Non-cystic Fibrosis Bronchiectasis
Conditions
Keywords
Inhaled tobramycin, tobramycin inhalation powder, bronchiectasis, pulmonary Pseudomonas aeruginosa infection, dose-finding study
Brief summary
The purpose of this study was to support the selection of a safe and tolerable tobramycin inhalation powder (TIP) dose, and regimen that exhibits effective bacterial reduction of P. aeruginosa in non-cystic fibrosis bronchiectasis (BE) patients with P. aeruginosa colonization.
Detailed description
This was a blinded, randomized, dose and regimen finding trial utilizing a three treatment cohort design where active TIP and TIP/Placebo cyclical (3 capsules o.d \[Cohort A\], 5 capsules o.d. \[Cohort B\] or 4 capsules b.i.d. \[Cohort C\]) versus Placebo were administered for a total of 112 days. Novartis decided to close the recruitment of new subjects into this study earlier than scheduled. Subjects who had a signed informed consent form and entered screening by 10-Sep-2018 still participated in the study. The latest possible randomization was on 08-Oct-2018. All subjects enrolled in the study (107 enrolled subjects out of 180 planned) continued as planned through to their last scheduled visit. The early recruitment halt of the study was not due to safety or lack of efficacy.
Interventions
DRUGTIP
TIP dose regimen
DRUGTIP and placebo
TIP and inhaled placebo dose regimen
DRUGPlacebo
Inhaled placebo dose regimen
Sponsors
Queen's University, Belfast
University Hospital, Antwerp
University of Milan
Fundacion Clinic per a la Recerca Biomédica
Erasmus Medical Center
Papworth Hospital NHS Foundation Trust
Royal Brompton & Harefield NHS Foundation Trust
University of Dundee
University of Edinburgh
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Written informed consent must be obtained before any assessment is performed. * Male and female patients of ≥ 18 years of age at screening (Visit 1). * Proven diagnosis of non-CF BE as documented by computed tomography or high-resolution computed tomography * At least 2 or more exacerbations treated with oral antibiotics OR 1 or more exacerbation requiring intravenous antibiotic treatment within 12 months prior to screening. * FEV1 ≥ 30% predicted at screening (Visit 1). * P. aeruginosa, must be documented in a respiratory sample at least 1 time within 12 months and also present in the expectorated sputum culture at Visit 1. Key
Exclusion criteria
* Patients with a history of cystic fibrosis. * Patients with a primary diagnosis of bronchial asthma. * Patients with a primary diagnosis of COPD associated with at least a 20 pack year smoking history. * Any significant medical condition that is either recently diagnosed or was not stable during the last 3 months, other than pulmonary exacerbations, and that in the opinion of the investigator makes participation in the trial against the patients' best interests. * Clinically significant (in the opinion of the investigator) hearing loss that interferes with patients' daily activities (such as normal conversations) or chronic tinnitus. Patients with a past history of clinically significant hearing loss in the opinion of the investigator may be eligible only if their hearing threshold at screening audiometry is 25dB or lower at frequencies 0.5-4 kHz. The use of a hearing device is reflective of a clinically significant hearing loss; hence patients using hearing aids at screening are not eligible. * Patients with active pulmonary tuberculosis. * Patients currently receiving treatment for nontuberculous mycobacterial (NTM) pulmonary disease. * Patients who are regularly receiving inhaled anti-pseudomonal antibiotic (during the study inhaled anti-pseudomonal antibiotics are not allowed other than the study drug).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (Visit 101/Day 1), Visit 102 (Day 8), Visit 103 (Day 29) | Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Change was determined using the formula = (Post-baseline value - baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Only values for all morphotypes presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The time to first onset of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. Participants were censored at the time of completion of study or early discontinuation if they did not have a pulmonary exacerbation during the study period. |
| Duration of Pulmonary Exacerbation by Exacerbation Category | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The duration of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. |
| Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The exposure adjusted rate of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. The Exposure adjusted rate = (Number of pulmonary exacerbations reported during the study period) / (sum of study duration in days for all participants/ 365.25). Only descriptive analysis performed. |
| Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | Pulmonary exacerbations are defined as events requiring antibiotic therapy AND for which at least 3 of the following 6 symptoms, signs, or findings were present outside of normal variation: 1. Increased sputum volume, or change in viscosity/consistency or purulence for more than 24 hours; 2. Increased shortness of breath at rest or on exercise for more than 24 hours; 3. Increased cough for more than 24 hours; 4. Fever of ≥38° Celsius within the last 24 hours; 5. Increased malaise/fatigue/lethargy for more than 24 hours; 6. A reduction in forced expiratory volume in the first second of expiration (FEV1) or forced vital capacity (FVC) of least 10% from screening. Participants were categorized as: a) Overall, b) Category 1: treated with oral antibiotics only and c) Category 2: treated with parenteral Antibiotics and/or requiring hospitalization. Only descriptive analysis performed. |
| Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The percentage of participants who permanently discontinued study drug due to pulmonary exacerbation compared to placebo was analyzed. |
| Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The time to permanent study drug discontinuation due to Pulmonary exacerbation. Participants were censored at the time of last contact if they did not permanently discontinue study drug due to pulmonary exacerbation requiring during the study period. Only descriptive analysis performed. |
| Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | From Baseline (Visit 101/Day 1) up to approximately Day 173 | The time to first use of anti-pseudomonal antibiotics administered compared to placebo was analyzed. Participants were censored at the time of last contact if they did not have anti-pseudomonal antibiotics over the entire study period. |
| Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The percentage of participants requiring anti-pseudomonal antibiotics compared to placebo was analyzed. Only descriptive analysis performed. |
| Duration of Anti-pseudomonal Antibiotics Usage | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The total number of days of new anti-pseudomonal antibiotic use compared to placebo was analyzed. Only descriptive analysis |
| Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The percentage of participants requiring hospitalization due to serious respiratory-related adverse events (other than those regularly scheduled hospitalization that were planned prior to study start) was analyzed to define severity of pulmonary exacerbations compared to placebo. Only descriptive analysis performed. |
| Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The duration of hospitalization due to serious respiratory-related adverse events (other than those regularly scheduled hospitalization that were planned prior to study start) was analyzed to define severity of pulmonary exacerbations compared to placebo. Only descriptive analysis performed. |
| Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (Visit 101/Day 1), Visit 104 (Day 57), Visit 105 (Day 85), Visit 106 (Day 113), End of Treatment (EOT), Visit 201 (Day 141), Visit 202 (Day 169) | Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Change was determined using the formula = (Post-baseline value - baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Only values for all morphotypes are presented. |
| Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | Time to first hospitalization due to serious respiratory-related AEs was analyzed to define severity of pulmonary exacerbations compared to placebo. Participants were censored at the time of last contact if they did not have a hospitalization due to serious respiratory-related adverse events over the entire study period. |
| Serum Tobramycin Concentration | Baseline (Visit 101/Day 1), Visit 102 (Day 8) and Visits 103 (Day 29): 0-1 hours and 1-2 hours post-dose. | The serum pharmacokinetic (PK) properties of tobramycin were assessed by evaluating tobramycin concentrations in serum collected from the non-cystic fibrosis bronchiectasis population post administration of o.d. or b.i.d. doses of TIP. Serum specimens for PK tobramycin concentration were assessed at Visit 101 (Day 1/start of treatment) 0 to 1 and 1 to 2 hours post-dose and Visit 102 (Day 8) 0 to 1 and 1 to 2 hours post-dose. Prior to protocol amendment #2, PK samples were assessed on Visits 103 (Day 29) rather than Visit 102. Only descriptive analysis performed. |
| Sputum Tobramycin Concentration | Baseline (Visit 101/Day 1): 0-1 hours and 1-2 hours post-dose; Visit 102 (Day 8):0-2 hours and 5-6 hours post-dose; Visits 103 (Day 29): 5 to 6 hours post-dose, Visit 104 (Day 57) and Visit 105 (Day 85): 3-4 hours post-dose. | The sputum pharmacokinetic (PK) properties of tobramycin were assessed by evaluating tobramycin concentrations in sputum collected from the non-cystic fibrosis bronchiectasis population post administration of o.d. or b.i.d. doses of TIP. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169) | The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed. |
| Number of Hospitalization Due to Serious Respiratory-related Adverse Events | Baseline (Visit 101/Day 1) to Visit 202 (Day 169) | The number of hospitalization due to serious respiratory-related AEs was analyzed to define severity of pulmonary exacerbations compared to placebo. Respiratory related adverse events were identified using the AEs captured under system organ class 'Respiratory, thoracic and mediastinal disorders' and 'Infections and infestations'. |
Countries
Belgium, France, Germany, Italy, Spain, United Kingdom
Participant flow
Recruitment details
A total of 107 subjects were enrolled in the trial from 6 countries (Belgium \[2 sites\], France \[4 sites\], Germany \[5 sites\], Italy \[6 sites\], Spain \[8 sites\] and United Kingdom \[9 sites\]).
Pre-assignment details
This study planned to recruit approximately 180 subjects to one of the 3 cohorts in a ratio of 1:1:1. The subjects within each cohort were randomized to blinded TIP or placebo with the following randomization scheme: TIP:TIP/Placebo cyclical:Placebo, in a 2:2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A (3 Capsules o.d.): TIP Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) | 14 |
| Cohort A (3 Capsules o.d.): TIP/PBO Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical | 13 |
| Cohort A (3 Capsules o.d.): PBO Cohort A (3 capsules o.d.): Inhaled placebo (PBO) | 7 |
| Cohort B (5 Capsules o.d.): TIP Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) | 15 |
| Cohort B (5 Capsules o.d.): TIP/PBO Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical | 14 |
| Cohort B (5 Capsules o.d.): PBO Cohort B (5 capsules o.d.): inhaled placebo (PBO) | 7 |
| Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) | 15 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical | 15 |
| Cohort C (4 Capsules b.i.d.): PBO Cohort C (4 capsules b.i.d.): inhaled placebo (PBO) | 7 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Post-Treatment Efficacy Follow-Up Phase | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Post-Treatment Efficacy Follow-Up Phase | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Post-Treatment Efficacy Follow-Up Phase | Subject Decision | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 2 | 0 |
| Treatment Phase | Adverse Event | 3 | 1 | 1 | 4 | 3 | 0 | 6 | 6 | 1 |
| Treatment Phase | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Treatment Phase | Protocol Deviation | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 |
| Treatment Phase | Subject Decision | 2 | 0 | 0 | 2 | 1 | 0 | 1 | 2 | 0 |
| Treatment Phase | Technical Problems | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort A (3 Capsules o.d.): TIP | Cohort A (3 Capsules o.d.): TIP/PBO | Cohort A (3 Capsules o.d.): PBO | Cohort B (5 Capsules o.d.): TIP | Cohort B (5 Capsules o.d.): TIP/PBO | Cohort B (5 Capsules o.d.): PBO | Cohort C (4 Capsules b.i.d.): TIP | Cohort C (4 Capsules b.i.d.): TIP/PBO | Cohort C (4 Capsules b.i.d.): PBO |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.4 Years STANDARD_DEVIATION 13.64 | 63.4 Years STANDARD_DEVIATION 12.66 | 57.5 Years STANDARD_DEVIATION 11.83 | 61.3 Years STANDARD_DEVIATION 7.45 | 64.3 Years STANDARD_DEVIATION 17.86 | 62.4 Years STANDARD_DEVIATION 16.71 | 69.1 Years STANDARD_DEVIATION 13.21 | 66.1 Years STANDARD_DEVIATION 12.23 | 60.8 Years STANDARD_DEVIATION 12.94 | 71.3 Years STANDARD_DEVIATION 10.39 |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 96 Participants | 12 Participants | 11 Participants | 7 Participants | 13 Participants | 11 Participants | 5 Participants | 15 Participants | 15 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 66 Participants | 9 Participants | 10 Participants | 3 Participants | 10 Participants | 7 Participants | 6 Participants | 9 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Male | 41 Participants | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 7 Participants | 1 Participants | 6 Participants | 7 Participants | 3 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 13 | 0 / 7 | 0 / 15 | 0 / 14 | 0 / 7 | 0 / 15 | 0 / 15 | 0 / 7 |
| other Total, other adverse events | 12 / 14 | 12 / 13 | 6 / 7 | 10 / 15 | 10 / 14 | 7 / 7 | 13 / 15 | 14 / 15 | 5 / 7 |
| serious Total, serious adverse events | 4 / 14 | 2 / 13 | 0 / 7 | 4 / 15 | 3 / 14 | 2 / 7 | 2 / 15 | 4 / 15 | 1 / 7 |
Outcome results
Primary
Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Change was determined using the formula = (Post-baseline value - baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Only values for all morphotypes presented.
Time frame: Baseline (Visit 101/Day 1), Visit 102 (Day 8), Visit 103 (Day 29)
Population: Full Analysis Set. Only the participants who had microbiological data at specified time points were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 6.80 log10 CFUs | Standard Deviation 1.202 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -2.61 log10 CFUs | Standard Deviation 2.6 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -2.82 log10 CFUs | Standard Deviation 1.44 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 7.67 log10 CFUs | Standard Deviation 1.507 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -3.23 log10 CFUs | Standard Deviation 2.204 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -2.80 log10 CFUs | Standard Deviation 2.823 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -2.04 log10 CFUs | Standard Deviation 2.274 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 6.10 log10 CFUs | Standard Deviation 2.419 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -1.56 log10 CFUs | Standard Deviation 2.885 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -3.98 log10 CFUs | Standard Deviation 1.865 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 6.98 log10 CFUs | Standard Deviation 1.804 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -3.57 log10 CFUs | Standard Deviation 2.218 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -4.54 log10 CFUs | Standard Deviation 1.283 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 6.79 log10 CFUs | Standard Deviation 0.908 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -4.36 log10 CFUs | Standard Deviation 1.101 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 5.73 log10 CFUs | Standard Deviation 1.885 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -2.58 log10 CFUs | Standard Deviation 2.871 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -3.47 log10 CFUs | Standard Deviation 1.583 |
| Pooled TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -3.30 log10 CFUs | Standard Deviation 1.937 |
| Pooled TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 6.57 log10 CFUs | Standard Deviation 1.625 |
| Pooled TIP | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -2.98 log10 CFUs | Standard Deviation 2.474 |
| Pooled TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | -2.96 log10 CFUs | Standard Deviation 2.618 |
| Pooled TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -3.58 log10 CFUs | Standard Deviation 1.878 |
| Pooled TIP/PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 6.74 log10 CFUs | Standard Deviation 1.892 |
| Pooled PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 29 | 0.05 log10 CFUs | Standard Deviation 1.518 |
| Pooled PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 8 | -0.72 log10 CFUs | Standard Deviation 1.765 |
| Pooled PBO | Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline | 7.09 log10 CFUs | Standard Deviation 2.012 |
Comparison: Day 8 Cohort A: TIP, Pooled PBO95% CI: [-3.62, -1.22]
Comparison: Day 8 Cohort A: TIP/PBO, Pooled PBO95% CI: [-3.3, -0.98]
Comparison: Day 8 Cohort B: TIP, Pooled PBO95% CI: [-3.2, -0.68]
Comparison: Day 8 Cohort B: TIP/PBO, Pooled PBO95% CI: [-4.38, -2.15]
Comparison: Day 8 Cohort C: TIP, Pooled PBO95% CI: [-5.06, -2.88]
Comparison: Day 8 Cohort C: TIP/PBO, Pooled PBO95% CI: [-4.57, -2.14]
Comparison: Day 8: Pooled TIP, Pooled PBO95% CI: [-3.66, -1.89]
Comparison: Day 8: Pooled TIP/PBO, Pooled PBO95% CI: [-3.79, -2.05]
Comparison: Day 29 Cohort A: TIP, Pooled PBO95% CI: [-4.28, -1.31]
Comparison: Day 29 Cohort A: TIP/PBO, Pooled PBO95% CI: [-4.03, -0.67]
Comparison: Day 29 Cohort B: TIP, Pooled PBO95% CI: [-4.04, -0.52]
Comparison: Day 29 Cohort B: TIP/PBO, Pooled PBO95% CI: [-5.16, -1.85]
Comparison: Day 29 Cohort C: TIP, Pooled PBO95% CI: [-6.13, -3.09]
Comparison: Day 29 Cohort C: TIP/PBO, Pooled PBO95% CI: [-4.68, -1.52]
Comparison: Day 29: Pooled TIP, Pooled PBO95% CI: [-4.43, -2.02]
Comparison: Day 29: Pooled TIP/PBO, Pooled PBO95% CI: [-4.19, -1.78]
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | 2.6 Score on Scale | Standard Deviation 11.48 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 6.1 Score on Scale | Standard Deviation 21.44 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 79.5 Score on Scale | Standard Deviation 14.28 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | 1.3 Score on Scale | Standard Deviation 17.63 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | 1.9 Score on Scale | Standard Deviation 11.36 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | -4.2 Score on Scale | Standard Deviation 12.05 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | -6.9 Score on Scale | Standard Deviation 15 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | -8.3 Score on Scale | Standard Deviation 22.19 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | -4.9 Score on Scale | Standard Deviation 12.03 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 71.2 Score on Scale | Standard Deviation 18.51 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 7.4 Score on Scale | Standard Deviation 17.4 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | -0.8 Score on Scale | Standard Deviation 13.67 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | 2.8 Score on Scale | Standard Deviation 13.18 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 77.4 Score on Scale | Standard Deviation 17.73 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | -9.1 Score on Scale | Standard Deviation 18.43 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 5.0 Score on Scale | Standard Deviation 18.51 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | 2.4 Score on Scale | Standard Deviation 11.52 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 74.4 Score on Scale | Standard Deviation 29.5 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | 2.4 Score on Scale | Standard Deviation 32.26 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | 3.8 Score on Scale | Standard Deviation 16.53 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 71.1 Score on Scale | Standard Deviation 18.86 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | 5.6 Score on Scale | Standard Deviation 13.24 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 0.0 Score on Scale | Standard Deviation 7.11 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | 4.4 Score on Scale | Standard Deviation 18.33 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | 1.1 Score on Scale | Standard Deviation 15.06 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 76.1 Score on Scale | Standard Deviation 23.54 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | -1.2 Score on Scale | Standard Deviation 14.93 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | 4.4 Score on Scale | Standard Deviation 6.19 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | -3.3 Score on Scale | Standard Deviation 14.36 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 6.7 Score on Scale | Standard Deviation 21.45 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | -1.7 Score on Scale | Standard Deviation 17.12 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 75.8 Score on Scale | Standard Deviation 17.15 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | 3.6 Score on Scale | Standard Deviation 12.35 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | 2.4 Score on Scale | Standard Deviation 14.8 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 4.2 Score on Scale | Standard Deviation 15.98 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | -2.8 Score on Scale | Standard Deviation 23.76 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | -0.6 Score on Scale | Standard Deviation 14.73 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | 1.2 Score on Scale | Standard Deviation 10.47 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 74.0 Score on Scale | Standard Deviation 23.87 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 1.0 Score on Scale | Standard Deviation 18.78 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at EoT | -2.3 Score on Scale | Standard Deviation 15.6 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 29 | -1.9 Score on Scale | Standard Deviation 12.31 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 169 | 3.9 Score on Scale | Standard Deviation 13.85 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Change from BL at Day 8 | -1.4 Score on Scale | Standard Deviation 11.87 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning | Baseline (BL) | 79.6 Score on Scale | Standard Deviation 16.96 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 7.1 Score on Scale | Standard Deviation 23.28 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 7.1 Score on Scale | Standard Deviation 26.54 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 10.6 Score on Scale | Standard Deviation 13.99 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 41.0 Score on Scale | Standard Deviation 17.83 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | -3.2 Score on Scale | Standard Deviation 25.35 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 4.9 Score on Scale | Standard Deviation 20.24 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | 0.7 Score on Scale | Standard Deviation 17.93 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 35.3 Score on Scale | Standard Deviation 19.29 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 0.0 Score on Scale | Standard Deviation 21.32 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 4.9 Score on Scale | Standard Deviation 20.24 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | -2.5 Score on Scale | Standard Deviation 15.28 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 33.1 Score on Scale | Standard Deviation 20.26 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 12.8 Score on Scale | Standard Deviation 16.26 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 14.4 Score on Scale | Standard Deviation 19.72 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 10.0 Score on Scale | Standard Deviation 11.87 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 6.7 Score on Scale | Standard Deviation 17.91 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | -3.6 Score on Scale | Standard Deviation 23.51 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 41.1 Score on Scale | Standard Deviation 27.83 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | -2.4 Score on Scale | Standard Deviation 13.25 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 3.8 Score on Scale | Standard Deviation 19.73 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 39.4 Score on Scale | Standard Deviation 21.7 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | 1.1 Score on Scale | Standard Deviation 23.12 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | -1.1 Score on Scale | Standard Deviation 18.06 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | -1.4 Score on Scale | Standard Deviation 11.7 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 5.6 Score on Scale | Standard Deviation 13.24 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 5.6 Score on Scale | Standard Deviation 15.96 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 9.2 Score on Scale | Standard Deviation 14.93 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | -1.8 Score on Scale | Standard Deviation 26.19 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 40.0 Score on Scale | Standard Deviation 20.7 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | -0.6 Score on Scale | Standard Deviation 23.46 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 5.3 Score on Scale | Standard Deviation 21.19 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | -1.4 Score on Scale | Standard Deviation 21.43 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 7.4 Score on Scale | Standard Deviation 16.52 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 7.4 Score on Scale | Standard Deviation 16.3 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 37.7 Score on Scale | Standard Deviation 19.91 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 2.6 Score on Scale | Standard Deviation 16.5 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 2.1 Score on Scale | Standard Deviation 22.02 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 38.9 Score on Scale | Standard Deviation 22.52 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | -1.2 Score on Scale | Standard Deviation 21.53 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 4.9 Score on Scale | Standard Deviation 18.31 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 8 | 0.0 Score on Scale | Standard Deviation 16.43 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 169 | 0.9 Score on Scale | Standard Deviation 19.57 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at EoT | 1.6 Score on Scale | Standard Deviation 16.67 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Baseline (BL) | 41.7 Score on Scale | Standard Deviation 16.67 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions | Change from BL at Day 29 | 3.1 Score on Scale | Standard Deviation 14.49 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -6.7 Score on Scale | Standard Deviation 18.66 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | 5.6 Score on Scale | Standard Deviation 18.83 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | 5.5 Score on Scale | Standard Deviation 25.27 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -2.1 Score on Scale | Standard Deviation 24.4 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 51.33 Score on Scale | Standard Deviation 38.33 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | -3.3 Score on Scale | Standard Deviation 18.09 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -7.2 Score on Scale | Standard Deviation 16.44 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | -2.8 Score on Scale | Standard Deviation 14.35 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 60.5 Score on Scale | Standard Deviation 28.6 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -6.1 Score on Scale | Standard Deviation 18.53 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -5.3 Score on Scale | Standard Deviation 27.9 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 45.8 Score on Scale | Standard Deviation 19.98 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | 0.0 Score on Scale | Standard Deviation 22.44 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | -6.7 Score on Scale | Standard Deviation 22.02 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -19.4 Score on Scale | Standard Deviation 23 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | -2.9 Score on Scale | Standard Deviation 18.06 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | -1.3 Score on Scale | Standard Deviation 16.27 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -6.7 Score on Scale | Standard Deviation 23.39 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 50.5 Score on Scale | Standard Deviation 33.04 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -2.6 Score on Scale | Standard Deviation 8.41 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | 0.9 Score on Scale | Standard Deviation 11.51 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -5.8 Score on Scale | Standard Deviation 31.36 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 46.2 Score on Scale | Standard Deviation 30.29 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -0.4 Score on Scale | Standard Deviation 16.23 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | -3.9 Score on Scale | Standard Deviation 26.43 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -9.8 Score on Scale | Standard Deviation 30.43 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | 7.3 Score on Scale | Standard Deviation 22.54 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 53.8 Score on Scale | Standard Deviation 26.72 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -6.2 Score on Scale | Standard Deviation 27.48 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | 3.1 Score on Scale | Standard Deviation 14.44 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | 0.2 Score on Scale | Standard Deviation 17.83 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -2.3 Score on Scale | Standard Deviation 22.04 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 47.6 Score on Scale | Standard Deviation 29.41 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -10.2 Score on Scale | Standard Deviation 25.44 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | 0.4 Score on Scale | Standard Deviation 24.43 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | -7.6 Score on Scale | Standard Deviation 24.47 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | 0.6 Score on Scale | Standard Deviation 19.04 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -5.3 Score on Scale | Standard Deviation 19.05 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | -0.7 Score on Scale | Standard Deviation 15.62 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 54.8 Score on Scale | Standard Deviation 29.1 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 169 | -4.8 Score on Scale | Standard Deviation 16.77 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 29 | -1.1 Score on Scale | Standard Deviation 17.68 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at Day 8 | -7.4 Score on Scale | Standard Deviation 17.76 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Baseline (BL) | 49.8 Score on Scale | Standard Deviation 27.97 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning | Change from BL at EoT | 0.4 Score on Scale | Standard Deviation 20.3 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 56.0 Score on Scale | Standard Deviation 13.05 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | -0.4 Score on Scale | Standard Deviation 11.21 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 10.3 Score on Scale | Standard Deviation 6.83 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 7.1 Score on Scale | Standard Deviation 11.76 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 7.0 Score on Scale | Standard Deviation 11.94 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | 4.1 Score on Scale | Standard Deviation 15.65 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 0.6 Score on Scale | Standard Deviation 19.97 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 53.8 Score on Scale | Standard Deviation 18.12 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 6.5 Score on Scale | Standard Deviation 14.66 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 0.9 Score on Scale | Standard Deviation 16.42 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | 1.9 Score on Scale | Standard Deviation 18.52 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 13.9 Score on Scale | Standard Deviation 16.12 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 6.3 Score on Scale | Standard Deviation 24.57 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 56.8 Score on Scale | Standard Deviation 17.63 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 10.7 Score on Scale | Standard Deviation 8.63 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | -2.7 Score on Scale | Standard Deviation 24.33 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | -0.6 Score on Scale | Standard Deviation 20.73 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 55.9 Score on Scale | Standard Deviation 21.69 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 3.3 Score on Scale | Standard Deviation 9.99 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 3.6 Score on Scale | Standard Deviation 14.69 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | 6.7 Score on Scale | Standard Deviation 16.52 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 52.3 Score on Scale | Standard Deviation 22.39 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 9.8 Score on Scale | Standard Deviation 12.3 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 6.9 Score on Scale | Standard Deviation 22.57 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 5.6 Score on Scale | Standard Deviation 16.53 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 10.7 Score on Scale | Standard Deviation 12.52 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | -5.7 Score on Scale | Standard Deviation 25.58 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 61.9 Score on Scale | Standard Deviation 13.31 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | -0.6 Score on Scale | Standard Deviation 16.2 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | -6.5 Score on Scale | Standard Deviation 26.18 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 11.2 Score on Scale | Standard Deviation 12.05 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 55.0 Score on Scale | Standard Deviation 17.98 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 6.8 Score on Scale | Standard Deviation 19.65 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 7.6 Score on Scale | Standard Deviation 12.76 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | 2.9 Score on Scale | Standard Deviation 15.58 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 2.8 Score on Scale | Standard Deviation 13.85 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 57.4 Score on Scale | Standard Deviation 17.83 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | -1.4 Score on Scale | Standard Deviation 21.59 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | -0.7 Score on Scale | Standard Deviation 20.58 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 2.8 Score on Scale | Standard Deviation 18.57 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 169 | 1.6 Score on Scale | Standard Deviation 19.98 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 8 | 1.0 Score on Scale | Standard Deviation 12.09 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Baseline (BL) | 53.8 Score on Scale | Standard Deviation 14.42 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at EoT | 4.0 Score on Scale | Standard Deviation 12.12 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms | Change from BL at Day 29 | 2.3 Score on Scale | Standard Deviation 13.48 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | 10.3 Score on Scale | Standard Deviation 16.96 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 63.1 Score on Scale | Standard Deviation 24.28 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | 1.5 Score on Scale | Standard Deviation 19.66 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | 5.6 Score on Scale | Standard Deviation 14.36 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | -0.5 Score on Scale | Standard Deviation 23.95 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | -7.2 Score on Scale | Standard Deviation 17.17 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | -5.0 Score on Scale | Standard Deviation 24.47 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | -2.2 Score on Scale | Standard Deviation 19.76 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 67.2 Score on Scale | Standard Deviation 14.26 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | -1.1 Score on Scale | Standard Deviation 18.17 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 53.3 Score on Scale | Standard Deviation 21.68 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | 10.7 Score on Scale | Standard Deviation 13.41 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | 2.2 Score on Scale | Standard Deviation 20.17 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | 2.0 Score on Scale | Standard Deviation 21.33 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | -0.4 Score on Scale | Standard Deviation 23.79 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 64.3 Score on Scale | Standard Deviation 29.77 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | -9.0 Score on Scale | Standard Deviation 25.3 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | -1.4 Score on Scale | Standard Deviation 13.88 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | -1.0 Score on Scale | Standard Deviation 14.87 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | -2.7 Score on Scale | Standard Deviation 21.82 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 57.8 Score on Scale | Standard Deviation 26.86 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | 3.6 Score on Scale | Standard Deviation 17.43 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | 0.9 Score on Scale | Standard Deviation 20.3 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | -6.1 Score on Scale | Standard Deviation 15.94 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | -0.9 Score on Scale | Standard Deviation 19.82 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | 6.7 Score on Scale | Standard Deviation 16.92 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | -4.2 Score on Scale | Standard Deviation 20.95 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 67.6 Score on Scale | Standard Deviation 24.67 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | -4.0 Score on Scale | Standard Deviation 24.27 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | -4.5 Score on Scale | Standard Deviation 23.88 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | 0.7 Score on Scale | Standard Deviation 19.65 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | 0.0 Score on Scale | Standard Deviation 22.01 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | 3.8 Score on Scale | Standard Deviation 17.01 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 57.8 Score on Scale | Standard Deviation 24.11 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | 4.4 Score on Scale | Standard Deviation 17.13 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | -2.3 Score on Scale | Standard Deviation 19.06 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | -2.7 Score on Scale | Standard Deviation 18.03 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | -6.0 Score on Scale | Standard Deviation 24.17 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 66.3 Score on Scale | Standard Deviation 23.46 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | -1.5 Score on Scale | Standard Deviation 18.99 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Baseline (BL) | 63.9 Score on Scale | Standard Deviation 19.79 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 29 | 1.8 Score on Scale | Standard Deviation 16 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 8 | -1.4 Score on Scale | Standard Deviation 14.67 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at EoT | 1.0 Score on Scale | Standard Deviation 19.7 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning | Change from BL at Day 169 | -4.4 Score on Scale | Standard Deviation 15.51 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | 4.9 Score on Scale | Standard Deviation 15.51 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 3.0 Score on Scale | Standard Deviation 13.49 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | 3.3 Score on Scale | Standard Deviation 24.27 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 66.2 Score on Scale | Standard Deviation 19.21 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 3.0 Score on Scale | Standard Deviation 21.71 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 51.3 Score on Scale | Standard Deviation 22.53 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 2.1 Score on Scale | Standard Deviation 26.14 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 2.1 Score on Scale | Standard Deviation 23.61 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | -5.1 Score on Scale | Standard Deviation 20.41 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | -2.5 Score on Scale | Standard Deviation 26.05 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 36.5 Score on Scale | Standard Deviation 21.18 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | 22.8 Score on Scale | Standard Deviation 18.14 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 29.6 Score on Scale | Standard Deviation 23.67 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 17.8 Score on Scale | Standard Deviation 27.89 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | 25.3 Score on Scale | Standard Deviation 21.73 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | -1.5 Score on Scale | Standard Deviation 24.5 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | -4.2 Score on Scale | Standard Deviation 28.43 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 63.5 Score on Scale | Standard Deviation 26.17 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | -5.6 Score on Scale | Standard Deviation 26.73 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | -2.6 Score on Scale | Standard Deviation 12.49 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | -0.7 Score on Scale | Standard Deviation 21.91 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | -4.2 Score on Scale | Standard Deviation 25.42 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 48.5 Score on Scale | Standard Deviation 19.95 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 1.5 Score on Scale | Standard Deviation 30.1 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | 2.6 Score on Scale | Standard Deviation 23.95 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 5.7 Score on Scale | Standard Deviation 15.38 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 55.7 Score on Scale | Standard Deviation 26.8 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 8.5 Score on Scale | Standard Deviation 15.66 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | 4.8 Score on Scale | Standard Deviation 19.89 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | 11.9 Score on Scale | Standard Deviation 21.91 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | 8.7 Score on Scale | Standard Deviation 21.19 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 9.6 Score on Scale | Standard Deviation 23.78 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 49.7 Score on Scale | Standard Deviation 23.13 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 6.9 Score on Scale | Standard Deviation 27.25 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | 7.2 Score on Scale | Standard Deviation 26.36 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 56.9 Score on Scale | Standard Deviation 25.22 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | 0.4 Score on Scale | Standard Deviation 23.07 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 2.8 Score on Scale | Standard Deviation 17.67 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | 0.5 Score on Scale | Standard Deviation 24.15 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | 0.8 Score on Scale | Standard Deviation 22.95 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 169 | -0.5 Score on Scale | Standard Deviation 19.37 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at EoT | -0.6 Score on Scale | Standard Deviation 18.04 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Baseline (BL) | 51.9 Score on Scale | Standard Deviation 25.24 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 29 | -1.2 Score on Scale | Standard Deviation 15.72 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning | Change from BL at Day 8 | 5.0 Score on Scale | Standard Deviation 14.18 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 67.7 Score on Scale | Standard Deviation 25.56 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | 1.4 Score on Scale | Standard Deviation 26.19 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -7.1 Score on Scale | Standard Deviation 21.81 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | -2.2 Score on Scale | Standard Deviation 19.46 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -9.1 Score on Scale | Standard Deviation 28.03 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | -3.7 Score on Scale | Standard Deviation 31.92 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | -8.6 Score on Scale | Standard Deviation 29.28 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 68.9 Score on Scale | Standard Deviation 26.09 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -8.3 Score on Scale | Standard Deviation 27.7 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -8.6 Score on Scale | Standard Deviation 31.32 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 64.3 Score on Scale | Standard Deviation 29.29 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | 0.0 Score on Scale | Standard Deviation 13.28 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | 0.0 Score on Scale | Standard Deviation 15.71 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -10.1 Score on Scale | Standard Deviation 16.07 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | 8.3 Score on Scale | Standard Deviation 30.14 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | -4.2 Score on Scale | Standard Deviation 24.44 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -10.0 Score on Scale | Standard Deviation 22.5 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 73.1 Score on Scale | Standard Deviation 18.63 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -14.8 Score on Scale | Standard Deviation 23.37 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | -9.3 Score on Scale | Standard Deviation 17.62 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 56.4 Score on Scale | Standard Deviation 27.76 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | 6.8 Score on Scale | Standard Deviation 26.66 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | 4.3 Score on Scale | Standard Deviation 14.01 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | 0.0 Score on Scale | Standard Deviation 17.37 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | 1.9 Score on Scale | Standard Deviation 13.26 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 54.5 Score on Scale | Standard Deviation 27.42 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | 4.0 Score on Scale | Standard Deviation 7.49 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | 1.0 Score on Scale | Standard Deviation 9.23 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | 12.7 Score on Scale | Standard Deviation 11.88 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -3.7 Score on Scale | Standard Deviation 25.46 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -0.4 Score on Scale | Standard Deviation 24.26 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | 1.0 Score on Scale | Standard Deviation 16.04 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 62.6 Score on Scale | Standard Deviation 27.39 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | 0.4 Score on Scale | Standard Deviation 18.72 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -2.9 Score on Scale | Standard Deviation 22.92 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | -4.5 Score on Scale | Standard Deviation 19.73 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 65.7 Score on Scale | Standard Deviation 24.75 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | 0.9 Score on Scale | Standard Deviation 25.15 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -7.4 Score on Scale | Standard Deviation 24.27 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -7.6 Score on Scale | Standard Deviation 22.83 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at EoT | -3.0 Score on Scale | Standard Deviation 30.13 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Baseline (BL) | 64.6 Score on Scale | Standard Deviation 30.69 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 169 | -5.1 Score on Scale | Standard Deviation 18.16 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 8 | -2.6 Score on Scale | Standard Deviation 19.33 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden | Change from BL at Day 29 | -5.1 Score on Scale | Standard Deviation 25.91 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality
The QoL-B consists of 37 items across 8 domains: Physical Functioning (PF), Role Functioning (RF), Vitality, Emotional Function (EF), Social Functioning (SF), Treatment Burden (TB), Health Perception (HP) and Respiratory Symptoms (RS). Each of the 37 items is scored from 1 to 4, and each of the 8 scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning and HRQoL. A total score is not calculated since functioning can vary greatly from one domain to another. Only descriptive analysis performed.
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | -5.6 Score on Scale | Standard Deviation 25.26 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 8.1 Score on Scale | Standard Deviation 20.55 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 56.4 Score on Scale | Standard Deviation 22.89 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | -4.3 Score on Scale | Standard Deviation 30.95 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 6.8 Score on Scale | Standard Deviation 18.45 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | 4.6 Score on Scale | Standard Deviation 15.23 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 3.7 Score on Scale | Standard Deviation 22.89 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 47.9 Score on Scale | Standard Deviation 17.21 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 1.9 Score on Scale | Standard Deviation 24.54 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | 2.8 Score on Scale | Standard Deviation 24.22 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 3.7 Score on Scale | Standard Deviation 24.22 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | -12.1 Score on Scale | Standard Deviation 26.04 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | -9.9 Score on Scale | Standard Deviation 28.57 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | -6.1 Score on Scale | Standard Deviation 31.18 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 52.4 Score on Scale | Standard Deviation 21.54 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 2.2 Score on Scale | Standard Deviation 21.47 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | 3.4 Score on Scale | Standard Deviation 18.36 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | 3.2 Score on Scale | Standard Deviation 28.05 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 44.4 Score on Scale | Standard Deviation 26.51 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 4.8 Score on Scale | Standard Deviation 17.27 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | -0.7 Score on Scale | Standard Deviation 24.66 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | -2.8 Score on Scale | Standard Deviation 22.78 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 47.4 Score on Scale | Standard Deviation 25.36 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 5.2 Score on Scale | Standard Deviation 20.52 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | -0.7 Score on Scale | Standard Deviation 29.24 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | -5.6 Score on Scale | Standard Deviation 23.77 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | 2.2 Score on Scale | Standard Deviation 30.35 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 51.9 Score on Scale | Standard Deviation 18.63 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 1.1 Score on Scale | Standard Deviation 19.21 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 2.2 Score on Scale | Standard Deviation 11.27 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 2.8 Score on Scale | Standard Deviation 22.22 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 51.9 Score on Scale | Standard Deviation 23.11 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 2.6 Score on Scale | Standard Deviation 23.43 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | -4.2 Score on Scale | Standard Deviation 27.39 |
| Pooled TIP | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | -5.6 Score on Scale | Standard Deviation 26.77 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | 3.0 Score on Scale | Standard Deviation 17.57 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 48.1 Score on Scale | Standard Deviation 20.92 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | 2.7 Score on Scale | Standard Deviation 27.19 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | 2.4 Score on Scale | Standard Deviation 20.69 |
| Pooled TIP/PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | 80.6 Score on Scale | Standard Deviation 19.74 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at EoT | -1.2 Score on Scale | Standard Deviation 23.97 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Baseline (BL) | 46.2 Score on Scale | Standard Deviation 25.46 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 29 | 1.8 Score on Scale | Standard Deviation 19.69 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 8 | -2.9 Score on Scale | Standard Deviation 16.08 |
| Pooled PBO | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality | Change from BL at Day 169 | -2.5 Score on Scale | Standard Deviation 20.36 |
Secondary
Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Change was determined using the formula = (Post-baseline value - baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Only values for all morphotypes are presented.
Time frame: Baseline (Visit 101/Day 1), Visit 104 (Day 57), Visit 105 (Day 85), Visit 106 (Day 113), End of Treatment (EOT), Visit 201 (Day 141), Visit 202 (Day 169)
Population: Full Analysis Set. Only the participants who had microbiological data at specified time points were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 6.80 log10 CFUs | Standard Deviation 1.202 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -2.47 log10 CFUs | Standard Deviation 2.446 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -2.49 log10 CFUs | Standard Deviation 1.896 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -0.90 log10 CFUs | Standard Deviation 2.113 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -2.94 log10 CFUs | Standard Deviation 1.977 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -1.72 log10 CFUs | Standard Deviation 3.066 |
| Cohort A (3 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | -0.62 log10 CFUs | Standard Deviation 2.324 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 7.67 log10 CFUs | Standard Deviation 1.507 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -0.72 log10 CFUs | Standard Deviation 2.677 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -0.82 log10 CFUs | Standard Deviation 2.117 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -1.03 log10 CFUs | Standard Deviation 2.002 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -1.08 log10 CFUs | Standard Deviation 1.907 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -2.94 log10 CFUs | Standard Deviation 2.492 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | -1.19 log10 CFUs | Standard Deviation 1.885 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | 0.10 log10 CFUs | Standard Deviation 1.551 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -2.81 log10 CFUs | Standard Deviation 3.653 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -0.84 log10 CFUs | Standard Deviation 1.766 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | 0.46 log10 CFUs | Standard Deviation 1.651 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 6.10 log10 CFUs | Standard Deviation 2.419 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -1.82 log10 CFUs | Standard Deviation 2.331 |
| Cohort B (5 Capsules o.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -0.90 log10 CFUs | Standard Deviation 1.894 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -2.17 log10 CFUs | Standard Deviation 2.863 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | -1.27 log10 CFUs | Standard Deviation 2.684 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 6.98 log10 CFUs | Standard Deviation 1.804 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -1.62 log10 CFUs | Standard Deviation 2.804 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -3.88 log10 CFUs | Standard Deviation 2.47 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -1.86 log10 CFUs | Standard Deviation 2.607 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -1.99 log10 CFUs | Standard Deviation 3.02 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -2.60 log10 CFUs | Standard Deviation 2.531 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -3.17 log10 CFUs | Standard Deviation 2.378 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -3.53 log10 CFUs | Standard Deviation 2.22 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -0.92 log10 CFUs | Standard Deviation 2.385 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 6.79 log10 CFUs | Standard Deviation 0.908 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -3.08 log10 CFUs | Standard Deviation 1.624 |
| Cohort C (4 Capsules b.i.d.): TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | 0.62 log10 CFUs | Standard Deviation 1.038 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -0.49 log10 CFUs | Standard Deviation 2.305 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 5.73 log10 CFUs | Standard Deviation 1.885 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -2.00 log10 CFUs | Standard Deviation 2.951 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -1.54 log10 CFUs | Standard Deviation 3.534 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -1.29 log10 CFUs | Standard Deviation 3.3 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -0.87 log10 CFUs | Standard Deviation 3.64 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | 1.33 log10 CFUs | Standard Deviation 4.219 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | 0.03 log10 CFUs | Standard Deviation 1.882 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -2.25 log10 CFUs | Standard Deviation 2.646 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -2.01 log10 CFUs | Standard Deviation 2.192 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -2.76 log10 CFUs | Standard Deviation 2.446 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -0.68 log10 CFUs | Standard Deviation 2.067 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 6.57 log10 CFUs | Standard Deviation 1.625 |
| Pooled TIP | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -2.79 log10 CFUs | Standard Deviation 2.141 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -3.01 log10 CFUs | Standard Deviation 2.641 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | -0.51 log10 CFUs | Standard Deviation 3.036 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -1.50 log10 CFUs | Standard Deviation 2.707 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | -0.96 log10 CFUs | Standard Deviation 2.576 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -1.42 log10 CFUs | Standard Deviation 2.65 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -1.34 log10 CFUs | Standard Deviation 2.793 |
| Pooled TIP/PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 6.74 log10 CFUs | Standard Deviation 1.892 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 169 | 0.62 log10 CFUs | Standard Deviation 2.694 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at EOT | -0.34 log10 CFUs | Standard Deviation 1.445 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 57 | 0.20 log10 CFUs | Standard Deviation 1.408 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Baseline (BL) | 7.09 log10 CFUs | Standard Deviation 2.012 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 85 | -0.36 log10 CFUs | Standard Deviation 2.238 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 141 | -0.06 log10 CFUs | Standard Deviation 2.191 |
| Pooled PBO | Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) | Change from BL at Day 113 | -0.20 log10 CFUs | Standard Deviation 1.513 |
Comparison: Day 57 Cohort A: TIP, Pooled PBO95% CI: [-3.82, -0.36]
Comparison: Day 57 Cohort A: TIP/PBO, Pooled PBO95% CI: [-2.21, 1.29]
Comparison: Day 57 Cohort B: TIP, Pooled PBO95% CI: [-3.87, 0.08]
Comparison: Day 57 Cohort B: TIP/PBO, Pooled PBO95% CI: [-3.34, 0.16]
Comparison: Day 57 Cohort C: TIP, Pooled PBO95% CI: [-5.5, -2.22]
Comparison: Day 57 Cohort C: TIP/PBO, Pooled PBO95% CI: [-3.26, 0.41]
Comparison: Day 57: Pooled TIP, Pooled PBO95% CI: [-3.98, -1.25]
Comparison: Day 57: Pooled TIP/PBO, Pooled PBO95% CI: [-2.5, 0.19]
Comparison: Day 85 Cohort A: TIP, Pooled PBO95% CI: [-4, -0.38]
Comparison: Day 85 Cohort A: TIP/PBO, Pooled PBO95% CI: [-3.81, 0.13]
Comparison: Day 85 Cohort B: TIP, Pooled PBO95% CI: [-4.96, -0.53]
Comparison: Day 85 Cohort B: TIP/PBO, Pooled PBO95% CI: [-5.44, -1.73]
Comparison: Day 85 Cohort C: TIP, Pooled PBO95% CI: [-4.9, -1.07]
Comparison: Day 85 Cohort C: TIP/PBO, Pooled PBO95% CI: [-4.66, -0.53]
Comparison: Day 85: Pooled TIP, Pooled PBO95% CI: [-4.11, -1.17]
Comparison: Day 85: Pooled TIP/PBO, Pooled PBO95% CI: [-4.12, -1.23]
Comparison: Day 113 Cohort A: TIP, Pooled PBO95% CI: [-4.55, -1.08]
Comparison: Day 113 Cohort A: TIP/PBO, Pooled PBO95% CI: [-1.61, 1.71]
Comparison: Day 113 Cohort B: TIP, Pooled PBO95% CI: [-4.93, -0.29]
Comparison: Day 113 Cohort B: TIP/PBO, Pooled PBO95% CI: [-3.62, -0.25]
Comparison: Day 113 Cohort C: TIP, Pooled PBO95% CI: [-4.94, -1.3]
Comparison: Day 113 Cohort C: TIP/PBO, Pooled PBO95% CI: [-4.37, -0.43]
Comparison: Day 113: Pooled TIP, Pooled PBO95% CI: [-4.24, -1.45]
Comparison: Day 113: Pooled TIP/PBO, Pooled PBO95% CI: [-2.73, -0.13]
Comparison: EoT Cohort A: TIP, Pooled PBO95% CI: [-3.64, -0.73]
Comparison: EoT Cohort A: TIP/PBO, Pooled PBO95% CI: [-1.61, 1.43]
Comparison: EoT Cohort B: TIP, Pooled PBO95% CI: [-2.81, 0.25]
Comparison: EoT Cohort B: TIP/PBO, Pooled PBO95% CI: [-3.14, -0.22]
Comparison: EoT Cohort C: TIP, Pooled PBO95% CI: [-3.89, -0.98]
Comparison: EoT Cohort C: TIP/PBO, Pooled PBO95% CI: [-3.12, -0.22]
Comparison: EoT: Pooled TIP, Pooled PBO95% CI: [-3.08, -0.85]
Comparison: EoT: Pooled TIP/PBO, Pooled PBO95% CI: [-2.25, -0.04]
Comparison: Day 141 Cohort A: TIP, Pooled PBO95% CI: [-2.63, 0.99]
Comparison: Day 141 Cohort A: TIP/PBO, Pooled PBO95% CI: [-1.83, 1.98]
Comparison: Day 141 Cohort B: TIP, Pooled PBO95% CI: [-2.03, 2.41]
Comparison: Day 141 Cohort B: TIP/PBO, Pooled PBO95% CI: [-3.68, -0.01]
Comparison: Day 141 Cohort C (4 capsules b.i.d.): TIP, Pooled PBO95% CI: [-2.78, 1.07]
Comparison: Day 141 Cohort C: TIP/PBO, Pooled PBO95% CI: [-3.36, 0.89]
Comparison: Day 141: Pooled TIP, Pooled PBO95% CI: [-1.97, 0.98]
Comparison: Day 141: Pooled TIP/PBO, Pooled PBO95% CI: [-2.45, 0.45]
Comparison: Day 169 Cohort A: TIP, Pooled PBO95% CI: [-3.24, 0.61]
Comparison: Day 169 Cohort A: TIP/PBO, Pooled PBO95% CI: [-3.05, 0.91]
Comparison: Day 169 Cohort B: TIP, Pooled PBO95% CI: [-2.73, 1.62]
Comparison: Day 169 Cohort B: TIP/PBO, Pooled PBO95% CI: [-4.22, -0.08]
Comparison: Day 169 Cohort C: TIP, Pooled PBO95% CI: [-2.48, 2.1]
Comparison: Day 169 Cohort C: TIP/PBO, Pooled PBO95% CI: [-2.33, 2.13]
Comparison: Day 169: Pooled TIP, Pooled PBO95% CI: [-2.24, 0.86]
Comparison: Day 169: Pooled TIP/PBO, Pooled PBO95% CI: [-2.61, 0.4]
Secondary
Duration of Anti-pseudomonal Antibiotics Usage
The total number of days of new anti-pseudomonal antibiotic use compared to placebo was analyzed. Only descriptive analysis
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 18.4 Days | Standard Deviation 10.39 |
| Cohort A (3 Capsules o.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 15.0 Days | Standard Deviation 10.02 |
| Cohort A (3 Capsules o.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 14.2 Days | Standard Deviation 7.79 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 19.8 Days | Standard Deviation 12.34 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 20.0 Days | Standard Deviation 12.03 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 20.0 Days | Standard Deviation 14.14 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 19.2 Days | Standard Deviation 14.84 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 15.0 Days | Standard Deviation 7.42 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 23.8 Days | Standard Deviation 15.2 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 25.7 Days | Standard Deviation 13.21 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 14.0 Days | Standard Deviation 10.92 |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 15.3 Days | Standard Deviation 10.07 |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 6.0 Days | — |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 20.0 Days | Standard Deviation 8.49 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 11.3 Days | Standard Deviation 2.75 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 10.8 Days | Standard Deviation 6.24 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 15.7 Days | Standard Deviation 10.9 |
| Pooled TIP | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 15.5 Days | Standard Deviation 7.29 |
| Pooled TIP | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 18.1 Days | Standard Deviation 11.43 |
| Pooled TIP | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 15.1 Days | Standard Deviation 10.23 |
| Pooled TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 14.3 Days | Standard Deviation 9.79 |
| Pooled TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 20.6 Days | Standard Deviation 12.24 |
| Pooled TIP/PBO | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 17.5 Days | Standard Deviation 12.12 |
| Pooled PBO | Duration of Anti-pseudomonal Antibiotics Usage | Parenteral | 12.7 Days | Standard Deviation 7.64 |
| Pooled PBO | Duration of Anti-pseudomonal Antibiotics Usage | Oral | 13.7 Days | Standard Deviation 7.41 |
| Pooled PBO | Duration of Anti-pseudomonal Antibiotics Usage | Overall | 14.6 Days | Standard Deviation 8.27 |
Secondary
Duration of Hospitalization Due to Serious Respiratory-related Adverse Events
The duration of hospitalization due to serious respiratory-related adverse events (other than those regularly scheduled hospitalization that were planned prior to study start) was analyzed to define severity of pulmonary exacerbations compared to placebo. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set. Only the participants with at least one hospitalization are included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 15.2 Days | Standard Deviation 5.19 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 22.0 Days | Standard Deviation 12.73 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 12.2 Days | Standard Deviation 6.06 |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 11.0 Days | — |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 19.0 Days | Standard Deviation 5.23 |
| Pooled TIP | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 16.2 Days | Standard Deviation 7.05 |
| Pooled TIP/PBO | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 15.2 Days | Standard Deviation 6.44 |
| Pooled PBO | Duration of Hospitalization Due to Serious Respiratory-related Adverse Events | 10.5 Days | Standard Deviation 0.71 |
Secondary
Duration of Pulmonary Exacerbation by Exacerbation Category
The duration of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 15.7 Days | Standard Deviation 6.22 |
| Cohort A (3 Capsules o.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 15.0 Days | Standard Deviation 5.52 |
| Cohort A (3 Capsules o.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 19.5 Days | Standard Deviation 12.02 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 15.4 Days | Standard Deviation 4.24 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 18.0 Days | Standard Deviation 8.26 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 19.3 Days | Standard Deviation 3.2 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 20.2 Days | Standard Deviation 6.37 |
| Cohort B (5 Capsules o.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 22.0 Days | Standard Deviation 12.73 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 16.0 Days | — |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 10.3 Days | Standard Deviation 5.12 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 8.3 Days | Standard Deviation 4.16 |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 14.0 Days | — |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 25.5 Days | Standard Deviation 27.09 |
| Cohort C (4 Capsules b.i.d.): TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 66.0 Days | — |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 16.3 Days | Standard Deviation 5.51 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 14.8 Days | Standard Deviation 6.73 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 16.8 Days | Standard Deviation 4.86 |
| Pooled TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 23.1 Days | Standard Deviation 18.73 |
| Pooled TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 18.6 Days | Standard Deviation 5.77 |
| Pooled TIP | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 19.0 Days | Standard Deviation 12.64 |
| Pooled TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 14.0 Days | Standard Deviation 5.24 |
| Pooled TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 16.6 Days | Standard Deviation 4.22 |
| Pooled TIP/PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 15.2 Days | Standard Deviation 7.39 |
| Pooled PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Parenteral | 10.0 Days | — |
| Pooled PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Oral | 15.6 Days | Standard Deviation 5.75 |
| Pooled PBO | Duration of Pulmonary Exacerbation by Exacerbation Category | Overall | 14.5 Days | Standard Deviation 5.61 |
Comparison: Overall Cohort A: TIP, Pooled PBO95% CI: [-27.15, 46.81]
Comparison: Overall Cohort A: TIP/PBO, Pooled PBO95% CI: [-22.63, 62.14]
Comparison: Overall Cohort B: TIP, Pooled PBO95% CI: [-31.32, 47.26]
Comparison: Overall Cohort B: TIP/PBO, Pooled PBO95% CI: [-26.49, 51.89]
Comparison: Overall Cohort C: TIP, Pooled PBO95% CI: [3.37, 89.61]
Comparison: Overall Cohort C: TIP/PBO, Pooled PBO95% CI: [-34.21, 40.64]
Comparison: Overall Pooled TIP, Pooled PBO95% CI: [-8.03, 50.89]
Comparison: Overall Pooled TIP/PBO, Pooled PBO95% CI: [-17.52, 41.29]
Secondary
Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period
The exposure adjusted rate of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. The Exposure adjusted rate = (Number of pulmonary exacerbations reported during the study period) / (sum of study duration in days for all participants/ 365.25). Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.71 pulmonary exacerbation per study years |
| Cohort A (3 Capsules o.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.34 pulmonary exacerbation per study years |
| Cohort A (3 Capsules o.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.85 pulmonary exacerbation per study years |
| Cohort A (3 Capsules o.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 1.22 pulmonary exacerbation per study years |
| Cohort A (3 Capsules o.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.39 pulmonary exacerbation per study years |
| Cohort B (5 Capsules o.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.29 pulmonary exacerbation per study years |
| Cohort B (5 Capsules o.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.43 pulmonary exacerbation per study years |
| Cohort B (5 Capsules o.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.86 pulmonary exacerbation per study years |
| Cohort B (5 Capsules o.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.85 pulmonary exacerbation per study years |
| Cohort B (5 Capsules o.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.20 pulmonary exacerbation per study years |
| Cohort B (5 Capsules o.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.34 pulmonary exacerbation per study years |
| Cohort C (4 Capsules b.i.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.16 pulmonary exacerbation per study years |
| Cohort C (4 Capsules b.i.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 0.66 pulmonary exacerbation per study years |
| Cohort C (4 Capsules b.i.d.): TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.16 pulmonary exacerbation per study years |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.46 pulmonary exacerbation per study years |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.55 pulmonary exacerbation per study years |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.73 pulmonary exacerbation per study years |
| Pooled TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.21 pulmonary exacerbation per study years |
| Pooled TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.42 pulmonary exacerbation per study years |
| Pooled TIP | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.48 pulmonary exacerbation per study years |
| Pooled TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 0.88 pulmonary exacerbation per study years |
| Pooled TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.35 pulmonary exacerbation per study years |
| Pooled TIP/PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.35 pulmonary exacerbation per study years |
| Pooled PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Overall | 1.41 pulmonary exacerbation per study years |
| Pooled PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Parenteral | 0.11 pulmonary exacerbation per study years |
| Pooled PBO | Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period | Oral | 1.19 pulmonary exacerbation per study years |
Secondary
Number of Hospitalization Due to Serious Respiratory-related Adverse Events
The number of hospitalization due to serious respiratory-related AEs was analyzed to define severity of pulmonary exacerbations compared to placebo. Respiratory related adverse events were identified using the AEs captured under system organ class 'Respiratory, thoracic and mediastinal disorders' and 'Infections and infestations'.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 6 Hospitalization |
| Cohort A (3 Capsules o.d.): TIP/PBO | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 0 Hospitalization |
| Cohort B (5 Capsules o.d.): TIP | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 2 Hospitalization |
| Cohort B (5 Capsules o.d.): TIP/PBO | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 5 Hospitalization |
| Cohort C (4 Capsules b.i.d.): TIP | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 2 Hospitalization |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 4 Hospitalization |
| Pooled TIP | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 10 Hospitalization |
| Pooled TIP/PBO | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 9 Hospitalization |
| Pooled PBO | Number of Hospitalization Due to Serious Respiratory-related Adverse Events | 2 Hospitalization |
Comparison: Cohort A (3 capsules o.d.): TIP, Pooled PBO95% CI: [0.83, 38.18]
Comparison: Cohort B (5 capsules o.d.): TIP, Pooled PBO95% CI: [0.21, 19.16]
Comparison: Cohort B (5 capsules o.d.): TIP/PBO, Pooled PBO95% CI: [0.43, 21.8]
Comparison: Cohort C (4 capsules b.i.d.): TIP, Pooled PBO95% CI: [0.19, 17.42]
Comparison: Cohort C (4 capsules b.i.d.): TIP/PBO, Pooled PBO95% CI: [0.47, 25.03]
95% CI: [0.47, 16.07]
Secondary
Percentage of Participants Requiring Anti-pseudomonal Antibiotics
The percentage of participants requiring anti-pseudomonal antibiotics compared to placebo was analyzed. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 6 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 8 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 5 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 5 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 4 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 4 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 13 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 13 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 6 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 5 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 10 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 2 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 7 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 6 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 7 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 8 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 10 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 4 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 3 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 12 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 1 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 13 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 2 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 14 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 6 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 7 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 8 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 11 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 4 Participants |
| Pooled TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 12 Participants |
| Pooled TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 27 Participants |
| Pooled TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 17 Participants |
| Pooled TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 8 Participants |
| Pooled TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 32 Participants |
| Pooled TIP | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 36 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 26 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 24 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 8 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 16 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 18 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 34 Participants |
| Pooled PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=No | 11 Participants |
| Pooled PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Oral | Any anti-pseudomonal antibiotic use?=Yes | 10 Participants |
| Pooled PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=Yes | 3 Participants |
| Pooled PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Parenteral | Any anti-pseudomonal antibiotic use?=No | 18 Participants |
| Pooled PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=No | 9 Participants |
| Pooled PBO | Percentage of Participants Requiring Anti-pseudomonal Antibiotics | Overall | Any anti-pseudomonal antibiotic use?=Yes | 12 Participants |
Secondary
Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events
The percentage of participants requiring hospitalization due to serious respiratory-related adverse events (other than those regularly scheduled hospitalization that were planned prior to study start) was analyzed to define severity of pulmonary exacerbations compared to placebo. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 3 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 10 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 1 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 13 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 2 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 13 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 1 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 1 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 12 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 14 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 1 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 4 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 11 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
| Pooled TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 37 Participants |
| Pooled TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 5 Participants |
| Pooled TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 1 Participants |
| Pooled TIP | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 1 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 36 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 5 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
| Pooled TIP/PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 1 Participants |
| Pooled PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with > 2 events | 0 Participants |
| Pooled PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 1 event | 2 Participants |
| Pooled PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No of participants with 0 event | 19 Participants |
| Pooled PBO | Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events | No. of participants with 2 events | 0 Participants |
Secondary
Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation
The percentage of participants who permanently discontinued study drug due to pulmonary exacerbation compared to placebo was analyzed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 2 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 1 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 2 Participants |
| Pooled TIP | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 41 Participants |
| Pooled TIP/PBO | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 40 Participants |
| Pooled PBO | Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation | 0 Participants |
Secondary
Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category
Pulmonary exacerbations are defined as events requiring antibiotic therapy AND for which at least 3 of the following 6 symptoms, signs, or findings were present outside of normal variation: 1. Increased sputum volume, or change in viscosity/consistency or purulence for more than 24 hours; 2. Increased shortness of breath at rest or on exercise for more than 24 hours; 3. Increased cough for more than 24 hours; 4. Fever of ≥38° Celsius within the last 24 hours; 5. Increased malaise/fatigue/lethargy for more than 24 hours; 6. A reduction in forced expiratory volume in the first second of expiration (FEV1) or forced vital capacity (FVC) of least 10% from screening. Participants were categorized as: a) Overall, b) Category 1: treated with oral antibiotics only and c) Category 2: treated with parenteral Antibiotics and/or requiring hospitalization. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 3 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 8 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 2 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 10 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 3 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 2 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 12 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 1 Participants |
| Cohort A (3 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 1 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 2 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 1 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 13 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 1 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 2 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 9 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 9 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 1 Participants |
| Cohort A (3 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 1 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 13 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 1 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 10 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 4 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 1 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 12 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 2 Participants |
| Cohort B (5 Capsules o.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 2 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 2 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 9 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 10 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 2 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 3 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 12 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 3 Participants |
| Cohort B (5 Capsules o.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 1 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 1 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 4 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 1 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 14 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 14 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 11 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 4 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 2 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 3 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 12 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 11 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 4 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 9 Participants |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 6 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 1 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 38 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 29 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 11 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 3 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 5 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 1 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 37 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 1 Participants |
| Pooled TIP | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 31 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 8 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 8 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 27 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 1 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 6 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 36 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 1 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 6 Participants |
| Pooled TIP/PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 2 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 1 event | 7 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No of participants with no events | 20 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 1 event | 5 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No of participants with no events | 13 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 3 events | 0 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 1 event | 1 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No. of participants with 2 events | 3 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Overall | No of participants with no events | 11 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 3 events | 0 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Parenteral | No. of participants with 2 events | 0 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 3 events | 0 Participants |
| Pooled PBO | Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category | Oral | No. of participants with 2 events | 3 Participants |
Secondary
Serum Tobramycin Concentration
The serum pharmacokinetic (PK) properties of tobramycin were assessed by evaluating tobramycin concentrations in serum collected from the non-cystic fibrosis bronchiectasis population post administration of o.d. or b.i.d. doses of TIP. Serum specimens for PK tobramycin concentration were assessed at Visit 101 (Day 1/start of treatment) 0 to 1 and 1 to 2 hours post-dose and Visit 102 (Day 8) 0 to 1 and 1 to 2 hours post-dose. Prior to protocol amendment #2, PK samples were assessed on Visits 103 (Day 29) rather than Visit 102. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1), Visit 102 (Day 8) and Visits 103 (Day 29): 0-1 hours and 1-2 hours post-dose.
Population: Pharmacokinetic Analysis Set. Prior to protocol amendment #2, PK samples were assessed on Visit 103 (Day 29) rather than Visit 102 (Day 8).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 103 (Day 29)/1-2 hr post dose | 0.768 microgram/milliliter | Standard Deviation 0.477 |
| Cohort A (3 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 103 (Day 29)/0-1 hr post dose | 0.607 microgram/milliliter | Standard Deviation 0.455 |
| Cohort A (3 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 0.256 microgram/milliliter | Standard Deviation 0.144 |
| Cohort A (3 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 0.481 microgram/milliliter | Standard Deviation 0.287 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 102 (Day 8)/1-2 hr post dose | 0.18 microgram/milliliter | — |
| Cohort A (3 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 103 (Day 29)/1-2 hr post dose | 0.0818 microgram/milliliter | Standard Deviation 0.0972 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 0.571 microgram/milliliter | Standard Deviation 0.349 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 102 (Day 8)/0-1 hr post dose | 0 microgram/milliliter | — |
| Cohort A (3 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 0.479 microgram/milliliter | Standard Deviation 0.47 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 103 (Day 29)/0-1 hr post dose | 0.0718 microgram/milliliter | Standard Deviation 0.0498 |
| Cohort B (5 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 102 (Day 8)/0-1 hr post dose | 1.81 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 103 (Day 29)/1-2 hr post dose | 1.37 microgram/milliliter | Standard Deviation 0.647 |
| Cohort B (5 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 0.517 microgram/milliliter | Standard Deviation 0.392 |
| Cohort B (5 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 0.4 microgram/milliliter | Standard Deviation 0.259 |
| Cohort B (5 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 102 (Day 8)/1-2 hr post dose | 1.67 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP | Serum Tobramycin Concentration | Visit 103 (Day 29)/0-1 hr post dose | 1.23 microgram/milliliter | Standard Deviation 1.08 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 102 (Day 8)/0-1 hr post dose | 0.258 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 103 (Day 29)/0-1 hr post dose | 0.103 microgram/milliliter | Standard Deviation 0.0983 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 102 (Day 8)/1-2 hr post dose | 0.588 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 0.441 microgram/milliliter | Standard Deviation 0.273 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 103 (Day 29)/1-2 hr post dose | 0.104 microgram/milliliter | Standard Deviation 0.096 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 0.624 microgram/milliliter | Standard Deviation 0.322 |
| Cohort C (4 Capsules b.i.d.): TIP | Serum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 0.64 microgram/milliliter | Standard Deviation 0.338 |
| Cohort C (4 Capsules b.i.d.): TIP | Serum Tobramycin Concentration | Visit 102 (Day 8)/0-1 hr post dose | 1.4 microgram/milliliter | — |
| Cohort C (4 Capsules b.i.d.): TIP | Serum Tobramycin Concentration | Visit 103 (Day 29)/1-2 hr post dose | 1.05 microgram/milliliter | Standard Deviation 0.622 |
| Cohort C (4 Capsules b.i.d.): TIP | Serum Tobramycin Concentration | Visit 103 (Day 29)/0-1 hr post dose | 1.05 microgram/milliliter | Standard Deviation 0.603 |
| Cohort C (4 Capsules b.i.d.): TIP | Serum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 0.59 microgram/milliliter | Standard Deviation 0.37 |
| Cohort C (4 Capsules b.i.d.): TIP | Serum Tobramycin Concentration | Visit 102 (Day 8)/1-2 hr post dose | 1.48 microgram/milliliter | — |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 103 (Day 29)/1-2 hr post dose | 0.307 microgram/milliliter | Standard Deviation 0.24 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 0.321 microgram/milliliter | Standard Deviation 0.21 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 0.476 microgram/milliliter | Standard Deviation 0.295 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 102 (Day 8)/0-1 hr post dose | 0.489 microgram/milliliter | Standard Deviation 0.257 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 102 (Day 8)/1-2 hr post dose | 0.447 microgram/milliliter | — |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Serum Tobramycin Concentration | Visit 103 (Day 29)/0-1 hr post dose | 0.339 microgram/milliliter | Standard Deviation 0.274 |
Secondary
Sputum Tobramycin Concentration
The sputum pharmacokinetic (PK) properties of tobramycin were assessed by evaluating tobramycin concentrations in sputum collected from the non-cystic fibrosis bronchiectasis population post administration of o.d. or b.i.d. doses of TIP. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1): 0-1 hours and 1-2 hours post-dose; Visit 102 (Day 8):0-2 hours and 5-6 hours post-dose; Visits 103 (Day 29): 5 to 6 hours post-dose, Visit 104 (Day 57) and Visit 105 (Day 85): 3-4 hours post-dose.
Population: Pharmacokinetic Analysis Set. Prior to protocol amendment #2, Sputum specimens for PK assessments were collected at Visit 103 (Day 29) 5 to 6 hours rather than Visit 102 (Day 8) 0 to 2 and 5 to 6 hours and on Visit 105 (Day 85) 3 to 4 hours rather than Visit 104 (Day 57) 3 to 4 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 1100 microgram/milliliter | Standard Deviation 2480 |
| Cohort A (3 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 104 (Day 57)/3-4 hr post dose | 198 microgram/milliliter | Standard Deviation 138 |
| Cohort A (3 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 103 (Day 29)/5-6 hr post dose | 389 microgram/milliliter | Standard Deviation 554 |
| Cohort A (3 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 102 (Day 8)/0-2 hr post dose | 1440 microgram/milliliter | Standard Deviation 1470 |
| Cohort A (3 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 1750 microgram/milliliter | Standard Deviation 2160 |
| Cohort A (3 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 105 (Day 85)/3-4 hr post dose | 791 microgram/milliliter | Standard Deviation 883 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 102 (Day 8)/0-2 hr post dose | 2390 microgram/milliliter | Standard Deviation 2730 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 105 (Day 85)/3-4 hr post dose | 45.7 microgram/milliliter | Standard Deviation 75.8 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 204 microgram/milliliter | Standard Deviation 445 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 104 (Day 57)/3-4 hr post dose | 0 microgram/milliliter | — |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 637 microgram/milliliter | Standard Deviation 608 |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 102 (Day 8)/5-6 hr post dose | 32.4 microgram/milliliter | — |
| Cohort A (3 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 103 (Day 29)/5-6 hr post dose | 136 microgram/milliliter | Standard Deviation 258 |
| Cohort B (5 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 103 (Day 29)/5-6 hr post dose | 915 microgram/milliliter | Standard Deviation 1450 |
| Cohort B (5 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 102 (Day 8)/0-2 hr post dose | 2460 microgram/milliliter | Standard Deviation 761 |
| Cohort B (5 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 105 (Day 85)/3-4 hr post dose | 101 microgram/milliliter | Standard Deviation 100 |
| Cohort B (5 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 2640 microgram/milliliter | Standard Deviation 2680 |
| Cohort B (5 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 1650 microgram/milliliter | Standard Deviation 2340 |
| Cohort B (5 Capsules o.d.): TIP | Sputum Tobramycin Concentration | Visit 104 (Day 57)/3-4 hr post dose | 96.4 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 102 (Day 8)/0-2 hr post dose | 4290 microgram/milliliter | Standard Deviation 3730 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 104 (Day 57)/3-4 hr post dose | 4540 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 2020 microgram/milliliter | Standard Deviation 2360 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 1100 microgram/milliliter | Standard Deviation 2310 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 102 (Day 8)/5-6 hr post dose | 4460 microgram/milliliter | — |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 103 (Day 29)/5-6 hr post dose | 16.3 microgram/milliliter | Standard Deviation 28.6 |
| Cohort B (5 Capsules o.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 105 (Day 85)/3-4 hr post dose | 61 microgram/milliliter | Standard Deviation 108 |
| Cohort C (4 Capsules b.i.d.): TIP | Sputum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 2820 microgram/milliliter | Standard Deviation 2250 |
| Cohort C (4 Capsules b.i.d.): TIP | Sputum Tobramycin Concentration | Visit 105 (Day 85)/3-4 hr post dose | 2810 microgram/milliliter | Standard Deviation 2200 |
| Cohort C (4 Capsules b.i.d.): TIP | Sputum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 631 microgram/milliliter | Standard Deviation 441 |
| Cohort C (4 Capsules b.i.d.): TIP | Sputum Tobramycin Concentration | Visit 102 (Day 8)/0-2 hr post dose | 1980 microgram/milliliter | Standard Deviation 2060 |
| Cohort C (4 Capsules b.i.d.): TIP | Sputum Tobramycin Concentration | Visit 103 (Day 29)/5-6 hr post dose | 620 microgram/milliliter | Standard Deviation 513 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 102 (Day 8)/0-2 hr post dose | 2290 microgram/milliliter | Standard Deviation 1560 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 102 (Day 8)/5-6 hr post dose | 1200 microgram/milliliter | Standard Deviation 51.6 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 105 (Day 85)/3-4 hr post dose | 121 microgram/milliliter | Standard Deviation 166 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 101 (Day 1)/1-2 hr post dose | 610 microgram/milliliter | Standard Deviation 463 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 103 (Day 29)/5-6 hr post dose | 134 microgram/milliliter | Standard Deviation 175 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 101 (Day 1)/0-1 hr post dose | 2060 microgram/milliliter | Standard Deviation 1840 |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Sputum Tobramycin Concentration | Visit 104 (Day 57)/3-4 hr post dose | 0 microgram/milliliter | Standard Deviation 0 |
Secondary
Time to First Hospitalization Due to Serious Respiratory-related Adverse Events
Time to first hospitalization due to serious respiratory-related AEs was analyzed to define severity of pulmonary exacerbations compared to placebo. Participants were censored at the time of last contact if they did not have a hospitalization due to serious respiratory-related adverse events over the entire study period.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Cohort A (3 Capsules o.d.): TIP/PBO | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Cohort B (5 Capsules o.d.): TIP | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Pooled TIP | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Pooled TIP/PBO | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
| Pooled PBO | Time to First Hospitalization Due to Serious Respiratory-related Adverse Events | NA Day |
Comparison: Cohort A (3 capsules o.d.): TIP, Pooled PBO95% CI: [0.77, 26.42]
Comparison: Cohort B (5 capsules o.d.): TIP, Pooled PBO95% CI: [0.28, 14.47]
Comparison: Cohort B (5 capsules o.d.): TIP/PBO, Pooled PBO95% CI: [0.2, 11.6]
Comparison: Cohort C (4 capsules b.i.d.): TIP, Pooled PBO95% CI: [0.06, 7.49]
Comparison: Cohort C (4 capsules b.i.d.): TIP/PBO, Pooled PBO95% CI: [0.62, 23.29]
Comparison: Pooled TIP, Pooled PBO95% CI: [0.35, 9.45]
Secondary
Time to First Onset of Pulmonary Exacerbation by Exacerbation Category
The time to first onset of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. Participants were censored at the time of completion of study or early discontinuation if they did not have a pulmonary exacerbation during the study period.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Cohort A (3 Capsules o.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Cohort A (3 Capsules o.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Cohort A (3 Capsules o.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Cohort A (3 Capsules o.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Pooled TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Pooled TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Pooled TIP | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Pooled TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | NA Days |
| Pooled TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Pooled TIP/PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | NA Days |
| Pooled PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Parenteral | NA Days |
| Pooled PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Overall | 173.00 Days |
| Pooled PBO | Time to First Onset of Pulmonary Exacerbation by Exacerbation Category | Oral | 173.00 Days |
Comparison: Overall Cohort A: TIP, Pooled PBO95% CI: [0.14, 3.18]
Comparison: Overall Cohort A: TIP/PBO, Pooled PBO95% CI: [0.18, 1.85]
Comparison: Overall Cohort B: TIP, Pooled PBO95% CI: [0.42, 3.77]
Comparison: Overall Cohort B: TIP/PBO, Pooled PBO95% CI: [0.2, 1.83]
Comparison: Overall Cohort C: TIP, Pooled PBO95% CI: [0.21, 2.17]
Comparison: Overall Cohort C: TIP/PBO, Pooled PBO95% CI: [0.44, 3.62]
Comparison: Overall Pooled TIP, Pooled PBO95% CI: [0.44, 2.23]
Comparison: Overall Pooled TIP/PBO, Pooled PBO95% CI: [0.34, 1.71]
Comparison: Oral Cohort A: TIP, Pooled PBO95% CI: [0.08, 1.83]
Comparison: Oral Cohort A: TIP/PBO, Pooled PBO95% CI: [0.25, 2.89]
Comparison: Oral Cohort B: TIP, Pooled PBO95% CI: [0.25, 3.93]
Comparison: Oral Cohort B: TIP/PBO, Pooled PBO95% CI: [0.19, 2.36]
Comparison: Oral Cohort C: TIP, Pooled PBO95% CI: [0.02, 1.57]
Comparison: Oral Cohort C: TIP/PBO, Pooled PBO95% CI: [0.16, 2.41]
Comparison: Oral Pooled TIP, Pooled PBO95% CI: [0.13, 1.31]
Comparison: Oral Pooled TIP/PBO, Pooled PBO95% CI: [0.28, 1.8]
Comparison: Parenteral Cohort A: TIP, Pooled PBO95% CI: [1.1, 104.19]
Comparison: Parenteral Cohort B: TIP, Pooled PBO95% CI: [0.41, 52.29]
Comparison: Parenteral Cohort B: TIP/PBO, Pooled PBO95% CI: [0.28, 37.06]
Comparison: Parenteral Cohort C: TIP, Pooled PBO95% CI: [0.1, 25.94]
Comparison: Parenteral Cohort C: TIP/PBO, Pooled PBO95% CI: [1.09, 117.34]
Comparison: Parenteral Pooled TIP, Pooled PBO95% CI: [0.5, 37.32]
Secondary
Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage
The time to first use of anti-pseudomonal antibiotics administered compared to placebo was analyzed. Participants were censored at the time of last contact if they did not have anti-pseudomonal antibiotics over the entire study period.
Time frame: From Baseline (Visit 101/Day 1) up to approximately Day 173
Population: Full Analysis Set. Only the participants who required antipseudomonal antibiotics were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Cohort A (3 Capsules o.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | 122.00 Days |
| Cohort A (3 Capsules o.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Cohort A (3 Capsules o.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Cohort A (3 Capsules o.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | 116.00 Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | 161.00 Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Pooled TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | NA Days |
| Pooled TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Pooled TIP | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Pooled TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | NA Days |
| Pooled TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | NA Days |
| Pooled TIP/PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Pooled PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Oral | 173.00 Days |
| Pooled PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Parenteral | NA Days |
| Pooled PBO | Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage | Overall | 141.00 Days |
Comparison: Overall Cohort A: TIP, Pooled PBO95% CI: [0.51, 3.13]
Comparison: Overall Cohort A: TIP/PBO, Pooled PBO95% CI: [0.15, 1.46]
Comparison: Overall Cohort B: TIP, Pooled PBO95% CI: [0.44, 3.21]
Comparison: Overall Cohort B: TIP/PBO, Pooled PBO95% CI: [0.32, 2.18]
Comparison: Overall Cohort C: TIP, Pooled PBO95% CI: [0.1, 1.27]
Comparison: Overall Cohort C: TIP/PBO, Pooled PBO95% CI: [0.43, 2.99]
Comparison: Overall Pooled TIP, Pooled PBO95% CI: [0.37, 1.76]
Comparison: Overall Pooled TIP/PBO, Pooled PBO95% CI: [0.36, 1.61]
Comparison: Oral Cohort A: TIP, Pooled PBO95% CI: [0.3, 2.55]
Comparison: Oral Cohort A: TIP/PBO, Pooled PBO95% CI: [0.2, 2.03]
Comparison: Oral Cohort B: TIP, Pooled PBO95% CI: [0.4, 3.6]
Comparison: Oral Cohort B: TIP/PBO, Pooled PBO95% CI: [0.31, 2.55]
Comparison: Oral Cohort C: TIP, Pooled PBO95% CI: [0.06, 1.27]
Comparison: Oral Cohort C: TIP/PBO, Pooled PBO95% CI: [0.45, 3.73]
Comparison: Oral Pooled TIP, Pooled PBO95% CI: [0.27, 1.6]
Comparison: Oral Pooled TIP/PBO, Pooled PBO95% CI: [0.4, 2.02]
Comparison: Parenteral Cohort A: TIP, Pooled PBO95% CI: [0.84, 16.52]
Comparison: Parenteral Cohort B: TIP, Pooled PBO95% CI: [0.22, 8.16]
Comparison: Parenteral Cohort B: TIP/PBO, Pooled PBO95% CI: [0.46, 10.05]
Comparison: Parenteral Cohort C: TIP, Pooled PBO95% CI: [0.05, 4.87]
Comparison: Parenteral Cohort C: TIP/PBO, Pooled PBO95% CI: [0.53, 12.49]
Comparison: Paremteral Pooled TIP, Pooled PBO95% CI: [0.33, 5.68]
Secondary
Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation
The time to permanent study drug discontinuation due to Pulmonary exacerbation. Participants were censored at the time of last contact if they did not permanently discontinue study drug due to pulmonary exacerbation requiring during the study period. Only descriptive analysis performed.
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A (3 Capsules o.d.): TIP | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Cohort A (3 Capsules o.d.): TIP/PBO | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Cohort B (5 Capsules o.d.): TIP | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Cohort B (5 Capsules o.d.): TIP/PBO | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Cohort C (4 Capsules b.i.d.): TIP/PBO | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Pooled TIP | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Pooled TIP/PBO | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |
| Pooled PBO | Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation | NA Days |