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Pharmacokinetic Evaluation of an 8 -Week Treatment With Inhaled Tobramycin

Primary Purpose

Pseudomonas Infections

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
tobramycin
tobramycin
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pseudomonas Infections focused on measuring Chronic infection with P. aeruginosa in Cystic Fibrosis subjects

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All Sexes

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

Sites / Locations

  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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%.
Change of MIC of P. aeruginosa during a continuous treatment with 1 x 300 mg/d and 2 x 300 mg/d TNS.
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.

Full Information

First Posted
March 4, 2008
Last Updated
February 22, 2017
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00634192
Brief Title
Pharmacokinetic Evaluation of an 8 -Week Treatment With Inhaled Tobramycin
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pseudomonas Infections
Keywords
Chronic infection with P. aeruginosa in Cystic Fibrosis subjects

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
tobramycin
Intervention Description
1x300mg/d inhaled
Intervention Type
Drug
Intervention Name(s)
tobramycin
Intervention Description
2x300mg/d inhaled
Primary Outcome Measure Information:
Title
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
Time Frame
8 wks
Secondary Outcome Measure Information:
Title
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.
Time Frame
8 wks
Title
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%.
Time Frame
8 weeks
Title
Change of MIC of P. aeruginosa during a continuous treatment with 1 x 300 mg/d and 2 x 300 mg/d TNS.
Time Frame
8 weeks
Title
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.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharma AG
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigator Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigator Site
City
Frankfurt
Country
Germany
Facility Name
Novartis Investigator site
City
Halle/Saale
Country
Germany
Facility Name
Novartis Investigator Site
City
Hamburg
Country
Germany
Facility Name
Novartis Investigator Site
City
Hannover
Country
Germany
Facility Name
Novartis Investigator Site
City
Heidelberg
Country
Germany
Facility Name
Novartis Investigator Site
City
Koeln
Country
Germany
Facility Name
Novartis Investigator Site
City
Munich
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
26626719
Citation
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.
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Pharmacokinetic Evaluation of an 8 -Week Treatment With Inhaled Tobramycin

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