Long Term Safety of Tobramycin Inhalation Powder in Patients With Cystic Fibrosis

NCT01519661 | Completed Phase 4 Results

• 2 other identifiers: CTBM100C24012011-002000-32
• Study Type: interventional
• Target: 157
• Locations: 10 countries
• Sites: 49

Brief Summary

This study assessed the long term safety data for the use of tobramycin inhalation powder in patients suffering from cystic fibrosis who have a chronic pulmonary infection with Pseudomonas aeruginosa.

Conditions

Pulmonary Infections; Pseudomonas Aeruginosa in Cystic Fibrosis

Keywords

Tobramycin Inhalation powder; Cystic fibrosis; Lung disease; Anti-bacterial agents

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths

  Adverse events were deemed treatment-emergent if the onset date/time was on or after the date and time of first study drug. All adverse events were included after this time during both on and off-treatment periods.

  337 days

Secondary Outcomes (11)

• Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted

  Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.

• Relative Change From Baseline in FVC Percent Predicted

  Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.

• Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted

  Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period.

• Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum

  Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337

• Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa

  Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337

Study Arms (1)

Tobramycin Inhalation Powder (TIP)

EXPERIMENTAL

Eligible patients were assigned to four capsules of TIP at 28mg dosage strength, inhaled b.i.d. in the morning and in the evening via the T-326 inhaler, for 28 days (on treatment), followed by 28 days of no study treatment (off treatment). Each treatment therefore consisted of 112mg tobramycin (4 capsules of 28mg each) with the total daily dose = 224mg tobramycin (112mg b.i.d.). These 56 days represented 1 cycle of therapy.

Drug: TBM100

Interventions

TBM100 DRUG

Tobramycin inhalation powder was assigned as four capsules at 28mg dosage strength. It was inhaled b.i.d in the morning and in the evening via the T-326 Inhaler.

Tobramycin Inhalation Powder (TIP)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of Cystic Fibrosis
• FEV1 at screening must be between 25 and 75 percent of normal predicted values for age, sex and height based on the Knudson equation
• Pseudomonas aeruginosa must be present in a sputum / deep cough throat swab culture or bronchoalveolar lavage within 6 months prior to screening and in the sputum/deep-throat cough swab culture at screening

You may not qualify if:

• History of sputum culture or deep cough throat swab culture yielding Burkholderia cenocepacia complex within 2 years prior to screening and /or sputum culture yielding Burkholderia cenocepacia at screening
• Hemoptysis more than 60mL at any time within 30 days prior to study drug administration
• History of hearing loss or chronic tinnitus deemed clinically significant
• Serum creatinine 2mg/dl or more, BUN 40mg/dl or more, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening
• Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics
• Patients who are regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic
• Any use of inhaled or systemic anti-pseudomonal antibiotic within 28 days prior to study drug administration
• Use of loop diuretics within 7 days prior to study drug administration

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (49)

Novartis Investigative Site

Little Rock, Arkansas, 72205, United States

Location

Novartis Investigative Site

Denver, Colorado, 80206, United States

Location

Novartis Investigative Site

Jacksonville, Florida, 32207, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30322, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Omaha, Nebraska, 68198, United States

Location

Novartis Investigative Site

Las Vegas, Nevada, 89107, United States

Location

Novartis Investigative Site

Morristown, New Jersey, 07962, United States

Location

Novartis Investigative Site

Akron, Ohio, 44308, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44106, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73104, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Novartis Investigative Site

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

Dallas, Texas, 75230, United States

Location

Novartis Investigative Site

Fort Worth, Texas, 76104, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78212, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53792-1615, United States

Location

Novartis Investigative Site

Milwaukee, Wisconsin, 53226, United States

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Novartis Investigative Site

Caba, Buenos Aires, C1425DTG, Argentina

Location

Novartis Investigative Site

Capital Federal, Buenos Aires, C1425EFD, Argentina

Location

Novartis Investigative Site

Córdoba, Córdoba Province, X5014AKN, Argentina

Location

Novartis Investigative Site

Paraná, Entre Ríos Province, E3100FKA, Argentina

Location

Novartis Investigative Site

New Lambton Heights, New South Wales, 2305, Australia

Location

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Calgary, Alberta, T2N 4n1, Canada

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T1C5, Canada

Location

Novartis Investigative Site

Giens, 83406, France

Location

Novartis Investigative Site

Montpellier, 34059, France

Location

Novartis Investigative Site

Paris, 75006, France

Location

Novartis Investigative Site

Reims, 51092, France

Location

Novartis Investigative Site

Roscoff, 29684, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Budapest, 1121, Hungary

Location

Novartis Investigative Site

Florence, FI, 50139, Italy

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Palermo, Italy, 90100, Italy

Location

Novartis Investigative Site

Messina, ME, 98125, Italy

Location

Novartis Investigative Site

Verona, VR, 37126, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Roma, 00161, Italy

Location

Novartis Investigative Site

Mexico City, Mexico City, 06720, Mexico

Location

Novartis Investigative Site

Monterrey, Nuevo León, 64460, Mexico

Location

Novartis Investigative Site

Barcelona, Catalonia, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Related Publications (1)

• Sommerwerck U, Virella-Lowell I, Angyalosi G, Viegas A, Cao W, Debonnett L. Long-term safety of tobramycin inhalation powder in patients with cystic fibrosis: phase IV (ETOILES) study. Curr Med Res Opin. 2016 Nov;32(11):1789-1795. doi: 10.1080/03007995.2016.1211516. Epub 2016 Sep 9.

  PMID: 27435882 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Lung Diseases

Condition Hierarchy (Ancestors)

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

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 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: January 27, 2012
• Study Start: January 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: February 10, 2015
• Results First Posted: February 10, 2015

Record last verified: 2015-02

Locations

HU (1); DE (2); AR (4); CA (3); IT (7); ES (2); ME (2); FR (5); AU (3); US (20)