Clinical trial NCT00885365: A Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI®
Official title: A Multicentre, Multinational, Open-Label, Randomised, Parallel Group Clinical Trial of Tobrineb®/Actitob®/Bramitob® (Tobramycin Solution for Nebulisation, 300mg Twice Daily in 4mL Unit Dose Vials) Compared to TOBI® in the Treatment of Patients With Cystic Fibrosis and Chronic Infection With Pseudomonas Aeruginosa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
P. aeruginosa
tobramycin
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2009-04-21
Enrollment: 324
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Patients of either sex aged ≥ 6;
* Clinical diagnosis of cystic fibrosis defined as: (1)Patients preferably registered in the National Registry of CF (or other documents depending on country legislation); (2) Evidence of two or more typical pulmonary clinical features observed in CF, e.g., persistent colonization/infection with typical CF pathogens, chronic cough and sputum production, persistent chest radiography abnormalities, airway obstruction, nasal polyps and/or digital clubbing;
* Positive response in the standard sweat test (sweat chloride concentration ≥ 60 mmol/l for the standard method or ≥ 80 mmol/L for a microduct technique) documented in the clinical records and/or gene mutation documented in the clinical records;
* Chronic colonization of P. aeruginosa: presence in a sputum or throat culture of a minimum of 2 positive samples for P. aeruginosa over the previous 12 months and/or presence of more than two precipitating antibodies against P. aeruginosa;
* Sputum containing P. aeruginosa susceptible to tobramycin (defined as a zone diameter ≥ 16 mm after testing with 10 µg tobramycin disk or as a minimal inhibition concentration based on microdilution testing system) as identified by local laboratory at screening visit;
* Forced expiratory volume in 1 sec (FEV₁) ≥ 40% and ≤ 80% of the predicted normal value;
* Written informed consent obtained by parents/legal representative according to local regulations) and by the patient (when appropriate).

Exclusion Criteria:

* Administration of antipseudomonal antibiotic therapy by any route in the previous 4 weeks;
* Evidence of impaired renal function (serum creatinine level ≥ 1.5 mg/dl);
* Evidence of impaired auditory function (auditory threshold in either ear above 20 dB at frequencies between 250 and 8000Hz);
* Sputum culture containing Burkholderia cepacia;
* Patients with end-stage lung disease, candidates for heart-lung transplantation;
* History of other clinically significant cardiac, renal, neurological, gastrointestinal, hepatic or endocrine disease related to cystic fibrosis, whose sequelae and/or treatment can interfere with the results of the present study;
* Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e., contraceptive methods other than rod containing a hormone that prevents user from getting pregnant and that will be placed under the skin, syringes that contain a contraceptive hormone, combined birth control pill, i.e., such that contains two hormones, some intrauterine devices (IUDs) and sexual abstinence). A pregnancy test in urine is to be carried out in women of a fertile age at screening and at the last clinic visit;
* Known hypersensitivity to aminoglycosides;
* Patients with evidence of alcohol or drug abuse, likely to be not compliant with the study protocol or likely to be not compliant with the study treatments;
* Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit.

Primary outcomes:
measure: Change From Baseline to End of the Treatment Period of Forced Expiratory Volume in 1 Second (FEV1), Expressed as Percentage of Predicted Normal
timeFrame: Day 0 (baseline), Week 4
Secondary outcomes:
measure: 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
timeFrame: Day 0 (baseline), Week 2, Week 4, Week 8
measure: Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Day 0 (baseline), Week 2, Week 4, Week 8
measure: Change From Baseline at End of Weeks 2, 4, and 8 of Forced Vital Capacity (FVC) Expressed as Percentage of Predicted Normal
timeFrame: Day 0 (baseline), Week 2, Week 4, Week 8
measure: Change From Baseline to End of Weeks 2, 4, and 8 of Absolute Forced Vital Capacity (FVC)
timeFrame: Day 0 (baseline), Week 2, Week 4, Week 8
measure: 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
timeFrame: Day 0 (baseline), Week 2, Week 4, Week 8
measure: Change From Baseline to End of Weeks 2, 4, and 8 of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF 25-75%)
timeFrame: Day 0 (baseline), Week 2, Week 4, Week 8
measure: Change From Baseline to End of Weeks 4 and 8 in Pseudomonas Aeruginosa Log10 Bacterial Load in Sputum
timeFrame: Day -10 to -1 (baseline), Week 4, Week 8
measure: Minimal Inhibitory Concentration Inhibiting Growth of 50% (MIC50) of Pseudomonas Aeruginosa
timeFrame: Week 4, Week 8
measure: Minimal Inhibitory Concentration Inhibiting Growth of 90% (MIC90) of Pseudomonas Aeruginosa
timeFrame: Week 4, Week 8
measure: Microbiological Outcome Summary by Visit
timeFrame: Day -10 to -1 (screening), Weeks 4 and 8
measure: Change From Baseline to End of Weeks 2, 4 and 8 in Body Weight
timeFrame: Day 0 (baseline), Weeks 2, 4 and 8
measure: Change From Baseline to End of Weeks 2, 4 and 8 in Body Mass Index (BMI)
timeFrame: Day 0 (baseline), Weeks 2, 4 and 8
measure: Count of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 0 to Week 8
measure: Participants With a Hearing Threshold >20 Decibel in at Least One Ear
timeFrame: Day -10 to -1 (screening), Weeks 4 and 8
Other outcomes:
Locations:
city: Praha
country: Czechia
facility: Centrum pro cystickou fibrosu, Pediatricka klinika UK 2.LF, Fakultní nemocnice v Motole
city: Caen
country: France
facility: CHR Clemenceau
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve, Clinique des maladies respiratoires
city: Paris
country: France
facility: Hopital Necker
city: GieBen
country: Germany
facility: Pädiatrische Pneumologie und Allergologie, Mukovizidose-Zentrum, Zentrum für Kinderheilkunde und Jugendmedizin
city: Krefeld
country: Germany
facility: HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin
city: Budapest
country: Hungary
facility: Fővárosi Önkormányzat Heim Pál
city: Mosdos
country: Hungary
facility: Kaposi Mór Oktatókórház
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Orvos- és Gyógyszerésztudományi Centrum
city: Gdansk
country: Poland
facility: Specjalistyczny ZOZ nad Matka i Dzieckiem, Poradnia Leczenia Mukowiscydozy
city: Kielce
country: Poland
facility: I Oddzial Chorob Dzieciecych, Wojewodzki Specjalistyczny Szpital Dzieciecy
city: Lodz
country: Poland
facility: Oddzial Kliniczny Interny Dzieciecej i Alergologii, Wojewodzki Szpital Specjalistyczny
city: Lublin
country: Poland
facility: Dzieciecy Szpital Kliniczny Akademii Medycznej, Klinika Chorob Pluc I Reumatologii
city: Multiple Locations
country: Poland
city: Poznan
country: Poland
facility: Klinika Pneumonologii, Alergologii Dzieciecej i Immunologii Klinicznej Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu
city: Rabka Zdroj
country: Poland
facility: Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj
city: Rzeszow
country: Poland
facility: Poradnia Mukowiscydozy Wojewodzkiej, Przychodni Specjalistycznej dla Dzieci, Szpitala Wojewodzkiego Nr 2
city: Warszawa
country: Poland
facility: Klinika Pediatrii Instytut Matki I Dziecka
city: Kazan
country: Russian Federation
facility: State Medical Institution: Republican Childrens Clinical Hospital under the Ministry of Health of the Republic of Tatarstan
city: Moscow
country: Russian Federation
facility: Federal State Institution: Scientific Research Pulmonology Institute under the Roszdrav
city: Moscow
country: Russian Federation
facility: State Medical Institution: Filatov Chidren's City Clinical Hospital #13
city: Nizhniy Novgorod
country: Russian Federation
facility: Federal State Institution "Nizhegorodskiy Research Institute of Children's Gastroenterology of Russian Medical Technologies"
city: Rostov-on-Don
country: Russian Federation
facility: State Medical Institution: Regional Children's Hospital Pulmonology Department
city: Smolensk
country: Russian Federation
facility: Regional State Medical Institution: Smolensk Regional Children's Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Medical Institution: City Children's Hospital of Saint Olga
city: Ufa
country: Russian Federation
facility: State Higher Educational Institution: Bashkir State Medical University under the Roszdrav
city: Voronezh
country: Russian Federation
facility: State Higher Educational Institution: Burdenko Voronezh State Medical Academy under the Roszdrav
city: Yaroslavl
country: Russian Federation
facility: Minicipal Medical Institution: Children's Clinical Hospital #1
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (Hospital Materno-Infantil Teresa Herrera)
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Tauli
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Ntra Sra. De la Candelaria
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet (Children)
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Children Clinical Hospital # 2
city: Donetsk
country: Ukraine
facility: Donetsk Regional Children Clinical Hospital
city: Kriviy Rig
country: Ukraine
facility: Kriviy Rig City Clinical Hospital # 8
city: Kyiv
country: Ukraine
facility: Institute of Phthysiology and Pulmonology n.a., F.G.Yanovskiy of the Academy of Medical Science of Ukraine
city: Kyiv
country: Ukraine
facility: Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Science of Ukraine
city: Lviv
country: Ukraine
facility: Lviv Regional Children Specialized Clinical Hospital
city: Odesa
country: Ukraine
facility: Odesa Regional Children Clinical Hospital
city: Simferopol
country: Ukraine
facility: Simferopol Central District Clinical Hospital
city: Zaporizhya
country: Ukraine
facility: Zaporizhya Regional Clinical Children Hospital
Study officials:
affiliation: Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj
name: Henryk Mazurek, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.