Second Open Label Extension to Bridging Study CTBM100C2303

Pseudomonas Aeruginosa Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01069705
• Other study ID #: CTBM100C2303E2
• Status: Completed
• Phase: Phase 3
• Start date: February 12, 2010
• Est. completion date: March 19, 2012

Study information

• Verified date: May 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 19, 2012
• Est. primary completion date: March 19, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Pseudomonas Aeruginosa
• Pulmonary Infections

Intervention

Drug:
• Tobramycin inhalation powder
Tobramycin dry powder for inhalation in capsules administered by the T-326 inhaler.

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Estonia	Novartis Investigative Site	Tallin
Estonia	Novartis Investigative Site	Tartu
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Vilnius
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Timisoara
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Samara
Russian Federation	Novartis Investigative Site	Yaroslavl
South Africa	Novartis Investigative Site	Durban

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Bulgaria,  Estonia,  Latvia,  Lithuania,  Romania,  Russian Federation,  South Africa, 

References & 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From time of first administration of study drug until study completion (up to 169 days)
Primary	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.	From time of consent to 4 weeks after study completion (up to 199 days)
Primary	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.	Pre-dose and post-dose of Day 1 and Day 29 of every Cycle (5, 6, 7)
Primary	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	Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary	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.	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary	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.	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary	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.	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary	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).	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary	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.	Baseline, Cycles 5, 6, 7 (Days 1, 29) and Follow-up (Week 57/Day 57)
Secondary	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.	Baseline, Cycles 5, 6, 7 (Days 1, 29)
Secondary	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.	From time of consent to 4 weeks after study completion (up to 199 days)
Secondary	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.	From time of consent to 4 weeks after study completion (up to 199 days)