PALS: Safety of AZLI in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa in the Lower Airways

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01404234
• Collaborator: (none)
• Enrollment: 61
• Locations: 29
• Arm: 1
• Duration (Months): 16
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an open-label, multicenter study in children ≤ 12 years of age with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (PA) infection in the lower airways using three 28-day courses of Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily, each followed by 28 days off AZLI. The total treatment duration was to be 6 months.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Pseudomonas Aeruginosa	Drug: AZLI	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Phase 3 Trial to Evaluate the Safety of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Children With Cystic Fibrosis (CF) and Chronic Pseudomonas Aeruginosa (PA) in the Lower Airways
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open-label AZLI Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment.	Drug: AZLI; AZLI 75 mg was administered 3 times daily via the investigational nebulizer.; Other Names: Cayston®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons [Baseline to Day 168]

   Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method.

Secondary Outcome Measures

1. Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years [Baseline to Day 28, 84, and 140]

   The change in FEV1 % predicted was assessed at the end of each 28-day AZLI treatment course. FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition.

2. Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years [Baseline to Day 28, 84, and 140]

   The change in CFQ-R RSS score was assessed at the end of each 28-day AZLI treatment course. The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms.

3. Change in Pseudomonas Aeruginosa (PA) Sputum Density [Baseline to Day 28, 84, and 140]

   The change in PA sputum density (log10 colony-forming units per gram [cfu/g]) was assessed at the end of each 28-day AZLI treatment course.

4. Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics [Baseline to Day 168]

   The percentage of participants who used additional (non-study) antipseudomonal antibiotics (IV, inhaled, oral, IV/inhaled, IV/inhaled/oral) was summarized (number and percent) for all subjects.

5. Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event [Baseline to Day 168]

6. Number of Days Participants Were Hospitalized Due to a Respiratory Event [Baseline to Day 168]

   The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported.

7. Percentage of Participants With Pulmonary Exacerbations [Baseline to Day 168]

   Pulmonary exacerbations were defined as respiratory hospitalizations or discrete courses of non-study IV/inhaled antipseudomonal antibiotics. Use of oral antibiotics alone for respiratory signs or symptoms was considered to be representative of milder clinical events and, therefore, was not included in the definition of pulmonary exacerbations.

8. Time to Pulmonary Exacerbation [Baseline to Day 168]

   The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.

9. Percentage of Participants With Study-drug Induced Bronchospasm [Pretreatment at Baseline to 30 minutes following treatment]

   Study-drug induced bronchospasm (airway reactivity) was assessed at the baseline visit as the percent change in FEV1 from the pretreatment measurement to 30 minutes following treatment for subjects ≥ 6 years or as from the Investigator's assessment for subjects < 6 years.

10. Adverse Event Rates Adjusted for Study Duration [Baseline to Day 168]

    Adverse events occurring in ≥ 5% of participants adjusted for study duration were summarized. The adjustment was made by using a standardized rate calculated as the sum of study duration across patients divided by 28 for the total number of patient months. Rate calculations presented are the number of adverse events (AEs) per patient month.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:

• Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR

• Abnormal nasal transepithelial potential difference (NPD) test OR

• A genotype with 2 identifiable mutations consistent with CF AND

• One or more clinical features consistent with CF.

• Documented positive lower respiratory tract culture for PA at the screening visit plus two documented positive lower respiratory tract cultures for PA within 12 months prior to study entry (must have been a minimum 3 months apart.)

• Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would have required administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.

Exclusion Criteria:

• Use of IV or inhaled antipseudomonal antibiotics within 14 days of study entry

• Presence of a condition or abnormality that would have compromised the participant's safety or the quality of study data, in the opinion of the investigator

• History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit

• History of hypersensitivity/adverse reaction to aztreonam

• History of hypersensitivity/adverse reaction to beta-agonists

• History of lung transplantation

• Administration of any investigational drug or device within 30 days prior to screening visit or within 6 half-lives of the investigational drug (whichever was longer)

• Hospitalization for pulmonary-related illness within 28 days prior to screening visit

• Changes in or initiation of chronic azithromycin treatment within 28 days prior to screening visit

• Changes in or initiation of hypertonic saline treatment within 7 days prior to screening visit; for subjects on a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic saline was allowed

• Changes in antimicrobial, bronchodilator (BD), corticosteroid or dornase alfa medications within 7 days prior to screening visit;

• Changes in physiotherapy technique or schedule within 7 days prior to screening visit

• Abnormal renal or hepatic function results at most recent test within the previous 90 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital - Denver	Aurora	Colorado	United States	80045
2	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida	United States	32207
3	Children's Memorial Hospital	Chicago	Illinois	United States	60614
4	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
5	Children's Hospital Boston	Boston	Massachusetts	United States	02115
6	Children's Mercy Hospital & Clinics	Kansas City	Missouri	United States	64108
7	SUNY Upstate Medical University	Syracuse	New York	United States	13210
8	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
9	Baylor College of Medicine	Houston	Texas	United States	77030
10	University of Utah	Salt Lake City	Utah	United States	84108
11	C.H.U de Bordeaux	Bordeaux		France
12	Centre Hospitalier Robert Bissons	Lisieux		France
13	Hopital Necker Enfants Malades	Paris Cedex 15		France
14	Charite Campus Virchow Klinikum	Berlin		Germany
15	Universitatsklinik St. Josef-Hospital	Bochum		Germany
16	Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde	Erlandgen		Germany
17	Universitatsklinikum Essen	Essen		Germany
18	J.W. Goethe University Hopsital	Frankfurt		Germany
19	Azienda Ospedaliero Universitaria - Policlinico di Catania	Catania		Italy
20	A. Meyer Children Hospital Florence	Florence		Italy
21	Azienda Ospedaliera Instituti Ospitalieri di Verona	Verona		Italy
22	Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem	Gdansk		Poland
23	Instytut Gruzlicy I Chorob Pluc	Rabka Zdroj		Poland
24	Instytut Matki i Dziecka	Warszawa		Poland
25	Pediatric Pneunmonology and Cystic Fibrosis Clinic	Barcelona		Spain
26	Hospital Infantil La Paz	Madrid		Spain
27	Hospital Infantil Universitario Nino Jesus	Madrid		Spain
28	Hospital Ramon y Cajal	Madrid		Spain
29	Hosp. Mat-Inf. Carlos Haya	Malaga		Spain

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Mark Bresnik, M.D., Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01404234
• Other Study ID Numbers: GS-US-205-0160
• First Posted: Jul 28, 2011
• Last Update Posted: May 29, 2014
• Last Verified: May 1, 2014

• Keywords provided by Gilead Sciences: Cystic fibrosis; CF; PA; Pseudomonas aeruginosa; AZLI; aztreonam; Chronic Pseudomonas aeruginosa
• Additional relevant MeSH terms: Pseudomonas Infections; Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at a total of 25 study sites in the United States and Europe. The first participant was screened on 29 December 2011. The last participant observation was on 03 April 2013.
Pre-assignment Detail	74 participants were screened; 61 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set.

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of Aztreonam for Inhalation Solution (AZLI), each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Period Title: Overall Study
STARTED	61
COMPLETED	59
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Overall Participants	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.0 (2.94)
Age, Customized (participants) [Number]
< 2 years	2 3.3%
≥ 2 years to < 6 years	7 11.5%
≥ 6 years to ≤ 12 years	52 85.2%
Sex: Female, Male (Count of Participants)
Female	31 50.8%
Male	30 49.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 8.2%
Not Hispanic or Latino	55 90.2%
Unknown or Not Reported	1 1.6%
Race/Ethnicity, Customized (participants) [Number]
Black or African Heritage	2 3.3%
White	55 90.2%
Other	3 4.9%
Not Permitted	1 1.6%
Region of Enrollment (participants) [Number]
France	5 8.2%
United States	29 47.5%
Spain	5 8.2%
Poland	11 18%
Germany	5 8.2%
Italy	6 9.8%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	16.3 (1.66)
Forced expiratory volume in 1 second (FEV1) % predicted (percentage of FEV1 % predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of FEV1 % predicted]	80.31 (19.494)
FEV1 (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	1.67 (0.627)
Forced vital capacity (FVC) (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	2.11 (0.687)
FEV25-75 (liters/sec) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters/sec]	1.82 (1.169)
CFQ-R RSS Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	71.73 (17.327)
Presence of Pseudomonas aeruginosa (PA) (participants) [Number]
Present	58 95.1%
Absent	3 4.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons
Description	Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set (enrolled and received at least 1 dose of study medication) who completed the study or discontinued study drug due to safety or tolerability reasons were analyzed. Two participants voluntarily withdrew from the study prior to completion (not due to AEs/safety or tolerability reasons).

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	59
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

2. Secondary Outcome

Title	Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years
Description	The change in FEV1 % predicted was assessed at the end of each 28-day AZLI treatment course. FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition.
Time Frame	Baseline to Day 28, 84, and 140

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set ≥ 6 years of age were analyzed.

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	52
Change at Day 28 (on-treatment, n = 52)	4.73 (11.703)
Change at Day 84 (on-treatment, n = 51)	1.72 (12.516)
Change at Day 140 (on-treatment, n = 50)	1.65 (10.340)

3. Secondary Outcome

Title	Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years
Description	The change in CFQ-R RSS score was assessed at the end of each 28-day AZLI treatment course. The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms.
Time Frame	Baseline to Day 28, 84, and 140

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set ≥ 6 years of age were analyzed.

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	52
Change at Day 28 (on-treatment, n = 51)	8.66 (14.903)
Change at Day 84 (on-treatment, n = 48)	9.38 (18.243)
Change at Day 140 (on-treatment, n = 48)	5.90 (15.372)

4. Secondary Outcome

Title	Change in Pseudomonas Aeruginosa (PA) Sputum Density
Description	The change in PA sputum density (log10 colony-forming units per gram [cfu/g]) was assessed at the end of each 28-day AZLI treatment course.
Time Frame	Baseline to Day 28, 84, and 140

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set ≥ 6 years of age were analyzed.

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
Change at Day 28 (on-treatment, n = 24)	-2.6 (2.50)
Change at Day 84 (on-treatment, n = 25)	-2.0 (2.14)
Change at Day 140 (on-treatment, n = 23)	-1.2 (2.13)

5. Secondary Outcome

Title	Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics
Description	The percentage of participants who used additional (non-study) antipseudomonal antibiotics (IV, inhaled, oral, IV/inhaled, IV/inhaled/oral) was summarized (number and percent) for all subjects.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
Never used non-study antipseudomonal antibiotics	42.6 69.8%
Used non-study antipseudomonal antibiotics	57.4 94.1%

6. Secondary Outcome

Title	Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
Never hospitalized	82.0 134.4%
Hospitalized at least once	18.0 29.5%

7. Secondary Outcome

Title	Number of Days Participants Were Hospitalized Due to a Respiratory Event
Description	The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	11
Mean (Standard Deviation) [days]	12.6 (8.90)

8. Secondary Outcome

Title	Percentage of Participants With Pulmonary Exacerbations
Description	Pulmonary exacerbations were defined as respiratory hospitalizations or discrete courses of non-study IV/inhaled antipseudomonal antibiotics. Use of oral antibiotics alone for respiratory signs or symptoms was considered to be representative of milder clinical events and, therefore, was not included in the definition of pulmonary exacerbations.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
No pulmonary exacerbation	62.3 102.1%
At least one pulmonary exacerbation	37.7 61.8%

9. Secondary Outcome

Title	Time to Pulmonary Exacerbation
Description	The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
Median (95% Confidence Interval) [days]	176.0

10. Secondary Outcome

Title	Percentage of Participants With Study-drug Induced Bronchospasm
Description	Study-drug induced bronchospasm (airway reactivity) was assessed at the baseline visit as the percent change in FEV1 from the pretreatment measurement to 30 minutes following treatment for subjects ≥ 6 years or as from the Investigator's assessment for subjects < 6 years.
Time Frame	Pretreatment at Baseline to 30 minutes following treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
Number [percentage of participants]	3.3 (6.06) 5.4%

11. Secondary Outcome

Title	Adverse Event Rates Adjusted for Study Duration
Description	Adverse events occurring in ≥ 5% of participants adjusted for study duration were summarized. The adjustment was made by using a standardized rate calculated as the sum of study duration across patients divided by 28 for the total number of patient months. Rate calculations presented are the number of adverse events (AEs) per patient month.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
Measure Participants	61
Cough	0.163
Nasal congestion	0.050
Rhinorrhoea	0.041
Wheezing	0.033
Sputum increased	0.033
Productive Cough	0.030
Lung disorder	0.025
Haemoptysis	0.019
Rhonchi	0.019
Oropharyngeal pain	0.017
Rales	0.017
Respiratory tract congestion	0.014
Abdominal pain	0.030
Diarrhoea	0.019
Vomiting	0.019
Abdominal pain upper	0.017
Pyrexia	0.061
Fatigue	0.025
Rhinitis	0.030
Pulmonary function test decreased	0.014
Forced expiratory volume decreased	0.011
Decreased appetite	0.017

Adverse Events

Time Frame	Baseline to Day 168
Arm/Group Title	AZLI
Arm/Group Description	Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer.
All Cause Mortality
	AZLI
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AZLI
	Affected / at Risk (%)	# Events
Total	13/61 (21.3%)
Gastrointestinal disorders
Appendiceal mucocoele	1/61 (1.6%)
Nausea	1/61 (1.6%)
Infections and infestations
Gastrointestinal infection	1/61 (1.6%)
Bronchopneumonia	2/61 (3.3%)
Infective pulmonary exacerbation of cystic fibrosis	2/61 (3.3%)
Metabolism and nutrition disorders
Hypoglycaemia	1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders
Lung disorder	5/61 (8.2%)
Other (Not Including Serious) Adverse Events
	AZLI
	Affected / at Risk (%)	# Events
Total	50/61 (82%)
Gastrointestinal disorders
Diarrhoea	7/61 (11.5%)
Abdominal pain	6/61 (9.8%)
Abdominal pain upper	5/61 (8.2%)
Vomiting	6/61 (9.8%)
General disorders
Fatigue	8/61 (13.1%)
Pyrexia	16/61 (26.2%)
Infections and infestations
Rhinitis	10/61 (16.4%)
Investigations
Pulmonary function test decreased	5/61 (8.2%)
Forced expiratory volume decreased	4/61 (6.6%)
Metabolism and nutrition disorders
Decreased appetite	5/61 (8.2%)
Respiratory, thoracic and mediastinal disorders
Wheezing	9/61 (14.8%)
Cough	36/61 (59%)
Sputum increased	9/61 (14.8%)
Productive cough	8/61 (13.1%)
Haemoptysis	6/61 (9.8%)
Rhonchi	6/61 (9.8%)
Rales	5/61 (8.2%)
Nasal congestion	12/61 (19.7%)
Respiratory tract congestion	5/61 (8.2%)
Rhinorrhoea	10/61 (16.4%)
Oropharyngeal pain	6/61 (9.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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