BI 409306 Cardiac Safety Trial in Healthy Volunteers

A Randomized, Double-blind, Double Dummy, Placebo-controlled, Three-way Crossover Study to Assess Cardiac Effects After Single Oral Doses of BI409306 Under Resting and Exercise Conditions in Healthy Male Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 409306; Drug: BI 409306

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1289.28.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

- Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests.

• Age of 18 to 45 years (incl.)
• BMI of 18.5 to 29.9 kg/m2 (incl.)
• Waist-to-height ratio less than 0.5
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
• Ready and able to use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the subject information.

Exclusion criteria:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator

• Repeated measurement of

  • Systolic blood pressure less than 90 mm Hg or more than140 mmHg
  • Diastolic blood pressure less than 50 mm Hg or more than 90 mmHg
  • Pulse rate less than 45 bpm or more than 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 PK 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)
• Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication
• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication
• Smoker (unless the subject quit smoking for at least 30 days prior to screening)
• Alcohol abuse (consumption of more than 30 g per day)
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
• Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
• Any suicidal ideation of type 2 to 5 on the C-SSRS in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
• Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour).

In addition, the following trial-specific exclusion criteria apply:

• CYP2C19 PM (no treatment allocation)
• History of macular degeneration
• Beard or unwillingness to shave for the trial (to facilitate appropriate measurements during CPX which requires wearing a face mask)
• Physical disability that precludes safe and adequate CPX investigation
• Known latex allergy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1 Placebo; 2 x single doses (1x resting conditions, 1 x exercise conditions)	Drug: Placebo; single dose, oral administration
Experimental: 2 BI 409306; 2 x single doses (1 x resting conditions, 1 x exercise conditions)	Drug: BI 409306; medium dose, single dose, oral administration; Drug: BI 409306; low dose, single dose, oral administration
Experimental: 3 BI 409306; 2 x single doses (1 x resting conditions, 1 x exercise conditions)	Drug: BI 409306; medium dose, single dose, oral administration; Drug: BI 409306; low dose, single dose, oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
- Slope between placebo-corrected change from baseline of heart rate at rest and plasma concentration between 0-10 hours	up to 10 hours
- Maximum difference to placebo of the change from baseline in heart rate at rest between 0-4 hours, per dose group	up to 4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
- Slope between placebo-corrected change from baseline of QTcF at rest and plasma concentration between 0-10 hours	up to 10 hours
- Maximum difference to placebo of the change from baseline of QTcF at rest to placebo between 0-4 hours, per dose group	up to 4 hours
- Slope between the difference of placebo and verum in maximal heart rate at exercise and plasma concentration	up to 58 hours
- Slope between placebo corrected change from max heart rate 1 and 5 minutes after end of exercise and plasma concentration	up to 58 hours

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 6, 2015
• First Submitted That Met QC Criteria: May 6, 2015
• First Posted (Estimate): May 8, 2015

Study Record Updates

• Last Update Posted (Estimate): September 24, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; BI 409306
• Other Study ID Numbers: 1289.28; 2014-005132-34 (EudraCT Number: EudraCT)