Cystic Fibrosis
Conditions
Brief summary
The primary objective of this trial is to assess the efficacy, safety and pharmacokinetics of twice daily inhaled doses of BI 1265162 delivered by Respimat® inhaler versus placebo in adolescents and adult patients with cystic fibrosis.
Interventions
DRUGBI 1265162
Inhalation solution
DRUGPlacebo
Inhalation solution
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, 12 years of age or older at screening; * Documented diagnosis of cystic fibrosis including: * positive sweat chloride ≥ 60 mEq/L, by pilocarpine iontophoresis OR * genotype with 2 identifiable mutations consistent with cystic fibrosis accompanied by one or more clinical features with cystic fibrosis phenotype; * Patients able to perform acceptable spirometric manoeuvres according to American Thoracic Society (ATS) standards; * FEV1 ≥ 40% and ≤ 90% of predicted values at screening and predose at Visit 2; * Women of childbearing potential (WOCBP) must be willing and able to use highly effective methods of birth control per ICH M3 (R2) that result in a failure rate of less than1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient (or patient's legal guardian) information; * Signed and dated written informed consent and assent in accordance with ICH Harmonized Guideline for Good Clinical Practice (GCP) and local legislation prior to admission in the trial.
Exclusion criteria
* Evidence of acute upper or lower respiratory tract infection within 4 weeks prior to randomization based on investigator's judgement; * Pulmonary exacerbation requiring use of i.v./oral/inhaled antibiotics or oral corticosteroids within 4 weeks prior to randomisation; * Patients with history of Acute Tubular Necrosis (ATN); * Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix; * Patients unable to inhale trial drug in an appropriate manner from the Respimat® inhaler based on investigator's judgement; * Patients who have started a new chronic medication for CF within 4 weeks of randomisation; * Patients who have previously received a lung transplant or patients who are currently on a waiting list to receive a lung transplant; * Patients with a significant history of allergy/hypersensitivity (including medication allergy) which is deemed relevant to the trial as judged by the investigator or with a known hypersensitivity to trial drug or its components. Significance in this context refers to any increased risk of hypersensitivity reaction to trial medication; * Any clinically significant laboratory abnormalities at screening as judged by the investigator, or any of the following: * Potassium \> upper limit of normal (ULN) in non-haemolysed blood * Abnormal renal function defined as estimated Glomerular Filtration Rate (eGFR) \< 60ml/min/1.73m² * Abnormal liver function, defined by serum level of either alanine transaminase (ALT), aspartate transaminase (AST) or total bilirubine ≥ 3 x upper limit of normal (ULN) * Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the investigator, would compromise the safety of the patient or the data quality. This includes significant haematological, hepatic, renal, cardiovascular and neurologic disease. Patients with diabetes may participate if their disease is under good control prior to screening; * Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled; * Previous randomisation in this trial; * Currently enrolled in another investigational device or drug trial, or less than 30 days or six half-lives (whichever is greater) since ending another investigational device or drug trial(s), or receiving other investigational treatment(s); * Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial; * Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment | At 30 minutes prior to dosing in Day 1 (baseline) and Day 29 (end of 4-week treatment period). | Trough FEV1 was measured within 30 minutes prior to dosing of study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57) | At 5 minutes (around 0.083 hours) post dosing at steady state on Day 29 for dose 57 (morning dose on Day 29). | Concentration of BI 1265162 in plasma at 0.083 hour at steady state following dose 57 (C0.083,ss,57) was reported. |
| Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment | At Day 1 (baseline) and Day 29 (end of 4-week treatment period). | The adult/adolescent format of the CFQ-R consists of 50 questions (qts) dividing into 12 domains: Physical functioning(8 qts), role limitations(4 qts), vitality(4 qts), emotional functioning(5 qts), social functioning(6 qts), body image(3 qts), eating disturbance(3 qts), treatment burden(3 qts), health perceptions(3 qts), weight(1 qts), respiratory symptoms(7 qts), and digestive system(3 qts). The score of some qts is first reversed if reversed coded, so that the score for each of the 50 qts ranges from 1 to 4 points (less symptoms). Then, a domain score for a domain with N qts is calculated as (sum of the scores of the N qts - N)/(N ✕ 4 - N) ✕ 100. Each domain score ranges from 0 to 100 (better health). The CFQ-R total score is summing up the domain scores and ranges from 0 to 1200 (better quality of life). The change from baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) total score after 4 weeks of treatment was reported. |
| Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | At Day 1 (baseline) and Day 29 (end of 4-week treatment period). | The 20-item Sputum Assessment Questionnaire (CASA-Q) consisted of 4 domains: Cough Symptoms Domain (3 items), Cough Impact Domain (8 items), Sputum Symptoms Domain (3 items), and Sputum Impact Domain (6 items). Score of each item has been reversed such that better responses have higher score, which ranges from 1 (worse) to 5 (better health). For each domain, the domain score was calculated by summing up the scores of the respective items and scaling to a value ranging from 0 to 100, with higher score associated with fewer symptoms/less impact due to cough or sputum. The 4 domain scores (sub-scores) were reported. |
| Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36 | From Day 1 (baseline) until end of 4 weeks of treatment period (Day 29) plus 7 days of follow-up, up to 36 days. | Percentage of patients with any treatment-emergent Adverse Events (AE) up to day 36 was reported. |
| Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment | At pre-dose in Day 1 (baseline) and Day 29 (end of 4-week treatment period). | Change from baseline in Lung Clearance Index (LCI) assessed by N2 Multiple Breath Washout (N2MBW) procedure after 4 weeks of treatment was reported. LCI was calculated as the ratio of cumulative expired volume (CEV) to functional residual capacity (FRC), which was LCI = CEV (milliliter/kilogram) / FRC (milliliter/kilogram) and hence, LCI was Unitless. The change from baseline after 4 weeks of treatment in LCI was then calculated as the LCI value measured after 4 weeks of treatment at Day 29 minus the LCI value measured at baseline on Day 1. |
| Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15) | At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 8 for dose 15 (morning dose on Day 8). | Pre-dose concentration measured of BI 1265162 in plasma at steady state after dose 15 (Cpre,ss, 15) was reported. |
| Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57) | At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 29 for dose 57 (morning dose on Day 29). | Pre-dose concentration measured of BI 1265162 in plasma at steady state after dose 57 (Cpre,ss, 57) was reported. |
| Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15) | At pre-dose (taken within 60 minutes prior to dosing) and 5 minutes (min), 30 min, 1 hour, and 4 hours post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8). | Area under the concentration-time curve of BI 1265162 in plasma from 0 to 4 hours at steady state after dose 15 (AUC0-4,ss,15) was reported. |
| Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15) | At 5 minutes (around 0.083 hours) post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8). | Concentration of BI 1265162 in plasma at 0.083 hour at steady state following dose 15 (C0.083,ss,15) was reported. |
Countries
Belgium, Canada, France, Germany, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This trial aimed to assess the efficacy, safety, and pharmacokinetics of different dose regimens of BI 1265162 taken twice daily by the Respimat® inhaler versus placebo in adult and adolescent patients with cystic fibrosis for a 4-week treatment period. Study was terminated without recruiting any adolescent patients.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 2 puffs of matching placebo were inhaled orally via the Respimat® inhaler twice daily for a treatment period of 4 weeks in patients with cystic fibrosis. | 18 |
| BI 1265162 20μg b.i.d. 2 puffs of 10 micrograms (μg) BI 1265162 (Total: 20μg) were inhaled orally via the Respimat® inhaler twice daily (b.i.d., daily dose: 40μg) for a treatment period of 4 weeks in patients with cystic fibrosis. | 6 |
| BI 1265162 50μg b.i.d. 2 puffs of 25 micrograms (μg) BI 1265162 (Total: 50μg) were inhaled orally via the Respimat® inhaler twice daily (b.i.d., daily dose: 100μg) for a treatment period of 4 weeks in patients with cystic fibrosis. | 5 |
| BI 1265162 100μg b.i.d. 2 puffs of 50 micrograms (μg) BI 1265162 (Total: 100μg) were inhaled orally via the Respimat® inhaler twice daily (b.i.d., daily dose: 200μg) for a treatment period of 4 weeks in patients with cystic fibrosis. | 5 |
| BI 1265162 200μg b.i.d. 2 puffs of 100 micrograms (μg) BI 1265162 (Total: 200μg) were inhaled orally via the Respimat® inhaler twice daily (b.i.d., daily dose: 400μg) for a treatment period of 4 weeks in patients with cystic fibrosis. | 18 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Not willing to travel due to COVID-19 pandemic | 0 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | BI 1265162 200μg b.i.d. | BI 1265162 100μg b.i.d. | BI 1265162 50μg b.i.d. | BI 1265162 20μg b.i.d. |
|---|---|---|---|---|---|---|
| Age, Continuous | 29.3 Years STANDARD_DEVIATION 10.1 | 31.3 Years STANDARD_DEVIATION 9.4 | 33.4 Years STANDARD_DEVIATION 10.2 | 36.8 Years STANDARD_DEVIATION 4.2 | 31.2 Years STANDARD_DEVIATION 8.6 | 26.8 Years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 51 Participants | 18 Participants | 5 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 50 Participants | 18 Participants | 4 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 16 Participants | 42 Participants | 15 Participants | 4 Participants | 2 Participants | 5 Participants |
| Trough forced expiratory volume in one second (FEV1) percent predicted | 59.40 Percentage of predicted trough FEV1 STANDARD_DEVIATION 11.29 | 61.11 Percentage of predicted trough FEV1 STANDARD_DEVIATION 12.89 | 57.94 Percentage of predicted trough FEV1 STANDARD_DEVIATION 13.76 | 65.50 Percentage of predicted trough FEV1 STANDARD_DEVIATION 7 | 63.02 Percentage of predicted trough FEV1 STANDARD_DEVIATION 14.4 | 69.93 Percentage of predicted trough FEV1 STANDARD_DEVIATION 15.99 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 18 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 18 |
| other Total, other adverse events | 11 / 18 | 0 / 6 | 2 / 5 | 2 / 5 | 15 / 18 |
| serious Total, serious adverse events | 1 / 18 | 0 / 6 | 0 / 5 | 0 / 5 | 1 / 18 |
Outcome results
Primary
Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment
Trough FEV1 was measured within 30 minutes prior to dosing of study medication.
Time frame: At 30 minutes prior to dosing in Day 1 (baseline) and Day 29 (end of 4-week treatment period).
Population: Treated set (TS): The TS included all patients who were randomized and treated with at least one dose of study drug. The treatment assignment was determined based on the first treatment the subjects received. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment | -0.6 Percentage of predicted trough FEV1 | Standard Deviation 8.03 |
| BI 1265162 20μg b.i.d. | Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment | -0.5 Percentage of predicted trough FEV1 | Standard Deviation 2.82 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment | -0.22 Percentage of predicted trough FEV1 | Standard Deviation 2.62 |
| BI 1265162 100μg b.i.d. | Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment | 2.82 Percentage of predicted trough FEV1 | Standard Deviation 3.57 |
| BI 1265162 200μg b.i.d. | Change From Baseline in Percent Predicted Trough Forced Expiratory Volume in 1 Second (FEV1) After 4 Weeks of Treatment | 0.45 Percentage of predicted trough FEV1 | Standard Deviation 5.42 |
Comparison: Mixed Model for Repeated Measures (MMRM) with fixed effects for baseline, visit, treatment, treatment-by-visit interaction, baseline-by-visit interaction, and random effect for patient was applied. No hypothesis testing was performed, as this trial was prematurely discontinued. MMRM only included data from 200µg BI and placebo, as the sample size of the BI 20µg, BI 50µg and BI 100µg dose levels was limited because of the premature discontinuation of the trial.p-value: 0.546895% CI: [-3.5, 6.5]Mixed model with repeated measurements
Secondary
Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15)
Area under the concentration-time curve of BI 1265162 in plasma from 0 to 4 hours at steady state after dose 15 (AUC0-4,ss,15) was reported.
Time frame: At pre-dose (taken within 60 minutes prior to dosing) and 5 minutes (min), 30 min, 1 hour, and 4 hours post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).
Population: Pharmacokinetic set (PKS): The PKS included all patients in the treated set who provided at least one pharmacokinetic parameter. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15) | 192 hours * picomole/liter (h*pmol/L) | Geometric Coefficient of Variation 45.3 |
| BI 1265162 20μg b.i.d. | Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15) | 541 hours * picomole/liter (h*pmol/L) | Geometric Coefficient of Variation 19.1 |
| BI 1265162 50μg b.i.d. | Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15) | 1020 hours * picomole/liter (h*pmol/L) | Geometric Coefficient of Variation 8.93 |
| BI 1265162 100μg b.i.d. | Area Under the Concentration-time Curve of BI 1265162 in Plasma From 0 to 4 Hours at Steady State After Dose 15 (AUC0-4,ss,15) | 1380 hours * picomole/liter (h*pmol/L) | Geometric Coefficient of Variation 71 |
Secondary
Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment
The 20-item Sputum Assessment Questionnaire (CASA-Q) consisted of 4 domains: Cough Symptoms Domain (3 items), Cough Impact Domain (8 items), Sputum Symptoms Domain (3 items), and Sputum Impact Domain (6 items). Score of each item has been reversed such that better responses have higher score, which ranges from 1 (worse) to 5 (better health). For each domain, the domain score was calculated by summing up the scores of the respective items and scaling to a value ranging from 0 to 100, with higher score associated with fewer symptoms/less impact due to cough or sputum. The 4 domain scores (sub-scores) were reported.
Time frame: At Day 1 (baseline) and Day 29 (end of 4-week treatment period).
Population: Treated set (TS): The TS included all patients who were randomized and treated with at least one dose of study drug. The treatment assignment was determined based on the first treatment the subjects received. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Symptom Domain Score | 4.167 Score on a scale | Standard Deviation 18.798 |
| Placebo | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Impact Domain Score | -0.521 Score on a scale | Standard Deviation 16.648 |
| Placebo | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Symptom Domain Score | 5.093 Score on a scale | Standard Deviation 15.95 |
| Placebo | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Impact Domain Score | -0.694 Score on a scale | Standard Deviation 16.497 |
| BI 1265162 20μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Symptom Domain Score | 10.417 Score on a scale | Standard Deviation 17.18 |
| BI 1265162 20μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Impact Domain Score | -4.167 Score on a scale | Standard Deviation 3.402 |
| BI 1265162 20μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Impact Domain Score | -6.250 Score on a scale | Standard Deviation 12.758 |
| BI 1265162 20μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Symptom Domain Score | 4.167 Score on a scale | Standard Deviation 8.333 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Impact Domain Score | 5.000 Score on a scale | Standard Deviation 11.562 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Impact Domain Score | -0.625 Score on a scale | Standard Deviation 12.771 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Symptom Domain Score | 10.000 Score on a scale | Standard Deviation 14.907 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Symptom Domain Score | 8.333 Score on a scale | Standard Deviation 8.333 |
| BI 1265162 100μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Symptom Domain Score | 3.333 Score on a scale | Standard Deviation 24.008 |
| BI 1265162 100μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Impact Domain Score | 1.250 Score on a scale | Standard Deviation 14.757 |
| BI 1265162 100μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Impact Domain Score | -0.833 Score on a scale | Standard Deviation 13.944 |
| BI 1265162 100μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Symptom Domain Score | 3.333 Score on a scale | Standard Deviation 16.245 |
| BI 1265162 200μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Impact Domain Score | 0.490 Score on a scale | Standard Deviation 11.11 |
| BI 1265162 200μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Sputum Symptom Domain Score | 5.392 Score on a scale | Standard Deviation 19.53 |
| BI 1265162 200μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Impact Domain Score | 0.735 Score on a scale | Standard Deviation 11.187 |
| BI 1265162 200μg b.i.d. | Change From Baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) (4 Separate Sub-scores) After 4 Weeks of Treatment | Cough Symptom Domain Score | 5.392 Score on a scale | Standard Deviation 15.574 |
Secondary
Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment
The adult/adolescent format of the CFQ-R consists of 50 questions (qts) dividing into 12 domains: Physical functioning(8 qts), role limitations(4 qts), vitality(4 qts), emotional functioning(5 qts), social functioning(6 qts), body image(3 qts), eating disturbance(3 qts), treatment burden(3 qts), health perceptions(3 qts), weight(1 qts), respiratory symptoms(7 qts), and digestive system(3 qts). The score of some qts is first reversed if reversed coded, so that the score for each of the 50 qts ranges from 1 to 4 points (less symptoms). Then, a domain score for a domain with N qts is calculated as (sum of the scores of the N qts - N)/(N ✕ 4 - N) ✕ 100. Each domain score ranges from 0 to 100 (better health). The CFQ-R total score is summing up the domain scores and ranges from 0 to 1200 (better quality of life). The change from baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) total score after 4 weeks of treatment was reported.
Time frame: At Day 1 (baseline) and Day 29 (end of 4-week treatment period).
Population: Treated set (TS): The TS included all patients who were randomized and treated with at least one dose of study drug. The treatment assignment was determined based on the first treatment the subjects received. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment | 5.941 Score on a scale | Standard Deviation 76.669 |
| BI 1265162 20μg b.i.d. | Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment | 27.083 Score on a scale | Standard Deviation 61.626 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment | 11.167 Score on a scale | Standard Deviation 33.968 |
| BI 1265162 100μg b.i.d. | Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment | -15.611 Score on a scale | Standard Deviation 62.167 |
| BI 1265162 200μg b.i.d. | Change From Baseline in Cystic Fibrosis Questionnaire Revised (CFQ-R) Total Score After 4 Weeks of Treatment | 24.236 Score on a scale | Standard Deviation 58.29 |
Secondary
Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment
Change from baseline in Lung Clearance Index (LCI) assessed by N2 Multiple Breath Washout (N2MBW) procedure after 4 weeks of treatment was reported. LCI was calculated as the ratio of cumulative expired volume (CEV) to functional residual capacity (FRC), which was LCI = CEV (milliliter/kilogram) / FRC (milliliter/kilogram) and hence, LCI was Unitless. The change from baseline after 4 weeks of treatment in LCI was then calculated as the LCI value measured after 4 weeks of treatment at Day 29 minus the LCI value measured at baseline on Day 1.
Time frame: At pre-dose in Day 1 (baseline) and Day 29 (end of 4-week treatment period).
Population: Treated set (TS): The TS included all patients who were randomized and treated with at least one dose of study drug. The treatment assignment was determined based on the first treatment the subjects received. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment | -0.824 Unitless | Standard Deviation 3.312 |
| BI 1265162 50μg b.i.d. | Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment | -0.238 Unitless | — |
| BI 1265162 100μg b.i.d. | Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment | -2.547 Unitless | — |
| BI 1265162 200μg b.i.d. | Change From Baseline in Lung Clearance Index (LCI) Assessed by N2 Multiple Breath Washout (N2MBW) Procedure After 4 Weeks of Treatment | -0.081 Unitless | Standard Deviation 1.001 |
Comparison: ANCOVA based on analysis of covariance with fixed effects for baseline and treatment was applied. Statistical analysis was performed for 200μg BI and placebo groups only. No hypothesis testing was performed, as this trial was prematurely discontinued. ANCOVA only included data from 200µg BI and placebo, as the sample size of the BI 20µg, BI 50µg and BI 100µg dose levels was limited because of the premature discontinuation of the trial.p-value: 0.303995% CI: [-2.4, 6.5]ANCOVA
Secondary
Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15)
Concentration of BI 1265162 in plasma at 0.083 hour at steady state following dose 15 (C0.083,ss,15) was reported.
Time frame: At 5 minutes (around 0.083 hours) post dosing at steady state on Day 8 for dose 15 (morning dose on Day 8).
Population: Pharmacokinetic set (PKS): The PKS included all patients in the treated set who provided at least one pharmacokinetic parameter. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15) | 207 picomole/liter (pmol/L) | Geometric Coefficient of Variation 59.9 |
| BI 1265162 20μg b.i.d. | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15) | 471 picomole/liter (pmol/L) | Geometric Coefficient of Variation 30 |
| BI 1265162 50μg b.i.d. | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15) | 1010 picomole/liter (pmol/L) | Geometric Coefficient of Variation 20.1 |
| BI 1265162 100μg b.i.d. | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 15 (C0.083,ss,15) | 1110 picomole/liter (pmol/L) | Geometric Coefficient of Variation 84.8 |
Secondary
Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57)
Concentration of BI 1265162 in plasma at 0.083 hour at steady state following dose 57 (C0.083,ss,57) was reported.
Time frame: At 5 minutes (around 0.083 hours) post dosing at steady state on Day 29 for dose 57 (morning dose on Day 29).
Population: Pharmacokinetic set (PKS): The PKS included all patients in the treated set who provided at least one pharmacokinetic parameter. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57) | 162 picomole/liter (pmol/L) | Geometric Coefficient of Variation 76.3 |
| BI 1265162 20μg b.i.d. | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57) | 463 picomole/liter (pmol/L) | Geometric Coefficient of Variation 15.4 |
| BI 1265162 50μg b.i.d. | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57) | 573 picomole/liter (pmol/L) | Geometric Coefficient of Variation 94 |
| BI 1265162 100μg b.i.d. | Concentration of BI 1265162 in Plasma at 0.083 Hour at Steady State Following Dose 57 (C0.083,ss,57) | 1080 picomole/liter (pmol/L) | Geometric Coefficient of Variation 165 |
Secondary
Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36
Percentage of patients with any treatment-emergent Adverse Events (AE) up to day 36 was reported.
Time frame: From Day 1 (baseline) until end of 4 weeks of treatment period (Day 29) plus 7 days of follow-up, up to 36 days.
Population: Treated set (TS): The TS included all patients who were randomized and treated with at least one dose of study drug. The treatment assignment was determined based on the first treatment the subjects received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36 | 66.7 Percentage of participants |
| BI 1265162 20μg b.i.d. | Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36 | 0 Percentage of participants |
| BI 1265162 50μg b.i.d. | Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36 | 40.0 Percentage of participants |
| BI 1265162 100μg b.i.d. | Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36 | 40.0 Percentage of participants |
| BI 1265162 200μg b.i.d. | Percentage of Patients With Treatment-emergent Adverse Events (AE) up to Day 36 | 83.3 Percentage of participants |
Secondary
Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15)
Pre-dose concentration measured of BI 1265162 in plasma at steady state after dose 15 (Cpre,ss, 15) was reported.
Time frame: At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 8 for dose 15 (morning dose on Day 8).
Population: Pharmacokinetic set (PKS): The PKS included all patients in the treated set who provided at least one pharmacokinetic parameter. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15) | 7.82 picomole/liter (pmol/L) | Geometric Coefficient of Variation 28 |
| BI 1265162 20μg b.i.d. | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15) | 24.3 picomole/liter (pmol/L) | Geometric Coefficient of Variation 31.8 |
| BI 1265162 50μg b.i.d. | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15) | 38.4 picomole/liter (pmol/L) | Geometric Coefficient of Variation 292 |
| BI 1265162 100μg b.i.d. | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 15 (Cpre,ss, 15) | 43.8 picomole/liter (pmol/L) | Geometric Coefficient of Variation 95.6 |
Secondary
Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57)
Pre-dose concentration measured of BI 1265162 in plasma at steady state after dose 57 (Cpre,ss, 57) was reported.
Time frame: At pre-dose (taken within 60 minutes prior to dosing) at steady state on Day 29 for dose 57 (morning dose on Day 29).
Population: Pharmacokinetic set (PKS): The PKS included all patients in the treated set who provided at least one pharmacokinetic parameter. Only participants with non-missing outcome measured were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57) | NA picomole/liter (pmol/L) | — |
| BI 1265162 20μg b.i.d. | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57) | 13.0 picomole/liter (pmol/L) | Geometric Coefficient of Variation 80.8 |
| BI 1265162 50μg b.i.d. | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57) | 22.3 picomole/liter (pmol/L) | Geometric Coefficient of Variation 48.3 |
| BI 1265162 100μg b.i.d. | Pre-dose Concentration Measured of BI 1265162 in Plasma at Steady State After Dose 57 (Cpre,ss, 57) | 37.2 picomole/liter (pmol/L) | Geometric Coefficient of Variation 56.9 |