Clinical Trial Results:
Open-Label Phase 2 Trial to Evaluate the Safety and Efficacy of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Pediatric Patients with Cystic Fibrosis (CF) and New Onset Lower Respiratory Tract Culture Positive for Pseudomonas aeruginosa (PA)
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Summary
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EudraCT number |
2011-001255-36 |
Trial protocol |
DE BE FR AT ES NL IE IT Outside EU/EEA |
Global end of trial date |
29 May 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Mar 2016
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First version publication date |
05 Aug 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GS-US-205-0162
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01375049 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Gilead Sciences
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Sponsor organisation address |
333 Lakeside Drive, Foster City, CA, United States, 94404
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Public contact |
Clinical Trial Mailbox, Gilead Sciences International Ltd, ClinicalTrialDisclosures@gilead.com
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Scientific contact |
Clinical Trial Mailbox, Gilead Sciences International Ltd, ClinicalTrialDisclosures@gilead.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000827-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 May 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 May 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This is an open-label, multi-center study in pediatric patients age 3 months to less than 18 years with cystic fibrosis (CF) and newly detected Pseudomonas
aeruginosa (PA) pulmonary colonization/infection. All eligible participants will be treated with a 28-day course of Aztreonam for Inhalation Solution (AZLI) 75 mg 3
times daily. After completion of study drug, subjects will be followed up through Day 196 for safety and recurrence of PA.
The primary objective is to evaluate the proportion of participants with PA-negative cultures at all time points during a 6-month monitoring period (through Day
196) after cessation of AZLI treatment. Microbiological cultures will be obtained at Baseline, Day 28 (end of AZLI treatment), Day 56 (1 month after completing
AZLI treatment), Day 112 (3 months after completing AZLI treatment), and Day 196 (6 months after completing AZLI treatment).
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Protection of trial subjects |
The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements.
This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Oct 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 5
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
Austria: 3
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Country: Number of subjects enrolled |
Belgium: 11
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Country: Number of subjects enrolled |
France: 12
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Country: Number of subjects enrolled |
Germany: 4
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Country: Number of subjects enrolled |
Italy: 5
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Country: Number of subjects enrolled |
United States: 56
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Worldwide total number of subjects |
105
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EEA total number of subjects |
49
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
24
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Children (2-11 years) |
65
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Adolescents (12-17 years) |
16
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled at a total of 46 study sites in the United States and Europe. The first participant was screened on 04 October 2011. The last participant observation occurred on 29 May 2013. | ||||||||||||||||
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Pre-assignment
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Screening details |
109 participants were screened; 105 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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AZLI | ||||||||||||||||
Arm description |
Participants received one 28-day course of Aztreonam for Inhalation Solution (AZLI), then were followed for a 24-week period (through Day 196). AZLI 75 mg was administered 3 times daily via the investigational eFlow® nebulizer. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
AZLI
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Investigational medicinal product code |
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Other name |
Cayston®
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Pharmaceutical forms |
Nebuliser solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
AZLI 75 mg administered 3 times daily via the investigational eFlow® nebulizer
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AZLI
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Reporting group description |
Participants received one 28-day course of Aztreonam for Inhalation Solution (AZLI), then were followed for a 24-week period (through Day 196). AZLI 75 mg was administered 3 times daily via the investigational eFlow® nebulizer. | ||
Subject analysis set title |
Evaluable Analysis Set
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The Evaluable Analysis Set consists of participants who completed study drug and did not receive an additional antipseudomonal antibiotic during the 28-day AZLI treatment course, and either completed the study through Day 196 with PA-negative cultures at every visit without the use of additional antipseudomonal antibiotics from Day 28 through Day 196 or had evidence of a positive PA-positive culture from Day 28 through Day 196.
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Subject analysis set title |
Sensitivity Analysis Set
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The Sensitivity Analysis Set consists of participants who completed study drug and did not receive an additional antipseudomonal antibiotic during the 28-day AZLI treatment course, and either completed the study through Day 196 with PA-negative cultures at every visit without the use of additional antipseudomonal antibiotics from Day 28 through Day 196 or had evidence of a PA-positive culture from Day 28 through Day 196 or used any additional antipseudomonal antibiotics from Day 28 through Day 196.
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Subject analysis set title |
Sensitivity Analysis Set-Met Primary Efficacy Endpoint
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in the Sensitivity Analysis Set ≥ 6 years of age who met the primary efficacy endpoint with available data for this assessment were analyzed.
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Subject analysis set title |
Sensitivity Analysis Set-Didn't Meet Primary Efficacy Endpoint
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in the Sensitivity Analysis Set ≥ 6 years of age who did not meet the primary efficacy endpoint with available data for this assessment were analyzed.
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Subject analysis set title |
Full Analysis Set < 6 years of age with evaluable PK profiles
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in the Full Analysis Set < 6 years of age with evaluable PK profiles were analyzed.
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Subject analysis set title |
Full Analysis Set - no additional antipseudomonal antibiotic
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants from the Full Analysis Set who completed study drug and did not receive an additional antipseudomonal antibiotic during the 28-day AZLI treatment course were included in the analysis at all time points.
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End point title |
Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set) [1] | ||||||||
End point description |
The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Evaluable Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 28 to Day 196
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No intergroup analysis was performed because the study was single-arm, and no analysis against a historic rate was performed because the study was not designed to demonstrate superiority or noninferiority. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set) [2] | ||||||||
End point description |
The percentage of participants with PA-negative cultures at all time points after cessation of active treatment at Day 28 (assessed at Days 56, 112, and 196) was summarized for the Sensitivity Analysis Set.
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End point type |
Primary
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End point timeframe |
Day 28 to Day 196
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No intergroup analysis was performed because the study was single-arm, and no analysis against a historic rate was performed because the study was not designed to demonstrate superiority or noninferiority. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in FEV1% Predicted | ||||||||||||||||||||||||
End point description |
Spirometry assessments were performed only in participants ≥ 6 years of age. Forced expiratory volume in 1 second (FEV1) % predicted was defined as FEV1 of the participant divided by the average FEV1 in the population for any person of similar age, sex and body composition.
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End point type |
Secondary
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End point timeframe |
Baseline to Days 28, 56, 112, and 196
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change From Baseline in CFQ-R RSS Score | ||||||||||||||||||||||||
End point description |
Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire – Revised (CFQ-R) Respiratory Symptoms Scale (RSS) only in participants ≥ 6 years of age. The range of scores (units) is 0 to 100 with higher scores indicating fewer symptoms.
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End point type |
Secondary
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End point timeframe |
Baseline to Days 28, 56, 112, and 196
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of Participants With PA-negative Cultures | ||||||||||||||||
End point description |
The percentage of participants with a PA-negative culture was summarized at each visit.
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End point type |
Secondary
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End point timeframe |
Days 28, 56, 112, and 196
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Use of Additional (Non-study) Antipseudomonal Antibiotics | ||||||||||||
End point description |
The percentage of participants who used additional (non-study) antipseudomonal antibiotics (an indication of PA exacerbation) while on treatment and posttreatment was summarized.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 196
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Weight | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to Days 28, 56, 112, and 196
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Height | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to Days 28, 56, 112, and 196
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Body Mass Index (BMI) | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to Days 28, 56, 112, and 196
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam | ||||||||||||
End point description |
The plasma concentration of aztreonam for participants < 6 years of age was obtained 1 hour after the first dose of AZLI on Day 1 and immediately prior to the last dose of AZLI on Day 28.
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End point type |
Secondary
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End point timeframe |
Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing)
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to Day 28 plus 30 days
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
AZLI
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Reporting group description |
Participants received one 28-day course of Aztreonam for Inhalation Solution (AZLI), then were followed for a 24-week period (through Day 196). AZLI 75 mg was administered 3 times daily via the investigational eFlow® nebulizer. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Sep 2012 |
Increased enrollment from approximately 80 subjects to approximately 105 subjects to meet the PIP commitment of 60 subjects evaluable for the primary endpoint and clarified enrollment of 10 subjects evaluable for the primary endpoint in each age subset throughout the protocol. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
