Multiple Rising Oral Doses of BI 691751 in Healthy Male Subjects

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 691751 in Healthy Male Subjects

It is the objective of this MRD trial to investigate pharmacokinetics, pharmcodynamics, safety and tolerability of rising doses BI 691751 over a treatment period of 14 days to support the further clinical development of this LTA4H-inhibitor. Special emphasis will be given to detect potential effects of BI 691751 on heart rate.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751; Drug: BI 691751

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1334.2.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Healthy male subjects according to the investigator´s assessment, based on a complete medical history including a physical examination, vital signs (BP (blood pressure), PR (pulse rate), 12-lead ECG (electro cardiogramm), and clinical laboratory tests
• Age of 18 to 50 years (incl.)
• BMI (body mass index) of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP(Good Clinical Practice) and local legislation
• Subject is able to understand and communicate in German

Exclusion criteria:

• Any finding in the medical examination (including BP (blood pressure), PR (pulse rate) or ECG (electro cardiogramm) is deviating from normal and judged as clinically relevant by the investigator
• Pulse rate outside 45-80 bpm (beats per minutes) or repeated measurement of systolic blood pressure greater than 140 mmHg, diastolic blood pressure greater than 90 mm Hg
• 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
• Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication
• Diseases of the central nervous system (such as epilepsy), other neurological disorders 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 (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking during inhouse-confinement
• Alcohol abuse (consumption of more 30 g per day for males)
• 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 in males) or any other relevant ECG finding at screening
• A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, 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
• Vulnerable subjects, e.g. subjects kept in detention, soldiers, employees of the sponsor or a clinical research organization, involved in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: BI 691751 Dose 1; multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1; Drug: BI 691751; BI 691751 Dose 2; Drug: BI 691751; BI 691751 Dose 3; Drug: BI 691751; BI 691751 Dose 4; Drug: BI 691751; BI 691751 Dose 5; Drug: BI 691751; BI 691751 Dose 6
Experimental: BI 691751 Dose 2; multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1; Drug: BI 691751; BI 691751 Dose 2; Drug: BI 691751; BI 691751 Dose 3; Drug: BI 691751; BI 691751 Dose 4; Drug: BI 691751; BI 691751 Dose 5; Drug: BI 691751; BI 691751 Dose 6
Experimental: BI 691751 Dose 3; multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1; Drug: BI 691751; BI 691751 Dose 2; Drug: BI 691751; BI 691751 Dose 3; Drug: BI 691751; BI 691751 Dose 4; Drug: BI 691751; BI 691751 Dose 5; Drug: BI 691751; BI 691751 Dose 6
Experimental: BI 691751 Dose 4; multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1; Drug: BI 691751; BI 691751 Dose 2; Drug: BI 691751; BI 691751 Dose 3; Drug: BI 691751; BI 691751 Dose 4; Drug: BI 691751; BI 691751 Dose 5; Drug: BI 691751; BI 691751 Dose 6
Experimental: BI 691751 Dose 5; multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1; Drug: BI 691751; BI 691751 Dose 2; Drug: BI 691751; BI 691751 Dose 3; Drug: BI 691751; BI 691751 Dose 4; Drug: BI 691751; BI 691751 Dose 5; Drug: BI 691751; BI 691751 Dose 6
Experimental: BI 691751 Dose 6; multiple dose given over 14 days	Drug: BI 691751; BI 691751 Dose 1; Drug: BI 691751; BI 691751 Dose 2; Drug: BI 691751; BI 691751 Dose 3; Drug: BI 691751; BI 691751 Dose 4; Drug: BI 691751; BI 691751 Dose 5; Drug: BI 691751; BI 691751 Dose 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Drug-related Adverse Events	Percentage of subjects with drug-related Adverse events (AEs)	From the time of administration of the respective treatment until 21 days after last administration of study drug or start of the post-study phase to the respective treatment, up to 35 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCt,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval t After Administration of the First Dose)	AUCt,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t after administration of the first dose). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.	0 minutes (min), 10min, 20min, 40min, 1 hour (h), 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after first drug administration
Cmax (Maximum Measured Concentration of the Analyte Inplasma)	Cmax (maximum measured concentration of the analyte inplasma). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.	0 minutes (min), 10min, 20min, 40min, 1 hour (h), 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h and 24h after first drug administration
AUCt,ss (Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t)	AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.	312 hours (h), 312 h 10 minutes (min), 312h 20min, 312h 40min, 313, 313h 30min, 314h, 315h, 316h, 318h, 320h, 322h, 324h and 336h after first drug administration
Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t)	Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t). This endpoint could not be calculated as no PK blood samples were analysed due to the early termination of the study.	312 hours (h), 312 h 10 minutes (min), 312h 20min, 312h 40min, 313, 313h 30min, 314h, 315h, 316h, 318h, 320h, 322h, 324h and 336h after first drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 23, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Estimate): February 29, 2016
• Last Update Submitted That Met QC Criteria: February 1, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: 1334.2; 2013-003813-17 (EudraCT Number: EudraCT)