Pulmonary InfectionsPhase 3NCT01069705
Second Open Label Extension to Bridging Study CTBM100C2303
A Phase 3 study testing Tobramycin inhalation powder in people with Pulmonary Infections and Pseudomonas Aeruginosa, run by Novartis Pharmaceuticals at 17 sites in 7 countries.
Trial summary
This was an open-label, single arm (uncontrolled) study in participants suffering from cystic fibrosis, who have completed their study participation in CTBM100C2303 and extension study one CTBM100C2303E1 (all visits), who were proven infected with Pseudomonas aeruginosa at enrollment into CTBM100C2303. Read more about this study
- Who is it for?
- Ages 6 to 21 years
- Conditions the study is for
- Pulmonary Infections, Pseudomonas Aeruginosa
- What is being tested?
- Tobramycin inhalation powder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 17 sitesin 7 countries
- Study dates
- 12 Feb 2010to 19 Mar 2012
- 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 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Completed all visits in study CTBM100C2303 and CTBM100C2303E1, and visit 11 of study CTBM100C2303E1 took place not more than 5 days before enrollment into this study.
- Confirmed diagnosis of cystic fibrosis participants with P. aeruginosa infection.
- Forced Expiratory Volume in one second (FEV1) at screening (at start of study CTBM100C2303) must be between 25% and 80% of normal predicted values.
Who cannot join
- Any use of inhaled anti-pseudomonal antibiotics between the termination of the trial CTMB100C2303E1 and the enrollment into this study.
- Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
Russia5 sites
Novartis Investigative Site
Kazan'
Novartis Investigative Site
Moscow
Novartis Investigative Site
Saint Petersburg
Novartis Investigative Site
Samara
Novartis Investigative Site
Yaroslavl
Bulgaria4 sites
Novartis Investigative Site
Pleven
Novartis Investigative Site
Plovdiv
Novartis Investigative Site
Sofia
Novartis Investigative Site
Varna
Estonia2 sites
Novartis Investigative Site
Tallinn
Novartis Investigative Site
Tartu
Lithuania2 sites
Novartis Investigative Site
Kaunas
Novartis Investigative Site
Vilnius
Romania2 sites
Novartis Investigative Site
Bucharest
Novartis Investigative Site
Timișoara
About this study
Official title: A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder After Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who Successfully Completed Participation in Study CTBM100C2303E1
This was an open-label, single arm (uncontrolled) study in participants suffering from cystic fibrosis, who have completed their study participation in CTBM100C2303 and extension study one CTBM100C2303E1 (all visits), who were proven infected with Pseudomonas aeruginosa at enrollment into CTBM100C2303.
- Conditions
- Pulmonary Infections, Pseudomonas Aeruginosa
- Being tested
- Tobramycin inhalation powder
- Keywords
- Tobramycin Inhalation Powder, Cystic fibrosis, Lung diseases, Anti-Bacterial Agents, Treatment of pulmonary infections with P. aeruginosa in cystic fibrosis participants
- Medical subject headings
- Pseudomonas Infections, Cystic Fibrosis, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobramycin inhalation powderDrug
Tobramycin dry powder for inhalation in capsules administered by the T-326 inhaler.
| Study group | Role | What they receive |
|---|---|---|
| Tobramycin Inhalation Powder (TIPnew) | Experimental | Participants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles. Receives: Drug: Tobramycin inhalation powder |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs)
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug.
Measured: From time of first administration of study drug until study completion (up to 169 days)
Number of Participants With Serious Adverse Events (SAEs)
A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes.
Measured: From time of consent to 4 weeks after study completion (up to 199 days)
Percentage of Participants With a Decrease of ≥20% in Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted From Pre-dose to 30-minute Post-dose
Airway Reactivity >= 20% relative decrease in FEV1% predicted from pre-dose to 30 minutes post-dose. Relative Change = 100 * (30 minutes Post-dose - Pre-dose)/Pre-dose assessed by the number and percentage of participants with a decrease of ≥ 20% in FEV1 % predicted from pre-dose to 30 minutes post-dose.
Measured: Pre-dose and post-dose of Day 1 and Day 29 of every Cycle (5, 6, 7)
Percentage of Participants With Frequency Decrease From Baseline in the Post-baseline Audiology Tests
Auditory acuity of participants was measured using a standard dual-channel audiometer at frequencies from 250 to 8000 Hertz, and an audiogram (pure-tone air conduction) and tympanogram were performed by an audiologist. The categories reported includes >= 10dB decrease in 3 consecutive frequencies in either ear, >= 15dB decrease in 2 consecutive frequencies in either ear, and >= 20dB decrease in at least one frequency in either ear
Measured: Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary outcomes (8)
Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to Each Post-baseline Visit
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 % predicted was a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) x 100.
Measured: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Relative Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to Each Post-baseline Visit
Percent Predicted Forced Vital Capacity (FVC%) is the maximal exhaled breath volume following a maximal inhaled breath. Overall change in percent predicted FVC = (observed value)/(predicted value) * 100%. A higher value indicates a greater response.
Measured: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Relative Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) Predicted to Each Post-baseline Visit
Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) is the forced expiratory flow from 25% to 75% of the Forced Vital Capacity (FVC). Relative change in FEF25-75% from baseline to pre-dose day X = (pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100.
Measured: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Change From Baseline in Pseudomonas Aeruginosa Sputum Density to Each Post-baseline Visit
Pseudomonas Aeruginosa Density refers to overall density, defined as the sum of Biotypes (mucoid, dry and small colony variant). Absolute change was determined using the formula; Change = Post-baseline value- baseline value. Absolute Change in Pseudomonas Aeruginosa Sputum density is measured in log 10 Colony Forming Units per gram (Log 10 CFU/g).
Measured: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Change From Baseline in Tobramycin Minimum Inhibitory Concentration (MIC) Values for Pseudomonas Aeruginosa to Each Post-baseline Visit
Minimum Inhibitory Concentration (MIC) is defined as the lowest concentration of an antimicrobial agent required to inhibit the visible growth of a microorganism after overnight incubation.
Measured: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Number of Participants Who Used New Antipseudomonal Antibiotic During Treatment Period
The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study Treatment period.
Measured: Baseline, Cycles 5, 6, 7 (Days 1, 29)
Percentage of Participants With Hospitalization Due to Respiratory Serious Adverse Events (SAEs)
A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes.
Measured: From time of consent to 4 weeks after study completion (up to 199 days)
Number of Days of Hospitalization Due to Respiratory Serious Adverse Events (SAEs)
The average number of days patients were hospitalized due to respiratory events during the study.
Measured: From time of consent to 4 weeks after study completion (up to 199 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2010 (estimated)
- Study start12 Feb 2010
- Primary completion19 Mar 2012
- Study completion19 Mar 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary InfectionsStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01069705
- Sponsor's protocol ID
- CTBM100C2303E2
- Status last verified
- May 2021
- First submitted
- 15 Feb 2010
- Last updated
- 2 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Konstan MW, Flume PA, Galeva I, Wan R, Debonnett LM, Maykut RJ, Angyalosi G. One-year safety and efficacy of tobramycin powder for inhalation in patients with cystic fibrosis. Pediatr Pulmonol. 2016 Apr;51(4):372-8. doi: 10.1002/ppul.23358. Epub 2015 Dec 27.
PubMed 26709158
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder After Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who Successfully Completed Participation in Study CTBM100C2303E1
- ClinicalTrials.gov ID
- NCT01069705
- Acronym / sponsor ID
- CTBM100C2303E2
- Conditions
- Pulmonary Infections, Pseudomonas Aeruginosa
- Keywords
- Tobramycin Inhalation Powder, Cystic fibrosis, Lung diseases, Anti-Bacterial Agents, Treatment of pulmonary infections with P. aeruginosa in cystic fibrosis participants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Feb 2010 (actual)
- Primary completion
- 19 Mar 2012 (actual)
- Study completion
- 19 Mar 2012 (actual)
- First posted
- 17 Feb 2010 (estimated)
- Results
- Posted 2 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was an open-label, single arm (uncontrolled) study in participants suffering from cystic fibrosis, who have completed their study participation in CTBM100C2303 and extension study one CTBM100C2303E1 (all visits), who were proven infected with Pseudomonas aeruginosa at enrollment into CTBM100C2303.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tobramycin Inhalation Powder (TIPnew) | Experimental | Drug: Tobramycin inhalation powderParticipants received four capsules of 28 mg TIPnew (112 mg), inhaled twice a day (b.i.d.) in the morning and the evening given in a cycle of 28 days on treatment followed by 28 days off treatment for three consecutive cycles. |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Completed all visits in study CTBM100C2303 and CTBM100C2303E1, and visit 11 of study CTBM100C2303E1 took place not more than 5 days before enrollment into this study.
- Confirmed diagnosis of cystic fibrosis participants with P. aeruginosa infection.
- Forced Expiratory Volume in one second (FEV1) at screening (at start of study CTBM100C2303) must be between 25% and 80% of normal predicted values.
Key exclusion criteria (2 listed)
- Any use of inhaled anti-pseudomonal antibiotics between the termination of the trial CTMB100C2303E1 and the enrollment into this study.
- Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
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 dry powder for inhalation in capsules administered by the T-326 inhaler. | Drug | Tobramycin Inhalation Powder (TIPnew) |
Primary outcome
Number of Participants With Adverse Events (AEs)
Time frame: From time of first administration of study drug until study completion (up to 169 days)
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug.
Number of Participants With Serious Adverse Events (SAEs)
Time frame: From time of consent to 4 weeks after study completion (up to 199 days)
A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participant or require medical or surgical intervention to prevent one of the aforementioned outcomes.
Percentage of Participants With a Decrease of ≥20% in Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted From Pre-dose to 30-minute Post-dose
Time frame: Pre-dose and post-dose of Day 1 and Day 29 of every Cycle (5, 6, 7)
Airway Reactivity >= 20% relative decrease in FEV1% predicted from pre-dose to 30 minutes post-dose. Relative Change = 100 * (30 minutes Post-dose - Pre-dose)/Pre-dose assessed by the number and percentage of participants with a decrease of ≥ 20% in FEV1 % predicted from pre-dose to 30 minutes post-dose.
Percentage of Participants With Frequency Decrease From Baseline in the Post-baseline Audiology Tests
Time frame: Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Auditory acuity of participants was measured using a standard dual-channel audiometer at frequencies from 250 to 8000 Hertz, and an audiogram (pure-tone air conduction) and tympanogram were performed by an audiologist. The categories reported includes >= 10dB decrease in 3 consecutive frequencies in either ear, >= 15dB decrease in 2 consecutive frequencies in either ear, and >= 20dB decrease in at least one frequency in either ear
8 secondary outcomes
Relative Change From Baseline of Forced Expiratory Volume in One Second (FEV1) Percent Predicted to Each Post-baseline Visit
Time frame: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Relative Change From Baseline of Forced Vital Capacity (FVC) Percent Predicted to Each Post-baseline Visit
Time frame: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Relative Change From Baseline of Forced Expiratory Flow Rate Over 25 and 75 Percent (FEF25-75%) Predicted to Each Post-baseline Visit
Time frame: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Change From Baseline in Pseudomonas Aeruginosa Sputum Density to Each Post-baseline Visit
Time frame: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Change From Baseline in Tobramycin Minimum Inhibitory Concentration (MIC) Values for Pseudomonas Aeruginosa to Each Post-baseline Visit
Time frame: Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Number of Participants Who Used New Antipseudomonal Antibiotic During Treatment Period
Time frame: Baseline, Cycles 5, 6, 7 (Days 1, 29)
Percentage of Participants With Hospitalization Due to Respiratory Serious Adverse Events (SAEs)
Time frame: From time of consent to 4 weeks after study completion (up to 199 days)
Number of Days of Hospitalization Due to Respiratory Serious Adverse Events (SAEs)
Time frame: From time of consent to 4 weeks after study completion (up to 199 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26709158Konstan MW, Flume PA, Galeva I, Wan R, Debonnett LM, Maykut RJ, Angyalosi G. One-year safety and efficacy of tobramycin powder for inhalation in patients with cystic fibrosis. Pediatr Pulmonol. 2016 Apr;51(4):372-8. doi: 10.1002/ppul.23358. Epub 2015 Dec 27.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
17 sites in 7 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 in people with Pulmonary Infections and Pseudomonas Aeruginosa, run by Novartis Pharmaceuticals at 17 sites in 7 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 3 inclusion and 2 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 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Russia, Bulgaria, Estonia, Lithuania, Romania and 2 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 2 Jun 2021). 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 Adverse Events (AEs) (time frame: From time of first administration of study drug until study completion (up to 169 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01069705, which also lists 1 linked publication.
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 2 Jun 2021.