Skip to main content
OpenTrials
Completed

NCT Number: NCT03934203

This Study in Healthy Men and Women Tests Whether BI 409306 Has an Effect on the ECG (Thorough QT Study)

The primary objective of this trial is to assess the effect of BI 409306 on the QT/QTc interval in healthy male and female volunteers as measured by the QTcF change from baseline compared with placebo.

Secondary objectives are to show the assay sensitivity of the trial, by reproducing the typical effect of the positive control moxifloxacin on the QT/QTc interval, and to assess the effect of BI 409306 on heart rate.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead single Electrocardiogram (ECG) and 12-lead Holter Electrocardiogram (ECG), and clinical laboratory tests
  • Age of 18 to 50 years (incl.)
  • Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
  • Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and local legislation
  • Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion:
  • Use of adequate contraception, e.g. non-hormonal intrauterine device plus condom
  • Sexually abstinent
  • A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  • Surgically sterilised (including hysterectomy)
  • Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH above 40 U/L and estradiol below 30 ng/L is confirmatory)

Exclusion criteria

  • Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
  • Repeated measurement of systolic blood pressure outside the range of 100 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm
  • Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease judged as clinically relevant by the investigator
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • History of relevant orthostatic hypotension, fainting spells, or blackouts
  • Chronic or relevant acute infections
  • History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
  • Further exclusion criteria apply

Treatment and study plan

BI 409306

Drug

Film-coated tablet

moxifloxacin

Drug

Film-coated tablet

Other names: Avalox®

Placebo matching to BI 409306

Drug

Film-coated tablet

Primary outcomes

  1. Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between 50 mg BI 409306 and placebo takes its maximum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  2. Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between 250 mg BI 409306 and placebo takes its maximum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

Secondary outcomes

  1. Change From Baseline in QTcF at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in QTcF Changes From Baseline Between Moxifloxacin and Placebo Takes Its Maximum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in QTcF changes from baseline between moxifloxacin and placebo takes its maximum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  2. Change From Baseline in QTcF at 2 Hours After Drug Administration (Assessment of Assay Sensitivity)

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 2 hours after drug administration.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  3. Change From Baseline in QTcF at 3 Hours After Drug Administration (Assessment of Assay Sensitivity)

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 3 hours after drug administration.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  4. Change From Baseline in QTcF at 4 Hours After Drug Administration (Assessment of Assay Sensitivity)

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    QTcF is the QT interval (Electrocardiogram (ECG) interval from the beginning of the QRS complex to the end of the T wave) corrected using Fridericia's formula. Change from baseline in QTcF at 4 hours after drug administration.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for moxifloxacin and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  5. Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Maximum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    Change from baseline in heart rate (HR) at each timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 50 milligram (mg) BI 409306 and placebo takes its maximum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  6. Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Maximum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 250 milligram (mg) BI 409306 and placebo takes its maximum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  7. Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 50 Milligram (mg) BI 409306 and Placebo Takes Its Minimum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 50 milligram (mg) BI 409306 and placebo takes its minimum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 50 mg BI 409306 and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

  8. Change From Baseline in Heart Rate (HR) at That Timepoint Between 20 Minutes to 24 Hours After Drug Administration Where the Difference of Means in Heart Rate Changes From Baseline Between 250 Milligram (mg) BI 409306 and Placebo Takes Its Minimum

    Time frame: Baseline, 20 minutes (min), 40 min, 1 hour (h), 1 h 30 min, 2 h, 2 h 30 min, 3 h, 4 h, 8 h, 12 h, 24 h after study drug administration

    Change from baseline in heart rate (HR) at that timepoint between 20 minutes to 24 hours after drug administration where the difference of means in heart rate changes from baseline between 250 milligram (mg) BI 409306 and placebo takes its minimum.

    A linear mixed-effects model for repeated measurements based on Schall and Ring (MMRM) was fitted to the observations for 250 mg BI 409306 and the 2 placebo periods.

    Total number of participants per treatment and timepoint can be lower than 47 due to participants having left their treatment sequence before being exposed to the respective treatment, or due to exclusion of individual participant ECG data at timepoints affected by ECG-relevant important protocol deviations.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

Thorough QT Study to Evaluate the Effects of BI 409306 as Single Dose on Cardiac Safety Parameters in Healthy Male and Female Subjects. A Randomized, Placebo Controlled, Double-blind, Five-period Crossover Study With (Open-label) Moxifloxacin as Positive Control

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
May 1, 2019
Registry last updated
Mar 12, 2024

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.