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Phase 3 Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy Regimen for the Treatment of Chronic Pseudomonas Aeruginosa Infection in Patients With CF (AZLI CAT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01641822
First received: July 13, 2012
Last updated: April 6, 2016
Last verified: April 2016
Results First Received: January 15, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Interventions: Drug: AZLI
Drug: Placebo to match AZLI
Drug: Tobramycin inhalation solution

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled at study sites in the United States. The first participant was screened on 13 December 2012. The last study visit occurred on 15 January 2015.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Following enrollment, participants received tobramycin inhalation solution (TIS) in the TIS Run-In Phase, and if still eligible were randomized 1 to 1 to receive aztreonam for inhalation solution (AZLI) or placebo to match AZLI alternating with TIS in the Comparative Phase.

Reporting Groups
  Description
TIS Run-In Treatment Group Enrolled participants received 28 days of TIS (300 mg 2 times daily) during the run-in phase.
AZLI Participants were randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens AZLI (75 mg 3 times daily) for 28 days followed by TIS (300 mg 2 times daily) for 28 days.
Placebo Participants were randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS (300 mg 2 times daily) for 28 days.

Participant Flow for 2 periods

Period 1:   Run-in Phase
    TIS Run-In Treatment Group     AZLI     Placebo  
STARTED     107     0     0  
COMPLETED     93 [1]   0     0  
NOT COMPLETED     14     0     0  
Noncompliance with study drug                 1                 0                 0  
Adverse Event                 3                 0                 0  
Withdrew consent                 1                 0                 0  
Protocol-specified criteria for withdraw                 9                 0                 0  
[1] 3 participants who completed the TIS Run-In Phase did not continue to the Comparative Phase.

Period 2:   Comparative Phase
    TIS Run-In Treatment Group     AZLI     Placebo  
STARTED     0 [1]   43     47  
Received Randomized Study Drug Treatment     0     42     46  
COMPLETED     0     37     37  
NOT COMPLETED     0     6     10  
Noncompliance with study drug                 0                 1                 0  
Investigator's discretion                 0                 0                 1  
Pregnancy                 0                 0                 1  
Adverse event, serious fatal                 0                 1                 0  
Withdrew consent                 0                 3                 7  
Protocol-specified criteria for withdraw                 0                 1                 1  
[1] Participants continuing into the Comparative Phase were randomized to the AZLI or Placebo group.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Analysis Set: all randomized participants

Reporting Groups
  Description
AZLI Participants were randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI (75 mg 3 times daily) for 28 days followed by TIS (300 mg 2 times daily) for 28 days.
Placebo Participants were randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: placebo to match AZLI for 28 days followed by TIS (300 mg 2 times daily) for 28 days.
Total Total of all reporting groups

Baseline Measures
    AZLI     Placebo     Total  
Number of Participants  
[units: participants]
  43     47     90  
Age  
[units: years]
Mean (Standard Deviation)
  28.8  (12.10)     28.0  (10.88)     28.4  (11.42)  
Age, Customized  
[units: participants]
     
6 - 12 years     3     1     4  
13 - 17 years     5     6     11  
≥ 18 years     35     40     75  
Gender  
[units: participants]
     
Female     24     28     52  
Male     19     19     38  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     5     4     9  
Not Hispanic or Latino     38     43     81  
Unknown or Not Reported     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     0     1     1  
White     41     45     86  
Other     2     1     3  
Region of Enrollment  
[units: participants]
     
United States     43     47     90  
FEV1 % predicted at Day 1 [1]
[units: percentage of FEV1 % predicted]
Mean (Standard Deviation)
  49.95  (17.500)     50.25  (15.131)     50.11  (16.213)  
CFQ-R Respiratory Score at Day 1 [2]
[units: units on a scale]
Mean (Standard Deviation)
  59.72  (18.408)     64.24  (15.044)     62.11  (16.773)  
[1] Forced expiratory volume (FEV)1 is defined as the maximal volume of air that can be exhaled in 1 second. FEV1 % predicted is defined as FEV1 of the participant divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition.
[2] Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS). The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms.



  Outcome Measures
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1.  Primary:   Rate of Protocol-defined Exacerbations (PDE) From Baseline Through Week 24   [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ]

2.  Secondary:   Average Actual Change From Baseline in FEV1 % Predicted Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)   [ Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20 ]

3.  Secondary:   Percentage of Participants Who Used Non-study IV or Inhaled Antibiotics for PDEs   [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ]

4.  Secondary:   Time to First Protocol-defined Pulmonary Exacerbation   [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ]

5.  Secondary:   Rate of Hospitalizations for a Respiratory Event   [ Time Frame: Baseline in the comparative phase to the end of study (average time on study during the Comparative Phase: 155.4 days) ]

6.  Secondary:   Average Change From Baseline in the CFQ-R Respiratory Symptom Scale (RSS) Score Across All Courses of AZLI/Placebo Treatment (Weeks 4, 12 and 20)   [ Time Frame: Comparative Phase: Baseline and Weeks 4, 12 and 20 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
e-mail: ClinicalTrialDisclosures@gilead.com



Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01641822     History of Changes
Other Study ID Numbers: GS-US-205-0170
2015-000398-11 ( EudraCT Number )
Study First Received: July 13, 2012
Results First Received: January 15, 2016
Last Updated: April 6, 2016
Health Authority: United States: Food and Drug Administration