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

Cystic Fibrosis Clinical Trial

Official title:

An Open-label, Crossover, Interventional Phase IV Study to Compare the Ease of Use of TIP With Nebulized TIS and Nebulized COLI for the Treatment of Pulmonary Pseudomonas Aeruginosa (P.a) in Patients With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01844778
• Other study ID #: CTBM100C2403
• Secondary ID: 2012-001565-33
• Status: Completed
• Phase: Phase 4
• First received: April 29, 2013
• Last updated: July 26, 2016
• Start date: August 2013
• Est. completion date: October 2015

Study information

• Verified date: July 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

Key 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);

Key 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.

Study Design

Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Tobramycin Inhalation Powder
Tobramycin Inhalation Powder was administered via TOBI® Podhaler (T-326 inhaler).
• Tobramycin inhalation solution
Tobramycin inhalation solution was administered via nebuliser
• Colistimethate
Colistimethate was administered via nebuliser.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Tübingen
Ireland	Novartis Investigative Site	Galway
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	St. Gallen
Switzerland	Novartis Investigative Site	Zürich
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	Novartis Investigative Site	Penarth	Vale of Glamorgan
United Kingdom	Novartis Investigative Site	Southampton	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Ireland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Change in P. Aeruginosa Sputum Density	Sputum samples were sent to a central laboratory at the start and end of 2 treatment periods. The absolute change in the number of colony forming units (CFU) of Pseudomonas aeruginosa in sputum = the value of end of on/off treatment period of the cycle minus the pre-dose value at the start of that cycle. A negative change from baseline indicates improvement.	days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)	No
Secondary	Number of Participants With Any Contaminated Delivery Device	Devices used to administer the drugs (the T-326 inhaler and nebulisers) were swabbed for contamination testing at the start and end of each treatment cycle (or discontinuation visit if the participant withdrew). No assessments were required from the T-326 inhaler when participants started the treatment period (days 1 and 57). Microbial contamination was measured according to device type and the frequency of organism growth (light/ moderate/ heavy). All nebulisers (neb) used by the participants were analyzed, including those for inhaling other medications, like mucolytics.	days (d) 1, 28, 57, 84	No
Secondary	Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values	MIC50/90 is the lowest concentration required to inhibit 50%/90% of the isolates tested. The MIC50/90 of a range of antibiotics for P.aeruginosa was determined at the start and end of each treatment cycle, and at the end of the off-treatment period of the second cycle.	days 1, 28, 57, 84, 112	No
Secondary	Number of Participants With Post-inhalation Bronchospasm	Bronchospasm was defined as the relative decrease of 20% or more in forced expiratory volume in 1 second (FEV1) percent predicted from pre-dose to 15 to 45 minutes post-dose.	days 1, 28, 57, 84	Yes