A Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI®

NCT00885365 | Completed Phase 3 Results

• 1 other identifier: CMA-0631-PR-0010 Core
• Study Type: interventional
• Target: 324
• Locations: 8 countries
• Sites: 44

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.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; P. aeruginosa; tobramycin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (14)

• 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

  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)

  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

  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)

  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

  Day 0 (baseline), Week 2, Week 4, Week 8

Study Arms (2)

Bramitob

EXPERIMENTAL

tobramycin / Bramitob administered 300mg twice a day for 4 weeks

Drug: tobramycin / Bramitob

TOBI

ACTIVE COMPARATOR

tobramycin / TOBI administered 300mg twice a day for 4 weeks

Drug: tobramycin / TOBI

Interventions

tobramycin / Bramitob DRUG

300mg/4ml solution, via a nebuliser, over a 4-week treatment in a twice-daily regimen

Also known as: Bramitob, Tobrineb, Actitob, Bethkis

Bramitob

tobramycin / TOBI DRUG

300mg/5ml solution administered via nebuliser, over a 4-week treatment in a twice-daily regimen

Also known as: TOBI

TOBI

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (44)

Centrum pro cystickou fibrosu, Pediatricka klinika UK 2.LF, Fakultní nemocnice v Motole

Prague, 150 06, Czechia

Location

CHR Clemenceau

Caen, 14 033, France

Location

Hopital Arnaud de Villeneuve, Clinique des maladies respiratoires

Montpellier, 34 295, France

Location

Hopital Necker

Paris, 75 015, France

Location

Pädiatrische Pneumologie und Allergologie, Mukovizidose-Zentrum, Zentrum für Kinderheilkunde und Jugendmedizin

GieBen, 35385, Germany

Location

HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin

Krefeld, 47805, Germany

Location

Fővárosi Önkormányzat Heim Pál

Budapest, H-1089, Hungary

Location

Kaposi Mór Oktatókórház

Mosdós, H-7254, Hungary

Location

Szegedi Tudományegyetem Szent-Györgyi Albert Orvos- és Gyógyszerésztudományi Centrum

Szeged, H6725, Hungary

Location

Specjalistyczny ZOZ nad Matka i Dzieckiem, Poradnia Leczenia Mukowiscydozy

Gdansk, 80-308, Poland

Location

I Oddzial Chorob Dzieciecych, Wojewodzki Specjalistyczny Szpital Dzieciecy

Kielce, 25-381, Poland

Location

Oddzial Kliniczny Interny Dzieciecej i Alergologii, Wojewodzki Szpital Specjalistyczny

Lodz, 93-513, Poland

Location

Dzieciecy Szpital Kliniczny Akademii Medycznej, Klinika Chorob Pluc I Reumatologii

Lublin, 20-093, Poland

Location

Unknown Facility

Multiple Locations, Poland

Location

Klinika Pneumonologii, Alergologii Dzieciecej i Immunologii Klinicznej Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu

Poznan, 60-572, Poland

Location

Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj

Rabka-Zdrój, 34-700, Poland

Location

Poradnia Mukowiscydozy Wojewodzkiej, Przychodni Specjalistycznej dla Dzieci, Szpitala Wojewodzkiego Nr 2

Rzeszów, 35-301, Poland

Location

Klinika Pediatrii Instytut Matki I Dziecka

Warsaw, 01-211, Poland

Location

State Medical Institution: Republican Childrens Clinical Hospital under the Ministry of Health of the Republic of Tatarstan

Kazan', 420138, Russia

Location

Federal State Institution: Scientific Research Pulmonology Institute under the Roszdrav

Moscow, 105077, Russia

Location

State Medical Institution: Filatov Chidren's City Clinical Hospital #13

Moscow, 123242, Russia

Location

Federal State Institution "Nizhegorodskiy Research Institute of Children's Gastroenterology of Russian Medical Technologies"

Nizhny Novgorod, 603950, Russia

Location

State Medical Institution: Regional Children's Hospital Pulmonology Department

Rostov-on-Don, 344085, Russia

Location

Saint-Petersburg State Medical Institution: City Children's Hospital of Saint Olga

Saint Petersburg, 194156, Russia

Location

Regional State Medical Institution: Smolensk Regional Children's Clinical Hospital

Smolensk, 214019, Russia

Location

State Higher Educational Institution: Bashkir State Medical University under the Roszdrav

Ufa, 450106, Russia

Location

State Higher Educational Institution: Burdenko Voronezh State Medical Academy under the Roszdrav

Voronezh, 394024, Russia

Location

Minicipal Medical Institution: Children's Clinical Hospital #1

Yaroslavl, 150003, Russia

Location

Complejo Hospitalario Universitario A Coruña (Hospital Materno-Infantil Teresa Herrera)

A Coruña, 15006, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Corporació Sanitaria Parc Tauli

Sabadell, 08208, Spain

Location

Hospital Universitario Ntra Sra. De la Candelaria

Santa Cruz de Tenerife, 38010, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Hospital Universitario Miguel Servet (Children)

Zaragoza, 50009, Spain

Location

Dnipropetrovsk City Children Clinical Hospital # 2

Dnipropetrovsk, 49101, Ukraine

Location

Donetsk Regional Children Clinical Hospital

Donetsk, 83052, Ukraine

Location

Kriviy Rig City Clinical Hospital # 8

Kryvyi Rih, 50047, Ukraine

Location

Institute of Phthysiology and Pulmonology n.a., F.G.Yanovskiy of the Academy of Medical Science of Ukraine

Kyiv, 03680, Ukraine

Location

Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Science of Ukraine

Kyiv, 04050, Ukraine

Location

Lviv Regional Children Specialized Clinical Hospital

Lviv, 79035, Ukraine

Location

Odesa Regional Children Clinical Hospital

Odesa, 65031, Ukraine

Location

Simferopol Central District Clinical Hospital

Simferopol, 95033, Ukraine

Location

Zaporizhya Regional Clinical Children Hospital

Zaporizhya, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 24464974 RESULT

Related Links

• Study Record on EU Clinical Trials Register including results

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Tobramycin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Chiesi Clinical Trials
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

Study Officials

• Henryk Mazurek, Doctor

  Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2009
• First Posted: April 21, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: June 27, 2018
• Results First Posted: June 20, 2014

Record last verified: 2018-04

Locations

CZ (1); HU (3); PL (9); RU (10); DE (2); ES (7); FR (3); UA (9)