Pharmacokinetic Evaluation of an 8 -Week Treatment With Inhaled Tobramycin

NCT00634192 | Completed Phase 3

• 1 other identifier: CTBM100DDE01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief 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).

Conditions

Pseudomonas Infections

Keywords

Chronic infection with P. aeruginosa in Cystic Fibrosis subjects

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (2)

1

EXPERIMENTAL

Drug: tobramycin

2

EXPERIMENTAL

Drug: tobramycin

Interventions

tobramycin DRUG

1x300mg/d inhaled

1

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis: lead

Study Sites (8)

Novartis Investigator Site

Berlin, Germany

Location

Novartis Investigator Site

Cologne, Germany

Location

Novartis Investigator Site

Frankfurt, Germany

Location

Novartis Investigator site

Halle, Germany

Location

Novartis Investigator Site

Hamburg, Germany

Location

Novartis Investigator Site

Hanover, Germany

Location

Novartis Investigator Site

Heidelberg, Germany

Location

Novartis Investigator Site

Munich, Germany

Location

Related 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 fibrosis patients. J Antimicrob Chemother. 2016 Mar;71(3):711-7. doi: 10.1093/jac/dkv399. Epub 2015 Nov 30.

  PMID: 26626719 RESULT

MeSH Terms

Conditions

Pseudomonas Infections

Interventions

Tobramycin

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Novartis Pharma AG

  Novartis Pharmaceuticals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2008
• First Posted: March 12, 2008
• Study Start: February 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: August 1, 2009
• Last Updated: February 24, 2017

Record last verified: 2017-02

Locations

DE (8)