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The objectives of the study are to demonstrate that Tobrineb®/Actitob®/Bramitob® is non-inferior to TOBI® in the primary efficacy variable, forced expiratory volume in one second (FEV1) percent of predicted normal, and to compare the safety in participants with cystic fibrosis and chronic infection of the lungs with Pseudomonas aeruginosa.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bramitob | Experimental | tobramycin / Bramitob administered 300mg twice a day for 4 weeks |
|
| TOBI | Active Comparator | tobramycin / TOBI administered 300mg twice a day for 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tobramycin / Bramitob | Drug | 300mg/4ml solution, via a nebuliser, over a 4-week treatment in a twice-daily regimen |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to End of the Treatment Period of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal | Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded. | Day 0 (baseline), Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal | Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded. Observed values are summarized (without last observation carry forward). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Henryk Mazurek, Doctor | Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centrum pro cystickou fibrosu, Pediatricka klinika UK 2.LF, Fakultní nemocnice v Motole | Prague | 150 06 | Czechia | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24464974 | Result | Mazurek H, Chiron R, Kucerova T, Geidel C, Bolbas K, Chuchalin A, Blanco-Aparicio M, Santoro D, Varoli G, Zibellini M, Cicirello HG, Antipkin YG. Long-term efficacy and safety of aerosolized tobramycin 300 mg/4 ml in cystic fibrosis. Pediatr Pulmonol. 2014 Nov;49(11):1076-89. doi: 10.1002/ppul.22989. Epub 2014 Jan 24. |
| Label | URL |
|---|---|
| Study Record on EU Clinical Trials Register including results | View source |
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406 participants screened, 324 participants randomized
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| ID | Title | Description |
|---|---|---|
| FG000 | Bramitob | tobramycin / Bramitob administered 300mg twice a day for 4 weeks |
| FG001 | TOBI | tobramycin / TOBI administered 300mg twice a day for 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| 4 Weeks ON Treatment |
|
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| tobramycin / TOBI | Drug | 300mg/5ml solution administered via nebuliser, over a 4-week treatment in a twice-daily regimen |
|
|
| Day 0 (baseline), Week 2, Week 4, Week 8 |
| Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Expiratory Volume in 1 Second (FEV1) | Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Three measurements were collected and the greatest FEV1 value was recorded. Observed values are summarized (without last observation carry forward). | Day 0 (baseline), Week 2, Week 4, Week 8 |
| Change From Baseline at End of Weeks 2, 4, and 8 of Forced Vital Capacity (FVC) Expressed as Percentage of Predicted Normal | FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. It is measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants. | Day 0 (baseline), Week 2, Week 4, Week 8 |
| Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Vital Capacity (FVC) | FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. It is measured via spirometry. | Day 0 (baseline), Week 2, Week 4, Week 8 |
| Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%), Expressed as Percentage of Predicted Normal | Difference in the forced expiratory flow rate in mid-exhalation as a percent of predicted to standard values measured from baseline to weeks 2 (treated), 4 (treated), and 8 (untreated). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants. | Day 0 (baseline), Week 2, Week 4, Week 8 |
| Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%) | Difference in the forced expiratory flow rate in mid-exhalation measured from baseline to weeks 2 (treated), 4 (treated), and 8 (untreated). | Day 0 (baseline), Week 2, Week 4, Week 8 |
| Change From Baseline to End of Weeks 4 and 8 in Pseudomonas Aeruginosa Log10 Bacterial Load in Sputum | If a participant had more than one Pseudomonas aeruginosa (PA) morphotype at a given visit, and therefore more than one bacterial load value, then the bacterial load value corresponding to the highest tobramycin minimal inhibitory concentration (MIC) value regardless of the PA morphotype was used. If the tobramycin MIC value was the same for different PA morphotypes, then the bacterial load value corresponding to morphotype 1 (mucoid colony) was used. If morphotype 1 was not available, bacterial load value corresponding to morphotype 2 (dry colony) was used. | Day -10 to -1 (baseline), Week 4, Week 8 |
| Minimal Inhibitory Concentration Inhibiting Growth of 50% (MIC50) of Pseudomonas Aeruginosa | MIC50 is the concentration of tobramycin required to inhibit 50% of Pseudomonas aeruginosa. MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains:
Overall MIC50 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used. | Week 4, Week 8 |
| Minimal Inhibitory Concentration Inhibiting Growth of 90% (MIC90) of Pseudomonas Aeruginosa | MIC90 is the concentration of tobramycin required to inhibit 90% of Pseudomonas aeruginosa. MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains:
Overall MIC90 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used. | Week 4, Week 8 |
| Microbiological Outcome Summary by Visit | Microbiological outcomes are derived considering all P. aeruginosa (PA) morphotypes together. Week 4 and Week 8 microbiological outcomes:
Superinfection supersedes eradication. Persistence for P. aeruginosa supersedes superinfection. Re-infection for P. aeruginosa supersedes superinfection. | Day -10 to -1 (screening), Weeks 4 and 8 |
| Change From Baseline to End of Weeks 2, 4 and 8 in Body Weight | Body weight was measured at all study visits as part of the physical examination. | Day 0 (baseline), Weeks 2, 4 and 8 |
| Change From Baseline to End of Weeks 2, 4 and 8 in Body Mass Index (BMI) | Day 0 (baseline), Weeks 2, 4 and 8 |
| Count of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Emergent Adverse Events defined as adverse events occurring after the first intake of study treatment (or the same day). The investigator assessed relation to study treatment as a binary question: Reasonable possibility of relatedness or no reasonable possibility of relatedness. The expression "reasonable possibility of relatedness" is meant to convey in general that there are facts (evidence) or arguments meant to suggest a causal relationship. A serious AE results in death, is life-threatening, requires hospitalization or prolongation of existing inpatient hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or an important medical event. The investigator rates the severity of the AE based on a three point scale: mild, moderate or severe. A severe event prevents any usual routine activity of the participant and causes severe discomfort. | Day 0 to Week 8 |
| Participants With a Hearing Threshold >20 Decibel in at Least One Ear | The potential ototoxic effects (hearing loss) of tobramycin were investigated by performing audiometric tests. Participants with a loss of auditory acuity greater than the 20 decibels auditory threshold are reported. | Day -10 to -1 (screening), Weeks 4 and 8 |
| CHR Clemenceau |
| Caen |
| 14 033 |
| France |
| Hopital Arnaud de Villeneuve, Clinique des maladies respiratoires | Montpellier | 34 295 | France |
| Hopital Necker | Paris | 75 015 | France |
| Pädiatrische Pneumologie und Allergologie, Mukovizidose-Zentrum, Zentrum für Kinderheilkunde und Jugendmedizin | GieBen | 35385 | Germany |
| HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin | Krefeld | 47805 | Germany |
| Fővárosi Önkormányzat Heim Pál | Budapest | H-1089 | Hungary |
| Kaposi Mór Oktatókórház | Mosdós | H-7254 | Hungary |
| Szegedi Tudományegyetem Szent-Györgyi Albert Orvos- és Gyógyszerésztudományi Centrum | Szeged | H6725 | Hungary |
| Specjalistyczny ZOZ nad Matka i Dzieckiem, Poradnia Leczenia Mukowiscydozy | Gdansk | 80-308 | Poland |
| I Oddzial Chorob Dzieciecych, Wojewodzki Specjalistyczny Szpital Dzieciecy | Kielce | 25-381 | Poland |
| Oddzial Kliniczny Interny Dzieciecej i Alergologii, Wojewodzki Szpital Specjalistyczny | Lodz | 93-513 | Poland |
| Dzieciecy Szpital Kliniczny Akademii Medycznej, Klinika Chorob Pluc I Reumatologii | Lublin | 20-093 | Poland |
| Multiple Locations | Poland |
| Klinika Pneumonologii, Alergologii Dzieciecej i Immunologii Klinicznej Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu | Poznan | 60-572 | Poland |
| Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj | Rabka-Zdrój | 34-700 | Poland |
| Poradnia Mukowiscydozy Wojewodzkiej, Przychodni Specjalistycznej dla Dzieci, Szpitala Wojewodzkiego Nr 2 | Rzeszów | 35-301 | Poland |
| Klinika Pediatrii Instytut Matki I Dziecka | Warsaw | 01-211 | Poland |
| State Medical Institution: Republican Childrens Clinical Hospital under the Ministry of Health of the Republic of Tatarstan | Kazan' | 420138 | Russia |
| Federal State Institution: Scientific Research Pulmonology Institute under the Roszdrav | Moscow | 105077 | Russia |
| State Medical Institution: Filatov Chidren's City Clinical Hospital #13 | Moscow | 123242 | Russia |
| Federal State Institution "Nizhegorodskiy Research Institute of Children's Gastroenterology of Russian Medical Technologies" | Nizhny Novgorod | 603950 | Russia |
| State Medical Institution: Regional Children's Hospital Pulmonology Department | Rostov-on-Don | 344085 | Russia |
| Saint-Petersburg State Medical Institution: City Children's Hospital of Saint Olga | Saint Petersburg | 194156 | Russia |
| Regional State Medical Institution: Smolensk Regional Children's Clinical Hospital | Smolensk | 214019 | Russia |
| State Higher Educational Institution: Bashkir State Medical University under the Roszdrav | Ufa | 450106 | Russia |
| State Higher Educational Institution: Burdenko Voronezh State Medical Academy under the Roszdrav | Voronezh | 394024 | Russia |
| Minicipal Medical Institution: Children's Clinical Hospital #1 | Yaroslavl | 150003 | Russia |
| Complejo Hospitalario Universitario A Coruña (Hospital Materno-Infantil Teresa Herrera) | A Coruña | 15006 | Spain |
| Complejo Hospitalario Universitario A Coruña | A Coruña | 15006 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Corporació Sanitaria Parc Tauli | Sabadell | 08208 | Spain |
| Hospital Universitario Ntra Sra. De la Candelaria | Santa Cruz de Tenerife | 38010 | Spain |
| Hospital Universitario La Fe | Valencia | 46009 | Spain |
| Hospital Universitario Miguel Servet (Children) | Zaragoza | 50009 | Spain |
| Dnipropetrovsk City Children Clinical Hospital # 2 | Dnipropetrovsk | 49101 | Ukraine |
| Donetsk Regional Children Clinical Hospital | Donetsk | 83052 | Ukraine |
| Kriviy Rig City Clinical Hospital # 8 | Kryvyi Rih | 50047 | Ukraine |
| Institute of Phthysiology and Pulmonology n.a., F.G.Yanovskiy of the Academy of Medical Science of Ukraine | Kyiv | 03680 | Ukraine |
| Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Science of Ukraine | Kyiv | 04050 | Ukraine |
| Lviv Regional Children Specialized Clinical Hospital | Lviv | 79035 | Ukraine |
| Odesa Regional Children Clinical Hospital | Odesa | 65031 | Ukraine |
| Simferopol Central District Clinical Hospital | Simferopol | 95033 | Ukraine |
| Zaporizhya Regional Clinical Children Hospital | Zaporizhya | Ukraine |
| Intent-to-Treat Population |
|
| Safety Population |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| 4 Weeks OFF Treatment |
|
Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Bramitob | tobramycin / Bramitob administered 300mg twice a day for 4 weeks |
| BG001 | TOBI | tobramycin / TOBI administered 300mg twice a day for 4 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Number | participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | centimeters |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kilograms/meters^2 |
| |||||||||||||||
| Time from diagnosis of chronic colonization of P. aeruginosa | Mean | Standard Deviation | years |
| |||||||||||||||
| Time from first Cystic Fibrosis diagnosis | Mean | Standard Deviation | years |
| |||||||||||||||
| Tobramycin Minimal Inhibitory Concentration (MIC) value | MIC is the lowest concentration of tobramycin that completely inhibits visible growth of a micro-organism. | Number | participants |
| |||||||||||||||
| Forced Expiratory Volume in 1 second (FEV1) | Number | participants |
| ||||||||||||||||
| Use of rhDNase | Baseline use of rhDNase is set to 'Yes' if a patient has used rhDNase on the same date or within the 10 days prior to start of study drug administration. If the timing of rhDNase use cannot be identified because of missing date, then the use of rhDNase at baseline is considered as 'Yes'. | Number | participants |
|
| 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 to End of the Treatment Period of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal | Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded. | Intent-to-Treat (ITT) Population, Last Observation Carried Forward (LOCF) | Posted | Mean | Standard Deviation | percentage predicted FEV1 | Day 0 (baseline), Week 4 |
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| Secondary | Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal | Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEV1 values for children were different than the reference normal values used with adult participants. Three measurements were collected and the greatest FEV1 value was recorded. Observed values are summarized (without last observation carry forward). | Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEV1 test. | Posted | Mean | Standard Deviation | percentage predicted FEV1 | Day 0 (baseline), Week 2, Week 4, Week 8 |
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| Secondary | Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Expiratory Volume in 1 Second (FEV1) | Pulmonary function measurements were performed by using a self-calibrated computer-operated pneumotochographic spirometer at all clinic visits. Three measurements were collected and the greatest FEV1 value was recorded. Observed values are summarized (without last observation carry forward). | Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEV1 test. | Posted | Mean | Standard Deviation | liters | Day 0 (baseline), Week 2, Week 4, Week 8 |
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| Secondary | Change From Baseline at End of Weeks 2, 4, and 8 of Forced Vital Capacity (FVC) Expressed as Percentage of Predicted Normal | FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. It is measured via spirometry. Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FVC values for children were different than the reference normal values used with adult participants. | Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FVC test. | Posted | Mean | Standard Deviation | percentage predicted FVC | Day 0 (baseline), Week 2, Week 4, Week 8 |
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| Secondary | Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Vital Capacity (FVC) | FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. It is measured via spirometry. | Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FVC test. | Posted | Mean | Standard Deviation | liters | Day 0 (baseline), Week 2, Week 4, Week 8 |
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| Secondary | Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%), Expressed as Percentage of Predicted Normal | Difference in the forced expiratory flow rate in mid-exhalation as a percent of predicted to standard values measured from baseline to weeks 2 (treated), 4 (treated), and 8 (untreated). Because this study included both adults and children and lung volume is an age-dependent variable, reference normal FEF 25-75% values for children were different than the reference normal values used with adult participants. | Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEF 25-75% test. | Posted | Mean | Standard Deviation | percentage predicted FEF 25-75% | Day 0 (baseline), Week 2, Week 4, Week 8 |
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| Secondary | Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%) | Difference in the forced expiratory flow rate in mid-exhalation measured from baseline to weeks 2 (treated), 4 (treated), and 8 (untreated). | Intent-to-Treat (ITT) Population, observed values. Differences in number of participants analyzed to the ITT population represent participants who missed visits, or failed to take the FEF 25-75% test. | Posted | Mean | Standard Deviation | liters/second | Day 0 (baseline), Week 2, Week 4, Week 8 |
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| Secondary | Change From Baseline to End of Weeks 4 and 8 in Pseudomonas Aeruginosa Log10 Bacterial Load in Sputum | If a participant had more than one Pseudomonas aeruginosa (PA) morphotype at a given visit, and therefore more than one bacterial load value, then the bacterial load value corresponding to the highest tobramycin minimal inhibitory concentration (MIC) value regardless of the PA morphotype was used. If the tobramycin MIC value was the same for different PA morphotypes, then the bacterial load value corresponding to morphotype 1 (mucoid colony) was used. If morphotype 1 was not available, bacterial load value corresponding to morphotype 2 (dry colony) was used. | Intent-to-Treat (ITT) Population; At Week 4, six Bramitob patients and seven TOBI patients were missing sputum samples. At Week 8, 11 Bramitob patients and 16 TOBI patients were missing sputum samples. | Posted | Mean | Standard Deviation | colony forming units/gram | Day -10 to -1 (baseline), Week 4, Week 8 |
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| Secondary | Minimal Inhibitory Concentration Inhibiting Growth of 50% (MIC50) of Pseudomonas Aeruginosa | MIC50 is the concentration of tobramycin required to inhibit 50% of Pseudomonas aeruginosa. MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains:
Overall MIC50 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used. | Intent-to-Treat (ITT) Population | Posted | Number | micrograms/milliliters | Week 4, Week 8 |
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| Secondary | Minimal Inhibitory Concentration Inhibiting Growth of 90% (MIC90) of Pseudomonas Aeruginosa | MIC90 is the concentration of tobramycin required to inhibit 90% of Pseudomonas aeruginosa. MIC values were calculated for three different Pseudomonas aeruginosa (PA) strains:
Overall MIC90 values are reported. If a participant has more than one PA morphotype at a given visit, then the highest tobramycin MIC value was used, regardless of PA morphotype. If a participant has more than one available result for each morphotype then the highest tobramycin MIC value was used. If the tobramycin MIC values are equal then the MIC value for the isolate with the highest bacterial load value was used. | Intent-to-Treat (ITT) Population | Posted | Number | micrograms/milliliters | Week 4, Week 8 |
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| Secondary | Microbiological Outcome Summary by Visit | Microbiological outcomes are derived considering all P. aeruginosa (PA) morphotypes together. Week 4 and Week 8 microbiological outcomes:
Superinfection supersedes eradication. Persistence for P. aeruginosa supersedes superinfection. Re-infection for P. aeruginosa supersedes superinfection. | Intent-to-Treat Population. | Posted | Number | percentage of participants | Day -10 to -1 (screening), Weeks 4 and 8 |
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| Secondary | Change From Baseline to End of Weeks 2, 4 and 8 in Body Weight | Body weight was measured at all study visits as part of the physical examination. | Intent-to-Treat (ITT) Population, observed values. Two participants from both treatment arms were missing data at Week 4. Three participants from Bramitob and 4 participants from TOBI were missing data at Week 8. | Posted | Mean | Standard Deviation | kilograms | Day 0 (baseline), Weeks 2, 4 and 8 |
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| Secondary | Change From Baseline to End of Weeks 2, 4 and 8 in Body Mass Index (BMI) | Intent-to-Treat (ITT) Population, observed values. Two participants from both treatment arms were missing data at Week 4. Three participants from Bramitob and 4 participants from TOBI were missing data at Week 8. | Posted | Mean | Standard Deviation | kilograms/meters^2 | Day 0 (baseline), Weeks 2, 4 and 8 |
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| Secondary | Count of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Emergent Adverse Events defined as adverse events occurring after the first intake of study treatment (or the same day). The investigator assessed relation to study treatment as a binary question: Reasonable possibility of relatedness or no reasonable possibility of relatedness. The expression "reasonable possibility of relatedness" is meant to convey in general that there are facts (evidence) or arguments meant to suggest a causal relationship. A serious AE results in death, is life-threatening, requires hospitalization or prolongation of existing inpatient hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or an important medical event. The investigator rates the severity of the AE based on a three point scale: mild, moderate or severe. A severe event prevents any usual routine activity of the participant and causes severe discomfort. | Safety population: all randomised patients who took at least one dose of study medication | Posted | Number | percentage of participants | Day 0 to Week 8 |
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| Secondary | Participants With a Hearing Threshold >20 Decibel in at Least One Ear | The potential ototoxic effects (hearing loss) of tobramycin were investigated by performing audiometric tests. Participants with a loss of auditory acuity greater than the 20 decibels auditory threshold are reported. | Safety population | Posted | Number | percentage of participants | Day -10 to -1 (screening), Weeks 4 and 8 |
|
|
Day 0 to Week 8
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bramitob | tobramycin / Bramitob administered 300mg twice a day for 4 weeks | 6 | 156 | 10 | 156 | ||
| EG001 | TOBI | tobramycin / TOBI administered 300mg twice a day for 4 weeks | 2 | 168 | 10 | 168 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Cystic fibrosis lung | Congenital, familial and genetic disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
Upon PI submission of publication to Sponsor, Sponsor will complete its review within 90 days after receipt. At Sponsor's request, publication may be delayed up to 120 additional days for Sponsor to file necessary patent applications. In multicenter trials, PIs will postpone single center publications until after multicenter data publication. If no multicenter publication occurs within 12 months of trial completion, PI may publish single center results, subject to review timelines listed above.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chiesi Clinical Trials | Chiesi Farmaceutici S.p.A. | clinicaltrials_info@chiesi.com |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D014031 | Tobramycin |
| ID | Term |
|---|---|
| D009328 | Nebramycin |
| D007612 | Kanamycin |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
Not provided
Not provided
| 13-17 years |
|
| > 17 years |
|
| Male |
|
| >=16 mcg/mL |
|
| Missing |
|
| >=50 % predicted |
|
| No |
|
The non-inferiority is shown if the lower limit of the two-sided 95% confidence interval is above the non-inferiority margin set at -4.5%.
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