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

NCT ID: NCT02712983

Last Updated: 2020-08-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-08

Study Completion Date

2019-03-20

Brief Summary

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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

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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.

Conditions

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Non-cystic Fibrosis Bronchiectasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Cohort A (3 capsules o.d.): TIP

Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)

Group Type EXPERIMENTAL

TIP

Intervention Type DRUG

TIP dose regimen

Cohort A (3 capsules o.d.): TIP/PBO

Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical

Group Type EXPERIMENTAL

TIP and placebo

Intervention Type DRUG

TIP and inhaled placebo dose regimen

Cohort A (3 capsules o.d.): PBO

Cohort A (3 capsules o.d.): Inhaled placebo (PBO)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Inhaled placebo dose regimen

Cohort B (5 capsules o.d.): TIP

Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)

Group Type EXPERIMENTAL

TIP

Intervention Type DRUG

TIP dose regimen

Cohort B (5 capsules o.d.): TIP/PBO

Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical

Group Type EXPERIMENTAL

TIP and placebo

Intervention Type DRUG

TIP and inhaled placebo dose regimen

Cohort B (5 capsules o.d.): PBO

Cohort B (5 capsules o.d.): inhaled placebo (PBO)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Inhaled placebo dose regimen

Cohort C (4 capsules b.i.d.): TIP

Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)

Group Type EXPERIMENTAL

TIP

Intervention Type DRUG

TIP dose regimen

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

Group Type EXPERIMENTAL

TIP and placebo

Intervention Type DRUG

TIP and inhaled placebo dose regimen

Cohort C (4 capsules b.i.d.): PBO

Cohort C (4 capsules b.i.d.): inhaled placebo (PBO)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Inhaled placebo dose regimen

Interventions

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TIP

TIP dose regimen

Intervention Type DRUG

TIP and placebo

TIP and inhaled placebo dose regimen

Intervention Type DRUG

Placebo

Inhaled placebo dose regimen

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Queen's University, Belfast

OTHER

Sponsor Role collaborator

University Hospital, Antwerp

OTHER

Sponsor Role collaborator

University of Milan

OTHER

Sponsor Role collaborator

Fundacion Clinic per a la Recerca Biomédica

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Papworth Hospital NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role collaborator

University of Dundee

OTHER

Sponsor Role collaborator

University of Edinburgh

OTHER

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharma

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Brussels, , Belgium

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Nice, Cedex1, France

Site Status

Novartis Investigative Site

Montpellier, Herault, France

Site Status

Novartis Investigative Site

Grenoble, , France

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Essen, North Rhine-Westphalia, Germany

Site Status

Novartis Investigative Site

Berlin, , Germany

Site Status

Novartis Investigative Site

Frankfurt, , Germany

Site Status

Novartis Investigative Site

Hanover, , Germany

Site Status

Novartis Investigative Site

Leipzig, , Germany

Site Status

Novartis Investigative Site

Monza, MB, Italy

Site Status

Novartis Investigative Site

Pisa, PI, Italy

Site Status

Novartis Investigative Site

Pordenone, PN, Italy

Site Status

Novartis Investigative Site

Milan, , Italy

Site Status

Novartis Investigative Site

Pavia, , Italy

Site Status

Novartis Investigative Site

Scafati, , Italy

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Valencia, Comunitat Valencia, Spain

Site Status

Novartis Investigative Site

Baracaldo - Vizcaya, , Spain

Site Status

Novartis Investigative Site

Barcelona, , Spain

Site Status

Novartis Investigative Site

Valencia, , Spain

Site Status

Novartis Investigative Site

Valladolid, , Spain

Site Status

Novartis Investigative Site

Cambridge, Cambridgeshire, United Kingdom

Site Status

Novartis Investigative Site

Dundee, Perthshire, United Kingdom

Site Status

Novartis Investigative Site

Birmingham, , United Kingdom

Site Status

Novartis Investigative Site

Edinburgh, , United Kingdom

Site Status

Novartis Investigative Site

Lancaster, , United Kingdom

Site Status

Novartis Investigative Site

Leeds, , United Kingdom

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Site Status

Novartis Investigative Site

Southampton, , United Kingdom

Site Status

Countries

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Belgium France Germany Italy Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 32855225 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31433997 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-003040-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTBM100G2202

Identifier Type: -

Identifier Source: org_study_id

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