Clinical trial NCT03123185: Safety and Pharmacokinetics of Single Rising Doses of BI 705564 and Food Effect on BI 705564 in Healthy Male Subjects
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 705564 (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design) and Food Effect on a Tablet Formulation of BI 705564 (Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Design) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 91
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigation of safety, tolerability, pharmacokinetics and pharmacodynamics of single rising doses of BI 705564 and of the food effect on BI 705564 in healthy male subjects

Detailed description: The primary objective of the single rising dose part under fasting and under fed conditions is to investigate safety and tolerability of BI 705564 in healthy male subjects following oral administration of single rising doses.

Secondary objectives are the exploration of pharmacokinetics (PK) including dose proportionality, and pharmacodynamics (PD) of BI 705564 after single rising doses.

The objective of the food effect part is to explore the relative bioavailability of BI 705564 tablets under fed and fasted conditions following the oral administration of single doses.

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 (Blood Pressure \[BP\], Pulse Rate \[PR\]), 12 lead 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

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 90 to 140mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 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)
* 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 specified trial days
* 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 the 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 Electrocardiogram \[ECG\] 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

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

* Male subjects with women of childbearing potential \[WOCBP\] partner who are unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 30 days after last administration of trial medication
* Repeated absolute B cell (CD19+) counts below 40/μL at screening
* Repeated platelet counts below 100 cells/nL at screening
* Serum potassium below normal range at screening
* A history or current clinical signs of acute pancreatitis

Primary outcomes:
measure: Number of Participants With Drug-related Adverse Events (AEs)
timeFrame: From drug administration until end of the treatment, up to 15 days (for SRD fasting and fed conditions).
measure: Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (FE Part)
timeFrame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
measure: Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (FE Part)
timeFrame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Secondary outcomes:
measure: Maximum Measured Concentration of BI 705564 in Plasma (Cmax) (SRD Part)
timeFrame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
measure: Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (SRD Part)
timeFrame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
measure: Area Under the Concentration-time Curve of BI 705564 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (FE Part)
timeFrame: Pharmacokinetic samples were collected pre-dose and at 0:30 (hour: minute), 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 after drug administration.
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: Humanpharmakologisches Zentrum Biberach
Study officials:
References: