Clinical trial NCT03576144: This Study in Healthy Men Tests How Different Doses of BI 1265162 Are Taken up in the Body and How Well They Are Tolerated.
Official title: Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhaled Doses of BI 1265162 in Healthy Male Subjects in a Randomised, Double Blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-07-03
Enrollment: 50
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: The primary objective of this trial is to investigate the safety and tolerability of BI 1265162 in healthy male subjects following inhalative administration of multiple rising doses.

Secondary objectives is the exploration of the pharmacokinetics (PK) including dose proportionality and time dependency of BI 1265162 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 (Blood Pressure (BP), Pulse Rate (PR)), 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.)
* Forced expiratory volume in 1 second (FEV1) and Forced vital capacity (FVC) of equal or greater than 80% of predicted normal, at screening and prior to randomisation
* 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 140 mmHg, diastolic blood pressure outside the range of 50 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 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 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)
* A history of chronic kidney disease (Estimated glomerular filtration rate (EGFR)\<59 mls/min including corrections as per ethnicity)
* 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
* The subject has a diagnosis history of pulmonary hyperreactivity
* Cannot use Respimat® appropriately
* Male subjects with woman of child bearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from the first administration of trial medication until 14 days after last administration of trial medication (BI 1265162 or placebo)

Primary outcomes:
measure: Percentage of Participants With Drug-related Adverse Events (AEs)
timeFrame: From first drug administration until 2 days after last drug administration, up to 10 days.
Secondary outcomes:
measure: Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval of 0 to 12 Hour (h) After Administration of the First Dose (AUC0-12)
timeFrame: Pharmacokinetic samples were taken within 1:30 hour:minute (h:m) before dosing and 0:02, 0:05, 0:10, 0:15, 0:20 , 0:40, 1:00, 2:00, 4:00, 8:00 and 12:00 h:m after dosing on day 1.
measure: Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax)
timeFrame: Pharmacokinetic samples were taken within 1:30 hour: minute (h:m) before dosing and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 8:00, 12:00 and 24:00 h:m after dosing on day 1.
measure: Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)
timeFrame: Pharmacokinetic samples were taken 0:05 hour: minute (h:m) before dosing and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 8:00 and 12:00 h:m after last dosing on day 8.
measure: Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
timeFrame: Pharmacokinetic samples were taken 0:05 hour: minute (h:m) before dosing and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 8:00 and 12:00 h:m after last dosing on day 8.
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
Study officials:
References: