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

Brief Title

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

Official Title

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 Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Actual dose (dose minus remainder in inhaler after inhalation) of tobramycin

Condition

Bronchiectasis

Intervention

Tobramycin

Study Arms / Comparison Groups

 Tobramycin

Description:  Patients with bronchiectasis

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

8

Start Date

October 2013

Completion Date

December 2014

Primary Completion Date

December 2014

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Huib Kerstjens, MD, PhD, , 

Location Countries

Netherlands

Location Countries

Netherlands

NCT ID

NCT02035488

Organization ID

Tobra-02

Responsible Party

Principal Investigator

Study Sponsor

University Medical Center Groningen

Study Sponsor

Huib Kerstjens, MD, PhD, Principal Investigator, University Medical Center Groningen

Verification Date

December 2014