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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University Medical Centre Groningen
Sponsor:
Information provided by (Responsible Party):
Onno Akkerman, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT02035488
First received: December 27, 2013
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Bronchiectasis
Drug: Tobramycin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Actual dose (dose minus remainder in inhaler after inhalation) of tobramycin [ Time Frame: one day ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Maximum plasma concentration (Cmax ) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
  • Time to maximum plasma concentration (Tmax) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
  • Absorption rate constant (Ka) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
  • Terminal elimination half-life (T1/2 el ) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
  • Clearance following pulmonary administration (CL/F) (F= bioavailability) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
  • Decrease of FEV1 in percentage measured by spirometry [ Time Frame: One day ] [ Designated as safety issue: Yes ]
  • Number of Participants with Adverse Events [ Time Frame: One day ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 8
Study Start Date: October 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tobramycin
Patients with bronchiectasis
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02035488

Contacts
Contact: Onno Akkerman, MD +31-50-3614902 o.w.akkerman@umcg.nl
Contact: Marcel Hoppentocht, PharmD m.hoppentocht@rug.nl

Locations
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: Onno Akkerman, MD    +31-50-3614902    o.w.akkerman@umcg.nl   
Principal Investigator: Onno Akkerman, MD         
Sponsors and Collaborators
University Medical Centre Groningen
Investigators
Principal Investigator: Huib Kerstjens, MD, PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: Onno Akkerman, Drs, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT02035488     History of Changes
Other Study ID Numbers: Tobra-02
Study First Received: December 27, 2013
Last Updated: January 10, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
Dry powder inhalation
Bronchiectasis
Tobramycin

Additional relevant MeSH terms:
Bronchiectasis
Bronchial Diseases
Respiratory Tract Diseases
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014