Non-cystic Fibrosis BronchiectasisPhase 2iBEST-1NCT02712983
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
A Phase 2 study testing TIP in people with Non-cystic Fibrosis Bronchiectasis, run by Novartis Pharmaceuticals at 34 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-cystic Fibrosis Bronchiectasis
- What is being tested?
- TIP
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 34 sitesin 6 countries
- Study dates
- 8 Feb 2017to 20 Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
34 sites in 6 countries.
34 sites in 6 countries
United Kingdom9 sites
Novartis Investigative Site
Birmingham, B15 2TH
Novartis Investigative Site
Cambridge, Cambridgeshire, CB23 3RE
Novartis Investigative Site
Dundee, Perthshire, DD1 9SY
Novartis Investigative Site
Edinburgh, ED16 4SA
Novartis Investigative Site
Lancaster, LA1 4RP
Novartis Investigative Site
Leeds, LS9 7TF
Novartis Investigative Site
London, SW 6NP
Novartis Investigative Site
Newcastle upon Tyne, NE7 7DN
Novartis Investigative Site
Southampton, SO16 6YD
Spain8 sites
Novartis Investigative Site
Baracaldo - Vizcaya, 48903
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Barcelona, Catalonia, 08041
Novartis Investigative Site
Barcelona, 08003
Novartis Investigative Site
Valencia, Comunitat Valencia, 46014
Novartis Investigative Site
Valencia, 46009
Novartis Investigative Site
Valladolid, 47003
Italy6 sites
Novartis Investigative Site
Milan, 20112
Novartis Investigative Site
Monza, MB, 20900
Novartis Investigative Site
Pavia, 27100
Novartis Investigative Site
Pisa, PI, 56124
Novartis Investigative Site
Pordenone, PN, 33170
Novartis Investigative Site
Scafati, 84018
Germany5 sites
Novartis Investigative Site
Berlin, 14059
Novartis Investigative Site
Essen, North Rhine-Westphalia, 45239
Novartis Investigative Site
Frankfurt, 60596
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Leipzig, 04357
France4 sites
Novartis Investigative Site
Grenoble, 38043
Novartis Investigative Site
Montpellier, Herault, 34059
Novartis Investigative Site
Nice, Cedex1, 06001
Novartis Investigative Site
Toulouse, 31059
Belgium2 sites
Novartis Investigative Site
Brussels, 1070
Novartis Investigative Site
Leuven, 3000
About this study
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
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.
Read the 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.
- Conditions
- Non-cystic Fibrosis Bronchiectasis
- Being tested
- TIP, TIP and placebo, Placebo
- Keywords
- Inhaled tobramycin, tobramycin inhalation powder, bronchiectasis, pulmonary Pseudomonas aeruginosa infection, dose-finding study
- Medical subject headings
- Bronchiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TIPDrug
TIP dose regimen
TIP and placeboDrug
TIP and inhaled placebo dose regimen
PlaceboDrug
Inhaled placebo dose regimen
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (3 capsules o.d.): TIP | Experimental | Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) Receives: Drug: TIP |
| Cohort A (3 capsules o.d.): TIP/PBO | Experimental | Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Receives: Drug: TIP and placebo |
| Cohort A (3 capsules o.d.): PBO | Placebo comparator | Cohort A (3 capsules o.d.): Inhaled placebo (PBO) Receives: Drug: Placebo |
| Cohort B (5 capsules o.d.): TIP | Experimental | Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) Receives: Drug: TIP |
| Cohort B (5 capsules o.d.): TIP/PBO | Experimental | Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Receives: Drug: TIP and placebo |
| Cohort B (5 capsules o.d.): PBO | Placebo comparator | Cohort B (5 capsules o.d.): inhaled placebo (PBO) Receives: Drug: Placebo |
| Cohort C (4 capsules b.i.d.): TIP | Experimental | Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) Receives: Drug: TIP |
| Cohort C (4 capsules b.i.d.): TIP/PBO | Experimental | Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Receives: Drug: TIP and placebo |
| Cohort C (4 capsules b.i.d.): PBO | Placebo comparator | Cohort C (4 capsules b.i.d.): inhaled placebo (PBO) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Visit 101/Day 1), Visit 102 (Day 8), Visit 103 (Day 29)
Secondary outcomes (24)
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.
Measured: 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)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: From Baseline (Visit 101/Day 1) up to approximately Day 173
Percentage of Participants Requiring Anti-pseudomonal Antibiotics
The percentage of participants requiring anti-pseudomonal antibiotics compared to placebo was analyzed. Only descriptive analysis performed.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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'.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
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.
Measured: Baseline (Visit 101/Day 1), Visit 102 (Day 8) and Visits 103 (Day 29): 0-1 hours and 1-2 hours post-dose.
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.
Measured: 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.
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
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.
Measured: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2016 (estimated)
- Study start8 Feb 2017
- Primary completion20 Mar 2019
- Study completion20 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-cystic Fibrosis BronchiectasisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Queen's University, Belfast, University Hospital, Antwerp, University of Milan, Fundacion Clinic per a la Recerca Biomédica, Erasmus Medical Center, Papworth Hospital NHS Foundation Trust, Royal Brompton & Harefield NHS Foundation Trust, University of Dundee, University of Edinburgh
- Responsible party
- Sponsor
- Investigators
- Novartis Pharma, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02712983
- Sponsor's protocol ID
- CTBM100G2202
- Other IDs
- 2015-003040-39, 2015
- Acronym
- iBEST-1
- Status last verified
- Aug 2020
- First submitted
- 5 Feb 2016
- Last updated
- 25 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 32855225Loebinger 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.
PubMed 31433997
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02712983
- Acronym / sponsor ID
- iBEST-1 / CTBM100G2202
- Conditions
- Non-cystic Fibrosis Bronchiectasis
- Keywords
- Inhaled tobramycin, tobramycin inhalation powder, bronchiectasis, pulmonary Pseudomonas aeruginosa infection, dose-finding study
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Queen's University, Belfast, University Hospital, Antwerp, University of Milan, Fundacion Clinic per a la Recerca Biomédica, Erasmus Medical Center, Papworth Hospital NHS Foundation Trust, Royal Brompton & Harefield NHS Foundation Trust, University of Dundee, University of Edinburgh
- Study start
- 8 Feb 2017 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 18 Mar 2016 (estimated)
- Results
- Posted 14 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Cohort A (3 capsules o.d.): TIP | Experimental | Drug: TIPCohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) |
| Cohort A (3 capsules o.d.): TIP/PBO | Experimental | Drug: TIP and placeboCohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical |
| Cohort A (3 capsules o.d.): PBO | Placebo comparator | Drug: PlaceboCohort A (3 capsules o.d.): Inhaled placebo (PBO) |
| Cohort B (5 capsules o.d.): TIP | Experimental | Drug: TIPCohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) |
| Cohort B (5 capsules o.d.): TIP/PBO | Experimental | Drug: TIP and placeboCohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical |
| Cohort B (5 capsules o.d.): PBO | Placebo comparator | Drug: PlaceboCohort B (5 capsules o.d.): inhaled placebo (PBO) |
| Cohort C (4 capsules b.i.d.): TIP | Experimental | Drug: TIPCohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) |
| Cohort C (4 capsules b.i.d.): TIP/PBO | Experimental | Drug: TIP and placeboCohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical |
| Cohort C (4 capsules b.i.d.): PBO | Placebo comparator | Drug: PlaceboCohort C (4 capsules b.i.d.): inhaled placebo (PBO) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TIPTIP dose regimen | Drug | Cohort A (3 capsules o.d.): TIP, Cohort B (5 capsules o.d.): TIP, Cohort C (4 capsules b.i.d.): TIP |
| TIP and placeboTIP and inhaled placebo dose regimen | Drug | Cohort A (3 capsules o.d.): TIP/PBO, Cohort B (5 capsules o.d.): TIP/PBO, Cohort C (4 capsules b.i.d.): TIP/PBO |
| PlaceboInhaled placebo dose regimen | Drug | Cohort A (3 capsules o.d.): PBO, Cohort B (5 capsules o.d.): PBO, Cohort C (4 capsules b.i.d.): PBO |
Primary outcome
Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Time frame: Baseline (Visit 101/Day 1), Visit 102 (Day 8), Visit 103 (Day 29)
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.
24 secondary outcomes
Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
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)
Time to First Onset of Pulmonary Exacerbation by Exacerbation Category
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Duration of Pulmonary Exacerbation by Exacerbation Category
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage
Time frame: From Baseline (Visit 101/Day 1) up to approximately Day 173
Percentage of Participants Requiring Anti-pseudomonal Antibiotics
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Duration of Anti-pseudomonal Antibiotics Usage
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Percentage of Participants Requiring Hospitalization Due to Serious Respiratory-related Adverse Events
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Duration of Hospitalization Due to Serious Respiratory-related Adverse Events
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Number of Hospitalization Due to Serious Respiratory-related Adverse Events
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Time to First Hospitalization Due to Serious Respiratory-related Adverse Events
Time frame: Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Serum Tobramycin Concentration
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.
Sputum Tobramycin Concentration
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.
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Physical Functioning
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Role Functioning
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Vitality
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Emotional Functioning
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Social Functioning
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Treatment Burden
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Health Perceptions
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B)-Respiratory Symptoms
Time frame: Baseline, Visit 102 (Day 8), Visit 103 (Day 29), End of Treatment (Day 113) and Visit 202 (Day 169)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32855225Loebinger 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.
- Derived from this study: PubMed 31433997Loebinger 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.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharma study director
Novartis Pharmaceuticals
34 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TIP in people with Non-cystic Fibrosis Bronchiectasis, run by Novartis Pharmaceuticals at 34 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United Kingdom, Spain, Italy, Germany, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs) (time frame: Baseline (Visit 101/Day 1), Visit 102 (Day 8), Visit 103 (Day 29)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02712983, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2020; AzTrials last refreshed its copy on 26 Oct 2026.