Pharmacokinetic Study of Bramitob® Administered for Inhalation by PARI eFlow® vs PARI LC® PLUS Nebulizer

PHARMACOKINETIC STUDY OF BRAMITOB® ADMINISTERED FOR INHALATION BY PARI eFLOW® RAPID ELECTRONIC NEBULIZER VS PARI LC® PLUS NEBULIZER COUPLED WITH THE PARI TURBO BOY® N COMPRESSOR IN CYSTIC FIBROSIS PATIENTS INFECTED WITH PSEUDOMONAS AERUGINOSA

The purpose of this study is to assess pharmacokinetic and safety comparability of Bramitob® when administered for inhalation by using PARI eFlow® rapid electronic nebulizer vs PARI LC® PLUS nebulizer in Cystic Fibrosis Patients infected with Pseudomonas Aeruginosa

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Bramitob® administered by PARI LC® PLUS nebulizer; Drug: Bramitob® administered by PARI eFlow® rapid electronic nebulizer

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
    • University Hospital Brno Bohunice
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • SMSI Institude of Cardiology
• Slovakia
  • Banská Bystrica, Slovakia, 975 17
    • University hospital with Health Center
  • Brastislava, Slovakia, 826 06
    • Fakultná nemocnica s poliklinikou Bratislava (FNsP)
  • Kosice, Slovakia, 041 90
    • University Hospital of L. Pasteur, Pneumonology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main inclusion Criteria:

• Patients of either sex aged ≥ 18 years;
• Clinical diagnosis of cystic fibrosis (patients registered in the National Registry of cystic fibrosis or other documents, if applicable, depending on country legislation);
• Positive response (sweat chloride concentration ≥ 60 mmol/l) in the standard sweat test documented in the clinical records or sweat chloride concentration ≥ 40 mmol/l and at least two gene mutations consistent with CF documented in the clinical records;
• Chronic colonization of Pseudomonas aeruginosa
• FEV1 ≥ 35% of the predicted normal value calculated according to the recommendation of the Official Statement of the European Respiratory Society and American Thoracic Society

Main exclusion Criteria:

• 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;
• Received loop diuretics within 7 days before study drug administration;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PARI LC® PLUS nebulizer	Drug: Bramitob® administered by PARI LC® PLUS nebulizer; (tobramycin 300mg /4mL) solution administered by inhalation twice daily for 28 days; Other Names: Bramitob®, Tobrineb®, Actitob®
Active Comparator: PARI eFlow® rapid electronic nebulizer	Drug: Bramitob® administered by PARI eFlow® rapid electronic nebulizer; (tobramycin 300mg /4mL) solution administered by inhalation twice daily for 28 days; Other Names: Bramitob®, Tobrineb®,Actitob®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma tobramycin pharmacokinetic parameters (Cmax and AUC0-t) after twice daily inhalation of Bramitob® using PARI eFlow® nebulizer vs PARI LC® PLUS nebulizer	on day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma tobramycin pharmacokinetic parameters (Cmax, tmax and AUC0-t) after inhalation of Bramitob® using PARI eFlow® nebulizer vs PARI LC® PLUS nebulizer	on day 1
Sputum tobramycin pharmacokinetic parameters (Cmax, tmax and AUC0-t) after inhalation of Bramitob® using PARI eFlow® nebulizer vs PARI LC® PLUS nebulizer	on day 1 and on day 28
Accumulation of tobramycin in plasma and sputum after repeated doses calculated as the ratio: AUC0-t DAY 28 / AUC0-t DAY 1 and Cmax DAY 28 / Cmax DAY 1	day 1 - day 28
Safety assessed by adverse events, adverse drug reactions, incidence of bronchospasm, laboratory parameters, physical examination, body weight, vital signs results	day1-day28
Number of patients with minimum plasma tobramycin levels Cmin > 2mcg/mL and maximum plasma tobramycin levels Cmax > 12 mcg/mL	on day 28
Time necessary for the nebulization of the dose	on day 1 and on day 28

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Jozef Ružička, MD, PhD, Fakultná nemocnica s poliklinikou Bratislava, Slovakia; Principal Investigator: Andrej Somos, MD, University Hospital of L. Pasteur, Pneumonology Department, Rastislavova 43, 041 90, Kosice, Slovakia; Principal Investigator: Jana Skřičková, MD, PhD, University Hospital Brno Bohunice, Jihlavská 20, 625 00, Brno, Czech Republic; Principal Investigator: Eva Beresova, M.D, University hospital with Health Center, F.D. Roosevelta Banská Bystrica, L. Svoboda´s square 1, 975 17, Banská Bystrica, Slovakia; Principal Investigator: Svetlana Şciuca, M.D, PhD, SMSI Institude of Cardiology, MD-2025, 29/1 Testimitanu str., Chisinau, Republic of Moldova

Publications and helpful links

General Publications

• Govoni M, Poli G, Acerbi D, Santoro D, Cicirello H, Annoni O, Ruzicka J. Pharmacokinetic and tolerability profiles of tobramycin nebuliser solution 300 mg/4 ml administered by PARI eFlow((R)) rapid and PARI LC Plus((R)) nebulisers in cystic fibrosis patients. Pulm Pharmacol Ther. 2013 Apr;26(2):249-55. doi: 10.1016/j.pupt.2012.12.002. Epub 2012 Dec 8.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: April 29, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Cystic fibrosis, tobramycin,nebulizer, PK
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: CCD-0908-PR-0029; 2009-016780-11 (EudraCT Number)