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

NCT02035488 | Completed Phase 1 DMC

• 1 other identifier: Tobra-02
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Bronchiectasis

Keywords

Dry powder inhalation; Bronchiectasis; Tobramycin

Outcome Measures

Primary Outcomes (9)

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

  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

  One day

• Maximum plasma concentration (Cmax ) of tobramycin

  One day

• Time to maximum plasma concentration (Tmax) of tobramycin

  One day

• Absorption rate constant (Ka) of tobramycin

  One day

• Terminal elimination half-life (T1/2 el ) of tobramycin

  One day

• Clearance following pulmonary administration (CL/F) (F= bioavailability) of tobramycin

  One day

• Decrease of FEV1 in percentage measured by spirometry

  One day

• Number of Participants with Adverse Events

  One day

Study Arms (1)

Tobramycin

EXPERIMENTAL

Patients with bronchiectasis

Drug: Tobramycin

Interventions

Tobramycin DRUG

Tobramycin dry powder 30 mg inhalation per dose; Dose escalation: 30-60-120 and 240 mg, each one time. One dose per week.

Also known as: Dry powder tobramycin free base

Tobramycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Netherlands

Location

MeSH Terms

Conditions

Bronchiectasis

Interventions

Tobramycin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Huib Kerstjens, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Drs

Study Record Dates

• First Submitted: December 27, 2013
• First Posted: January 14, 2014
• Study Start: October 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 16, 2014

Record last verified: 2014-12

Locations

NL (1)