Phase 2
N=107
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
Non-cystic Fibrosis Bronchiectasis
Bottom Line
View on ClinicalTrials.gov: NCT02712983 ↗Enrolled (actual)
107
Serious AEs
20.6%
Results posted
Aug 2020
Primary outcome: Primary: Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) — 6.80; 7.67; 6.10; 6.98 log10 CFUs
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- TIP (Drug); TIP and placebo (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) |
6.80; 7.67; 6.10; 6.98; 6.79; 5.73 | — |
| SECONDARY Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) |
6.80; 7.67; 6.10; 6.98; 6.79; 5.73 | — |
| SECONDARY Time to First Onset of Pulmonary Exacerbation by Exacerbation Category |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Duration of Pulmonary Exacerbation by Exacerbation Category |
15.7; 18.0; 20.2; 10.3; 25.5; 14.8 | — |
| SECONDARY Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period |
1.71; 1.39; 1.29; 1.20; 0.66; 1.46 | — |
| SECONDARY Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category |
8; 9; 10; 9; 11; 9 | — |
| SECONDARY Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation |
2; 0; 1; 0; 0; 2 | — |
| SECONDARY Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage |
122.00; NA; 116.00; 161.00; NA; NA | — |
| SECONDARY Percentage of Participants Requiring Anti-pseudomonal Antibiotics |
8; 4; 6; 7; 3; 7 | — |
| SECONDARY Duration of Anti-pseudomonal Antibiotics Usage |
18.4; 20.0; 19.2; 25.7; 15.3; 15.7 | — |
| SECONDARY Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events |
10; 13; 13; 12; 14; 11 | — |
| SECONDARY Duration of Hospitalization Due to Serious Respiratory-related Adverse Events |
15.2; 22.0; 12.2; 11.0; 19.0; 16.2 | — |
| SECONDARY Number of Hospitalization Due to Serious Respiratory-related Adverse Events |
6; 0; 2; 5; 2; 4 | — |
| SECONDARY Time to First Hospitalization Due to Serious Respiratory-related Adverse Events |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Serum Tobramycin Concentration |
0.256; 0.479; 0.4; 0.441; 0.59; 0.321 | — |
| SECONDARY Sputum Tobramycin Concentration |
1750; 637; 2640; 2020; 2820; 2060 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning |
51.33; 60.5; 45.8; 50.5; 46.2; 53.8 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning |
63.1; 67.2; 53.3; 64.3; 57.8; 67.6 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality |
56.4; 47.9; 52.4; 44.4; 47.4; 51.9 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning |
79.5; 71.2; 77.4; 74.4; 71.1; 76.1 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning |
66.2; 51.3; 36.5; 63.5; 48.5; 55.7 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden |
67.7; 68.9; 64.3; 73.1; 56.4; 54.5 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions |
41.0; 35.3; 33.1; 41.1; 39.4; 40.0 | — |
| SECONDARY Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms |
56.0; 53.8; 56.8; 55.9; 52.3; 61.9 | — |
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.
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).
Data sourced from ClinicalTrials.gov (NCT02712983). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.