Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)

NCT01844778 | Completed Phase 4 Results

• 2 other identifiers: CTBM100C24032012-001565-33
• Study Type: interventional
• Target: 60
• Locations: 5 countries
• Sites: 21

Brief Summary

The purpose of this interventional Phase IV study was to explore the ease of use of TIP and prevalence of microbial contamination of the T-326 Inhaler compared with TIS and colistimethate administered via nebuliser for the treatment of Cystic Fibrosis (CF) patients chronically infected with P. aeruginosa. It was anticipated that the data from this study would provide clinicians with further guidance on the relative differences between the speed and ease of use of these treatments as well as useful information on the prevalence of microbial contamination of the inhalation devices in "real world" use.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI,; colistimethate; Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI, colistimethate

Outcome Measures

Primary Outcomes (1)

• Mean Total Administration Time

  The mean total time for administration of TIP via T-326 inhaler versus the total time for administration of COLI or TIS was assessed from information entered by participants into an ediary during the last 7 days prior to the last dose of a cycle. The total time included the setup, preparation, administration and cleaning/disinfection time.

  days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)

Secondary Outcomes (4)

• Change in P. Aeruginosa Sputum Density

  days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)

• Number of Participants With Any Contaminated Delivery Device

  days (d) 1, 28, 57, 84

• Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values

  days 1, 28, 57, 84, 112

• Number of Participants With Post-inhalation Bronchospasm

  days 1, 28, 57, 84

Study Arms (3)

TIS/TIP

ACTIVE COMPARATOR

During the first cycle of treatment, participants received nebulized TIS, 300 mg twice per day for 28 days followed by 28 days off-treatment. During the second cycle, participants received 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

Drug: Tobramycin Inhalation Powder; Drug: Tobramycin inhalation solution

COLI/TIP

ACTIVE COMPARATOR

During the first cycle, participants received nebulized COLI, 1 million or 2 million units twice or thrice per day (or the participant's usual dose and regimen) for 56 days (no off-treatment period) or 28 days on-treatment followed by 28 days off-treatment (cycling regimen), depending on local treatment guidelines. During the second cycle, participants received TIP, 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

Drug: Tobramycin Inhalation Powder; Drug: Colistimethate

TIP/TIP

ACTIVE COMPARATOR

During the first and second cycles, participants received TIP, 112 mg (four 28 mg capsules) twice per day for 28 days followed by 28 days off-treatment.

Drug: Tobramycin Inhalation Powder

Interventions

Tobramycin Inhalation Powder DRUG

Tobramycin Inhalation Powder was administered via TOBI® Podhaler (T-326 inhaler).

Also known as: TIP

COLI/TIP; TIP/TIP; TIS/TIP

Tobramycin inhalation solution DRUG

Tobramycin inhalation solution was administered via nebuliser

Also known as: TIS

TIS/TIP

Colistimethate DRUG

Colistimethate was administered via nebuliser.

Also known as: COLI

COLI/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:

• Provide written informed consent, HIPAA authorization, and assent (as appropriate for minors) prior to the performance of any study-related procedure
• Confirmed diagnosis of Cystic Fibrosis (CF)
• Male and female patients 6 years of age or older at screening
• Forced Expiratory Volume in 1 second (FEV1) at screening (Visit 1) must be at least 25% and less than or equal to 90% of normal predicted values for age, sex, and height based on the NHANES III values (Hankinson, 1999) for patients 18 years of age or greater, and based on values from Wang (Wang 1993) for patients less than 18 years of age.
• Documented use of any of the nebulized antibiotics based on local practice:
• Tobramycin Inhalation Solution, colistimethate, or Tobramycin Inhalation Powder for at least 1 cycle within the last 6 months or
• Colistimethate continuous use for at least 8 weeks within the last 6 months This cycle of treatment (or continuous colistimethate treatment period) is in addition to the treatment cycle during which the subject is being screened.
• P. aeruginosa must be present in a sputum or deep cough throat swab culture or bronchoalveolar lavage (BAL) (only for BAL a threshold level of 10\^3 CFU/mL is required) within 6 months prior to screening, and in the sputum or deep cough throat swab culture at screening or rescreening (Visit 1);

You may not qualify if:

• History of sputum culture or deep cough throat swab (or BAL) culture yielding Burkholderia cenocepacia complex within 2 years prior to prescreening or sputum culture yielding B. cenocepacia complex at screening (Visit 1)
• History of hearing loss or chronic tinnitus deemed clinically significant by the investigator
• Serum creatinine 176.8 μmol/L (2 mg/dL) or greater, blood urea nitrogen (BUN) 14.28 mmol/L (40 mg/dL) or greater, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening
• Known local or systemic hypersensitivity to aminoglycosides
• Regularly receiving more than 1 class of inhaled antipseudomonal antibiotic
• Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening
• Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax
• Body mass index less than 12 kg/m2
• History of malignancy of any organ system, treated or untreated
• Clinically significant laboratory abnormalities (not associated with the study indication) at screening (Visit 1)
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

München, 81241, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Galway, Ireland

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28046, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Novartis Investigative Site

Basel, Switzerland, 4031, Switzerland

Location

Novartis Investigative Site

Zurich, Switzerland, 8032, Switzerland

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Novartis Investigative Site

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Novartis Investigative Site

Penarth, Vale of Glamorgan, CF64 2XX, United Kingdom

Location

Novartis Investigative Site

Birmingham, West Midlands, b9 5ss, United Kingdom

Location

Novartis Investigative Site

Bristol, BS1 3NU, United Kingdom

Location

Novartis Investigative Site

East Yorkshire, HU16 5JQ, United Kingdom

Location

Novartis Investigative Site

Exeter, EX2 5DW, United Kingdom

Location

Novartis Investigative Site

Liverpool, L14 3PE, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (1)

• Greenwood J, Schwarz C, Sommerwerck U, Nash EF, Tamm M, Cao W, Mastoridis P, Debonnett L, Hamed K. Ease of use of tobramycin inhalation powder compared with nebulized tobramycin and colistimethate sodium: a crossover study in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infection. Ther Adv Respir Dis. 2017 Jul;11(7):249-260. doi: 10.1177/1753465817710596.

  PMID: 28614995 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Interventions

colistinmethanesulfonic acid

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 1, 2013
• Study Start: August 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 27, 2016
• Results First Posted: May 24, 2016

Record last verified: 2016-07

Locations

DE (4); IE (1); CH (3); GB (8); ES (5)