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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01775137
First received: January 22, 2013
Last updated: November 5, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Long-term Safety of TIP
Drug: TBM100
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 45
Study Start Date: February 2013
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TBM100
TIP 112 mg/b.i.d
Drug: TBM100
Tobramycin inhalation powder (TIP) 112mg/b.i.d

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01775137

Locations
United States, Ohio
Novartis Investigative Site
Akron, Ohio, United States, 44308
United States, South Carolina
Novartis Investigative Site
Charleston, South Carolina, United States, 29425
United States, Texas
Novartis Investigative Site
Dallas, Texas, United States, 75230
Novartis Investigative Site
Houston, Texas, United States, 77030
Argentina
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1425DTG
Novartis Investigative Site
Capital Federal, Buenos Aires, Argentina, C1425EFD
Novartis Investigative Site
Córdoba, Cordoba, Argentina, X5014AKN
Australia, New South Wales
Novartis Investigative Site
New Lambton Heights, New South Wales, Australia, 2305
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3052
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3T1C5
Germany
Novartis Investigative Site
Essen, Germany, 45147
Hungary
Novartis Investigative Site
Budapest, Hungary, 1121
Italy
Novartis Investigative Site
Firenze, FI, Italy, 50139
Novartis Investigative Site
Messina, ME, Italy, 98125
Novartis Investigative Site
Verona, VR, Italy, 37126
Novartis Investigative Site
Palermo, Italy, 90100
Novartis Investigative Site
Roma, Italy, 00161
Mexico
Novartis Investigative Site
Mexico, Distrito Federal, Mexico, 06720
Novartis Investigative Site
Monterrey, Nuevo León, Mexico, 64020
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46026
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01775137     History of Changes
Other Study ID Numbers: CTBM100C2401E1 
Study First Received: January 22, 2013
Results First Received: July 28, 2015
Last Updated: November 5, 2015
Health Authority: Hungary: Gyógyszerészeti és Egészségügyi Minőség- és Szervezetfejlesztési Intézet
Australia:Therapeutic Goods Administration
Italy: Italian Medicines Agency (AIFA)
Germany: BfArM - Bundesinstitut fuer Arzneimittel und Medizinprodukte
Mexico: Comisión Federal para la Protección Contra Riesgos Sanitarios
Argentina: Administración Nacional de Medicamentos Alimentos y Tecnología Medica
Spain: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)
United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Novartis:
CF, Open-label, TIP, phase IV, extension study

ClinicalTrials.gov processed this record on May 26, 2016