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Ext. Long-term Safety Study in CF Patients: Single Arm TIP

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ClinicalTrials.gov Identifier: NCT01775137
Recruitment Status : Completed
First Posted : January 24, 2013
Results First Posted : November 6, 2015
Last Update Posted : November 6, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 22, 2013
First Posted Date  ICMJE January 24, 2013
Results First Submitted Date  ICMJE July 28, 2015
Results First Posted Date  ICMJE November 6, 2015
Last Update Posted Date November 6, 2015
Study Start Date  ICMJE February 2013
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs/SAEs Leading to Discontinuation of Study Drug and Deaths Over 12 Treatment Cycles [ Time Frame: Baseline (start of study treatment in core study) to Day 673 (end of the extension study) ]
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. 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. Based on the severity, AEs were categorised into 3 types as mild, moderate and severe. Death was a fatal event leading to permanent cessations of all vital functions of the body.
Original Primary Outcome Measures  ICMJE
 (submitted: January 22, 2013)
Incidence of treatment emergent adverse events in 2 years [ Time Frame: 2 years ]
Safety of TIP measured in terms of total number of treatment emergent adverse events (including the core and extension periods)
Change History Complete list of historical versions of study NCT01775137 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
  • Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles [ Time Frame: Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) ]
    FEV1 was defined as the volume of air expired in 1 second. FEV1 was assessed as a pulmonary function by using spirometry tests in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. FEV1% predicted is 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*FEV1% predicted - baseline FEV1% predicted) / baseline FEV1 % predicted) x 100.
  • Absolute Change From Baseline in Pseudomonas Aeruginosa Sputum Density Over 12 Treatment Cycles [ Time Frame: Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day ]
    Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Absolute change was determined using the formula = (Post-baseline value- baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes.
  • Tobramycin Minimum Inhibitory Concentration (MIC) 50 and MIC 90 Values for Pseudomonas Aeruginosa Over 12 Treatment Cycles [ Time Frame: Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) ]
    MIC was defined as the lowest concentration of an antimicrobial agent required to inhibit the visible growth of a microorganism after overnight incubation. Tobramycin MIC 50 and MIC 90 values were defined as the lowest concentration of tobramycin required to inhibit 50% and 90%, respectively, of the P. aeruginosa strains tested (mucoid,dry and small colony variant biotypes).
  • Percentage of Participants Who Used New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles [ Time Frame: Baseline of core study, Day 673 (end of the extension study) ]
    The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study.
  • Total Number of Days of New Anti-pseudomonal Antibiotics Use Over 12 Treatment Cycles [ Time Frame: Baseline of core study, Day 673 (end of the extension study) ]
    The total number of days with usage of new anti-pseudomonal antibiotic were determined.
  • Time to Use of New Anti-pseudomonal Antibiotics Over 12 Treatment Cycles [ Time Frame: Baseline of core study, Day 673 (end of the extension study) ]
    Time to first usage of anti-pseudomonal antibiotic was determined using Kaplan Meier estimate. Participants without an event were censored at the date of the last available post-baseline measurement.
  • The Percentage of the Participants Hospitalized Due to Serious Respiratory-related AEs Were Determined During the Study. [ Time Frame: Baseline of core study, Day 673 (end of the extension study) ]
    The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the study.
  • Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles [ Time Frame: Baseline of core study, Day 673 (end of the extension study) ]
    The total number of hospitalization days due to serious respiratory-related adverse events was analyzed using Kaplan-Meier estimate.
  • Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) Over 12 Treatment Cycles [ Time Frame: Baseline of core study, Day 673 (end of the extension study) ]
    The day of first hospitalization due to serious respiratory-related adverse events was analysed using Kaplan Meier estimate.
  • Acute Relative Change From Pre-dose to 30-minute Post-dose in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 12 Treatment Cycles [ Time Frame: Baseline (start of study treatment in core study), Day 29, Day 85, Day 141, Day 197, Day 253, Day 309, Day 337, Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) ]
    FEV1 was defined as the volume of air expired in 1 second. FEV1 was assessed as a pulmonary function by using spirometry tests in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. Relative change in FEV1 % predicted was calculated by using the formula = 100 *(30-min post-dose value - pre-dose value) / pre-dose value.
  • Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted Over 6 Treatment Cycles in Extension Study [ Time Frame: Baseline (start of study treatment in extension study), Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) ]
    FEV1 was defined as the volume of air expired in 1 second. FEV1 was assessed as a pulmonary function by using spirometry tests in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria. FEV1% predicted is 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*FEV1% predicted - baseline FEV1% predicted) / baseline FEV1 % predicted) x 100.
  • Absolute Change From Baseline in Pseudomonas Aeruginosa Density Over 6 Treatment Cycles in Extension Study [ Time Frame: Baseline (start of study treatment in extension study), Day 365, Day 421, Day 477, Day 533, Day 589, Day 645, 673 (end of the extension study) ]
    Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Absolute change was calculated by using the formula = (Value at actual time point - start of extension value).
  • Percentage of Participants Who Used New Anti-pseudomonal Antibiotics in Extension Study [ Time Frame: Baseline of extension study, Day 673 (end of extension study) ]
    The rate of anti-pseudomonal antibiotics use were determined from the collection of concomitant medication during the study.
  • Total Number of Days of New Anti-pseudomonal Antibiotics Use in Extension Study [ Time Frame: Baseline of extension study, Day 673 (end of extension study) ]
    The total number of days with usage of new anti-pseudomonal antibiotic were determined.
  • Time to Use of New Anti-pseudomonal Antibiotics in Extension Study [ Time Frame: Baseline of extension study, Day 673 (end of extension study) ]
    Time to first usage of anti-pseudomonal antibiotic was determined using Kaplan Meier estimate. Participants without an event were censored at the date of the last available post-baseline measurement.
  • Percentage of Participants Hospitalized Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study [ Time Frame: Baseline of extension study, Day 673 (end of the extension study) ]
    The percentage of the participants hospitalized due to serious respiratory-related AEs were determined during the extension study.
  • Number of Hospitalization Days Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study [ Time Frame: Baseline of extension study, Day 673 (end of extension study) ]
    The total number of hospitalisation days due to serious respiratory-related adverse events was analysed using Kaplan-Meier estimate.
  • Time to First Hospitalization Due to Respiratory Related Serious Adverse Events (SAEs) in Extension Study [ Time Frame: Baseline of extension study, Day 673 (end of extension study) ]
    The day of first hospitalization due to serious respiratory related adverse events was analysed using Kaplan Meier estimate.
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs/SAEs Leading to Discontinuation of Study Drug and Deaths Over 6 Treatment Cycles in Extension Study [ Time Frame: Baseline (start of study treatment in extension study) to Day 673 (end of the extension study) ]
    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. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalisation, 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. Death was a fatal event leading to permanent cessations of all vital functions of the body.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2013)
  • Relative change in predicted FEV1 [ Time Frame: 2 years ]
    Change in relative predicted Forced Expiratory Volume in one second (FEV1) across 12 cycles of TIP treatment, from baseline to the end of the dosing periods
  • Absolute change in predicted FEV1 [ Time Frame: 2 years ]
    Change in predicted absolute Forced Expiratory Volume in one second (FEV1) across 12 cycles of TIP treatment, from baseline to the end of the dosing periods
  • Acute changes in FEV1 percent predicted [ Time Frame: 2 years ]
    Acute changes in Forced Expiratory Volume in one second (FEV1) predicted percent from pre-dose to 30 min post-dose by visit, across 12 cycles of TIP treatment from baseline to the end of dosing periods
  • Absolute change in P.aeruginosa sputum density [ Time Frame: 2 years ]
    Absolute change measured via P. aeruginosa sputum density by biotype, across 12 cycles of TIP treatment from baseline to the end of the dosing period
  • P.aeruginosa tobramycin MIC change [ Time Frame: 2 years ]
    Change in terms of P.aeruginosa tobramycin Minimal inhibitory capacity across 12 cycles of TIP treatment from baseline to the end of dosing period
  • Number of hospitalizations due to serious respiratory related AEs [ Time Frame: 2 years ]
    Total number of hospitalizations due to serious respiratory related adverse events across 12 cycles of TIP treatment from baseline to the end of dosing periods
  • Usage of anti-pseudomonal antibiotics [ Time Frame: 2 years ]
    Usage of (overall, oral, intravenous) anti-pseudomonal antibiotics across 12 cycles of TIP treatment from baseline to the end of dosing period
  • clinical laboratory and audiology results [ Time Frame: 2 years ]
    Safety (lab & audiology) profile of TIP by visit across 12 cycles of TIP treatment from baseline to the end of dosing periods
  • Relative change in predicted FEV1 during extension period [ Time Frame: 1 year ]
    Change in relative predicted Forced Expiratory Volume in one second (FEV1) during the extension period only
  • Absolute change in predicted FEV1 during extension period [ Time Frame: 1 year ]
    Change in predicted absolute Forced Expiratory Volume in one second (FEV1) during the extension period only
  • Acute changes in FEV1 percent predicted during the extension period [ Time Frame: 1 year ]
    Acute changes in Forced Expiratory Volume in one second (FEV1) predicted percent from pre-dose to 30 min post-dose by visit during the extension period only
  • Absolute change in P.aeruginosa sputum density during the extension period [ Time Frame: 1 year ]
    Absolute change measured via P. aeruginosa sputum density by biotype during the extension period only
  • P.aeruginosa tobramycin MIC change during the extension period [ Time Frame: 1 year ]
    Change in terms of P.aeruginosa tobramycin Minimal inhibitory capacity during the extension period only
  • Number of hospitalizations due to serious respiratory related AEs during the extension [ Time Frame: 1 year ]
    Total number of hospitalizations due to serious respiratory related adverse events during the extension period only
  • clinical laboratory and audiology results during the extension period [ Time Frame: 1 year ]
    Safety (lab & audiology) profile of TIP by visit during the extension period only
  • Usage of anti-pseudomonal antibiotics [ Time Frame: 1 year ]
    Usage of (overall, oral, intravenous) anti-pseudomonal antibiotics during the extension period only
  • Incidence of treatment emergent adverse events for the extension study only [ Time Frame: 1 year ]
    Safety of TIP measured in terms of total number of treatment emergent adverse events during the extension period only
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ext. Long-term Safety Study in CF Patients: Single Arm TIP
Official Title  ICMJE A 48 Week Extension to CTBM100C2401, a Single Arm, Open-label, Multicenter, Phase IV Extension Trial to Assess Long Term Safety of Tobramycin Inhalation Powder (TIP) in Patients With Cystic Fibrosis Who Completed Participation in CTBM100C2401.
Brief Summary The purpose of this extension study is to collect additional 48 weeks of safety data from patients taking TIP who have completed the core study CTBM100C2401. The purpose of collecting second year safety data through this study is to obtain long-term (2 years) safety data of TIP.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE Long-term Safety of TIP
Intervention  ICMJE Drug: TBM100
Tobramycin inhalation powder (TIP) 112mg/b.i.d
Study Arms  ICMJE Experimental: TBM100
TIP 112 mg/b.i.d
Intervention: Drug: TBM100
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 5, 2015)
45
Original Estimated Enrollment  ICMJE
 (submitted: January 22, 2013)
120
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Completion of the core study CTBM100C2401 and able to comply with all protocol requirements of the extension study

Exclusion Criteria:

  • Serum creatinine 2mg/dl, BUN 40mg/dl or proteinuria 2+ or more at the time of entry into the extension
  • Use of loop diuretics within 7 days prior to entry into the extension study
  • Pregnant or nursing women
  • Women of child bearing potential unless using highly effective method of contraception as indicated in the protoco
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   Germany,   Hungary,   Italy,   Mexico,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01775137
Other Study ID Numbers  ICMJE CTBM100C2401E1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP