- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00982930
Open Label Extension to Bridging Study CTBM100C2303
May 7, 2021 updated by: Novartis Pharmaceuticals
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) Subjects Who Completed Participation in Study CTBM100C2303.
This was an open-label, single arm (uncontrolled) study in participants suffering from cystic fibrosis, who had completed their study participation in CTBM100C2303 (all visits) and who were proven infected with Pseudomonas aeruginosa (P.
aeruginosa) at enrollment into CTBM100C2303.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
55
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Tallin, Estonia
- Novartis Investigative Site
-
-
-
-
-
Yaroslavl, Russian Federation
- Novartis Investigative Site
-
-
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
Ages Eligible for Study
6 years to 21 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Completed all visits in study CTBM100C2303, and visit 4 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 (study CTBM100C2303) must be between 25% and 80% of normal predicted values.
Exclusion Criteria:
- Any use of inhaled anti-pseudomonal antibiotics between the termination of the core trial CTMB100C2303 and the enrollment into this study.
- Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
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: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tobramycin Inhalation Powder (TIP)
Participants received 112 mg (four 28 mg capsules) of TIP administered by the T-326 Inhaler, twice a day (b.i.d.), given in a cycle of 28 days on treatment followed by 28 days off treatment (one cycle = 56 days) for up to 3 cycles.
|
Tobramycin inhalation powder, 112 mg (4 capsules of 28 mg), inhalation capsules, b.i.d.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Adverse Events (AEs)
Time Frame: From first administration of study drug to study completion (up to approximately 25 weeks)
|
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product.
|
From first administration of study drug to study completion (up to approximately 25 weeks)
|
Percentage of Participants With Serious Adverse Events (SAEs)
Time Frame: From time of consent to 4 weeks after study completion (up to approximately 29 weeks)
|
SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
|
From time of consent to 4 weeks after study completion (up to approximately 29 weeks)
|
Percentage of Death Cases
Time Frame: From time of consent to 4 weeks after study completion (up to approximately 29 weeks)
|
From time of consent to 4 weeks after study completion (up to approximately 29 weeks)
|
|
Percentage of Participants With Adverse Events and Serious Adverse Events Leading to Permanent Study Discontinuation
Time Frame: From first administration of study drug to study completion (up to approximately 25 weeks)
|
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product.
SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
|
From first administration of study drug to study completion (up to approximately 25 weeks)
|
Shift From Baseline in Laboratory Parameters to Above Upper/Lower Limit of Normal
Time Frame: From baseline to study completion (up to approximately 25 weeks)
|
Shift from baseline in hematology and biochemistry values to above upper/below lower limit of normal at any time post-baseline were reported.
Baseline for safety analyses was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303.
Change to low referred to number of participants with normal or high values at baseline.
Change to high referred to number of participants with normal or low values at baseline.
|
From baseline to study completion (up to approximately 25 weeks)
|
Acute Relative Change in Airways Reactivity [Forced Expiratory Value in One Second (FEV1) Percent (%) Predicted] From Pre-dose to 30 Minutes After Completion of First Dose of Study Drug
Time Frame: Pre-dose and 30 minutes Post-dose on Day 1 and Day 29 of every Cycle (2, 3, 4)
|
Airway Reactivity was defined as ≥20% FEV1 relative decrease in percent predicted from pre dose to 30 minutes post dose.
FEV1 was defined as the volume of air expired in 1 second.
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 = 100* (30 minutes post dose - pre dose) / pre dose assessed by number and percentage of participants with a decrease in ≥20% FEV1 percent predicted from pre dose to 30 minutes post dose.
Baseline for was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303.
|
Pre-dose and 30 minutes Post-dose on Day 1 and Day 29 of every Cycle (2, 3, 4)
|
Percentage of Participants With Frequency Decrease From Baseline in the Post-baseline Audiology Tests
Time Frame: From first dose of study drug to study completion (up to approximately 25 weeks)
|
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.
|
From first dose of study drug to study completion (up to approximately 25 weeks)
|
Number of Participants With Adverse Events (AEs) Associated With the Use of New Antipseudomonal Antibiotic
Time Frame: From first administration of study drug to study completion (up to approximately 25 weeks)
|
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment.
An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not related to the medicinal product.
SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
|
From first administration of study drug to study completion (up to approximately 25 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing at Each Cycle and Study Completion
Time Frame: Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
FEV1 was defined as the volume of air expired in 1 second.
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 = 100* (30 minutes post dose - pre dose) / pre dose assessed by number and percentage of participants with a decrease in ≥20% FEV1 percent predicted from pre dose to 30 minutes post dose.
Baseline for was defined as the last measurement prior to first dose of study drug in the core study CTBM100C2303.
Termination referred to the last available pre dose post-baseline measurement.
|
Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Change From Baseline in Forced Vital Capacity (FVC) Percent (%) Predicted to End of Dosing at Each Cycle and Study Completion
Time Frame: Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Relative change from baseline in FVC % predicted to end of dosing in each cycle and study completion were reported.
Relative change from baseline was defined as: Relative change = 100* (Post baseline- baseline) / baseline.
Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303.
Termination referred to the last available pre dose post-baseline measurement.
|
Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Change From Baseline in Forced Expiratory Flow Rate Over 25 Percent and 75 Percent (FEF25-75%) Predicted to End of Dosing at Each Cycle and Study Completion
Time Frame: Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Relative change from baseline in FEF25-75% predicted to end of dosing in each cycle and study completion were reported.
Relative change from baseline was defined as: Relative change = 100* (Post baseline- baseline) / baseline.
Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303.
Termination referred to the last available pre dose post-baseline measurement.
|
Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Absolute Change From Baseline in Sputum Pseudomonas Aeruginosa Density [log10 Colony Forming Units (CFU) Per Gram Sputum] to End of Dosing at Each Cycle and Study Completion
Time Frame: Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
P. aeruginosa sputum density referred to overall density, defined as the sum of biotypes (mucoid, dry and small colony variant).
If sub-isolates existed for CFU biotype mucoid or dry, then the sum of sub-isolates was analyzed.
Absolute change from baseline was defined as: Absolute change = Post Baseline - Baseline.
Baseline was defined as last measurement prior to first dose of study drug in the core study CTBM100C2303.
Termination referred to the last available pre dose post-baseline measurement.
|
Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Change From Baseline in Pseudomonas Aeruginosa Minimum Inhibitory Concentration (MIC) to End of Dosing at Each Cycle and Study Completion
Time Frame: Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Change in tobramycin MIC values for P. aeruginosa were reported for specimens and were used to assess the change in pathogen susceptibility to tobramycin before (baseline) and after (post-baseline) the treatment.
Maximum MIC values from all biotypes were used.
Change from baseline was defined as: Change = Post-baseline - Baseline.
Baseline was defined as last measurement prior to first dose of study drug in the core studyCTBM100C2303.Termination referred to the last available pre dose post-baseline measurement.
|
Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)
|
Percentage of Participants With Anti-Pseudomonal Antibiotic Use During The Treatment Period
Time Frame: From first administration of study drug to study completion (up to approximately 25 weeks)
|
From first administration of study drug to study completion (up to approximately 25 weeks)
|
|
Number of Days of Hospitalization Due to Respiratory Serious Adverse Events
Time Frame: From first administration of study drug to study completion (up to approximately 25 weeks)
|
SAEs included adverse events that resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
For calculation of days in hospitalization due to respiratory events, the end date was defined as the discharge date (if provided and even if after the end of the extension study), and otherwise as the date of last visit.
|
From first administration of study drug to study completion (up to approximately 25 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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)
August 12, 2009
Primary Completion (Actual)
October 1, 2011
Study Completion (Actual)
October 6, 2011
Study Registration Dates
First Submitted
September 21, 2009
First Submitted That Met QC Criteria
September 22, 2009
First Posted (Estimate)
September 23, 2009
Study Record Updates
Last Update Posted (Actual)
June 2, 2021
Last Update Submitted That Met QC Criteria
May 7, 2021
Last Verified
May 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTBM100C2303E1
- 2008-004764-39 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
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
-
Hospital de Clinicas de Porto AlegreUnknownCystic Fibrosis | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in Children | Cystic Fibrosis With ExacerbationBrazil
-
University of Colorado, DenverCystic Fibrosis FoundationTerminatedCystic Fibrosis-related Diabetes | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in ChildrenUnited States
-
Royal College of Surgeons, IrelandThe Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin and other collaboratorsActive, not recruitingCystic Fibrosis | Adherence, Medication | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in Children | Cystic Fibrosis Liver DiseaseUnited Kingdom, Ireland
-
Herlev and Gentofte HospitalCopenhagen University Hospital, DenmarkActive, not recruitingMyocardial Infarction | Heart Diseases | Heart Failure | Stroke | Cystic Fibrosis | Heart Failure, Diastolic | Heart Failure, Systolic | Left Ventricular Dysfunction | Cystic Fibrosis-related Diabetes | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of Pancreas | Cystic Fibrosis, Pulmonary | Cystic...Denmark
-
The Hospital for Sick ChildrenCanadian Cystic Fibrosis FoundationActive, not recruitingCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in ChildrenCanada
-
Arrowhead PharmaceuticalsTerminatedCystic Fibrosis, PulmonaryAustralia, New Zealand
-
AzurRx SASCompletedCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of PancreasTurkey, Hungary
-
Dartmouth-Hitchcock Medical CenterTrustees of Dartmouth CollegeWithdrawnCystic Fibrosis-related Diabetes | Cystic Fibrosis Liver Disease | CF - Cystic FibrosisUnited States
-
University Hospital, BordeauxCompleted
-
University of PortsmouthUniversity Hospital Southampton NHS Foundation Trust; Loughborough University; Queen Alexandra HospitalTerminated
Clinical Trials on Tobramycin inhalation powder
-
Novartis PharmaceuticalsCompletedCystic FibrosisUnited States, Germany, United Kingdom, Colombia, Spain, France, Netherlands, Israel, Canada, Italy, Chile, Australia, Hungary, Mexico
-
Novartis PharmaceuticalsCompletedCystic FibrosisSpain, Germany, Switzerland, United Kingdom, Ireland
-
NovartisTerminatedCystic FibrosisUnited States, Argentina, Brazil, Bulgaria, Canada, Chile, Lithuania, Mexico
-
Novartis PharmaceuticalsCompletedPseudomonas Aeruginosa | Pulmonary InfectionsRussian Federation, Romania, Estonia, Latvia, Lithuania, Bulgaria, South Africa
-
Novartis PharmaceuticalsCompletedCystic FibrosisRussian Federation, Egypt, Romania, Estonia, Latvia, Lithuania, Bulgaria, South Africa, India
-
Novartis PharmaceuticalsTerminated
-
Erik Allen JensenUniversity of FloridaActive, not recruiting
-
Dartmouth-Hitchcock Medical CenterNovartis PharmaceuticalsTerminatedCystic FibrosisUnited States
-
University Medical Center GroningenRecruiting
-
Washington University School of MedicineCompleted