Tobramycin nebulisation with I-neb (TONI) study in children with cystic fibrosis: pharmacokinetics and safety

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2012-002503-17-NL
• Date of registration: 14/08/2012
• Prospective Registration: Yes
• Primary sponsor: Erasmus University Medical Centre
• Public title: Tobramycin nebulisation with I-neb (TONI) study in children with cystic fibrosis: pharmacokinetics and safety
• Scientific title: Tobramycin nebulisation with I-neb (TONI) study in children with cystic fibrosis: pharmacokinetics and safety - TONI study in children with CF
• Date of first enrolment: 21/12/2012
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002503-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Tobramycin nebulisation with PariLCPlus nebuliser (standard) compared to I-neb nebuliser (new) Number of treatment arms in the trial: 2

Countries of recruitment

Netherlands

Contacts

• Name: HM Janssens
• Affiliation: Erasmus University Medical Centre

• Name: HM Janssens
• Affiliation: Erasmus University Medical Centre

Key inclusion & exclusion criteria

Inclusion criteria:
The criteria of inclusion will be the following:
• Clinical diagnosis of CF and a positive sweat test or two CF-related mutations;
• Either: early PA infection or colonization with PA requiring eradication with inhaled tobramycin, or: chronic PA colonization requiring maintenance therapy with inhaled tobramycin;
• Age 6-18 years;
• Ability to breathe through a mouthpiece and to use both types of inhalers;
• Ability to perform lung function tests;
• Written informed consent (parents; >12 years: child and parents).

Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
The criteria of exclusion will be the following:
• Acute exacerbation of pulmonary infection;
• Known impaired kidney function (estimated creatinine clearance < 60 ml/min);
• Start of nephrotoxic or ototoxic drugs, e.g. aminoglycosides, within 1 month prior to start or during the study;
• Therapy (e.g. furosemide) or disease which may complicate evaluation of the study protocol, as judged by the investigator;
• Participation in another drug-investigating clinical study at the start or within 1 month prior to the start;
• Inability to follow instructions of the investigator.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Cystic fibrosis
MedDRA version: 14.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Bramitob
Product Name: Bramitob
Product Code: 033841
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: TOBRAMYCIN
CAS Number: 32986-56-4
Current Sponsor code: TONI-2012
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 600 -

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1,5 years

Secondary Objective: 1) To assess safety of I-neb tobramycin inhalation therapy, 2) to compare pharmacokinetics of I-neb tobramycin inhalation in children with CF aged 6-11 years with children aged 12-18 years and 3) to compare patient compliance and satisfaction with both nebulisers.

Primary end point(s): Primary endpoint: systemic bioavailability of inhaled tobramycin, defined as serum tobramycin AUC0-24hr.

Main Objective: To investigate whether pharmacokinetics of the recommended dose of inhaled tobramycin, defined as serum tobramycin Area Under the Curve (AUC0-24hr), with the I-neb (75 mg) is equivalent to the PariLCPlus (300 mg) nebuliser in children with CF aged 6-18 years.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints will include:
• Change in hearing function (measured by HFPTA and DPOAE);
• Change in NAG/creatinine ratio as measure of early renal toxicity;
• Serum tobramycin peak and trough levels;
• Change in FEV1 before and after nebulisation (safety parameter);
• Compliance rate;
• Patient satisfaction (use/cleaning of device);
• Differences in AUC0-24 between age groups 6-11 and 12-18 years.

Timepoint(s) of evaluation of this end point: 1,5 years

Secondary ID(s)

TONI-2012

Source(s) of Monetary Support

Erasmus University Medical Centre