Cystic FibrosisPhase 3EAGERNCT00388505
Safety of Tobramycin Inhalation Powder (TIP) vs Tobramycin Solution for Inhalation in Patients With Cystic Fibrosis
A Phase 3 study testing Tobramycin Inhalation Powder and Tobramycin Solution for Inhalation in people with Cystic Fibrosis, run by Novartis Pharmaceuticals at 72 sites in 14 countries.
Trial summary
This study compares the safety of the tobramycin solution for inhalation with the tobramycin dry powder formulation, used with a simple inhaler Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Tobramycin Inhalation Powder and Tobramycin Solution for Inhalation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 517 participants
- Where
- 72 sitesin 14 countries
- Study dates
- Feb 2006to Mar 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Confirmed diagnosis of cystic fibrosis
- Male and female patients at least 6 years of age at the time of screening.
- Forced expiratory volume in one second (FEV1) at screening must be at least 25% and less than or equal to 75% of normal predicted values for age, sex, and height based on Knudson criteria.
- Pseudomonas aeruginosa, a type of bacteria, must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum/ deep-throat cough swab culture at the screening visit.
- Able to comply with all protocol requirements.
- Clinically stable in the opinion of the investigator.
- Use of an effective means of contraception in females of childbearing potential.
- Provide written informed consent, Health Authority Portability and Accountability Act (HIPAA) authorization (where applicable), and assent (as appropriate) prior to the performance of any study-related procedure.
Who cannot join
- History of sputum culture or deep-throat cough swab (or BAL) culture yielding Burkholderia cepacia (B cepacia), a type of bacteria, within 2 years prior to screening and/or sputum culture yielding B cepacia at screening.
- Coughing up more than 60 cc of blood from the respiratory tract at any time within 30 days prior to study drug administration.
- Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
- Females who are pregnant (positive pregnancy test), lactating, or are planning to become pregnant during the study.
- History of hearing loss or chronic ringing in the ears deemed clinically significant by the investigator.
- Use of systemic or inhaled antipseudomonal antibiotics within 28 days prior to study drug administration.
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- Use of loop diuretics within 7 days prior to study drug administration.
- Use of any investigational treatment within 28 days prior to study drug administration.
- Initiation of treatment with chronic macrolide therapy, dornase alpha treatment or inhaled corticosteroids within 28 days prior to study drug administration (patients may be taking these therapies at the time of enrollment, but they must have initiated treatment more than 28 days prior to study drug administration).
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
72 sites in 14 countries.
72 sites in 14 countries
United States24 sites
Novartis Investigative Site
Albany, New York, 12208
Emory University CF Center
Atlanta, Georgia, 30322
Novartis Investigative Site
Boston, Massachusetts, 02115
Novartis Investigative Site
Buffalo, New York, 14222
Novartis Investigative Site
Burlington, Vermont, 05401
University of Virginia Health System
Charlottesville, Virginia, 22903
Rush University Center
Chicago, Illinois, 60612
Novartis Investigative Site
Hartford, Connecticut, 06102
Penn State College of Medicine
Hershey, Pennsylvania, 17033
Novartis Investigative Site
Lebanon, New Hampshire, 03756
Novartis Investigative Site
Livingston, New Jersey, 07039
Novartis Investigative Site
Long Branch, New Jersey, 07740
University of Louisville
Louisville, Kentucky, 40202
West Virginia University Health Sciences Center
Morgantown, West Virginia, 26506
Novartis Investigative Site
Morristown, New Jersey, 07967
Novartis Investigative Site
New Hyde Park, New York, 11040
Novartis Investigative Site
New York, New York, 10011
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of Rochester
Rochester, New York, 14642
Novartis Investigative Site
Somerset, New Jersey, 08873
Novartis Investigative Site
Stony Brook, New York, 11794
Novartis Investigative Site
Syracuse, New York, 13210
Novartis Investigative Site
Valhalla, New York, 10595
Germany11 sites
Novartis Investigative Site
Berlin
Novartis Investigative Site
Bochum
Novartis Investigative Site
Bonn
Novartis Investigative Site
Cologne
Novartis Investigative Site
Essen
Klinikum der Johann-Wolfgang-Goethe-Universitaet
Frankfurt, 60596
Novartis Investigative Site
Frankfurt
Novartis Investigative Site
Hamburg
Novartis Investigative Site
Hanover
Novartis Investigative Site
München
Ludwig-Maximilians-Universitaet
Munich, 80337
Spain6 sites
Novartis Investigative Site
Barakaldo
Novartis Investigative Site
Barcelona
Novartis Investigative Site
Madrid
Novartis Investigative Site
Málaga
Novartis Investigative Site
Seville
Novartis Investigative Site
Valencia
United Kingdom6 sites
Novartis Investigative Site
Belfast
Novartis Investigative Site
Birmingham
Novartis Investigative Site
Cambridge
Novartis Investigative Site
Leeds
Novartis Investigative Site
London
Novartis Investigative Site
Sheffield
Canada4 sites
Novartis Investigative Site
Calgary
Novartis Investigative Site
Hamilton
Novartis Investigative Site
Ste-Foy
Novartis Investigative Site
Vancouver
Colombia4 sites
Novartis Investigative Site
Baranquilla
Novartis Investigative Site
Bogotá
Novartis Investigative Site
Cali
Novartis Investigative Site
Medellín
Italy4 sites
Novartis Investigator Site
Genoa
Novartis Investigative Site
Palermo
Novartis Investigative Site
Potenza
Novartis Investigative Site
Roma
France3 sites
Novartis Investigative Site
Montpellier
Novartis Investigative Site
Paris
Novartis Investigative Site
Rouen
Israel3 sites
Novartis Investigative Site
Haifa
Novartis Investigative Site
Jerusalem
Novartis Investigative Site
Petah Tikva
Hungary2 sites
Novartis Investigative Site
Hungary
Novartis Investigative Site
Kaposvár
Netherlands2 sites
Novartis Investigative Site
Groesbeek
Novartis Investigative Site
Rotterdam
About this study
Official title: A Randomized, Open-label Multicentre Phase 3 Trial to Assess the Safety of Tobramycin Inhalation Powder Compared to Tobramycin Solution for Inhalation in Cystic Fibrosis Subjects
This study compares the safety of the tobramycin solution for inhalation with the tobramycin dry powder formulation, used with a simple inhaler
- Conditions
- Cystic Fibrosis
- Being tested
- Tobramycin Inhalation Powder, Tobramycin Solution for Inhalation
- Keywords
- tobramycin
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobramycin Inhalation PowderDrug
Tobramycin Inhalation Powder (TIP) capsules for inhalation.
Tobramycin Solution for InhalationDrug
Tobramycin solution for inhalation (TOBI), supplied as 300 mg/5mL ampoules administered with a nebulizer
| Study group | Role | What they receive |
|---|---|---|
| Tobramycin inhalation powder (TIP) | Experimental | Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles. Receives: Drug: Tobramycin Inhalation Powder |
| Tobramycin solution for inhalation (TOBI) | Active comparator | Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles. Receives: Drug: Tobramycin Solution for Inhalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events
An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.
Measured: 25 weeks
Secondary outcomes (8)
Serum Tobramycin Concentrations
Serum tobramycin concentrations were measured in a subset of participants at Week 1 (start of cycle 1), Week 5 (End of Cycle 1), Week 17 (start of cycle 3) and Week 21 (end of cycle 3). Serum samples were collected at pre-dose and post-dose at specified intervals; one specimen between 0 to 2 hours; two additional specimens between 2 and 5 hours (sample times must have been a minimum of 2 hours apart).
Measured: Weeks 1, 5, 17 and 21
Percentage of Participants With a Decrease From Baseline in Auditory Acuity
Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer.
Measured: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Forced expiratory volume in one second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 is then converted to a percentage of normal (percent predicted) based on height, weight, and race. FEV1 was measured at Baseline (prior to beginning study treatment) and predose on Day 28 of Cycles 1, 2 and 3 and at the follow-up visit.
Relative change = 100 * ((Day 28 of Cycle 3 value - Baseline value)/ Baseline value).
Measured: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Patient's self-reported treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM, a validated instrument) which was modified by adding four study-specific questions; the standard fourteen questions of the TSQM were not altered. Responses to nearly all items are rated on a five-point or seven-point rating scale and the items are factored into 4 domains. The TSQM domain scores range from 0 to 100 with higher scores representing higher satisfaction for that domain.
Measured: Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Three Pseudomonas aeruginosa biotypes were assessed in patient's sputum; mucoid, dry and small colony variant. Overall density is defined as the sum of all bio-types in Pseudomonas aeruginosa density.
Measured: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
The minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. The MIC of tobramycin against total Pseudomonas aeruginosa colonization was assessed over the course of the study.
Measured: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
Antipseudomonal Antibiotic Usage During the Study
The average number of days patients required antipseudomonal antibiotics during the course of the study.
Measured: 25 Weeks
Hospitalization Due to Respiratory Events During the Study
The average number of days patients were hospitalized due to respiratory events during the course of the study.
Measured: 25 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2006 (estimated)
- Study startFeb 2006
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 517 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Konstan, MD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00388505
- Sponsor's protocol ID
- CTBM100C2302
- Acronym
- EAGER
- Status last verified
- Jun 2012
- First submitted
- 16 Oct 2006
- Last updated
- 24 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Multicentre Phase 3 Trial to Assess the Safety of Tobramycin Inhalation Powder Compared to Tobramycin Solution for Inhalation in Cystic Fibrosis Subjects
- ClinicalTrials.gov ID
- NCT00388505
- Acronym / sponsor ID
- EAGER / CTBM100C2302
- Conditions
- Cystic Fibrosis
- Keywords
- tobramycin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 517 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 17 Oct 2006 (estimated)
- Results
- Posted 24 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study compares the safety of the tobramycin solution for inhalation with the tobramycin dry powder formulation, used with a simple inhaler
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tobramycin inhalation powder (TIP) | Experimental | Drug: Tobramycin Inhalation PowderParticipants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles. |
| Tobramycin solution for inhalation (TOBI) | Active comparator | Drug: Tobramycin Solution for InhalationParticipants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of cystic fibrosis
- Male and female patients at least 6 years of age at the time of screening.
- Forced expiratory volume in one second (FEV1) at screening must be at least 25% and less than or equal to 75% of normal predicted values for age, sex, and height based on Knudson criteria.
- Pseudomonas aeruginosa, a type of bacteria, must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum/ deep-throat cough swab culture at the screening visit.
- Able to comply with all protocol requirements.
Key exclusion criteria (10 listed)
- History of sputum culture or deep-throat cough swab (or BAL) culture yielding Burkholderia cepacia (B cepacia), a type of bacteria, within 2 years prior to screening and/or sputum culture yielding B cepacia at screening.
- Coughing up more than 60 cc of blood from the respiratory tract at any time within 30 days prior to study drug administration.
- Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
- Females who are pregnant (positive pregnancy test), lactating, or are planning to become pregnant during the study.
- History of hearing loss or chronic ringing in the ears deemed clinically significant by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tobramycin Inhalation PowderTobramycin Inhalation Powder (TIP) capsules for inhalation. | Drug | Tobramycin inhalation powder (TIP) |
| Tobramycin Solution for InhalationTobramycin solution for inhalation (TOBI), supplied as 300 mg/5mL ampoules administered with a nebulizer | Drug | Tobramycin solution for inhalation (TOBI) |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events
Time frame: 25 weeks
An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.
8 secondary outcomes
Serum Tobramycin Concentrations
Time frame: Weeks 1, 5, 17 and 21
Percentage of Participants With a Decrease From Baseline in Auditory Acuity
Time frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)
Time frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication
Time frame: Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).
Change From Baseline in Pseudomonas Aeruginosa Sputum Density
Time frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).
Change From Baseline in Tobramycin Minimum Inhibitory Concentration
Time frame: Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)
Antipseudomonal Antibiotic Usage During the Study
Time frame: 25 Weeks
Hospitalization Due to Respiratory Events During the Study
Time frame: 25 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Konstan, MD principal investigator
University Hospitals Cleveland Medical Center
72 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tobramycin Inhalation Powder and Tobramycin Solution for Inhalation in people with Cystic Fibrosis, run by Novartis Pharmaceuticals at 72 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in United States, Germany, Spain, United Kingdom, Canada and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (time frame: 25 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2012.