Clinical trial NCT03230487: This Study Tests How Healthy Men Tolerate Different Doses of BI1015550. The Study Also Tests How BI 1015550 is Taken up by the Body
Official title: Safety, Tolerability, and Pharmacokinetics of Single (Part 1) and Multiple Rising Oral Doses (Part 2) of BI 1015550 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-07-26
Enrollment: 42
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Part 1 (SRD (Single-rising dose)):

The primary objective of this trial part is to investigate the safety and tolerability of BI 1015550 in healthy male subjects following oral administration of single rising doses.

Secondary objectives are the exploration of the pharmacokinetics of BI 1015550 after single dosing.

Part 2 (MRD (Multiple-rising dose)):

In Part 2, the primary objective is to investigate the safety and tolerability of BI 1015550 in healthy male subjects following oral administration of multiple rising doses.

Secondary objectives are the exploration of the pharmacokinetics of BI 1015550 after multiple dosing.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs, 12-lead Electrocardiogram (ECG), and clinical laboratory tests
* Age of 18 to 45 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

Exclusion Criteria:

* Any finding in the medical examination (including vital signs 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 90 to 140 mmHg, diastolic blood pressure outside the range of 55 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (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)
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders, including but not limited to mood disorders and any history of suicidality.
* 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)
* Use of drugs within 30 days prior to administration of trial medication if that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
* Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
* Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (consumption of more than 20 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, 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
* Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two months after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two months)

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

* Positive or missing fecal occult blood (no retest allowed),
* Positive testing for fecal calprotectin (retest allowed)
* Positive testing for hematuria if confirmed by microscopic urine analysis (retest allowed)
* Any lifetime history of suicidal behavior (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior)
* Any suicidal ideation (i.e. type 1-5) on the Columbia Suicidal Severity Rating (C-SSRS) in the past 12 months (i.e.passive/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) (only Part 2)

Primary outcomes:
measure: Number [N (%)] of subjects with drug-related Adverse Events (AEs)
timeFrame: Up to 9 days (Part 1)
measure: Number [N (%)] of subjects with drug-related Adverse Events (AEs)
timeFrame: Up to 28 days (Part 2)
Secondary outcomes:
measure: Part 1 (SRD): AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 120 hours
measure: Part 1 (SRD): Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: up to 120 hours
measure: Part 2 (MRD): After the first dose - AUCtau,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval tau after administration of the first dose)
timeFrame: up to 48 hours
measure: Part 2 (MRD): After the first dose - Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: up to 48 hours
measure: Part 2 (MRD): After the last dose - AUCtau,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval tau)
timeFrame: up to 504 hours
measure: Part 2 (MRD): After the last dose - Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval tau)
timeFrame: up to 504 hours
measure: RA,Cmax (accumulation ratio based on Cmax,ss)
timeFrame: up to 504 hours
measure: RA,AUC (accumulation ratio based on AUC0-tau)
timeFrame: up to 504 hours
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
Study officials:
References: