A Single Arm 48-Week Follow-on Safety Study to a Core Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI® - Full Text View

Purpose

This is a 48-week extension study to CMA-0631-PR-0010 Core Study. Patients who have a positive culture for P. aeruginosa at visit 4 of the first 8-week core study period and/or if deemed appropriate by the Investigators will be able to be included in the 48-week follow-on period (Extension Study) to continue the treatment only with Bramitob® (tobramycin nebuliser solution, 300 mg twice daily in 4 mL unit dose vials).

Condition	Intervention	Phase
Cystic Fibrosis	Drug: tobramycin	Phase 3

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Single Arm 48-Week Follow-on Safety Study to the Core Study (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:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Tobramycin Tobramycin sulfate

U.S. FDA Resources

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

Primary Outcome Measures:

to assess safety profile in terms of incidence of adverse events/adverse drug reactions, frequency of cystic fibrosis exacerbations, audiometric test, laboratory parameters (hematology and blood chemistry), vitals signs (hr and bp), physical examination. [ Time Frame: up to 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

to assess whether prolonged use of aerosolized tobramycin is required to sustain FEV1 increase (FEV1 expressed in liters and % predicted) [ Time Frame: up to 48 weeks ] [ Designated as safety issue: No ]
Categorical results of microbiological tests referred to P. aeruginosa (negativisation, persistence, superinfection, re-infection); susceptibility testing of isolated P. aeruginosa strains (MIC90 and MIC50) [ Time Frame: up to 48 weeks ] [ Designated as safety issue: No ]
Changes in body weight and BMI [ Time Frame: up to 48 weeks ] [ Designated as safety issue: No ]
to assess health related quality of life [ Time Frame: Initial visit, Week 20, Week 44 ] [ Designated as safety issue: No ]

Enrollment:	209
Study Start Date:	September 2009
Study Completion Date:	May 2011
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Intervention Details:

300mg/4ml solution, via a nebuliser, over a 48-week period in a twice-daily regimen, with 6 "on" cycles of 4 weeks duration during the 48-week period.

Other Name: Tobrineb®/Actitob®/Bramitob®

Eligibility

Ages Eligible for Study:	6 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Successful completion of Core Study
At least 6 years of age
Males and females

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111383

Locations

France
CHR Clemenceau
Caen, France, 14 033
Hopital Arnaud de Villeneuve, Clinique des maladies respiratoires
Montpellier, France, 34 295
Hopital Necker
Paris, France, 75 015
Poland
Specjalistyczny ZOZ nad Matka i Dzieckiem, Poradnia Leczenia Mukowiscydozy
Gdansk, Poland, 80-308
I Oddzial Chorob Dzieciecych, Wojewodzki Specjalistyczny Szpital Dzieciecy
Kielce, Poland, 25-381
Oddzial Kliniczny Interny Dzieciecej i Alergologii, Wojewodzki Szpital Specjalistyczny
Lodz, Poland, 93-513
Dzieciecy Szpital Kliniczny Akademii Medycznej, Klinika Chorob Pluc I Reumatologii
Lublin, Poland, 20-093
Klinika Pneumonologii, Alergologii Dzieciecej i Immunologii Klinicznej Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu
Poznan, Poland, 60-572
Klinika Pneumonologii i Mukowiscydozy, Instytut Gruzlicy i Chorob Pluc w Rabce Zdroj
Rabka Zdroj, Poland, 34-700
Poradnia Mukowiscydozy Wojewodzkiej, Przychodni Specjalistycznej dla Dzieci, Szpitala Wojewodzkiego Nr 2
Rzeszow, Poland, 35-301
Klinika Pediatrii Instytut Matki I Dziecka
Warszawa, Poland, 01-211
Ukraine
Dnipropetrovsk City Children Clinical Hospital # 2
Dnipropetrovsk, Ukraine, 49101
Donetsk Regional Children Clinical Hospital
Donetsk, Ukraine, 83052
Kriviy Rig City Clinical Hospital # 8
Kriviy Rig, Ukraine, 50047
Institute of Phthysiology and Pulmonology n.a., F.G.Yanovskiy of the Academy of Medical Science of Ukraine
Kyiv, Ukraine, 03680
Institute of Pediatrics, Obstetrics and Gynecology of the Academy of Medical Science of Ukraine
Kyiv, Ukraine, 04050
Lviv Regional Children Specialized Clinical Hospital
Lviv, Ukraine, 79035
Odesa Regional Children Clinical Hospital
Odesa, Ukraine, 65031
Simferopol Central District Clinical Hospital
Simferopol, Ukraine, 95033
Zaporizhya Regional Clinical Children Hospital
Zaporizhya, Ukraine

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:

Wine JJ. Cystic fibrosis: How do CFTR mutations cause cystic fibrosis? Curr Biol. 1995 Dec 1;5(12):1357-9. Review. No abstract available.

Lewis PA. The epidemiology of cystic fibrosis. In: Hodson ME, Geddes DM. Cystic Fibrosis 2nd edition, Arnold, London 2000; 1a: 2-12.

Dodge JA, Morison S, Lewis PA, Coles EC, Geddes D, Russell G, Littlewood JM, Scott MT. Incidence, population, and survival of cystic fibrosis in the UK, 1968-95. UK Cystic Fibrosis Survey Management Committee. Arch Dis Child. 1997 Dec;77(6):493-6.

Lucotte G, Hazout S, De Braekeleer M. Complete map of cystic fibrosis mutation DF508 frequencies in Western Europe and correlation between mutation frequencies and incidence of disease. Hum Biol. 1995 Oct;67(5):797-803.

Bossi A, Battistini F, Braggion C, Magno EC, Cosimi A, de Candussio G, Gagliardini R, Giglio L, Giunta A, Grzincich GL, La Rosa M, Lombardo M, Lucidi V, Manca A, Mastella G, Moretti P, Padoan R, Pardo F, Quattrucci S, Raia V, Romano L, Salvatore D, Taccetti G, Zanda M. [Italian Cystic Fibrosis Registry: 10 years of activity] Epidemiol Prev. 1999 Jan-Mar;23(1):5-16. Italian.

Yamashiro Y, Shimizu T, Oguchi S, Shioya T, Nagata S, Ohtsuka Y. The estimated incidence of cystic fibrosis in Japan. J Pediatr Gastroenterol Nutr. 1997 May;24(5):544-7.

Imaizumi Y. Incidence and mortality rates of cystic fibrosis in Japan, 1969-1992. Am J Med Genet. 1995 Aug 28;58(2):161-8.

Wood RE, Boat TF, Doershuk CF. Cystic fibrosis. Am Rev Respir Dis. 1976 Jun;113(6):833-78. Review. No abstract available.

Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059-65.

Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066-73.

Anderson MP, Gregory RJ, Thompson S, Souza DW, Paul S, Mulligan RC, Smith AE, Welsh MJ. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science. 1991 Jul 12;253(5016):202-5.

Trapnell BC, Chu CS, Paakko PK, Banks TC, Yoshimura K, Ferrans VJ, Chernick MS, Crystal RG. Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6565-9.

Høiby N. Microbiology of lung infections in cystic fibrosis patients. Acta Paediatr Scand 1982; 301: 33-54.

Moss RB, Babin S, Hsu YP, Blessing-Moore J, Lewiston NJ. Allergy to semisynthetic penicillins in cystic fibrosis. J Pediatr. 1984 Mar;104(3):460-6.

Hodson ME, Gallagher CG, Govan JR. A randomised clinical trial of nebulised tobramycin or colistin in cystic fibrosis. Eur Respir J. 2002 Sep;20(3):658-64.

Ramsey BW, Dorkin HL, Eisenberg JD, Gibson RL, Harwood IR, Kravitz RM, Schidlow DV, Wilmott RW, Astley SJ, McBurnie MA, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993 Jun 17;328(24):1740-6.

Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, Vasiljev-K M, Borowitz D, Bowman CM, Marshall BC, Marshall S, Smith AL. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med. 1999 Jan 7;340(1):23-30.

Gilligan PH. Microbiology of airway disease in patients with cystic fibrosis. Clin Microbiol Rev. 1991 Jan;4(1):35-51. Review.

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.

Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5-40. Review. No abstract available.

Pin I, Gibson PG, Kolendowicz R, Girgis-Gabardo A, Denburg JA, Hargreave FE, Dolovich J. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax. 1992 Jan;47(1):25-9.

Henry DA, Campbell ME, LiPuma JJ, Speert DP. Identification of Burkholderia cepacia isolates from patients with cystic fibrosis and use of a simple new selective medium. J Clin Microbiol. 1997 Mar;35(3):614-9. Erratum in: J Clin Microbiol 1999 Apr;37(4):1237.

Bauernfeind A, Rotter K, Weisslein-Pfister C. Selective procedure to isolate haemophilus influenzae from sputa with large quantities of Pseudomonas aeruginosa. Infection. 1987 Jul-Aug;15(4):278-80.

Johansen HK, Høiby N. Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis in Denmark. Thorax. 1992 Feb;47(2):109-11.

Responsible Party:	Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier:	NCT01111383 History of Changes
Other Study ID Numbers:	CMA-0631-PR-0010 Extension
Study First Received:	April 13, 2010
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 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 May 23, 2013

A Single Arm 48-Week Follow-on Safety Study to a Core Study Comparing the Efficacy and Tolerability of Tobrineb®/Actitob®/Bramitob® Versus TOBI® (CT03Ext)