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

NCT ID: NCT01844778

Last Updated: 2016-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2015-10-31

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.

Detailed Description

Patients who were on colistimethate (COLI), Tobramycin Inhalation Powder (TIP) or Tobramycin Inhalation Solution (TIS) were recruited for the study. They went through one treatment cycle on their usual inhaled antibiotic treatment, and were all transferred to TIP for the second treatment cycle. The primary endpoint was the total administration time of TIP vs TIS vs colistimethate, defined as the total time taken to prepare the delivery device and drug, administer the drug, and clean and disinfect the delivery device.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TIS/TIP

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.

Group Type: ACTIVE_COMPARATOR

Tobramycin Inhalation Powder

Intervention Type: DRUG

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

Tobramycin inhalation solution

Intervention Type: DRUG

Tobramycin inhalation solution was administered via nebuliser

COLI/TIP

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.

Group Type: ACTIVE_COMPARATOR

Tobramycin Inhalation Powder

Intervention Type: DRUG

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

Colistimethate

Intervention Type: DRUG

Colistimethate was administered via nebuliser.

TIP/TIP

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.

Group Type: ACTIVE_COMPARATOR

Tobramycin Inhalation Powder

Intervention Type: DRUG

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

Interventions

Tobramycin Inhalation Powder

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

Intervention Type: DRUG

Tobramycin inhalation solution

Tobramycin inhalation solution was administered via nebuliser

Intervention Type: DRUG

Colistimethate

Colistimethate was administered via nebuliser.

Intervention Type: DRUG

Other Intervention Names

TIP; TIS; COLI

Eligibility Criteria

Inclusion Criteria

• 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);

Exclusion Criteria

• 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.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Tübingen, , Germany

Novartis Investigative Site

Galway, , Ireland

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Palma de Mallorca, Balearic Islands, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, Madrid, Spain

Novartis Investigative Site

Valencia, Valencia, Spain

Novartis Investigative Site

Basel, Switzerland, Switzerland

Novartis Investigative Site

Zurich, Switzerland, Switzerland

Novartis Investigative Site

Sankt Gallen, , Switzerland

Novartis Investigative Site

Southampton, Hampshire, United Kingdom

Novartis Investigative Site

Penarth, Vale of Glamorgan, United Kingdom

Novartis Investigative Site

Birmingham, West Midlands, United Kingdom

Novartis Investigative Site

Bristol, , United Kingdom

Novartis Investigative Site

East Yorkshire, , United Kingdom

Novartis Investigative Site

Exeter, , United Kingdom

Novartis Investigative Site

Liverpool, , United Kingdom

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Countries

Germany; Ireland; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28614995 (View on PubMed)

Other Identifiers

2012-001565-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTBM100C2403

Identifier Type: -

Identifier Source: org_study_id