Bronchiectasis, Cystic Fibrosis
Conditions
Brief summary
This study is open to adults aged 18 years and older with cystic fibrosis bronchiectasis. The purpose of this study is to find out whether a medicine called BI 1291583 is tolerated by people with cystic fibrosis bronchiectasis. Participants are put randomly into 2 groups. One group takes BI 1291583 tablets and the other group takes placebo tablets. Placebo tablets look like BI 1291583 tablets but do not contain any medicine. Participants in both groups take 1 tablet once a day for 12 weeks. Participants have twice the chance of being placed in the BI 1291583 group than in the placebo group. Participants are in the study for about 6 months. During this time, they visit the study site 7 times. At the visits, the doctors check the health of the participants and note any health problems that could have been caused by BI 1291583.
Interventions
DRUGBI 1291583
Once daily oral administration of 5 milligram (mg) tablets of BI 1291583 for 12 weeks.
DRUGPlacebo to BI 1291583
Once daily oral administration of tablets of placebo matching BI 1291583 for 12 weeks.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age of patients when signing the informed consent ≥18 years 2. Historical clinical diagnosis of Cystic fibrosis (CF) (symptoms of CF and sweat chloride ≥ 60 mmol/L and/or 2 CF-causing Cystic fibrosis transmembrane conductance regulator (CFTR) mutations) 3. Investigator-confirmed diagnosis of Bronchiectasis (BE) by Computed tomography (CT) scan and clinical history consistent with BE (e.g., cough, chronic sputum production, recurrent respiratory infections). Subjects whose past chest CT records are not available will undergo a chest CT scan during Screening. Historical scans must not be older than 5 years 4. History of pulmonary exacerbations requiring antibiotic treatment. In the 12 months before Visit 1, patients must have had either: 1. at least 2 exacerbations, or 2. at least 1 exacerbation and an St. George's Respiratory Questionnaire (SGRQ) Symptoms score of \>40 at screening visit 1 For patients on stable oral or inhaled antibiotics as chronic treatment for BE, at least one exacerbation must have occurred while on stable antibiotics. 5. Patients must be able to provide spontaneous or induced sputum samples. Further inclusion criteria apply.
Exclusion criteria
1. Moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment) or Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) \> 3.0x Upper limit of normal (ULN) at Visit 1 2. Estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula \< 30 mL/min at Visit 1 3. Absolute blood neutrophil count \< 1,000/mm\^3 (equivalent to \< 1000 cells/μL or \< 10\^9 cells/L) at Visit 1 4. Any findings in the medical examination (including blood pressure (BP), pulse rate (PR), or electrocardiogram (ECG)) and/or laboratory value assessed at Visit 1 or during screening period that in the opinion of the investigator may put the patient at risk by participating in the trial 5. Positive serological tests for hepatitis B, hepatitis C (also confirmed with Hepatitis C virus ribonucleic acid (HCV RNA)), or human immunodeficiency virus (HIV) infection, or known infection status. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Any Treatment Emergent Adverse Events | From first dose of trial drug administration until last dose of trial drug administration plus 28 days of residual effect period, up to 16 weeks. | Occurrence of any treatment emergent adverse events is expressed as percentages of participants with treatment emergent adverse events. Percentages are rounded to one decimal place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change From Baseline in NE Activity, in Sputum, at Week 8 After First Drug Administration | Before the first drug administration (baseline: mean value of screening and Week 0 prior to the first treatment intake) and Week 8 after first study drug administration. | Relative change from baseline in neutrophil elastase (NE) activity, in sputum, at Week 8 after first drug administration is reported. Relative change from baseline at Week 8 in neutrophil elastase was calculated as below: Relative fluorescence unit (RFU) at Week 8-Relative fluorescence unit at baseline)\*100%/Relative fluorescence unit at baseline. |
| Area Under the Curve of BI 1291583 in Plasma Over a Uniform Dosing Interval Tau=6h After the First Dose (AUC0-6) | Before drug administration and 1 hour (h), 3.5h, 6h after administration of the first dose of BI 1291583 at Day 1. | Area under the curve of BI 1291583 in plasma over a uniform dosing interval tau=6h after the first dose (AUC0-6) is reported. |
| Area Under the Curve of BI 1291583 in Plasma Over a Uniform Dosing Interval Tau=6h at Steady State (AUC0-6,ss) | Before drug administration at Day 85 and 1 hour (h), 3.5h, 6h after administration of BI 1291583 at Day 85. | Area under the curve of BI 1291583 in plasma over a uniform dosing interval tau=6h at steady state (AUC0-6,ss) is reported. |
| Maximum Measured Concentration of BI 1291583 in Plasma After the First Dose | Before drug administration and 1 hour (h), 3.5h, 6h, and 8h after administration of the first dose of BI 1291583 at Day 1. | Maximum measured concentration of BI 1291583 in plasma after the first dose is reported. |
| Maximum Measured Concentration of BI 1291583 in Plasma at Steady State | Before drug administration at Day 85 and 1 hour (h), 3.5h, 6h after administration of BI 1291583 at Day 85. | Maximum measured concentration of BI 1291583 in plasma at steady state is reported. |
Countries
Belgium, France, Germany, Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
This was a randomised, double-blind, placebo-controlled, parallel group trial evaluating safety, tolerability, pharmacodynamics and pharmacokinetics of BI 1291583 one tablet once daily over 12 weeks versus placebo in adult patients with cystic fibrosis bronchiectasis (Clairafly™).
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 Participants with cystic fibrosis bronchiectasis administered orally once daily tablets of placebo matching BI 1291583 for 12 weeks. | 7 |
| 5 mg BI 1291583 Participants with cystic fibrosis bronchiectasis administered orally once daily 5 milligram (mg) tablets of BI 1291583 for 12 weeks. | 15 |
| Total | 22 |
Baseline characteristics
| Characteristic | 5 mg BI 1291583 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 11 | 32.4 years STANDARD_DEVIATION 10.3 | 32.4 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 21 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 22 Participants | 7 Participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 15 |
| other Total, other adverse events | 6 / 7 | 13 / 15 |
| serious Total, serious adverse events | 1 / 7 | 5 / 15 |
Outcome results
Primary
Occurrence of Any Treatment Emergent Adverse Events
Occurrence of any treatment emergent adverse events is expressed as percentages of participants with treatment emergent adverse events. Percentages are rounded to one decimal place.
Time frame: From first dose of trial drug administration until last dose of trial drug administration plus 28 days of residual effect period, up to 16 weeks.
Population: Treated Set (TS): included all randomised patients who were documented to have taken at least one dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Occurrence of Any Treatment Emergent Adverse Events | 85.7 Percentage of participants |
| BI 1291583 5 mg | Occurrence of Any Treatment Emergent Adverse Events | 93.3 Percentage of participants |
Secondary
Area Under the Curve of BI 1291583 in Plasma Over a Uniform Dosing Interval Tau=6h After the First Dose (AUC0-6)
Area under the curve of BI 1291583 in plasma over a uniform dosing interval tau=6h after the first dose (AUC0-6) is reported.
Time frame: Before drug administration and 1 hour (h), 3.5h, 6h after administration of the first dose of BI 1291583 at Day 1.
Population: Pharmacokinetic set (PKS): This patient set included all patients from the treated set (TS) who provided at least one post-dose plasma BI 1291583 concentration that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK), or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve of BI 1291583 in Plasma Over a Uniform Dosing Interval Tau=6h After the First Dose (AUC0-6) | 14.0 hours *nanomole/Liter (h*nmol/L) | Geometric Coefficient of Variation 65.3 |
Secondary
Area Under the Curve of BI 1291583 in Plasma Over a Uniform Dosing Interval Tau=6h at Steady State (AUC0-6,ss)
Area under the curve of BI 1291583 in plasma over a uniform dosing interval tau=6h at steady state (AUC0-6,ss) is reported.
Time frame: Before drug administration at Day 85 and 1 hour (h), 3.5h, 6h after administration of BI 1291583 at Day 85.
Population: Pharmacokinetic set (PKS): This patient set included all patients from the treated set (TS) who provided at least one post-dose plasma BI 1291583 concentration that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK), or due to PK non-evaluability. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve of BI 1291583 in Plasma Over a Uniform Dosing Interval Tau=6h at Steady State (AUC0-6,ss) | 65.9 hours *nanomole/Liter (h*nmol/L) | Geometric Coefficient of Variation 64.5 |
Secondary
Maximum Measured Concentration of BI 1291583 in Plasma After the First Dose
Maximum measured concentration of BI 1291583 in plasma after the first dose is reported.
Time frame: Before drug administration and 1 hour (h), 3.5h, 6h, and 8h after administration of the first dose of BI 1291583 at Day 1.
Population: Pharmacokinetic set (PKS): This patient set included all patients from the treated set (TS) who provided at least one post-dose plasma BI 1291583 concentration that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK), or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 1291583 in Plasma After the First Dose | 3.33 nmol/L | Geometric Coefficient of Variation 74.4 |
Secondary
Maximum Measured Concentration of BI 1291583 in Plasma at Steady State
Maximum measured concentration of BI 1291583 in plasma at steady state is reported.
Time frame: Before drug administration at Day 85 and 1 hour (h), 3.5h, 6h after administration of BI 1291583 at Day 85.
Population: Pharmacokinetic set (PKS): This patient set included all patients from the treated set (TS) who provided at least one post-dose plasma BI 1291583 concentration that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK), or due to PK non-evaluability. Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 1291583 in Plasma at Steady State | 11.6 nmol/L | Geometric Coefficient of Variation 69.9 |
Secondary
Relative Change From Baseline in NE Activity, in Sputum, at Week 8 After First Drug Administration
Relative change from baseline in neutrophil elastase (NE) activity, in sputum, at Week 8 after first drug administration is reported. Relative change from baseline at Week 8 in neutrophil elastase was calculated as below: Relative fluorescence unit (RFU) at Week 8-Relative fluorescence unit at baseline)\*100%/Relative fluorescence unit at baseline.
Time frame: Before the first drug administration (baseline: mean value of screening and Week 0 prior to the first treatment intake) and Week 8 after first study drug administration.
Population: Treated Set (TS): included all randomised patients who were documented to have taken at least one dose of investigational treatment. Only participants with a value at baseline and at Week 8 are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative Change From Baseline in NE Activity, in Sputum, at Week 8 After First Drug Administration | 39.69 percent change in RFU | Standard Deviation 134.67 |
| BI 1291583 5 mg | Relative Change From Baseline in NE Activity, in Sputum, at Week 8 After First Drug Administration | -65.95 percent change in RFU | Standard Deviation 49.37 |