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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2015-003040-39-ES
• Date of registration: 30/08/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public 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
• Scientific 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
• Date of first enrolment: 29/09/2016
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003040-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 9
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Ireland, Italy, Netherlands, Spain, Switzerland, United Kingdom

Contacts

• Name: Departamento Médico Oncología
• Affiliation: Novartis Farmacéutica, S.A.

• Name: Departamento Médico Oncología
• Affiliation: Novartis Farmacéutica, S.A.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

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.
• History of hearing loss or chronic tinnitus deemed clinically significant by the investigator.
• Patients with active pulmonary tuberculosis.
• Patients currently receiving treatment for nontuberculous mycobacterial (NTM) pulmonary disease.
• Patients who are regularly receiving inhaled antipseudomonal antibiotic (during the study inhaled antipseudomonal antibiotics are not allowed other than the study drug).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Pseudomonas aeruginosa infection in patients with non-cystic fibrosis bronchiectasis
MedDRA version: 19.0 Level: PT Classification code 10006445 Term: Bronchiectasis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.0 Level: PT Classification code 10070295 Term: Infective exacerbation of bronchiectasis System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Trade Name: TOBI Podhaler
Product Name: Tobramycin inhalation powder
Product Code: TBM100
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Current Sponsor code: TBM100
Other descriptive name: TOBRAMYCIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 28-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): P. aeruginosa density in sputum: change in P. aeruginosa bacterial load in sputum as
assessed by the change in log10 colony forming units (CFUs) from baseline.

Secondary Objective: Key secondary objectives (for the full list please refer to the protocol):

- To assess the effect of different doses of TIP administered o.d. and one b.i.d. dose and different regimens (TIP and TIP/placebo cyclical) on the frequency, rate (by patient- months), severity and time to onset of pulmonary exacerbations at the end of the treatment epoch and over the entire study, each compared to placebo.
- To assess the efficacy profile of different doses of TIP administered o.d. and one b.i.d. dose and different regimens (TIP and TIP/placebo cyclical), as measured by the time to first use, proportion of patients requiring anti-pseudomonal antibiotics (overall, oral, intravenous) and the duration of treatment, each compared to placebo.
- To assess the time to first hospitalization, proportion of patients requiring hospitalization and the duration of hospitalization due to serious respiratory-related AEs.

Timepoint(s) of evaluation of this end point: Baseline to Day 29

Main Objective: - To evaluate the effect of different doses of TIP administered o.d. and one b.i.d. dose on the change in P. aeruginosa bacterial load in sputum as assessed by the change in colony forming units (CFUs) from baseline to Day 29 of treatment, each compared to placebo.
- To assess the safety and tolerability with different doses of TIP administered o.d. and b.i.d. and different regimens (TIP and TIP/placebo cyclical) during the treatment epoch (112 days) and during the follow-up epoch (56 days) for each as compared to placebo.

Secondary Outcome(s)

Secondary end point(s): 1) Frequency of pulmonary exacerbations (compared to placebo)
2) Time to first use of antipseudomonal antibiotics (compared to placebo)
3) Serum tobramycin concentration
4) Sputum tobramycin concentration
5) P. aeruginosa density in sputum over the entire study duration: Change in P. aeruginosa bacterial load in sputum from baseline as assessed by the change in
colony forming units (CFUs) of P. aeruginosa.
6) Respiratory Symptom Scale Quality of Life Questionnaire for Bronchiectasis (QOL-B): Change from baseline on the Respiratory Symptom Scale QOL-B. Respiratory Symptoms is 1 out of 8 domains of the QOL-B instrument and is graded on a 4-point Likert scale.
7) Rate of pulmonary Exacerbations (compared to placebo)
8) Severity of pulmonary exacerbations (compared to placebo)
9) Time to onset of pulmonary exacerbations (compared to placebo)
10) Proportion of patients requiring antipseudomonal antibiotics (compared to placebo)
11) Duration of antipseudomonal antibiotic treatment (compared to placebo)

Timepoint(s) of evaluation of this end point: 1) 112 days of treatment and 56 days of follow-up
2) 112 days of treatment and 56 days of follow-up
3) Day 29
4) Day 85
5) 112 days of treatment and 56 days of follow-up
6) 112 days of treatment and 56 days of follow-up
7) 112 days of treatment and 56 days of follow-up
8) 112 days of treatment and 56 days of follow-up
9) 112 days of treatment and 56 days of follow-up
10) 112 days of treatment and 56 days of follow-up
11) 112 days of treatment and 56 days of follow-up

Secondary ID(s)

CTBM100G2202

Source(s) of Monetary Support

Novartis Pharma Services AG

Queen's University of Belfast

Ethics review

Status: Approved
Approval date:
Contact: