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Aztreonam Lysine for Pseudomonas Infection Eradication Study (ALPINE)

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ClinicalTrials.gov Identifier: NCT01375049
Recruitment Status : Completed
First Posted : June 17, 2011
Results First Posted : July 1, 2014
Last Update Posted : July 17, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Intervention Drug: Aztreonam for Inhalation Solution (AZLI)
Enrollment 105
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.
Pre-assignment Details 109 participants were screened; 105 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Arm/Group Title AZLI
Hide Arm/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.
Period Title: Overall Study
Started 105
Completed 55
Not Completed 50
Reason Not Completed
Adverse Event             2
Lost to Follow-up             1
Withdrawal by Subject             2
Protocol-Specified Withdrawal Criteria             45
Arm/Group Title AZLI
Hide Arm/Group Description Participants received one 28-day course of 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.
Overall Number of Baseline Participants 105
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 105 participants
6.26  (4.743)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 105 participants
3 months to < 2 years 24
≥ 2 years to < 6 years 25
≥ 6 years to < 18 years 56
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants
Female
47
  44.8%
Male
58
  55.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 105 participants
Asian 1
Black or African Heritage 1
White 99
Other 2
Not Permitted to be Recorded 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 105 participants
Hispanic 5
Not Hispanic 93
Not Permitted to be Recorded 7
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 105 participants
France 12
United States 56
Spain 6
Poland 3
Belgium 11
Austria 3
Netherlands 5
Germany 4
Italy 5
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 105 participants
24.8  (15.69)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 105 participants
113.9  (33.02)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 105 participants
17.1  (2.57)
Presence of Pseudomonas aeruginosa (PA)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 105 participants
Present at baseline 45
Absent at baseline 57
[1]
Measure Description: Of the 105 participants in the safety analysis set, 3 participants did not provide baseline samples (ie, oropharyngeal swab sample). All participants had a positive PA culture within 30 days of baseline.
1.Primary Outcome
Title Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Evaluable Analysis Set)
Hide 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.
Time Frame Day 28 to Day 196
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable Analysis Set
Arm/Group Title AZLI - Evaluable Analysis Set
Hide Arm/Group Description:

Participants received one 28-day course of 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.

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.

Overall Number of Participants Analyzed 79
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58.2
(47.4 to 69.1)
2.Primary Outcome
Title Percentage of Participants With PA-negative Cultures at All Time Points After Cessation of Active Treatment (Sensitivity Analysis Set)
Hide 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.
Time Frame Day 28 to Day 196
Hide Outcome Measure Data
Hide Analysis Population Description
Sensitivity Analysis Set
Arm/Group Title AZLI - Sensitivity Analysis Set
Hide Arm/Group Description:

Participants received one 28-day course of 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.

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.

Overall Number of Participants Analyzed 98
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
46.9
(37.1 to 56.8)
3.Secondary Outcome
Title Change From Baseline in FEV1% Predicted
Hide 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.
Time Frame Baseline to Days 28, 56, 112, and 196
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Sensitivity Analysis Set ≥ 6 years of age with available data for this assessment were analyzed.
Arm/Group Title AZLI - Met Primary Efficacy Endpoint AZLI - Did Not Meet Primary Efficacy Endpoint
Hide Arm/Group Description:

This group included participants who met the primary efficacy endpoint, defined as having PA-negative cultures at all time points after cessation of active treatment through Day 196.

Participants received one 28-day course of 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.

This group included participants who did not meet the primary efficacy endpoint, defined as having any PA-positive culture at Day 28 through Day 196 or having used anti-PA antibiotics through Day 196.

Participants received one 28-day course of 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.

Overall Number of Participants Analyzed 25 27
Mean (Standard Deviation)
Unit of Measure: percentage of FEV1% predicted
Change at Day 28 (n=25 [met], 26 [did not meet]) -0.23  (10.373) -0.38  (12.347)
Change at Day 56 (n=25 [met], 26 [did not meet]) -0.20  (10.949) -4.24  (7.513)
Change at Day 112 (n=25 [met], 19 [did not meet]) 0.32  (9.830) -5.10  (7.948)
Change at Day 196 (n=25 [met], 8 [did not meet]) -2.47  (8.895) -8.85  (11.510)
4.Secondary Outcome
Title Change From Baseline in CFQ-R RSS Score
Hide 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.
Time Frame Baseline to Days 28, 56, 112, and 196
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Sensitivity Analysis Set ≥ 6 years of age with available data for this assessment were analyzed.
Arm/Group Title AZLI - Met Primary Efficacy Endpoint AZLI - Did Not Meet Primary Efficacy Endpoint
Hide Arm/Group Description:

This group included participants who met the primary efficacy endpoint, defined as having PA-negative cultures at all time points after cessation of active treatment through Day 196.

Participants received one 28-day course of 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.

This group included participants who did not meet the primary efficacy endpoint, defined as having any PA-positive culture at Day 28 through Day 196 or having used anti-PA antibiotics through Day 196.

Participants received one 28-day course of 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.

Overall Number of Participants Analyzed 25 31
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change at Day 28 (n=24 [met], 29 [did not meet]) 8.33  (15.883) 5.36  (8.937)
Change at Day 56 (n=24 [met], 27 [did not meet]) 6.37  (16.433) 6.17  (11.040)
Change at Day 112 (n=24 [met], 21 [did not meet]) 5.79  (14.397) 1.46  (14.636)
Change at Day 196 (n=24 [met], 10 [did not meet]) 6.13  (18.002) 5.83  (9.663)
5.Secondary Outcome
Title Percentage of Participants With PA-negative Cultures
Hide Description The percentage of participants with a PA-negative culture was summarized at each visit.
Time Frame Days 28, 56, 112, and 196
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title AZLI
Hide Arm/Group Description:
Participants received one 28-day course of 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.
Overall Number of Participants Analyzed 101
Measure Type: Number
Unit of Measure: percentage of participants
Day 28 89.1
Day 56 75.2
Day 112 63.4
Day 196 47.5
6.Secondary Outcome
Title Use of Additional (Non-study) Antipseudomonal Antibiotics
Hide Description The percentage of participants who used additional (non-study) antipseudomonal antibiotics (an indication of PA exacerbation) while on treatment and posttreatment was summarized.
Time Frame Baseline to Day 196
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI
Hide Arm/Group Description:
Participants received one 28-day course of 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.
Overall Number of Participants Analyzed 105
Measure Type: Number
Unit of Measure: percentage of participants
On-treatment 1.9
Posttreatment 43.8
7.Secondary Outcome
Title Change From Baseline in Weight
Hide Description [Not Specified]
Time Frame Baseline to Days 28, 56, 112, and 196
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI
Hide Arm/Group Description:
Participants received one 28-day course of 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.
Overall Number of Participants Analyzed 105
Mean (Standard Deviation)
Unit of Measure: kg
Change at Day 28 (On-Treatment, n = 104) 0.3  (0.70)
Change at Day 56 (Posttreatment, n = 101) 0.5  (0.72)
Change at Day 112 (Posttreatment, n = 90) 0.8  (1.02)
Change at Day 196 (Posttreatment, n = 69) 1.5  (3.8)
8.Secondary Outcome
Title Change From Baseline in Height
Hide Description [Not Specified]
Time Frame Baseline to Days 28, 56, 112, and 196
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI
Hide Arm/Group Description:
Participants received one 28-day course of 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.
Overall Number of Participants Analyzed 105
Mean (Standard Deviation)
Unit of Measure: cm
Change at Day 28 (On-Treatment, n = 104) 0.6  (0.87)
Change at Day 56 (Posttreatment, n = 101) 1.4  (1.27)
Change at Day 112 (Posttreatment, n = 90) 2.6  (2.00)
Change at Day 196 (Posttreatment, n = 69) 4.5  (2.86)
9.Secondary Outcome
Title Change From Baseline in Body Mass Index (BMI)
Hide Description [Not Specified]
Time Frame Baseline to Days 28, 56, 112, and 196
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title AZLI
Hide Arm/Group Description:
Participants received one 28-day course of 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.
Overall Number of Participants Analyzed 105
Mean (Standard Deviation)
Unit of Measure: kg/m^2
Change at Day 28 (On-Treatment, n = 104) 0.1  (0.57)
Change at Day 56 (Posttreatment, n = 101) 0.1  (0.71)
Change at Day 112 (Posttreatment, n = 90) 0.0  (0.97)
Change at Day 196 (Posttreatment, n = 69) 0.0  (0.93)
10.Secondary Outcome
Title Pharmacokinetics (PK) Peak and Trough Plasma Concentrations of Aztreonam
Hide 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.
Time Frame Day 1 (1 hour postdose) and Day 28 (immediately prior to dosing)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set < 6 years of age with evaluable PK profiles were analyzed.
Arm/Group Title AZLI
Hide Arm/Group Description:
Participants received one 28-day course of 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.
Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 (1 hour postdose, n = 40) 578  (560.0)
Day 28 (immediately prior to dosing, n = 43) 125  (166.3)
Time Frame Baseline to Day 28 plus 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZLI
Hide Arm/Group Description

Treatment-emergent adverse events and treatment-emergent serious adverse events were collected from Baseline through Day 28 plus 30 days.

Participants received one 28-day course of 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.

All-Cause Mortality
AZLI
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
AZLI
Affected / at Risk (%)
Total   8/105 (7.62%) 
Hepatobiliary disorders   
Hepatitus acute  1  1/105 (0.95%) 
Infections and infestations   
Infectious mononucleosis  1  1/105 (0.95%) 
Pseudomonas infection  1  2/105 (1.90%) 
Viral infection  1  1/105 (0.95%) 
Investigations   
Pseudomonas test positive  1  1/105 (0.95%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/105 (0.95%) 
Lung disorder  1  1/105 (0.95%) 
Skin and subcutaneous tissue disorders   
Rash  1  1/105 (0.95%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZLI
Affected / at Risk (%)
Total   66/105 (62.86%) 
Gastrointestinal disorders   
Diarrhoea  1  7/105 (6.67%) 
Vomiting  1  7/105 (6.67%) 
General disorders   
Pyrexia  1  15/105 (14.29%) 
Infections and infestations   
Rhinitis  1  8/105 (7.62%) 
Investigations   
Pseudomonas test positive  1  20/105 (19.05%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  42/105 (40.00%) 
Rhinorrhoea  1  10/105 (9.52%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
EMail: ClinicalTrialDisclosures@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01375049    
Other Study ID Numbers: GS-US-205-0162
First Submitted: June 15, 2011
First Posted: June 17, 2011
Results First Submitted: May 29, 2014
Results First Posted: July 1, 2014
Last Update Posted: July 17, 2014