Open Label Extension to Bridging Study CTBM100C2303

NCT00982930 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CTBM100C2303E12008-004764-39
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Pseudomonas Aeruginosa; Cystic Fibrosis

Keywords

Tobramycin Inhalation Powder; Cystic fibrosis; Lung diseases; Anti-Bacterial Agents

Outcome Measures

Primary Outcomes (8)

• Percentage of Participants With Adverse Events (AEs)

  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)

  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

  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

  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

  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

  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

  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

  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 Outcomes (7)

• Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted to End of Dosing at Each Cycle and Study Completion

  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

  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

  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

  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

  Baseline, Day 29 of Cycle 2, 3, 4, Day 57 of Follow Up and Termination (Study Completion)

Study Arms (1)

Tobramycin Inhalation Powder (TIP)

EXPERIMENTAL

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.

Drug: Tobramycin inhalation powder

Interventions

Tobramycin inhalation powder DRUG

Tobramycin inhalation powder, 112 mg (4 capsules of 28 mg), inhalation capsules, b.i.d.

Tobramycin Inhalation Powder (TIP)

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Tallinn, Estonia

Location

Novartis Investigative Site

Yaroslavl, Russia

Location

Related Publications (1)

• 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.

  PMID: 26709158 RESULT

MeSH Terms

Conditions

Pseudomonas Infections; Cystic Fibrosis; Lung Diseases

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pancreatic Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2009
• First Posted: September 23, 2009
• Study Start: August 12, 2009
• Primary Completion: October 1, 2011
• Study Completion: October 6, 2011
• Last Updated: June 2, 2021
• Results First Posted: June 2, 2021

Record last verified: 2021-05

Locations

ES (1); RU (1)