Back to resultsDose-finding Study to Assess the Efficacy, Safety and Tolerability of Tobramycin Inhalation Powder in Patients With Non-Cystic Fibrosis Bronchiectasis and Pulmonary P. Aeruginosa Infection (iBEST-1)
Primary Purpose
Non-cystic Fibrosis Bronchiectasis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TIP
TIP and placebo
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Non-cystic Fibrosis Bronchiectasis focused on measuring Inhaled tobramycin, tobramycin inhalation powder, bronchiectasis, pulmonary Pseudomonas aeruginosa infection, dose-finding study
Eligibility 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).
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Arm Label
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
Arm Description
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort A (3 capsules o.d.): Inhaled placebo (PBO)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): inhaled placebo (PBO)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): inhaled placebo (PBO)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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 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.
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.
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.
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.
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 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 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.
Percentage of Participants Requiring Anti-pseudomonal Antibiotics
The percentage of participants requiring anti-pseudomonal antibiotics compared to placebo was analyzed. Only descriptive analysis performed.
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
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02712983
First Posted
February 5, 2016
Last Updated
August 24, 2020
Sponsor
Novartis Pharmaceuticals
Collaborators
Queen's University Belfast, UK, University Hospital Antwerp, BE, University of Milan, IT, Fundacion Clinic per a la Recerca Biomedica, Erasmus Medical Center, Papworth Hospital Cambridge, UK, Royal Brompton Hospital Trust, UK, University of Dundee, University of Edinburgh
1. Study Identification
Unique Protocol Identification Number
NCT02712983
Brief Title
Dose-finding Study to Assess the Efficacy, Safety and Tolerability of Tobramycin Inhalation Powder in Patients With Non-Cystic Fibrosis Bronchiectasis and Pulmonary P. Aeruginosa Infection
Acronym
iBEST-1
Official Title
A Randomized, Blinded, Parallel Group, Multi-center Dose-finding Study, to Assess the Efficacy, Safety and Tolerability of Different Doses of Tobramycin Inhalation Powder in Patients With Non-Cystic Fibrosis Bronchiectasis and Pulmonary P. Aeruginosa Infection
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
February 8, 2017 (Actual)
Primary Completion Date
March 20, 2019 (Actual)
Study Completion Date
March 20, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
Collaborators
Queen's University Belfast, UK, University Hospital Antwerp, BE, University of Milan, IT, Fundacion Clinic per a la Recerca Biomedica, Erasmus Medical Center, Papworth Hospital Cambridge, UK, Royal Brompton Hospital Trust, UK, University of Dundee, University of Edinburgh
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-cystic Fibrosis Bronchiectasis
Keywords
Inhaled tobramycin, tobramycin inhalation powder, bronchiectasis, pulmonary Pseudomonas aeruginosa infection, dose-finding study
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A (3 capsules o.d.): TIP
Arm Type
Experimental
Arm Description
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Arm Title
Cohort A (3 capsules o.d.): TIP/PBO
Arm Type
Experimental
Arm Description
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Arm Title
Cohort A (3 capsules o.d.): PBO
Arm Type
Placebo Comparator
Arm Description
Cohort A (3 capsules o.d.): Inhaled placebo (PBO)
Arm Title
Cohort B (5 capsules o.d.): TIP
Arm Type
Experimental
Arm Description
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Arm Title
Cohort B (5 capsules o.d.): TIP/PBO
Arm Type
Experimental
Arm Description
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Arm Title
Cohort B (5 capsules o.d.): PBO
Arm Type
Placebo Comparator
Arm Description
Cohort B (5 capsules o.d.): inhaled placebo (PBO)
Arm Title
Cohort C (4 capsules b.i.d.): TIP
Arm Type
Experimental
Arm Description
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Arm Title
Cohort C (4 capsules b.i.d.): TIP/PBO
Arm Type
Experimental
Arm Description
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Arm Title
Cohort C (4 capsules b.i.d.): PBO
Arm Type
Placebo Comparator
Arm Description
Cohort C (4 capsules b.i.d.): inhaled placebo (PBO)
Intervention Type
Drug
Intervention Name(s)
TIP
Intervention Description
TIP dose regimen
Intervention Type
Drug
Intervention Name(s)
TIP and placebo
Intervention Description
TIP and inhaled placebo dose regimen
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inhaled placebo dose regimen
Primary Outcome Measure Information:
Title
Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Description
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)
Secondary Outcome Measure Information:
Title
Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Description
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)
Title
Time to First Onset of Pulmonary Exacerbation by Exacerbation Category
Description
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)
Title
Duration of Pulmonary Exacerbation by Exacerbation Category
Description
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)
Title
Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period
Description
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)
Title
Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category
Description
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)
Title
Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation
Description
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)
Title
Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation
Description
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)
Title
Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage
Description
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
Title
Percentage of Participants Requiring Anti-pseudomonal Antibiotics
Description
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)
Title
Duration of Anti-pseudomonal Antibiotics Usage
Description
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)
Title
Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events
Description
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)
Title
Duration of Hospitalization Due to Serious Respiratory-related Adverse Events
Description
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)
Title
Number of Hospitalization Due to Serious Respiratory-related Adverse Events
Description
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)
Title
Time to First Hospitalization Due to Serious Respiratory-related Adverse Events
Description
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)
Title
Serum Tobramycin Concentration
Description
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.
Title
Sputum Tobramycin Concentration
Description
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.
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions
Description
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)
Title
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharma
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Nice
State/Province
Cedex1
ZIP/Postal Code
06001
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier cedex 5
State/Province
Herault
ZIP/Postal Code
34059
Country
France
Facility Name
Novartis Investigative Site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Essen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
45239
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
14059
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04357
Country
Germany
Facility Name
Novartis Investigative Site
City
Monza
State/Province
MB
ZIP/Postal Code
20900
Country
Italy
Facility Name
Novartis Investigative Site
City
Pisa
State/Province
PI
ZIP/Postal Code
56124
Country
Italy
Facility Name
Novartis Investigative Site
City
Pordenone
State/Province
PN
ZIP/Postal Code
33170
Country
Italy
Facility Name
Novartis Investigative Site
City
Milan
ZIP/Postal Code
20112
Country
Italy
Facility Name
Novartis Investigative Site
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Novartis Investigative Site
City
Scafati
ZIP/Postal Code
84018
Country
Italy
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Cataluna
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08041
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunitat Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
Novartis Investigative Site
City
Baracaldo - Vizcaya
ZIP/Postal Code
48903
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Novartis Investigative Site
City
Valladolid
ZIP/Postal Code
47003
Country
Spain
Facility Name
Novartis Investigative Site
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB23 3RE
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Dundee
State/Province
Perthshire
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Edinburgh
ZIP/Postal Code
ED16 4SA
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Lancaster
ZIP/Postal Code
LA1 4RP
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SW 6NP
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
32855225
Citation
Loebinger MR, Polverino E, Chalmers JD, Tiddens HAWM, Goossens H, Tunney M, Ringshausen FC, Hill AT, Pathan R, Angyalosi G, Blasi F, Elborn SJ, Haworth CS; iBEST-1 Trial Team. Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study. Eur Respir J. 2021 Jan 5;57(1):2001451. doi: 10.1183/13993003.01451-2020. Print 2021 Jan.
Results Reference
derived
PubMed Identifier
31433997
Citation
Loebinger MR, Polverino E, Blasi F, Elborn SJ, Chalmers JD, Tiddens HA, Goossens H, Tunney M, Zhou W, Angyalosi G, Hill AT, Haworth CS; iBEST-1 Trial Team. Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection: Design of a dose-finding study (iBEST-1). Pulm Pharmacol Ther. 2019 Oct;58:101834. doi: 10.1016/j.pupt.2019.101834. Epub 2019 Aug 18.
Results Reference
derived
Learn more about this trial
Dose-finding Study to Assess the Efficacy, Safety and Tolerability of Tobramycin Inhalation Powder in Patients With Non-Cystic Fibrosis Bronchiectasis and Pulmonary P. Aeruginosa Infection
We'll reach out to this number within 24 hrs