Randomized, Controlled Study of CF Patients Between 3 Months and Less Than 7 Years (EARLY)

A Randomized, Double-Blind, Placebo-Controlled, Crossover Multi-Center Study to Assess the Efficacy and Safety of Inhaled Tobramycin Nebuliser Solution (TOBI®) for the Treatment of Early Infections of P. Aeruginosa in Cystic Fibrosis Subjects Aged From 3 Months to Less Than 7 Years

This study investigated the efficacy of inhaled TOBI treatment for early infections of P. aeruginosa in paediatric patients with cystic fibrosis.

Study Overview

• Status: Completed
• Conditions: Treatment of Early Pulmonary Infections With P. Aeruginosa in Cystic Fibrosis Patients
• Intervention / Treatment: Drug: Placebo; Drug: TOBI

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3T1C5
      • Novartis Investigative Site
• Egypt
  • Alexandria, Egypt, 21131
    • Novartis Investigative Site
• France
  • Bordeaux, France, 33076
    • Novartis Investigative Site
  • Paris, France, 75019
    • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
• Greece
  • Patras, Greece, 265 00
    • Novartis Investigative Site
  • GR
    • Thessaloniki, GR, Greece, 546 29
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 546 42
      • Novartis Investigative Site
• Hungary
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Debrecen, Hungary, 4043
    • Novartis Investigative Site
  • Kaposvar, Hungary, 7400
    • Novartis Investigative Site
  • Szeged, Hungary, 6725
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
• Romania
  • Bucuresti, Romania, 20395
    • Novartis Investigative Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Novartis Investigative Site
  • Voronezh, Russian Federation, 394036
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Switzerland
  • Zürich, Switzerland, 8032
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of cystic fibrosis
• Early lower respiratory tract infection with P. aeruginosa,

Exclusion Criteria:

• Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
• Administration of loop diuretics within 7 days prior to study drug administration.
• Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TOBI (tobramycin inhaled solution)/Placebo; Participants randomized to TOBI received the investigational treatment for 28 days twice daily (bi)d in the first treatment cycle. At the end of first treatment cycle, participants who were positive for P. aeruginosa entered the open label (OL) phase of the study and received TOBI for 28 days bid. Participants who were negative for P. aeruginosa at the end of first treatment cycle and agreed to participate in the cross-over treatment period received placebo for 28 days bid (second treatment cycle).	Drug: Placebo; Placebo; Drug: TOBI; TOBI (tobramycin inhaled solution)
Placebo Comparator: Placebo/TOBI; Participants randomized to placebo group received 0.9 % saline (NaCl) for 28 days bid in the first treatment cycle. At the end of first treatment cycle, participants who were positive for P. aeruginosa entered the OL phase of the study and received TOBI for 28 days bid. Participants who were negative for P. aeruginosa at the end of first treatment cycle and agreed to participate in the cross-over treatment period received TOBI for 28 days bid (second treatment cycle).	Drug: Placebo; Placebo; Drug: TOBI; TOBI (tobramycin inhaled solution)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants P Aeruginosa-free After Completion of the First Treatment Cycle	Sputum/throat swab cultures were assessed.	Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Free From P. Aeruginosa 28 Days After Termination of the Second Treatment Cycle	Sputum/throat swab cultures were assessed.	Day 91
Percentage of Participants P Aeruginosa-free at Termination of the Double Blind Period	Sputum/throat swab cultures were assessed.	Day 91

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Ratjen F, Moeller A, McKinney ML, Asherova I, Alon N, Maykut R, Angyalosi G; EARLY study group. Eradication of early P. aeruginosa infection in children <7 years of age with cystic fibrosis: The early study. J Cyst Fibros. 2019 Jan;18(1):78-85. doi: 10.1016/j.jcf.2018.04.002. Epub 2018 Apr 21.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 5, 2010
• First Submitted That Met QC Criteria: March 5, 2010
• First Posted (Estimate): March 8, 2010

Study Record Updates

• Last Update Posted (Estimate): July 15, 2016
• Last Update Submitted That Met QC Criteria: June 6, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Cystic fibrosis; Lung disease; anti-bacterial agents; Tobramycin Inhalation solution
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Infections; Cystic Fibrosis
• Other Study ID Numbers: CTBM100C2304; 2009-016590-15 (EudraCT Number)