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 multiple rising doses. Secondary objectives is the exploration of the pharmacokinetics (PK) including dose proportionality and time dependency of BI 1265162 after multiple dosing
Interventions
DRUGBI 1265162
Multiple rising inhaled doses
DRUGPlacebo
Multiple rising inhaled doses
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 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 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events (AEs) | From first drug administration until 2 days after last drug administration, up to 10 days. | Percentage of participants with drug-related adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. | 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). |
| Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax) | 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. | Maximum measured concentration of the BI 1265162 in plasma after administration of the first dose (Cmax). |
| Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 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. | Area under the concentration-time curve of the BI 1265162 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss). |
| Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 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. | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss). |
Countries
Germany
Participant flow
Recruitment details
This Multiple rising dose (MRD) trial was designed as double-blind, randomised, and placebo-controlled within parallel dose groups.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended a specialist site 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 |
|---|---|
| Placebo Matching BI 1265162 Participants were administered single and multiple dose of placebo matching BI 1265162 solution for inhalation orally via Respimat® A5 inhaler. On days 1 and 8 participant received a single dose in the morning only. On all other trial days (Days 2 to 7), placebo matching BI 1265162 was administered twice daily. | 10 |
| 10 Microgram (μg) BI 1265162 Participants were administered single and multiple dose of 10 μg BI 1265162 solution for inhalation orally via Respimat® A5 inhaler. On days 1 and 8 participant received a single dose in the morning only. On all other trial days (Days 2 to 7), 10 μg BI 1265162 was administered twice daily. | 8 |
| 30 μg BI 1265162 Participants were administered single and multiple dose of 30 μg BI 1265162 solution for inhalation orally via Respimat® A5 inhaler. On days 1 and 8 participant received a single dose in the morning only. On all other trial days (Days 2 to 7), 30 μg BI 1265162 was administered twice daily. | 8 |
| 100 μg BI 1265162 Participants were administered single and multiple dose of 100 μg BI 1265162 solution for inhalation orally via Respimat® A5 inhaler. On days 1 and 8 participant received a single dose in the morning only. On all other trial days (Days 2 to 7), 100 μg BI 1265162 was administered twice daily. | 8 |
| 300 μg BI 1265162 Participants were administered single and multiple dose of 300 μg BI 1265162 solution for inhalation orally via Respimat® A5 inhaler. On days 1 and 8 participant received a single dose in the morning only. On all other trial days (Days 2 to 7), 300 μg BI 1265162 was administered twice daily. | 8 |
| 600 μg BI 1265162 Participants were administered single and multiple dose of 600 μg BI 1265162 solution for inhalation orally via Respimat® A5 inhaler. On days 1 and 8 participant received a single dose in the morning only. On all other trial days (Days 2 to 7), 600 μg BI 1265162 was administered twice daily. | 8 |
| Total | 50 |
Baseline characteristics
| Characteristic | Placebo Matching BI 1265162 | 10 Microgram (μg) BI 1265162 | 30 μg BI 1265162 | 100 μg BI 1265162 | 300 μg BI 1265162 | 600 μg BI 1265162 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.4 Years STANDARD_DEVIATION 6.9 | 34.0 Years STANDARD_DEVIATION 4.7 | 27.6 Years STANDARD_DEVIATION 6.6 | 33.9 Years STANDARD_DEVIATION 5.6 | 32.4 Years STANDARD_DEVIATION 6.8 | 35.5 Years STANDARD_DEVIATION 7.6 | 32.8 Years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 10 Participants | 8 Participants | 8 Participants | 7 Participants | 7 Participants | 8 Participants | 48 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 50 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 10 | 1 / 8 | 2 / 8 | 5 / 8 | 4 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events (AEs)
Percentage of participants with drug-related adverse events (AEs).
Time frame: From first drug administration until 2 days after last drug administration, up to 10 days.
Population: Treated set (TS): The TS included included all participants who received at least 1 dose of trial drug. This was the full analysis set population in the sense of International council for harmonisation - efficacy guideline 9: statistical principles for clinical trials (ICH-E9).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 0.0 Percentage of participants (%) |
| 10 Microgram (μg) BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 12.5 Percentage of participants (%) |
| 30 μg BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 12.5 Percentage of participants (%) |
| 100 μg BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 50.0 Percentage of participants (%) |
| 300 μg BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 50.0 Percentage of participants (%) |
| 600 μg BI 1265162 | Percentage of Participants With Drug-related Adverse Events (AEs) | 12.5 Percentage of participants (%) |
Secondary
Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)
Area under the concentration-time curve of the BI 1265162 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss).
Time frame: 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.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 104 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 18.8 |
| 10 Microgram (μg) BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 284 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 40 |
| 30 μg BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 1190 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 29.4 |
| 100 μg BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 3800 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 29.3 |
| 300 μg BI 1265162 | Area Under the Concentration-time Curve of the BI 1265162 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | 7010 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 36.4 |
Comparison: Dose proportionality for AUCτ,ss of BI 1265162 in plasma was assessed using a power model (regression model applied to log-transformed data). The corresponding ANCOVA model included the logarithm of the dose as a covariate. No statistical hypotheses were tested in a confirmatory sense.90% CI: [0.9972, 1.1069]ANCOVA
Secondary
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)
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).
Time frame: 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.
Population: Pharmacokinetic parameter set (PKS): This subject set included all subjects in the TS who provided at least 1 PK parameter that was not excluded because of protocol deviations relevant to the statistical evaluation of Pharmacokinetic (PK) endpoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 1265162 | 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) | 82.5 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 24.5 |
| 10 Microgram (μg) BI 1265162 | 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) | 226 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 23.2 |
| 30 μg BI 1265162 | 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) | 734 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 22.5 |
| 100 μg BI 1265162 | 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) | 2430 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 35.2 |
| 300 μg BI 1265162 | 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) | 6320 Picomoles*Hour Per Litre (pmol*h/L) | Geometric Coefficient of Variation 21.3 |
Comparison: Dose proportionality for AUC0-12 of BI 1265162 in plasma was assessed using a power model (regression model applied to log-transformed data). The corresponding ANCOVA model included the logarithm of the dose as a covariate. No statistical hypotheses were tested in a confirmatory sense.90% CI: [0.9997, 1.0951]ANCOVA
Secondary
Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)
Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss).
Time frame: 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.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 1265162 | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 55.6 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 25.7 |
| 10 Microgram (μg) BI 1265162 | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 143 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 38.5 |
| 30 μg BI 1265162 | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 640 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 42.7 |
| 100 μg BI 1265162 | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 1710 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 35.5 |
| 300 μg BI 1265162 | Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | 3670 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 39.9 |
Comparison: Dose proportionality for Cmax,ss of BI 1265162 in plasma was assessed using a power model (regression model applied to log-transformed data). The corresponding ANCOVA model included the logarithm of the dose as a covariate. No statistical hypotheses were tested in a confirmatory sense.90% CI: [0.9722, 1.1001]ANCOVA
Secondary
Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax)
Maximum measured concentration of the BI 1265162 in plasma after administration of the first dose (Cmax).
Time frame: 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.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 1265162 | Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax) | 55.2 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 36.1 |
| 10 Microgram (μg) BI 1265162 | Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax) | 158 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 27.4 |
| 30 μg BI 1265162 | Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax) | 391 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 24.4 |
| 100 μg BI 1265162 | Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax) | 1330 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 43.5 |
| 300 μg BI 1265162 | Maximum Measured Concentration of the BI 1265162 in Plasma After Administration of the First Dose (Cmax) | 4000 Picomoles Per Litre (pmol/L) | Geometric Coefficient of Variation 28 |
Comparison: Dose proportionality for Cmax of BI 1265162 in plasma was assessed using a power model (regression model applied to log-transformed data). The corresponding ANCOVA model included the logarithm of the dose as a covariate. No statistical hypotheses were tested in a confirmatory sense.90% CI: [0.9451, 1.0732]ANCOVA