BI 409306 Cardiac Safety Trial in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: BI 409306

• Registration Number: NCT02438683
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

This trial will be conducted to further evaluate, in a controlled setting, potential cardiac effects of an anticipated therapeutic and supra-therapeutic dose of BI 409306 under resting and exercise conditions. Since the drug is being developed in part for a disease with an expectedly high number of elderly (AD), the characterization of cardiac safety of BI 409306 is considered to be important for the development of this compound.

This trial will be conducted to further evaluate, in a controlled setting, potential cardiac effects of an anticipated therapeutic and supra-therapeutic dose of BI 409306 under resting and exercise conditions.

Since the drug is being developed in part for a disease with an expectedly high number of elderly (AD), the characterization of cardiac safety of BI 409306 is considered to be important for the development of this compound.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-04
• Study First Submitted: 2015-05-06
• Study First Submitted QC: 2015-05-06
• Study First Posted: 2015-05-08
• Primary Completion: 2015-08-12
• Study Completion: 2015-08-13
• Results First Submitted: 2023-08-10
• Results First Submitted QC: 2024-04-08
• Results First Posted: 2024-09-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo under resting/exercise conditions	Placebo	Participants received matching Placebo oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting/exercise conditions.
BI 409306 50 mg under resting/exercise conditions	BI 409306	Participants received BI 409306 50 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting/exercise conditions.
BI 409306 200 mg under resting/exercise conditions	BI 409306	Participants received BI 409306 200 mg oral dose with 240 mL of water after a standardized light breakfast on Day 1 and Day 3 under resting/exercise conditions.

Primary Outcome Measures

Name	Time	Method
Slope of the Placebo-corrected Change From Baseline of Heart Rate at Rest and Plasma Concentration Between 0 to 10 Hours	Baseline and up to 10 hours	Slope of the placebo-corrected change from baseline in resting heart rate (ΔΔHR) vs. plasma concentration of BI 409306, as assessed from 0 to 10 hours (h) after intake of trial medication. The predicted mean value (90% CI) of ΔΔHR at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Primary analysis excluded measurement with missing values. Patients with available data were included.
Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 50 mg Dose Group	Baseline and up to 4 hours	For 50 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table.
Maximum Difference to Placebo of the Change From Baseline in Heart Rate at Rest Between 0 to 4 Hours, Per 200 mg Dose Group	Baseline and up to 4 hours	For 200 mg dose, the maximal difference in the change from baseline in resting HR for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in heart rate at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 1 hour. Predicted mean changes from baseline (90% Cis) are shown in the measured value table.

Secondary Outcome Measures

Name	Time	Method
Slope of Placebo-corrected Change From Baseline of Time Between Start of the Q Wave and End of the T Wave in an ECG Corrected for Heart Rate Using the Fridericia Correction Formula (QTcF) at Rest and Plasma Concentration Between 0 to 10 Hours	Baseline and up to 10 hours	Slope of placebo-corrected change from baseline in resting Fridericia correction formula QTcF vs. plasma concentration of BI 409306, as assessed from 0 to 10 h after intake of trial medication. The predicted mean value (90% CI) of ΔΔQTcF at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table. Patients with available data were included.
Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 50 mg Dose Group	Baseline and up to 4 hours	For 50 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table.
Maximum Difference to Placebo of the Change From Baseline of QTcF at Rest to Placebo Between 0 to 4 Hours, Per 200 mg Dose Group	Baseline and up to 4 hours	For 200 mg dose, the maximal difference in the change from baseline in resting Fridericia correction formula QTcF for BI 409306 treatment compared with placebo treatment, as assessed from 0 to 4 hours after intake of trial medication (change from baseline in resting QTcF at rest between 0-4 hours at the time when maximum difference to placebo of the change from baseline was reached). The note "Not Calculated" represents that the endpoint was not planned to be analyzed for the particular arm and category as only pairwise comparisons were built, no difference to placebo is build. Maximum difference reached at 20 minutes. The predicted mean changes from baseline (90% Cis) are shown in the measured value table.
Slope of the Placebo-corrected Maximum Heart Rate During Exercise vs. Plasma Concentration of BI 409306	20 minutes and 2 hours 20 minutes after drug intake	Slope of the placebo-corrected maximum heart rate during exercise vs. plasma concentration of BI 409306. Patients with available data were included. Exercise testing was completed before gMean Cmax was reached for BI 409306 200 mg arm. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table.
Slope of the Placebo Corrected Change From Maximum Heart Rate 1 and 5 Minutes After End of Exercise and Plasma Concentration	20 minutes and 2 hours 20 minutes after drug intake	Slope of the placebo-corrected difference between maximum heart rate (HR) during exercise and recovery HR at 1 and 5 minutes (min) after the end of exercise vs. plasma concentration of BI 409306. The note "Not Calculated" represents that the plasma concentrations 1 min after the end of exercise did not reach gMean Cmax for the perticular arm. Patients with available data were included. The predicted mean value (90% CI) at geometric Mean of Cmax of the corresponding dose group is presented in the measured values table.

Trial Locations

Locations (1)

1289.28.1 Boehringer Ingelheim Investigational Site; 🇩🇪 Biberach, Germany