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Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis

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ClinicalTrials.gov Identifier: NCT02035488
Recruitment Status : Completed
First Posted : January 14, 2014
Last Update Posted : December 16, 2014
Sponsor:
Information provided by (Responsible Party):
Onno Akkerman, University Medical Center Groningen

Tracking Information
First Submitted Date  ICMJE December 27, 2013
First Posted Date  ICMJE January 14, 2014
Last Update Posted Date December 16, 2014
Study Start Date  ICMJE October 2013
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2014)
  • Actual dose (dose minus remainder in inhaler after inhalation) of tobramycin [ Time Frame: one day ]
  • Area Under the plasma concentration versus time curve from 0 -12 hours (AUC0-12) of tobramycin •Area Under the plasma concentration versus time curve from 0 -12 hours (AUC0-12) of tobramycin [ Time Frame: One day ]
  • Maximum plasma concentration (Cmax ) of tobramycin [ Time Frame: One day ]
  • Time to maximum plasma concentration (Tmax) of tobramycin [ Time Frame: One day ]
  • Absorption rate constant (Ka) of tobramycin [ Time Frame: One day ]
  • Terminal elimination half-life (T1/2 el ) of tobramycin [ Time Frame: One day ]
  • Clearance following pulmonary administration (CL/F) (F= bioavailability) of tobramycin [ Time Frame: One day ]
  • Decrease of FEV1 in percentage measured by spirometry [ Time Frame: One day ]
  • Number of Participants with Adverse Events [ Time Frame: One day ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis
Official Title  ICMJE Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis
Brief Summary Bronchiectasis is a persistent and frequently progressive condition characterized by dilated and thick-walled bronchi retaining sputum. The main symptoms of bronchiectasis are cough and chronic sputum production. Until now, most patients with non-CF bronchiectasis receive inhaled tobramycin every other month, by use of a nebulizer. However, this delivery system has several disadvantages, like a low lung deposition and pollution with tobramycin in the surrounding environment. With an efficient dry powder inhaler (DPI), a three to six fold higher lung deposition compared to a nebulizer can be obtained. Therapy with a DPI is also less time consuming compared to nebulisation. We will investigate dry powder tobramycin (DP tobramycin) in a novel device in patients with non-CF bronchiectasis. The main objectives of this study are to investigate the pharmacokinetic properties of DP tobramycin at different dosages together with the local tolerability of DP tobramycin via the Cyclops® at different dosages.
Detailed Description

Rationale: Bronchiectasis is a persistent and frequently progressive condition characterized by dilated and thick-walled bronchi retaining sputum. The main symptoms of bronchiectasis are cough and chronic sputum production. There is a state of constant colonization with bacteria, which frequently causes exacerbations. The presence of Pseudomonas aeruginosa is an unfavorable prognostic indicator and is associated with increased sputum production, more extensive bronchiectasis on HR-CT of the thorax, more hospitalizations and reduced quality of life. Until now, most patients with non-CF bronchiectasis who are colonized with P. aeruginosa receive inhaled tobramycin every other month, by use of a nebulizer. However, this delivery system has several disadvantages, like a low lung deposition and pollution with tobramycin in the surrounding environment. With an efficient dry powder inhaler (DPI), a three to six fold higher lung deposition compared to a nebulizer can be obtained. Therapy with a DPI is also less time consuming compared to nebulisation. Nebulised tobramycin is used most in routine care; there is also one, rather poorly characterized DPI for tobramycin available, though this DPI is not registrered for non-CF bronchiectasis. We will investigate dry powder tobramycin (DP tobramycin) in a novel device in patients with non-CF bronchiectasis colonized with P. aeruginosa.

Objective: The main objectives are to investigate the pharmacokinetic properties of DP tobramycin at different dosages together with the local tolerability of DP tobramycin via the Cyclops® at different dosages.

Study design: single center, single ascending, single dose, response study. Study population: 8 patients with non-CF bronchiectasis

Main study parameters:

The following pharmacokinetic parameters will be calculated: actual dose (dose minus remainder in inhaler after inhalation), AUC0-12 (area under the curve from 0 -12 h), Cmax (maximum plasma concentration), Tmax (time to maximum plasma concentration), Ka (absorption rate constant), T1/2 el (terminal elimination half-life), CL/F (clearance following pulmonary administration (F= bioavailability)).

Local tolerability of DP tobramycin is determined by scoring adverse events, specifically coughing, and lung function measurement.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All participants included in this study are patients recruited from the outpatient department of pulmonology. To investigate safety, lung function tests will be performed and the occurrence of adverse events will be scored.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Bronchiectasis
Intervention  ICMJE Drug: Tobramycin
Tobramycin dry powder 30 mg inhalation per dose; Dose escalation: 30-60-120 and 240 mg, each one time. One dose per week.
Other Name: Dry powder tobramycin free base
Study Arms  ICMJE Experimental: Tobramycin
Patients with bronchiectasis
Intervention: Drug: Tobramycin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2014)
8
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Age 18 years or older
  • Obtained informed consent
  • Patients having bronchiectasis (confirmed with HR-CT of the chest)

Exclusion criteria:

  • Pregnant or breast feeding
  • Subjects with known or suspected renal, auditory, vestibular or neuromuscular dysfunction, or with severe, active haemoptysis,
  • History of adverse events on previous tobramycin or other aminoglycoside use
  • No concurrent use of cyclosporin, cisplatin, amfotericin B, cephalosporins, polymyxins, vancomycin and NSAIDs.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02035488
Other Study ID Numbers  ICMJE Tobra-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Onno Akkerman, University Medical Center Groningen
Study Sponsor  ICMJE University Medical Center Groningen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Huib Kerstjens, MD, PhD University Medical Center Groningen
PRS Account University Medical Center Groningen
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP