Aztreonam for Inhalation Solution vs Tobramycin Inhalation Solution in Patients With Cystic Fibrosis & Pseudomonas Aeruginosa

This study has been completed.

Sponsor:

Collaborators:

Chiltern International Inc.

ClinPhone, Inc.

Covance

Information provided by:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT00757237

First received: September 22, 2008

Last updated: June 7, 2011

Last verified: June 2011

History of Changes

Results First Received: April 8, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Cystic Fibrosis
Interventions:	Drug: Aztreonam for Inhalation Solution (AZLI) Drug: Tobramycin Inhalation Solution (TIS)

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
Seventy-three sites in the United States (US) and European Union (EU) enrolled a total of 274 participants in the study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 274 participants enrolled in the study, 273 were randomized between 07 August 2008 and 12 November 2009. One subject experienced a serious adverse event (SAE) between Visits 1 and 2; this subject did not receive study drug. A total of 268 participants received study drug (136 AZLI; 132 TIS).

Reporting Groups

	Description
AZLI (75 mg TID)	AZLI (75 mg/1 mL aztreonam lysine when reconstituted in diluent [0.17% saline]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day (TID) for 28 days for each treatment cycle using the investigational nebulizer.
TIS (300 mg BID)	TIS (300 mg/5 mL) was self-administered by inhalation two times a day (BID) for 28 days for each treatment cycle using the PARI LC PLUS(TM) Nebulizer with Compressor.

Participant Flow: Overall Study

	AZLI (75 mg TID)	TIS (300 mg BID)
STARTED	137	136
Treated	136	132
COMPLETED	124	111
NOT COMPLETED	13	25
Lost to Follow-up	0	1
Protocol Violation	0	2
Physician Decision	2	3
Withdrawal by Subject	8	12
Safety or Tolerability	3	5
Unknown	0	2

Baseline Characteristics

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Reporting Groups

	Description
AZLI (75 mg TID)	AZLI (75 mg/1 mL aztreonam lysine when reconstituted in diluent [0.17% saline]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day (TID) for 28 days for each treatment cycle using the investigational nebulizer.
TIS (300 mg BID)	TIS (300 mg/5 mL) was self-administered by inhalation two times a day (BID) for 28 days for each treatment cycle using the PARI LC PLUS(TM) Nebulizer with Compressor.
Total	Total of all reporting groups

Baseline Measures

	AZLI (75 mg TID)	TIS (300 mg BID)	Total
Number of Participants [units: participants]	136	132	268
Age [units: participants]
>= 6 years to <= 12 years	8	5	13
> 12 years to < 18 years	20	26	46
>= 18 years	108	101	209
Age [units: years] Mean ± Standard Deviation	25.8 ± 9.1	25.1 ± 9.0	25.5 ± 9.0
Gender [units: participants]
Female	68	66	134
Male	68	66	134
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0	0	0
Asian	1	0	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	1	1
White	130	131	261
More than one race	0	0	0
Unknown or Not Reported	5	0	5
Region of Enrollment [units: participants]
United States	44	50	94
Europe	92	82	174
Body Mass Index (BMI) [units: kg/m^2] Mean ± Standard Deviation	20.22 ± 2.95	20.49 ± 2.82	20.35 ± 2.88
Inhaled Tobramycin Use in the Previous 12 Months [units: participants]
< 84 days	21	19	40
>= 84 days	115	113	228
Disease Severity ^[1] [units: participants]
<= 50% predicted	60	57	117
> 50% predicted	76	75	151
Forced Expiratory Volume (FEV1) Percent Predicted ^[2] [units: percent] Mean ± Standard Deviation	52.30 ± 15.56	52.24 ± 14.57	52.27 ± 15.06
Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score ^[3] [units: units on a scale] Mean ± Standard Deviation	62.87 ± 20.42	58.02 ± 20.76	60.44 ± 20.69

[1]	Forced Expiratory Volume (FEV1) percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. This baseline measure indicates the number of participants with FEV1 greater than 50% and less than or equal to 50% of the predicted value based on age, gender, and height at screening.
[2]	FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height.
[3]	The CFQ-R is a validated, patient-reported outcome tool measuring health-related quality of life for children and adults with CF. The CFQ-R contains both general and CF-specific scales. Respiratory symptoms (e.g., coughing, congestion, wheezing) are assessed with the CFQ-R Respiratory Symptoms Scale (RSS). The range of scores (units) is 0 to 100 with higher scores indicating fewer symptoms.

Outcome Measures

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1. Primary:

Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted at Day 28 [ Time Frame: Baseline and end of treatment Course 1 (Day 28) ]

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2. Primary:

Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses [ Time Frame: Baseline, and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) ]

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3. Secondary:

Relative Change From Baseline in FEV1 Percent Predicted at Day 28 in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization [ Time Frame: Baseline and end of treatment Course 1 (Day 28) ]

Show Outcome Measure 3

4. Secondary:

Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization [ Time Frame: Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) ]

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5. Secondary:

Time to Need for Intravenous (IV) Antipseudomonal Antibiotics for Respiratory Events [ Time Frame: Day 0 to Day 168 (end of study) ]

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6. Secondary:

Time to First Respiratory Hospitalization [ Time Frame: Day 0 to Day 168 (end of study) ]

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7. Other Pre-specified:

Actual Change From Baseline in CF Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28 [ Time Frame: Baseline and end of treatment Course 1 (Day 28) ]

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8. Other Pre-specified:

Mean Actual Change From Baseline in CFQ-R RSS Score Across 3 Treatment Courses [ Time Frame: Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20) ]

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9. Other Pre-specified:

Treatment Satisfaction Questionnaire for Medication (TSQM) - Global Satisfaction Results at Week 20 [ Time Frame: At Week 20 ]

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10. Other Pre-specified:

Total Number of Respiratory Hospitalizations [ Time Frame: Day 0 to Day 168 (end of study) ]

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11. Other Pre-specified:

Number of Respiratory Events Requiring IV and/or Inhaled Antipseudomonal Antibiotics (Other Than Randomized Treatment) [ Time Frame: Day 0 through Day 168 (end of study) ]

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12. Other Pre-specified:

Time to Need for Inhaled and/or IV Antipseudomonal Antibiotics for Respiratory Event (Other Than Randomized Treatment) [ Time Frame: Day 0 to Day 168 (end of study) ]

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Serious Adverse Events

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Other Adverse Events

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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:

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.

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.

Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Restriction Description:

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 scholarly 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.

Limitations and Caveats

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
No text entered.

Results Point of Contact:

Name/Title: Mark Bresnik, MD, Director, Clinical Research
Organization: Gilead Sciences, Inc.
phone: (650) 522-5934
e-mail: mark.bresnik@gilead.com

No publications provided

Responsible Party:	Mark Bresnik, MD/Medical Monitor, GSI
ClinicalTrials.gov Identifier:	NCT00757237 History of Changes
Other Study ID Numbers:	GS-US-205-0110
Study First Received:	September 22, 2008
Results First Received:	April 8, 2011
Last Updated:	June 7, 2011
Health Authority:	Austria: Federal Office for Safety in Health Care Belgium: Federal Agency for Medicinal Products and Health Products Denmark: Danish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Ireland: Irish Medicines Board Italy: The Italian Medicines Agency Netherlands: Medicines Evaluation Board Poland: Ministry of Health Portugal: National Pharmacy and Medicines Institute Spain: Ministry of Health Switzerland: Swissmedic United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

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