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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 (iBEST-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02712983
Recruitment Status : Completed
First Posted : March 18, 2016
Last Update Posted : May 20, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is 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.

Condition or disease Intervention/treatment Phase
Non-cystic Fibrosis Bronchiectasis Drug: TIP Drug: TIP and placebo Drug: Placebo Phase 2

Detailed Description:
This is a blinded, randomized, dose- and regimen finding trial where active TIP doses or placebo is given in addition to the local standard care.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : February 8, 2017
Actual Primary Completion Date : March 20, 2019
Actual Study Completion Date : March 20, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TIP dose regimen 1
Tobramycin inhalation powder (TIP)
Drug: TIP
TIP dose regimen

Experimental: TIP and placebo dose regimen 1
Tobramycin inhalation powder (TIP) and inhaled placebo
Drug: TIP and placebo
TIP and inhaled placebo dose regimen

Placebo Comparator: Placebo dose regimen 1
Inhaled placebo
Drug: Placebo
Inhaled placebo dose regimen

Experimental: TIP dose regimen 2
Tobramycin inhalation powder (TIP)
Drug: TIP
TIP dose regimen

Experimental: TIP and placebo dose regimen 2
Tobramycin inhalation powder (TIP) and inhaled placebo
Drug: TIP and placebo
TIP and inhaled placebo dose regimen

Placebo Comparator: Placebo dose regimen 2
Inhaled placebo
Drug: Placebo
Inhaled placebo dose regimen

Experimental: TIP dose regimen 3
Tobramycin inhalation powder (TIP)
Drug: TIP
TIP dose regimen

Experimental: TIP and placebo dose regimen 3
Tobramycin inhalation powder (TIP) and inhaled placebo
Drug: TIP and placebo
TIP and inhaled placebo dose regimen

Placebo Comparator: Placebo dose regimen 3
Inhaled placebo
Drug: Placebo
Inhaled placebo dose regimen




Primary Outcome Measures :
  1. P. aeruginosa density in sputum [ Time Frame: Baseline to Day 29 ]
    Change in P. aeruginosa bacterial load in sputum as assessed by the change in log10 colony forming units (CFUs) from baseline.


Secondary Outcome Measures :
  1. Frequency of pulmonary exacerbations [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Defined as frequency of pulmonary exacerbations compared to placebo.

  2. Time to first use of antipseudomonal antibiotics [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Measured by the time to first use of anti-pseudomonal antibiotics compared to placebo

  3. Serum tobramycin concentration [ Time Frame: Day 29 ]
  4. Sputum tobramycin concentration [ Time Frame: Day 85 ]
  5. P. aeruginosa density in sputum over the entire study duration [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    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) [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    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 [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Defined as rate of pulmonary exacerbations compared to placebo.

  8. Severity of pulmonary exacerbations [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Defined as severity of pulmonary exacerbations compared to placebo.

  9. Time to onset of pulmonary exacerbations [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Defined as time to onset of pulmonary exacerbations compared to placebo.

  10. Proportion of patients requiring anti-pseudomonal antibiotics [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Measured by proportion of patients requiring anti-pseudomonal antibiotics compared to placebo

  11. Duration of anti-pseudomonal antibiotic treatment [ Time Frame: 112 days of treatment and 56 days of follow-up ]
    Measured by duration of use of anti-pseudomonal antibiotics compared to placebo



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02712983


Locations
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Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1070
Novartis Investigative Site
Leuven, Belgium, 3000
France
Novartis Investigative Site
Bayonne, Bayonne Cedex, France, 64109
Novartis Investigative Site
Nice, Cedex1, France, 06001
Novartis Investigative Site
Montpellier cedex 5, Herault, France, 34059
Novartis Investigative Site
Grenoble, France, 38043
Novartis Investigative Site
Toulouse, France, 31059
Germany
Novartis Investigative Site
Essen, North Rhine-Westphalia, Germany, 45239
Novartis Investigative Site
Berlin, Germany, 14059
Novartis Investigative Site
Frankfurt, Germany, 60596
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Leipzig, Germany, 04357
Italy
Novartis Investigative Site
Monza, MB, Italy, 20900
Novartis Investigative Site
Pisa, PI, Italy, 56124
Novartis Investigative Site
Pordenone, PN, Italy, 33170
Novartis Investigative Site
Milan, Italy, 20112
Novartis Investigative Site
Pavia, Italy, 27100
Novartis Investigative Site
Scafati, Italy, 84018
Spain
Novartis Investigative Site
Barcelona, Cataluna, Spain, 08035
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08041
Novartis Investigative Site
Valencia, Comunitat Valencia, Spain, 46014
Novartis Investigative Site
Baracaldo - Vizcaya, Spain, 48903
Novartis Investigative Site
Barcelona, Spain, 08003
Novartis Investigative Site
Valencia, Spain, 46009
Novartis Investigative Site
Valladolid, Spain, 47003
United Kingdom
Novartis Investigative Site
Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
Novartis Investigative Site
Dundee, Perthshire, United Kingdom, DD1 9SY
Novartis Investigative Site
Birmingham, United Kingdom, B15 2TH
Novartis Investigative Site
Edinburgh, United Kingdom, ED16 4SA
Novartis Investigative Site
Glasgow, United Kingdom, G51 4TF
Novartis Investigative Site
Lancaster, United Kingdom, LA1 4RP
Novartis Investigative Site
Leeds, United Kingdom, LS9 7TF
Novartis Investigative Site
London, United Kingdom, SW 6NP
Novartis Investigative Site
Newcastle upon Tyne, United Kingdom, NE7 7DN
Novartis Investigative Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharma Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02712983     History of Changes
Other Study ID Numbers: CTBM100G2202
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Inhaled tobramycin; tobramycin inhalation powder; bronchiectasis; pulmonary Pseudomonas aeruginosa infection; dose-finding study

Additional relevant MeSH terms:
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Bronchiectasis
Infection
Respiratory Aspiration
Fibrosis
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Bronchial Diseases
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents