electrocardiogram recording without signs of clinically relevant pathology

Exclusion Criteria:

• A history of relevant diseases of vital organs, of the central nervous system or other organs
• Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study intervention will not be normal
• Known hypersensitivity to the study interventions (active substances, or excipients of the preparations)
• Known severe allergies e.g. allergies to more than 3 allergens, allergies affecting the lower respiratory tract - allergic asthma, allergies requiring therapy with corticosteroids, urticaria or significant nonallergic drug reactions
• Febrile illness within 1 week before study intervention administration
• Known or suspected disorder of the liver (e.g. bile secretion/flow disorder, Morbus Meulengracht (Gilbert´s syndrome), drug-induced hepatitis etc.)
• History of disorder of the pancreas or evidence for past or present pancreas disorders indicated by clinically relevant lipase or amylase levels above ULN and typical clinical symptoms of pancreas disorders as e.g. upper abdominal pain spread to the back, weight loss, fatty or pale stools
• Participants with thyroid disorders as evidenced by assessment of thyroid stimulating hormone (TSH) levels outside the normal reference range at screening (inclusion with normal fT3/fT4 levels allowed)
• History of known or suspected malignant tumors
• History of hypokalemia
• Use of CYP3A4 inhibitors from 14 days before study intervention administration until the last study visit
• Use of CYP3A4 inducers within 4 weeks (or at least five half-lives of the active substance whatever is longer) prior to study intervention administration
• Smoking more than 10 cigarettes daily
• Suspicion of drug or alcohol abuse
• Plasmapheresis within 3 months prior to study drug administration
• Excluded physical therapies that might alter the PK or safety results of the study (e.g. physiotherapy, acupuncture, etc.) from 7 days before first study drug administration until follow-up
• Systolic blood pressure below 100 mmHg or above 140 mmHg at screening. Difference of systolic BP between both arms >15 mmHg
• Diastolic blood pressure below 50 mmHg or above 90 mmHg at screening
• Heart rate below 50 beats/ min or above 90 beats/ min at screening
• History of COVID-19
• Prior contact with SARS-CoV-2 positive or COVID-19 patient within the last 4 weeks prior admission to the ward
• Positive SARS-CoV-2 viral test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention ABCD; Intervention A: Day 1 and 2: Supra-therapeutic dose of BAY1817080, three times daily (tid) Day 3: Supra-therapeutic dose of BAY1817080 and placebo to moxifloxacin, once Intervention B: Day 1 and 2: therapeutic dose of BAY1817080 and placebo to BAY1817080, tid Day 3: therapeutic dose of BAY1817080, placebo to BAY1817080 and placebo to moxifloxacin, once Intervention C: Day 1 and 2: Placebo to BAY1817080, tid Day 3: Placebo to BAY1817080 and moxifloxacin, once Intervention D: Day 1 and 2: Placebo to BAY1817080, tid Day 3: Placebo to BAY1817080 and placebo to moxifloxacin, once Subjects will receive intervention A, B, C and D sequentially. The washing-out period between each intervention is at least 14 days	Drug: BAY1817080; Film-coated tablet; Drug: Moxifloxacin; Film-coated tablet; Drug: Placebo; Matched placebo as film-coated tablet
Experimental: Intervention BCDA; Subjects will receive intervention B, C, D and A sequentially. The washing-out period between each intervention is at least 14 days	Drug: BAY1817080; Film-coated tablet; Drug: Moxifloxacin; Film-coated tablet; Drug: Placebo; Matched placebo as film-coated tablet
Experimental: Intervention CDAB; Subjects will receive intervention C, D, A and B sequentially. The washing-out period between each intervention is at least 14 days	Drug: BAY1817080; Film-coated tablet; Drug: Moxifloxacin; Film-coated tablet; Drug: Placebo; Matched placebo as film-coated tablet
Experimental: Intervention DABC; Subjects will receive intervention D, A, B and C sequentially. The washing-out period between each intervention is at least 14 days Note: the intervention sequences in this and above arms are examples, the actual order of intervention may differ from these examples	Drug: BAY1817080; Film-coated tablet; Drug: Moxifloxacin; Film-coated tablet; Drug: Placebo; Matched placebo as film-coated tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 therapeutic dose	Baseline and Day 3
Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after multiple oral doses of BAY1817080 supra-therapeutic dose	Baseline and Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-matched, placebo-corrected change from baseline of the individually corrected QT interval after a single oral dose of moxifloxacin		Baseline and Day 3
Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose		Baseline and Day 3
Time-matched, placebo-corrected change from baseline of the QT interval corrected according to Fridericia (QTcF) and Bazett (QTcB) after a single oral dose of moxifloxacin		Baseline and Day 3
AUC(0-24)md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose	Area under the concentration vs. time curve from zero to 24 hours after multiple doses	Predose and up to 24 hours after last dose of BAY1817080 at Day 3
AUC after a single oral dose of moxifloxacin	Area under the concentration vs. time curve from zero to infinity after single dose	Predose and up to 24 hours after single dose of moxifloxacin at Day 3
Cmax,md after multiple oral doses of BAY1817080 therapeutic or supra-therapeutic dose	Maximum observed drug concentration in measured matrix after multiple doses	Up to 24 hours after last dose of BAY1817080 at Day 3
Cmax after a single oral dose of moxifloxacin	Maximum observed drug concentration in measured matrix after single dose	Up to 24 hours after single dose of moxifloxacin at Day 3
Incidences of treatment-emergent adverse events (TEAEs) after BAY1817080 therapeutic or supra-therapeutic dose		From the start of BAY1817080 administration until 7 days after last dose, assessed up to 10 days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): November 9, 2020
• Study Completion (Actual): January 21, 2021

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Endometriosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: 21198; 2020-000516-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

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