Clinical Trial Results:
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
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Summary
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EudraCT number |
2011-001362-18 |
Trial protocol |
DE ES FR IT Outside EU/EEA |
Global end of trial date |
03 Apr 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-205-0160
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01404234 | ||
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 |
03 Apr 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 |
03 Apr 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 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.
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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 |
29 Dec 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 |
Poland: 11
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
France: 5
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Country: Number of subjects enrolled |
Germany: 5
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
United States: 29
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Worldwide total number of subjects |
61
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EEA total number of subjects |
32
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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) |
2
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Children (2-11 years) |
45
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Adolescents (12-17 years) |
14
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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 |
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. | ||||||||||
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Pre-assignment
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Screening details |
74 participants were screened; 61 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 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. | ||||||||||
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 |
Aztreonam for Inhalation solution (AZLI) 75 mg powder and solvent for nebuliser solution administered via the investigational nebulizer at a minimum of 4 hours between doses.
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Baseline characteristics reporting groups
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Reporting group title |
AZLI
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 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. | ||
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End point title |
Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons [1] | ||||||||
End point 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.
Two participants voluntarily withdrew from the study prior to completion (not due to AEs/safety or tolerability reasons) and were not included in the analysis.
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End point type |
Primary
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End point timeframe |
Baseline to Day 168
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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 |
Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years | ||||||||||||||
End point 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.
Participants ≥ 6 years of age were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 28, 84, and 140
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years | ||||||||||||||
End point 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.
Participants ≥ 6 years of age were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 28, 84, and 140
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change in Pseudomonas Aeruginosa (PA) Sputum Density | ||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 28, 84, and 140
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 168
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline to Day 168
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Days Participants Were Hospitalized Due to a Respiratory Event | ||||||||
End point description |
The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 168
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Pulmonary Exacerbations | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 168
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to Pulmonary Exacerbation | ||||||
End point description |
The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 168
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| No statistical analyses for this end point | |||||||
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End point title |
Percentage of Participants With Study-drug Induced Bronchospasm | ||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Pretreatment at Baseline to 30 minutes following treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Adverse Event Rates Adjusted for Study Duration | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 168
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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 168
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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 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
