A Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI® (CT03Core)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:
NCT00885365
First received: April 20, 2009
Last updated: November 18, 2011
Last verified: November 2011
  Purpose

To demonstrate that Tobrineb®/Actitob®/Bramitob® is non-inferior to TOBI® in primary efficacy variable, forced expiratory volume in one second (FEV1) percent of predicted normal, and to compare their safety in patients with cystic fibrosis and chronic infection of the lungs with P. aeruginosa.


Condition Intervention Phase
Cystic Fibrosis
Drug: tobramycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Chiesi Farmaceutici S.p.A.:

Primary Outcome Measures:
  • Change from baseline of FEV1, expressed as percentage of predicted normal at the end of the treatment phase (week 4). [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Other pulmonary function parameters, such as FEV1 % predicted measured at Visit 3 and Visit 5, FEV1 expressed as litres, FVC as litres and % predicted, FEF25-75% expressed as litres and % predicted measured at Visit 3, Visit 4 and Visit 5. [ Time Frame: Week 2, Week 4, Week 8 ] [ Designated as safety issue: No ]
  • Audiometric tests [ Time Frame: Screening, Week 4, Week 8 ] [ Designated as safety issue: Yes ]
  • Hematology and blood chemistry [ Time Frame: Screening, Week 4 ] [ Designated as safety issue: Yes ]
  • Vital Signs, Physical Examination [ Time Frame: Screening, Day 0, Week 2, Week 4, Week 8 ] [ Designated as safety issue: Yes ]
  • Categorical results of microbiological tests referred to P. aeruginosa (PA) (negative or positive culture, superinfection, re-infection); sputum culture & MIC50 & MIC90 of isolated PA strains; PA bacterial load (CFUs) performed at visit 4 [ Time Frame: Screening, Week 4, Week 8 ] [ Designated as safety issue: No ]
  • Adverse Events [ Time Frame: entire study ] [ Designated as safety issue: Yes ]

Enrollment: 324
Study Start Date: April 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Tobrineb®/Actitob®/Bramitob®, tobramycin 300mg/4ml solution
Drug: tobramycin
300mg/4ml solution, via a nebuliser, over a 4-week treatment in a twice-daily regimen
Other Name: Tobrineb®/Actitob®/Bramitob®
Active Comparator: 2
TOBI® Nebuliser tobramycin 300mg/5 ml solution
Drug: tobramycin
300mg/5 ml solution administered via nebuliser, over a 4-week treatment in a twice-daily regimen
Other Name: TOBI®

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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;
  • 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 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 (Visit 1).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00885365

  Show 43 Study Locations
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Henryk Mazurek, Doctor Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj
  More Information

Publications:
Lewis PA. The epidemiology of cystic fibrosis. In: Hodson ME, Geddes DM. Cystic Fibrosis 2nd edition, Arnold, London 2000; 1a: 2-12.
Høiby N. Microbiology of lung infections in cystic fibrosis patients. Acta Paediatr Scand 1982; 301: 33-54.
Ramsey BW, Schaeffler BL, Montgomery AB, et al. Survival and lung function during two years of treatment with intermittent tobramycin solution for inhalation in CF patients. Presented at European Cystic Fibrosis Conference (June 1999), The Hague, The Netherlands.
Van Dalfsen JM, Lin L, Burns JL, et al. Microbiology effect of 18 months of intermittent inhaled tobramycin in patients with CF. Presented at European Cystic Fibrosis Conference (June 1999), The Hague, The Netherlands.
Lenoir G, Aryayev N, et al. Highly concentrated aerosolized Tobramycin in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection. Eur. Respir. J 2005:26 (suppl. 49) 620s.
Chuchalin A, Gyurkovics K, et al. Long term administration of aerosolised tobramycin, in patients with cystic fibrosis. Eur. Respir. J.2005: 26 (suppl 49) 3942s.

Responsible Party: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT00885365     History of Changes
Other Study ID Numbers: CMA-0631-PR-0010 Core
Study First Received: April 20, 2009
Last Updated: November 18, 2011
Health Authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Ukraine: State Pharmacological Center - Ministry of Health
Germany: Ethics Commission
Hungary: National Institute of Pharmacy
Czech Republic: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
France: Institutional Ethical Committee

Keywords provided by Chiesi Farmaceutici S.p.A.:
cystic fibrosis
P. aeruginosa
tobramycin

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014