Healthy
Conditions
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 single rising doses. Secondary objective is the exploration of the pharmacokinetics (PK) of BI 1265162 after single dosing.
Detailed description
To investigate safety, tolerability and pharmacokinetics of BI 1265162 in man.
Interventions
DRUGBI 1265162
Single rising dose groups
DRUGPlacebo
Single rising dose groups
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.) * Forced Expiratory Volume in one 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 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 * 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 (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 * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events (AEs) | From drug administration until end of trial examination, up to 9 days | Percentage of participants with drug-related adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | Pharmacokinetic samples were taken pre-dose and 0:02 (hour: minute), 0:05, 0:10, 0:15, 0:20 , 0:30, 0:45, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 48:00 and 72:00 (Last time point only taken for 1200 µg) after drug administration | Maximum measured concentration of BI 1265162 in plasma (Cmax). |
| Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | Pharmacokinetic samples were taken pre-dose and 0:02 (hour: minute), 0:05, 0:10, 0:15, 0:20 , 0:30, 0:45, 1:00 after drug administration | Area under the concentration-time curve of the BI 1265162 in plasma over the time interval 0 to 1 hour post-dose (AUC0-1) |
Countries
Germany
Participant flow
Recruitment details
This was single-blind, partially randomised, and placebo controlled within parallel dose groups trial. A total of 57 participants were entered and 56 were treated. The dose range for Treatment A to Treatment G was 3 μg to 1200 μg.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| 3 Microgram BI 1265162 3 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| 10 Microgram BI 1265162 10 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| 30 Microgram BI 1265162 30 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| 100 Microgram BI 1265162 100 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| 300 Microgram BI 1265162 300 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| 600 Microgram BI 1265162 600 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| 1200 Microgram BI 1265162 1200 microgram BI 1265162 solution for inhalation was administered orally via Respimat® inhaler. | 6 |
| Placebo Matching BI 1265162 Subjects administered single dose of placebo matching BI 1265162 solution for inhalation orally via Respimat® inhaler. | 14 |
| Total | 56 |
Baseline characteristics
| Characteristic | 3 Microgram BI 1265162 | 10 Microgram BI 1265162 | 30 Microgram BI 1265162 | 100 Microgram BI 1265162 | 300 Microgram BI 1265162 | 600 Microgram BI 1265162 | 1200 Microgram BI 1265162 | Placebo Matching BI 1265162 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.3 Years STANDARD_DEVIATION 3.6 | 31.8 Years STANDARD_DEVIATION 5.2 | 28.7 Years STANDARD_DEVIATION 4.7 | 44.7 Years STANDARD_DEVIATION 5.6 | 32.0 Years STANDARD_DEVIATION 7.3 | 34.5 Years STANDARD_DEVIATION 8.9 | 38.8 Years STANDARD_DEVIATION 9.8 | 35.1 Years STANDARD_DEVIATION 11 | 34.7 Years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 13 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 14 Participants | 55 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 14 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 0 / 6 | 1 / 6 | 2 / 14 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 14 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events (AEs)
Percentage of participants with drug-related adverse events (AEs).
Time frame: From drug administration until end of trial examination, up to 9 days
Population: Treated set(TS): This subject set included all subjects who had received at least 1 dose of trial medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0 Percentage of participants (%) |
| 10 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0 Percentage of participants (%) |
| 30 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0 Percentage of participants (%) |
| 100 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants (%) |
| 300 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 16.7 Percentage of participants (%) |
| 600 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0 Percentage of participants (%) |
| 1200 Microgram BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0 Percentage of participants (%) |
| Placebo Matching BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0 Percentage of participants (%) |
Secondary
Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1)
Area under the concentration-time curve of the BI 1265162 in plasma over the time interval 0 to 1 hour post-dose (AUC0-1)
Time frame: Pharmacokinetic samples were taken pre-dose and 0:02 (hour: minute), 0:05, 0:10, 0:15, 0:20 , 0:30, 0:45, 1:00 after drug administration
Population: The Pharmacokinetic set (PKS) included all subjects of the TS who received BI 1265162 and provided at least 1 PK parameter that was not excluded due to relevant protocol violations or due to PK non-evaluability. Only subjects with non-missing values were included in the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 3 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 10.4 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 42.4 |
| 10 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 28.7 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 49 |
| 30 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 73.7 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 43.4 |
| 100 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 299.0 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 45.2 |
| 300 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 706.0 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 25.9 |
| 600 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 1700.0 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 34.5 |
| 1200 Microgram BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma Over the Time Interval 0 to 1 Hour Post-dose (AUC0-1) | 3920.0 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 76.4 |
Comparison: The model consisted of a regression model applied to log-transformed data. The corresponding ANCOVA model included the logarithm of the dose as a covariate.95% CI: [0.9207, 1.0577]
Secondary
Maximum Measured Concentration of BI 1265162 in Plasma (Cmax)
Maximum measured concentration of BI 1265162 in plasma (Cmax).
Time frame: Pharmacokinetic samples were taken pre-dose and 0:02 (hour: minute), 0:05, 0:10, 0:15, 0:20 , 0:30, 0:45, 1:00, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 48:00 and 72:00 (Last time point only taken for 1200 µg) after drug administration
Population: The Pharmacokinetic set (PKS) included all subjects of the TS who received BI 1265162 and provided at least 1 PK parameter that was not excluded due to relevant protocol violations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 3 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 17.8 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 32.9 |
| 10 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 50.1 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 46.6 |
| 30 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 129.0 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 40.1 |
| 100 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 462.0 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 53.2 |
| 300 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 1090.0 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 26 |
| 600 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 3130.0 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 30.6 |
| 1200 Microgram BI 1265162 | Maximum Measured Concentration of BI 1265162 in Plasma (Cmax) | 6500.0 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 73.1 |
Comparison: The model consisted of a regression model applied to log-transformed data. The corresponding ANCOVA model included the logarithm of the dose as a covariate.95% CI: [0.9155, 1.0457]