DPI-Tobra-Kind Cyclops® in Children With Cystic Fibrosis

September 30, 2021 updated by: Onno Akkerman, University Medical Center Groningen

Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin Via the Cyclops® in Children With Cystic Fibrosis

The goal is to investigate the pharmacokinetic properties of dry powder tobramycin via the Cyclops® at different dosages in children with cystic fibrosis, together with the local tolerability.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Rationale: Cystic fibrosis is the most common life-shortening autosomal recessive disease among Caucasian populations. It is a chronic progressive disease causing deterioration of pulmonary function, and of general condition as well. Although it is a multisystem disease, the primary cause of death is respiratory failure, resulting from chronic pulmonary infection.

Pseudomonas aeruginosa is the predominant pathogen. The presence of P. aeruginosa in patients with CF is an unfavourable prognostic indicator and is associated with accelerated lung tissue destruction and loss of lung function, subsequently leading tot increased morbidity and mortality. Preventing, limiting and treating chronic infection with P. aeruginosa is therefore crucial in the management of CF, to improve survival and quality of life.

Currently most children with CF who are colonized with P. aeruginosa receive inhaled tobramycin every other month, mostly by use of a nebulizer. This delivery system however has several disadvantages. For example, the nebulisation itself and the cleaning of the nebulizer is time consuming. This places a high burden on a CF patient, especially for children, which will negatively influence compliance and quality of inhalation, thereby jeopardizing effective treatment. Therapy with a (disposable) dry powder inhaler (DPI) is less time consuming. Besides this, nebulisation brings the risk of auto-re-infection of the patient (contamination of nebulisation fluid and/or device). Other more technical disadvantages of nebulisation are a low lung deposition and pollution with tobramycin in the surrounding environment. With an efficient DPI, a three to six fold higher lung deposition compared to a nebulizer can be obtained. Nebulised tobramycin is used most in routine care, but sometimes a DPI is used, for example the Podhaler®. Although the dispersion behaviour of these dry powder systems is often good, the engineering processes make the products expensive, and the high excipient fractions make the inhaled powder doses high. Furthermore because these devices are not disposable, there is a risk of bacterial resistance development in the device. Next to this is the hygroscopic nature of tobramycin a risk for good dispersion when a used DPI is store inappropriately. In this situation powder residues in the inhaler become sticky or even liquefied when they absorb moisture from the air. There is one disposable DPI for tobramycin available, called the Cyclops®, but this DPI is not registered for children with CF yet. The investigators will therefore investigate dry powder tobramycin (DP tobramycin) in the Cyclops® in children with CF.

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

Study design: Single center, single ascending, single dose study.

Study population: 10 patients with CF, age 6 - 18 years.

Main study parameters/endpoints: 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: Target population of this study consists of children aged 6-18 years, because no information is available for inhalation of tobramycin using the Cyclops® in this population. Moreover, especially for children with CF a more easy to use and less time consuming treatment may improve their quality of life. Children participating in this study will receive instructions before using the DPI and their inspiratory flow will be tested. After each test dose serum samples will be collected with dry blood spot via a finger prick. To investigate safety, lung function tests will be performed before and 15, 30 and 90 minutes after inhalation and the occurrence of adverse events will be scored. Tobramycin is a registered drug for the treatment of chronic P. aeruginosa infection in CFpatients of 6 years and older. Inhalation of tobramycin is proven to be effective and safe in multiple studies. Dry powder tobramycin inhalation via the Cyclops® has been evaluated in adults with non-CF bronchiectasis. In this study a good drug dose - serum concentration correlation was obtained in adults, and the dry powder tobramycin inhalation via the Cyclops has been found safe with only mild tobramycin-related cough was reported once.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Netherlands
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen
        • Contact:
          • Anne Akkerman-Nijland, Drs.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Clinical diagnosis of CF and a positive sweat test or two CF-related mutations;
  • Age 6 - 18 years
  • Ability to breathe through a mouthpiece and to use the Cyclops
  • Ability to perform pulmonary function tests
  • Written informed consent (child and parents)

Exclusion criteria:

  • Acute exacerbation of pulmonary infection
  • FEV1 < 60%
  • Subjects with known or suspected renal, auditory, vestibular of neuromuscular dysfunction, or with severe, active haemoptysis
  • History of adverse events on previous tobramycin or other aminoglycoside use
  • No concurrent use of cisplatin, cyclosporine, amphotericin B, cephalosporins, polymyxins, vancomycin and NSAID's

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Tobramycin
Tobramycin dry powder inhalation with 30, 60 and 90 mg. Nebulisation with 300 mg tobramycin
Drug: Tobramycin
Tobramycin dry powder inhalation with 30, 60 and 90 mg. Nebulisation with 300 mg tobramycin
Other Names:
  • Tobramycin dry powder

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
AUC 0-12
Time Frame: 0-12 hours after dry powder inhalation
Area under the curve from 0 - 12 h
0-12 hours after dry powder inhalation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cmax
Time Frame: 0-12 hours after dry powder inhalation
maximum plasma concentration
0-12 hours after dry powder inhalation
Tmax
Time Frame: 0-12 hours after dry powder inhalation
Time to maximum plasma concentration
0-12 hours after dry powder inhalation
Ka
Time Frame: 0-12 hours after dry powder inhalation
Absorption rate constant
0-12 hours after dry powder inhalation
T 1/2 el
Time Frame: 0-12 hours after dry powder inhalation
Terminal elimination half-life
0-12 hours after dry powder inhalation
CL/F
Time Frame: 0-12 hours after dry powder inhalation
Clearance following pulmonary administration
0-12 hours after dry powder inhalation
Local tolerability
Time Frame: Before and 15, 30 and 90 minutes after inhalation
Local tolerability determined by scoring adverse events, specifically coughing, and lung function
Before and 15, 30 and 90 minutes after inhalation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Medical Center Groningen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Gerard Koppelman, Prof., University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 29, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 13, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 26, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 2, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DPI-Tobra-Kind

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cystic Fibrosis

Clinical Trials on Tobramycin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings