A comparative, randomised, two period, multi-center, cross-over 14 weeks bioequivalence study of Tobramycin PARI (T100) versus TOBI® (Novartis) in cystic fibrosis patients with bronchopulmonary chronic Pseudomonas aeruginosa infection - T-100 BE

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2010-023235-41-PL
• Date of registration: 28/01/2011
• Prospective Registration: Yes
• Primary sponsor: PARI Pharma GmbH
• Public title: A comparative, randomised, two period, multi-center, cross-over 14 weeks bioequivalence study of Tobramycin PARI (T100) versus TOBI® (Novartis) in cystic fibrosis patients with bronchopulmonary chronic Pseudomonas aeruginosa infection - T-100 BE
• Scientific title: A comparative, randomised, two period, multi-center, cross-over 14 weeks bioequivalence study of Tobramycin PARI (T100) versus TOBI® (Novartis) in cystic fibrosis patients with bronchopulmonary chronic Pseudomonas aeruginosa infection - T-100 BE
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023235-41
• 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: yes Placebo: no Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Poland

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed by patient (or appropriate legal representative) the written informed consent including data protection agreement after the nature of the study has been fully explained prior to any screening procedure.
2. Patient is a male or female and at least 4 years of age at the time of screening.
3. Patient’s diagnosis of cystic fibrosis (CF) was confirmed by
· one or more specific clinical features consistent with CF
and
· elevated chloride concentration in the sweat = 60 mEq/l (by quantitative pilocarpine
iontophoresis test - QPIT)
and/or
· presence of disease-associated CF transmembrane conductance regulator (CFTR)
mutations in both alleles.
4. Patient has adequate pulmonary function at screening defined as:
· FEV1 between at least 25% and less or equal to 85% of normal predicted values for age, sex and height based on Knudson criteria
and
· peripheral artery haemoglobin oxygen saturation (SaO2) of at least 88% at rest measured by pulse oximetry on room air.
5. Patient has a positive culture for PA at screening (Visit 1): patient should have PA isolated from sputum only if patient do not have a known history of positive PA culture within the last 2 months.
6. Patient is clinically stable at screening (no change in FEV1 > 20% within one month prior to screening Visit).
7. Patient is able to comply with all protocol requirements (e.g. able to produce sputum and perform pulmonary function tests).
8. Sexually active women of childbearing potential and sexually active men will use a highly effective method of contraception throughout the IMP treatment period. (See Appendix 1).
9. Females of childbearing potential have a negative serum pregnancy test (within 7 days before Visit 2/randomisation).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
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:
1. Use of investigational medications within 30 days before study entry or during the trial.
2. Inability to handle the study inhalers to inhale the test preparations.
3. Patient has a known local or systemic hypersensitivity or adverse reaction to inhaled
aminoglycosides or systemic aminoglycosides
4. Administration of anti-pseudomonas aminoglycoside antibiotics are not allowed within 30 days before first administration of IMP. Macrolide are permitted, provided that they are taken as a maintenance therapy for at least 6 weeks before entering the trial. Other antibiotics are not allowed within 7 days before first administration of IMP. (For details see Appendix 2).
5. Patient with haemoptysis at any time within 4 weeks prior to screening (Visit 1)
6. FEV1 < 25% predicted.
7. Patient has a positive sputum or deep throat cough culture (or BAL) with Burkholderia cepacia (B cepacia) at screening (Visit 1) and/or a history of positive culture yielding B cepacia within 1 year prior to screening.
8. Presence of allergic bronchopulmonary aspergillosis (ABPA).
9. Patient experienced severe respiratory infection within one month prior to screening (Visit 1) which requires hospitalization or treatment with i.v. antibiotics.
10. Elevated serum creatinine > 1.2 mg/dl or BUN 20 mg/dl or proteinuria of grade 2+ or greater.
11. Significant liver disease (> 2x upper standard limits and no thrombocytopenia or clinical active disease).
12. Patients with auditory or/and vestibular dysfunctions
13. Patient has a history of lung transplantation.
14. Patient has a co-existing medical condition or abnormality that would compromise the participant's safety or the quality of the study data, in the opinion of the investigator.
15. Active drug and alcohol abuse or psychiatric disease.


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

Health Condition(s) or Problem(s) studied

Cystic fibrosis with bronchopulmonary chronic Pseudomonas aeruginosa infection
MedDRA version: 12.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung

Intervention(s)

Product Name: Tobramycin
Product Code: T100
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Other descriptive name: Tobramycinum
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 170/1,7-

Trade Name: TOBI®
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: TOBRAMYCIN
CAS Number: 32986-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 300/5,0-

Primary Outcome(s)

Secondary Objective: Secondary endpoints:
· Mean plasma tobramycin peak concentration Cmaxplasma in after 4 weeks of each treatment
phase. The acceptance level for the 90% confidence interval of peak tobramycin Cmaxplasma is
70-133%
· Mean sputum tobramycin peak concentrations ( sputum
max C ) after 4 weeks of each treatment phase.
The statistical evaluation of this endpoint will be solely descriptive. Pharmacokinetics will be
measured at visit 3 and visit 5.

Primary end point(s): Comparison of mean plasma tobramycin AUC0-12h of T100 170 mg nebulised via eFlow® and the registered TOBI® 300 mg nebulised via PARI LC PLUS. [tobramycin AUC0-12h
?visit5 – visit3]. The acceptance level for the 90% confidence interval of mean plasma tobramycin AUC0-12h is 80-125%.

Main Objective: Primary endpoint:
· To determine the bioequivalence of the new Tobramycin PARI formulation to TOBI by evaluating
the plasma tobramycin concentrations measured as mean plasma AUC0-12h of the new T100
formulation nebulised via eFlow®, compared with the registered TOBI® nebulised via PARI LC
PLUS after 4 weeks of each treatment phase. Full pharmacokinetic tobramycin level in plasma
will be measured at visit 3 and 5. The acceptance level for the 90% confidence interval of mean
plasma tobramycin AUC0-12h is 80-125%.

Secondary ID(s)

12012.101