Clinical Trial Results:
Prospective randomized, placebo-controlled, double blind, multicenter study (phase III) to evaluate clinical efficacy and safety of avian polyclonal anti-Pseudomonas antibodies (IgY) in prevention of recurrence of Pseudomonas aeruginosa infection in cystic fibrosis patients
|
Summary
|
|
EudraCT number |
2011-000801-39 |
Trial protocol |
DE SE BE IT IE HU AT ES |
Global end of trial date |
27 Jun 2017
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
12 Apr 2019
|
First version publication date |
12 Apr 2019
|
Other versions |
|
Summary report(s) |
2018_12_14_IMPACTT_PsAer-IgY_FinalReportSynopsis_V01-F |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
PsAer-IgY
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01455675 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
clinicaltrials.gov: NCT01455675 | ||
|
Sponsors
|
|||
Sponsor organisation name |
Mukoviszidose Institute gGmbH
|
||
Sponsor organisation address |
In den Dauen 6, Bonn, Germany, 53117
|
||
Public contact |
Sponsor´s Project Manager , Mukoviszidose Institute gGmbH , +49 228987800, impactt@muko.info
|
||
Scientific contact |
Sponsor´s Project Manager , Mukoviszidose Institute gGmbH , +49 228987800, impactt@muko.info
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
14 Dec 2018
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
27 Jun 2017
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
27 Jun 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective is to find out, if continuous long-term local application of specific egg yolk antibodies (IgY) directed against PA - initiated after successfully treated acute PA infection - can prolong the time to recurrence of a sputum culture positive for PA.
The objective to prevent infections with PA is also to diminish the need of antibiotics and minimize the problem of bacterial resistance against antibiotics.
|
||
Protection of trial subjects |
Since eggs represent normal dietary components there is practically no risk of toxic side effects of IgY. Accordingly, adverse reactions have never been detected so far. Regarding the assessment of the immunogenic potential of IgY which - under theoretical
considerations - might reduce treatment efficacy by the induction of human anti IgY antibodies, it is important to stress that IgY is not immunogenic in humans, when it is given orally (Larsson et al 1991).
Patients with history of allergy/hypersensitivity to hens' egg proteins (including medication allergy) that is deemed relevant to the trial by the investigator are excluded from the trial. “Relevance” in this context refers to any increased risk of hypersensitivity reaction to trial medication. Clinically relevant diseases or medical conditions other than CF or CF-related conditions that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the data are an exclusion criteria as well. This includes, but is not limited to, significant hematological, hepatic, renal, cardiovascular, and neurological diseases
(diabetic patients may participate if their disease is under good control prior to inclusion). Patients who are pregnant cannot be included into the study. This will be tested at inclusion visit with a urine pregnancy test (in female patients older than 10 years
with secondary sexual characteristics) Insurance coverage is provided by Atrialis GmbH and Elscher Consulting respectively as stipulated by law, for all patients enrolled in the study from the time of patients„ inclusion into the study. This insurance covers any damage to health arising from participation in the study up to maximum sum required by law.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Nov 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 19
|
||
Country: Number of subjects enrolled |
Spain: 9
|
||
Country: Number of subjects enrolled |
Sweden: 7
|
||
Country: Number of subjects enrolled |
Austria: 9
|
||
Country: Number of subjects enrolled |
Belgium: 10
|
||
Country: Number of subjects enrolled |
Germany: 70
|
||
Country: Number of subjects enrolled |
Hungary: 18
|
||
Country: Number of subjects enrolled |
Ireland: 9
|
||
Country: Number of subjects enrolled |
Italy: 13
|
||
Worldwide total number of subjects |
164
|
||
EEA total number of subjects |
164
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
100
|
||
Adolescents (12-17 years) |
39
|
||
Adults (18-64 years) |
25
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
The trial was conducted at 47 sites in Germany, Belgium, Ireland, Sweden, Hungary, Poland, Austria, Italy and Spain. Patient recruitment took place from November 2011 to June 2015. first patient screened: 14NOV2011 first patient included: 29NOV2011 last patient included: | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
Patients from 5 years of age were included if they had a proven diagnosis of cystic fibrosis and had had a prior bronchopulmonary infection with Pseudomonas aeruginosa in the past 3 years that had been eradicated at the time of inclusion into the study. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Verum | |||||||||
Arm description |
IgY gargling solution Avian polyclonal anti-pseudomonas antibodies (IgY), 70 ml gargling solution contains 50 mg IgY with an activity against PA, once daily. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
avian polyclonal IgY antibody against Pseudomonas aeruginosa
|
|||||||||
Investigational medicinal product code |
Anti-Pseudomonas IgY
|
|||||||||
Other name |
||||||||||
Pharmaceutical forms |
Gargle
|
|||||||||
Routes of administration |
Oromucosal use
|
|||||||||
Dosage and administration details |
Gargling of 50 ml solution per day at night after teeth brushing before bed, containing
50 mg of Anti-Pseudomonas IgY with an activity of > or = 5 FKU (Fresenius Calvi units) / ml
ELISA unit / ml enzyme-linked immunosorbent assay unit / millitre
|
|||||||||
|
Arm title
|
Placebo | |||||||||
Arm description |
Avian gargling solution containing unspecific IgY antibody as Placebo | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo with unspecific anvian polyclonal IgY antibodies
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Gargle
|
|||||||||
Routes of administration |
Oromucosal use
|
|||||||||
Dosage and administration details |
gargling of 50 ml placebo solution per day at night after teeth brushing before bed.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
REMARK: A total of 171 patients were randomized to placebo (n=86) or to treatment (n=85). From the 86 patients allocated to placebo, only 81 received intervention, 5 patients declined to participate before receiving the intervention. From the 85 patients allocated to treatment, only 83 received intervention, 1 patient declined to participate before receiving the intervention and 1 patient had a PA infection before receiving the intervention. These 7 patients who dropped out before receiving intervention were not included in the database of the study and therefore were not considered in this report. In conclusion the overall trial reporting group of 164 subjects consists of 81 patients of the placebo group and 83 patients of the treatment group. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Full analysis set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Full Analysis Set (FAS) consists of all enrolled patients who received at least one dose of
assigned treatment. Following the intent-to-treat principle, patients are analyzed according to
the treatment assigned by randomisation.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Safety population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Safety population (SAF) consists of all patients who received at least one dose of study
treatment Patients are analyzed according to the treatment received.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Verum
|
||
Reporting group description |
IgY gargling solution Avian polyclonal anti-pseudomonas antibodies (IgY), 70 ml gargling solution contains 50 mg IgY with an activity against PA, once daily. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Avian gargling solution containing unspecific IgY antibody as Placebo | ||
Subject analysis set title |
Full analysis set
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Full Analysis Set (FAS) consists of all enrolled patients who received at least one dose of
assigned treatment. Following the intent-to-treat principle, patients are analyzed according to
the treatment assigned by randomisation.
|
||
Subject analysis set title |
Safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety population (SAF) consists of all patients who received at least one dose of study
treatment Patients are analyzed according to the treatment received.
|
||
|
|||||||||||||||||
End point title |
Time_to_Infection | ||||||||||||||||
End point description |
The confirmatory analysis of the primary endpoint was performed for the FAS. Additional efficacy analyses were conducted for the PP-population.
The primary efficacy endpoint was analyzed using a log rank test. Superiority of IgY would be claimed if the p-value from the comparison is <0.0115 at the interim, or <0.0464 at the final analysis. The median time to event for each treatment group was derived from a Kaplan-Meier analysis including a 95 % confidence interval for the medians.
Patients without an event were censored at the time of withdrawal, or after 24 months.
In Addition to the log rank test, a Cox Regression was performed with the Group Treatment adjusted by history of PA, Gender, Age (children/adults) and FEV (greater/smaller than median).
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Primary study endpoint was defined as the differences between gargling with Anti-pseudomonas IgY & gargling with placebo with respect to time from day 0 to recurrence of PA in sputum within the period of up to 104 weeks.
|
||||||||||||||||
|
|||||||||||||||||
| Notes [1] - n=1 declined to participate. n=1 infection before received mediation. [2] - (n=5) declined to participate. |
|||||||||||||||||
Statistical analysis title |
Statistical analysis of the primary endpoint | ||||||||||||||||
Statistical analysis description |
The primary efficacy endpoint is analysed using a log rank test. The null hypothesis is that there is no
difference in time to recurrence of PA in the sputum of active treatment and placebo, respectively. The
alternative hypothesis is that the active treatment is superior. Superiority of IgY will be claimed if the
p-value from the comparison is < 0.0464 at the final Analysis (an Interim Analysis was planed with a p-value smaller than 0.0115).
|
||||||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
164
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.9469 | ||||||||||||||||
Method |
Logrank | ||||||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||||||
Point estimate |
1.002
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
0.215 | ||||||||||||||||
upper limit |
34.55 | ||||||||||||||||
|
|||||||||||||||||
End point title |
FEV1 | ||||||||||||||||
End point description |
Change of the FEV1 values over time.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Period from baseline to end of study, where data have been collected at planned visits every 13 weeks.
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Statistical analysis for FEV1 | ||||||||||||||||
Statistical analysis description |
A preliminary longitudinal analysis was performed with a linear mixed effects model using classical techniques. This analysis shows that the data contains outliers and the assumption of normally distributed residuals was violated. For this reason, we developed a full Bayesian analysis which relaxes those model’s assumptions. In addition, this model is robust against outliers. The conclusions of this statistical analysis are based on the Bayesian analysis.
|
||||||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
164
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Slope | ||||||||||||||||
Point estimate |
0
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.002 | ||||||||||||||||
upper limit |
0.001 | ||||||||||||||||
|
|||||||||||||
End point title |
Number of Exacerbations | ||||||||||||
End point description |
This is a comparison of the number of exacerbations between the treated groups.
An exacerbation will be defined as change in at least two of the following signs:
1. Change in sputum volume or colour
2. Increased cough
3. Increased malaise, fatigue or lethargy
4. Anorexia or weight loss
5. Decrease in pulmonary function by 10% or more /Radiologic changes
6. Increased dyspnoea
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
The total number of exacerbations, from screening visit to end of study counted for each patient.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Analysis of the number of exacerbations | ||||||||||||
Statistical analysis description |
A Poisson regression model was planned for analysis but it was not appropriate to explain the data. The Residual Deviance was larger than the number of degrees of freedom. Therefore, we cannot rely on the results of this model. Conclusions are based on the Negative Binomial regression model, which fitted the data better (the residual deviance was smaller than the degrees of freedom).
|
||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||
Number of subjects included in analysis |
164
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
[3] | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
Negative Binomial regression | ||||||||||||
Parameter type |
Log odds ratio | ||||||||||||
Point estimate |
-0.39
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.23 | ||||||||||||
upper limit |
0.46 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.421
|
||||||||||||
| Notes [3] - A Negative Binomial regression model is applied, where treatment group effect is adjusted by gender and age at baseline (children/adults). |
|||||||||||||
|
|||||||||||||
End point title |
Days of illness in hospital | ||||||||||||
End point description |
This is a comparison of the number of days in hospitals between the treated groups.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
The total number of days in hospital, from screening visit to end of study counted for each patient.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical analysis of days in hospital | ||||||||||||
Statistical analysis description |
A Poisson regression model was planned for analysis but it was not appropriate to explain the data. The Residual Deviance was larger than the number of degrees of freedom. Therefore, we cannot rely on the results of this model. Conclusions are based on the Negative Binomial regression model, which fitted the data better (the residual deviance was smaller than the degrees of freedom).
|
||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||
Number of subjects included in analysis |
164
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [4] | ||||||||||||
P-value |
= 0.9 | ||||||||||||
Method |
Negative Binomial regresssion. | ||||||||||||
Parameter type |
Log odds ratio | ||||||||||||
Point estimate |
-0.08
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.57 | ||||||||||||
upper limit |
1.31 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.6525
|
||||||||||||
| Notes [4] - A Negative Binomial regression model is applied, where treatment group effect is adjusted by gender and age at baseline (children/adults). |
|||||||||||||
|
|||||||||||||
End point title |
Days out of school or work (sick leave) | ||||||||||||
End point description |
This is a comparison of the number of days out of school or work between the treated groups.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
The total number of days (sick leave) out of school or work, from screening visit to end of study counted for each patient.
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical analysis for days out of school/work | ||||||||||||
Statistical analysis description |
A Poisson regression model was planned for analysis but it was not appropriate to explain the data. The Residual Deviance was larger than the number of degrees of freedom. Therefore, we cannot rely on the results of this model. Conclusions are based on the Negative Binomial regression model, which fitted the data better (the residual deviance was smaller than the degrees of freedom).
|
||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||
Number of subjects included in analysis |
164
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [5] | ||||||||||||
P-value |
= 0.211 | ||||||||||||
Method |
Negative binomial regression | ||||||||||||
Parameter type |
Log odds ratio | ||||||||||||
Point estimate |
-0.33
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.87 | ||||||||||||
upper limit |
0.2 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.265
|
||||||||||||
| Notes [5] - A Negative Binomial regression model is applied, where treatment group effect is adjusted by gender and age at baseline (children/adults). |
|||||||||||||
|
|||||||||||||
End point title |
Days of use of antibiotics treatment | ||||||||||||
End point description |
This is a comparison of the number of days of use of antibiotics between the treated groups.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
The total number of days of use of antibiotics, from screening visit to end of study counted for each patient.
|
||||||||||||
|
|||||||||||||
| Notes [6] - Missing information from one patient. [7] - Missing information from two patients. [8] - Missing information from three patients. |
|||||||||||||
Statistical analysis title |
Statistical analysis of use of antibiotics | ||||||||||||
Statistical analysis description |
A Poisson regression model was planned for analysis but it was not appropriate to explain the data. The Residual Deviance was larger than the number of degrees of freedom. Therefore, we cannot rely on the results of this model. Conclusions are based on the Negative Binomial regression model, which fitted the data better (the residual deviance was smaller than the degrees of freedom).
|
||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||
Number of subjects included in analysis |
161
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [9] | ||||||||||||
P-value |
= 0.52 | ||||||||||||
Method |
Negative Binomial regression. | ||||||||||||
Parameter type |
Log odds ratio | ||||||||||||
Point estimate |
-0.14
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-57 | ||||||||||||
upper limit |
0.29 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.217
|
||||||||||||
| Notes [9] - A Negative Binomial regression model is applied, where treatment group effect is adjusted by gender and age at baseline (children/adults). |
|||||||||||||
|
|||||||||||||||||
End point title |
BMI | ||||||||||||||||
End point description |
Change of the BMI values over time.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Period from baseline to end of study, where data have been collected at planned visits every 13 weeks.
|
||||||||||||||||
|
|||||||||||||||||
| Notes [10] - 81 |
|||||||||||||||||
Statistical analysis title |
Statistical analysis of BMI | ||||||||||||||||
Statistical analysis description |
A preliminary longitudinal analysis was performed with a linear mixed effects model using classical techniques. This analysis shows that the data contains outliers and the assumption of normally distributed residuals was violated. For this reason, we developed a full Bayesian analysis which relaxes those model’s assumptions. In addition, this model is robust against outliers. The conclusions of this statistical analysis are based on the Bayesian analysis.
|
||||||||||||||||
Comparison groups |
Verum v Placebo
|
||||||||||||||||
Number of subjects included in analysis |
164
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
Method |
|||||||||||||||||
Parameter type |
Slope | ||||||||||||||||
Point estimate |
0.003
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-0.001 | ||||||||||||||||
upper limit |
0.007 | ||||||||||||||||
|
|||
|
Adverse events information [1]
|
|||
Timeframe for reporting adverse events |
From inclsuion visit to End of study visit(Termination), plus a follow-up period for SAEs of 30 days after termination for each patient.
|
||
Assessment type |
Non-systematic | ||
|
Dictionary used for adverse event reporting
|
|||
Dictionary name |
MedDRA | ||
Dictionary version |
4
|
||
| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: A total number of 1972 AEs was documented, 987 were in the placebo group and 980 in the treatment group. o deaths occurred. There were only few AEs judged to be related to the study drug: 5 adverse events in the treatment group and 20 in the placebo group. None of the adverse events judged to be related to the study drug was serious. In two cases, AEs led to premature withdrawal of the patients, one in the placebo and one in the treatment group. Generally, the study drug was well tolerated. |
|||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
04 Nov 2011 |
Protocol Version 1.3:
Definition of chronic PA-infection concretized
Exclusion criteria concerning atypic mycobacteria were defined more precisely
change in frequency of sample shipment to central laboratory |
||
20 Apr 2012 |
Protocol version 1.4:
deletion of precitpitine value >/= 1 as an inclusion criteria, as this is no concrete hint for an acute PA infection.
deletion of inclusion criteria "At inclusion no chronic infection with other gram-negative bacteria such as B. cepacica, S. maltophilia & A. xylosoxidans - or atypical mycobacteria or Aspergillus fumigatus" because it might be misleading in regard to one of the exclusion criteria which includes this aspect already. |
||
13 Jan 2014 |
Amendment Protocol version 1.5;
Longer stability data of the IMP from 12 months to 24 could be shown.
Protocol, Investigator brochure and patient information was adapted to updated IMPD.
Exclusion criteria infection with other gram-negative bacteria was defined more precisely including only those gram-negative infections were medication with PA-effective antibiotics is neccessary. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
