Pharmacokinetic Evaluation of an 8 -Week Treatment With Inhaled Tobramycin

Pseudomonas Infections Clinical Trial

Official title:

A Multicenter, Open Label, 2 Period Cross-over Study to Evaluate the PK of a 8 Week Continuous Treatment With 1x300mg/d and 2x300mg/d Tobramycin Inhaled With a 'Soft Mist' Nebulizer in Cystic Fibrosis (CF) Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634192
• Other study ID #: CTBM100DDE01
• Status: Completed
• Phase: Phase 3
• First received: March 4, 2008
• Last updated: February 22, 2017
• Start date: February 2008
• Est. completion date: August 2009

Study information

• Verified date: February 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to provide data about the pharmacokinetics (PK), safety and tolerability of two continuous treatment regimes of tobramycin nebulized solution delivered via a 'soft mist' nebulizer in Cystic Fibrosis (CF) subjects. Each treatment period will last 8 weeks. Additionally the PK of patients with a normal forced expiratory flow in 1 second (FEV1) (FEV1≥80% predicted) will be compared to patients with an abnormal FEV1 (FEV1<80% predicted).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2009
• Est. primary completion date: February 2009
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Male and female subjects aged =6 years at the time of screening, with an Informed Consent Form signed by patient and if appropriate by parent/legal guardians, prior to any study-related procedure.

• Confirmed diagnosis of CF by the presence of one or more clinical features of CF in addition to a quantitative pilocarpine iontophoresis sweat chloride test of >60 mEq/L; or identification of well-characterized disease-causing mutations in each CFTR gene; or an abnormal nasal transepithelial potential difference characteristic of CF.

• P aeruginosa must be present in sputum or deep throat swab (or bronchoalveolar lavage [BAL]) at the screening visit and within 6 months prior to screening.

Exclusion Criteria:

• History of sputum (or BAL) culture yielding Burkholderia cepacia (B cepacia) within 2 years prior to screening and/or sputum culture yielding B cepacia at screening.

• FEV1 <25% of normal predicted values for age, sex, and height based on Knudson criteria at screening.

• Hemoptysis of more than 60 cc at any time within 30 days prior to study drug administration.

• Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.

• GFR<60ml/min/1.73m2 calculated with the Formula by Schwartz, BUN 40 mg/dl or more, or an abnormal urinalysis defined as 2+ or greater proteinuria.

• History of tinnitus or pathologic audiometry

• diagnosis of Allergic bronchopulmonary aspergillosis (ABPA) at screening

• Initiation of treatment with macrolide antibiotics within 28 days prior to study drug administration (subjects may be taking macrolide antibiotics at the time of enrollment, but they must have initiated treatment at least 28 days prior to study drug administration).

• Use of loop diuretics within 7 days prior to study drug administration.

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Cystic Fibrosis
• Pseudomonas Infections

Intervention

Drug:
• tobramycin
1x300mg/d inhaled
• tobramycin
2x300mg/d inhaled

Locations

Country	Name	City	State
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Frankfurt
Germany	Novartis Investigator site	Halle/Saale
Germany	Novartis Investigator Site	Hamburg
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Heidelberg
Germany	Novartis Investigator Site	Koeln
Germany	Novartis Investigator Site	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Country where clinical trial is conducted

Germany, 

References & Publications (1)

van Koningsbruggen-Rietschel S, Heuer HE, Merkel N, Posselt HG, Staab D, Sieder C, Ziegler J, Krippner F, Rietschel E. Pharmacokinetics and safety of an 8 week continuous treatment with once-daily versus twice-daily inhalation of tobramycin in cystic fibr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the serum pharmacokinetics (PK) of inhaled tobramycin (AUC 0-90') of continuous daily dosing regimens with 2x300mg/d Tobramycin Nebuliser Solution (=TNS) inhaled with the PARI eFlow® rapid in Cystic Fibrosis (CF) subjects		8 wks
Secondary	Serum PK of inhaled tobramycin (AUC 0-90') of continuous daily dosing regimens with 1 x 300mg/d tobramycin nebulized solution (= TNS) inhaled with the PARI eFlow rapid in cystic fibrosis subjects.		8 wks
Secondary	Compare serum PK of inhaled tobramycin (trough-/peak-level)of both dosing regimens in CF-subjects with a FEV1=80% vs. CF-Subjects with a FEV1<80%.		8 weeks
Secondary	Change of MIC of P. aeruginosa during a continuous treatment with 1 x 300 mg/d and 2 x 300 mg/d TNS.		8 weeks
Secondary	Assess safety of a continuous daily dosing regimen with 1 x 300 mg/d and 2 x 300 mg/d TNS over 8 weeks, compared to historic safety data of the 4 week on/off dosing regimen with 2 x 300 mg/d.		8 weeks

External Links

•   Results of CTBM100DDE01 from Novartis Clinical Trials website