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Reason for termination was challenge with enrollment and recruitment. A significant decrease in the eligible patient population was main driver.
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The purpose of the study was to evaluate lung clearance index (LCI) by a standardized procedure in a well characterized study setting and to assess feasibility of LCI as a more sensitive method than forced expiratory volume at 1 second (FEV1) to measure effectiveness of antibiotic therapy in patients with CF aged 6 years and older with mild to moderate lung disease.
This study was terminated prematurely. The reason for trial termination was challenge with enrollment and patient recruitment. A significant decrease in the eligible patient population had been identified as main driver.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tobramycin ALL | Experimental | 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TIS or TIP | Drug | 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Baseline, week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study | Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry | Baseline, week 4 |
| Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Jörg Ziegler, PhD | Novartis Pharma GmbH, Nürnberg, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Dresden | 01307 | Germany | |||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32532226 | Derived | Sutharsan S, Naehrig S, Mellies U, Sieder C, Ziegler J. An 8 week open-label interventional multicenter study to explore the lung clearance index as endpoint for clinical trials in cystic fibrosis patients >/=8 years of age, chronically infected with Pseudomonas aeruginosa. BMC Pulm Med. 2020 Jun 12;20(1):167. doi: 10.1186/s12890-020-01201-y. |
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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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At least 35 patients were planned to be recruited in the study. However, in total, 17 patients entered into the study and completed.
Reason for termination was challenge with enrollment and recruitment. A significant decrease in the eligible patient population was main driver.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tobramycin Inhalation Solution(TIS) | 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) twice a day (BID) 28days on / 28 days off |
| FG001 | Tobramycin Inhalation Powder (TIP) | TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tobramycin Inhalation Solution(TIS) | 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) twice a day (BID) 28days on / 28 days off |
| BG001 | Tobramycin Inhalation Powder (TIP) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, week 4 |
|
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tobramycin Inhalation Solution(TIS) | 300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) twice a day (BID) 28days on / 28 days off |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (19.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 8627788300 | novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 3, 2015 | Oct 6, 2017 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 10, 2017 | Oct 6, 2017 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D011552 | Pseudomonas Infections |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000074443 | Lysine Acetyltransferase 5 |
| ID | Term |
|---|---|
| D051548 | Histone Acetyltransferases |
| D000070837 | Lysine Acetyltransferases |
| D000123 | Acetyltransferases |
| D000217 | Acyltransferases |
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Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum. |
| Baseline, week 4 |
| Change From Baseline in Lung Clearance Index (LCI) After 1 Week | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Baseline, week 1 |
| Change of Lung Clearance Index (LCI) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | week 4, week 8 |
| Change of Forced Expiratory Volume at 1 Second(FEV1) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry | week 4, week 8 |
| Change of Colony-forming Units (CFU) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum. | week 4, week 8 |
| Erlangen |
| 91054 |
| Germany |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Frankfurt | 60590 | Germany |
| Novartis Investigative Site | Germering | 82110 | Germany |
| Novartis Investigative Site | Jena | 07740 | Germany |
TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|
|
| Secondary | Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study | Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. | Posted | Least Squares Mean | Standard Error | % predicted | Baseline, week 4 |
|
|
|
|
| Secondary | Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study | Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum. | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. n is the number of patients of safety set with a non-missing value at the specific time point. | Posted | Least Squares Mean | Standard Error | CFU per gram sputum | Baseline, week 4 |
|
|
|
|
| Secondary | Change From Baseline in Lung Clearance Index (LCI) After 1 Week | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, week 1 |
|
|
|
|
| Secondary | Change of Lung Clearance Index (LCI) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal. | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. | Posted | Least Squares Mean | Standard Error | Units on a scale | week 4, week 8 |
|
|
|
|
| Secondary | Change of Forced Expiratory Volume at 1 Second(FEV1) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. | Posted | Least Squares Mean | Standard Error | % predicted | week 4, week 8 |
|
|
|
|
| Secondary | Change of Colony-forming Units (CFU) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle) | Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum. | Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. n is the number of patients of safety set with a non-missing value at the specific time point. | Posted | Least Squares Mean | Standard Error | CFU per gram sputum | week 4, week 8 |
|
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Tobramycin Inhalation Powder (TIP) | TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off | 0 | 12 | 0 | 12 | 3 | 12 |
| Sunburn | Injury, poisoning and procedural complications | MedDRA (19.0) | Systematic Assessment |
|
| Forced expiratory volume decreased | Investigations | MedDRA (19.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (19.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single- site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D014166 | Transferases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
|
|