Cystic FibrosisPhase 4NCT01844778
Ease of Use and Microbial Contamination of Tobramycin Inhalation Powder (TIP) Versus Nebulised Tobramycin Inhalation Solution (TIS) and Nebulised Colistimethate (COLI)
A Phase 4 study testing Tobramycin Inhalation Powder, Tobramycin inhalation solution and Colistimethate in people with Cystic Fibrosis, run by Novartis Pharmaceuticals at 21 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Tobramycin Inhalation Powder, Tobramycin inhalation solution and Colistimethate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 21 sitesin 5 countries
- Study dates
- Aug 2013to Oct 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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);
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
21 sites in 5 countries.
21 sites in 5 countries
United Kingdom8 sites
Novartis Investigative Site
Birmingham, West Midlands, b9 5ss
Novartis Investigative Site
Bristol, BS1 3NU
Novartis Investigative Site
East Yorkshire, HU16 5JQ
Novartis Investigative Site
Exeter, EX2 5DW
Novartis Investigative Site
Liverpool, L14 3PE
Novartis Investigative Site
Newcastle upon Tyne, NE1 4LP
Novartis Investigative Site
Penarth, Vale of Glamorgan, CF64 2XX
Novartis Investigative Site
Southampton, Hampshire, SO16 6YD
Spain5 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, Madrid, 28046
Novartis Investigative Site
Palma de Mallorca, Balearic Islands, 07120
Novartis Investigative Site
Seville, Andalusia, 41013
Novartis Investigative Site
Valencia, Valencia, 46026
Germany4 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
München, 81241
Novartis Investigative Site
Tübingen, 72076
Switzerland3 sites
Novartis Investigative Site
Basel, Switzerland, 4031
Novartis Investigative Site
Sankt Gallen, 9007
Novartis Investigative Site
Zurich, Switzerland, 8032
About this study
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
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.
Read the 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
- Being tested
- Tobramycin Inhalation Powder, Tobramycin inhalation solution, Colistimethate
- Keywords
- Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI,, colistimethate, Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI, colistimethate
- Medical subject headings
- Cystic Fibrosis, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobramycin Inhalation PowderDrug
Also called TIP
Tobramycin Inhalation Powder was administered via TOBI® Podhaler (T-326 inhaler).
Tobramycin inhalation solutionDrug
Also called TIS
Tobramycin inhalation solution was administered via nebuliser
ColistimethateDrug
Also called COLI
Colistimethate was administered via nebuliser.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Tobramycin Inhalation Powder |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)
Secondary outcomes (4)
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.
Measured: days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)
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.
Measured: days (d) 1, 28, 57, 84
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.
Measured: days 1, 28, 57, 84, 112
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.
Measured: days 1, 28, 57, 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2013 (estimated)
- Study startAug 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01844778
- Sponsor's protocol ID
- CTBM100C2403
- Other IDs
- 2012-001565-33
- Status last verified
- Jul 2016
- First submitted
- 29 Apr 2013
- Last updated
- 27 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28614995
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01844778
- Acronym / sponsor ID
- CTBM100C2403
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI,, colistimethate, Cystic Fibrosis, Pseudomonas aeruginosa, FEV1, tobramycin inhalation powder, TOBI, colistimethate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 1 May 2013 (estimated)
- Results
- Posted 24 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TIS/TIP | Active comparator | Drug: Tobramycin Inhalation Powder, Drug: Tobramycin inhalation solutionDuring 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. |
| COLI/TIP | Active comparator | Drug: Tobramycin Inhalation Powder, Drug: ColistimethateDuring 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. |
| TIP/TIP | Active comparator | Drug: Tobramycin Inhalation PowderDuring 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. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tobramycin Inhalation PowderAlso: TIPTobramycin Inhalation Powder was administered via TOBI® Podhaler (T-326 inhaler). | Drug | COLI/TIP, TIP/TIP, TIS/TIP |
| Tobramycin inhalation solutionAlso: TISTobramycin inhalation solution was administered via nebuliser | Drug | TIS/TIP |
| ColistimethateAlso: COLIColistimethate was administered via nebuliser. | Drug | COLI/TIP |
Primary outcome
Mean Total Administration Time
Time frame: days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)
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.
4 secondary outcomes
Change in P. Aeruginosa Sputum Density
Time frame: days 1, 28 (cycle 1); 57, 84, 112 (cycle 2)
Number of Participants With Any Contaminated Delivery Device
Time frame: days (d) 1, 28, 57, 84
Minimum Inhibitory Concentration (MIC) - MIC50 and MIC90 Tobramycin Values
Time frame: days 1, 28, 57, 84, 112
Number of Participants With Post-inhalation Bronchospasm
Time frame: days 1, 28, 57, 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28614995Greenwood 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
21 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tobramycin Inhalation Powder, Tobramycin inhalation solution and Colistimethate in people with Cystic Fibrosis, run by Novartis Pharmaceuticals at 21 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, Spain, Germany, Switzerland, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Total Administration Time (time frame: days 22 through 28 (cycle 1), days 78 through 84 (cycle 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01844778, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2016.