Clinical Trial Results:
Phase I/II study of Induction Chemotherapy with weekly RAD001, Carboplatine and Paclitaxel in Unresectable or Inoperable Locally Advanced Head and Neck
Squamous Cell Carcinoma (HNSCC)
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Summary
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EudraCT number |
2008-005702-39 |
Trial protocol |
FR |
Global end of trial date |
31 Jan 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jul 2016
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First version publication date |
23 Jul 2016
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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 |
O08-1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01333085 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GERCOR
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Sponsor organisation address |
151 rue du faubourg Saint Antoine, PARIS, France, 75011
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Public contact |
Regulatory affairs, GERCOR, 33 1 40 29 85 00, regulatory.affairs@gercor.com.fr
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Scientific contact |
coordinating investigator, Pr Sandrine FAIVRE, 33 1 40 29 85 00, regulatory.affairs@gercor.com.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Jan 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jan 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 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 |
Phase I:
To determine the safety profile of weekly RAD001 in combination with carboplatin and paclitaxel in chemonaive patients with unresectable or inoperable locally advanced HNSCC.
Phase II: To assess anti-tumor activity of the combination in these patients.
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Protection of trial subjects |
Premedication
Administration of paclitaxel should be preceded by an anti-allergic premedication with solumedrol 80 mg IV and polaramine 5 mg IV, and an anti-emetic prophylaxis at the discretion of the investigator.
Dose adjustments:
Doses will be reduced for hematological and other adverse events. Dose adjustments are to be made according to the system showing the greatest degree of toxicity. Adverse events will be graded using the NCI CTCAE version 3.0.
Except for nausea and vomiting, dose reductions are definitive. A maximum of 2 dose reductions are allowed. First dose reduction has to be done on RAD001 and the second one on carboplatin and/or paclitaxel. Patients who should experience a third dose reduction must be dropped out of study. Anemia should be treated according to investigator’s discretion. No dose reduction is allowed, but erythropoietin use is permitted.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Oct 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
France: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
35
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From 65 to 84 years |
14
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85 years and over |
1
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Recruitment
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Recruitment details |
Patient enrollment occurred from 15 October 2009 (first patient was treated in phase I) to 20 November 2012 (laste patient enrolled in phase II). This study was conducted in France in five centers (Hôpital Beaujon - Clichy; Hôpital St Joseph, Institut Curie - Paris; Centre Léon Bérard Lyon; Institut Claudius Regaud -Toulouse) | ||||||||||||||||||
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Pre-assignment
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Screening details |
Patient with inoperable Locally Advanced Head and Neck Squamous cell carcinoma. Phase I (permitted to identify the recommended dose level): 7 patients were enrolled: 4 at dose level 1 (RAD001 30mg) and 3 at dose level 2 (RAD001 50mg). Phase II: 43 patients were enrolled at dose RAD001 50mg. | ||||||||||||||||||
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Period 1
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Period 1 title |
Paclitaxel - Carboplatin - RAD001 50mg (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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Paclitaxel - Carboplatin - RAD001 50mg | ||||||||||||||||||
Arm description |
Patients received in first-line 9 weekly cycles of RAD001 (50mg) in combination with carboplatin (AUC2) and paclitaxel (60mg/m²). Recommended dose was RAD001 50mg | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Paclitaxel: 60mg/m² IV in 1 hour
Before infusion of paclitaxel at D1, D8, D15 a premedication was recommended with one injection of 5 mg polaramine.
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Investigational medicinal product name |
Carboplatin AUC2
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin AUC2 in 1 hour
Dose of carboplatin is calculated according to creatinine clearance estimated by Calvert formula and area under curve (AUC).
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Investigational medicinal product name |
RAD001
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Investigational medicinal product code |
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Other name |
Everolimus
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
RAD001 is presented as 10mg tablets. It was orally administrated weekly at a dose of 50mg. It was swallowed 1 hour before or 2 hours after lunch with a glass of water.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 50 patients were included in phase I and phase II. 4 patients treated at dose level RAD001 30mg and 3 patients at dose level RAD001 50mg, permitted to identify the recommended dose level (RAD001 50mg) 46 patients treated at the dose level recommended (3 patients phase I and 43 patients phase II) were evalauted (overall period) |
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Baseline characteristics reporting groups
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Reporting group title |
Paclitaxel - Carboplatin - RAD001 50mg
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Reporting group description |
Analysis of the data’s, including the patients treated at recommended dose of RAD001 (50mg/week). (3 patients in phase I and 43 patients in phase II). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Paclitaxel - Carboplatin - RAD001 50mg
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Reporting group description |
Patients received in first-line 9 weekly cycles of RAD001 (50mg) in combination with carboplatin (AUC2) and paclitaxel (60mg/m²). Recommended dose was RAD001 50mg | ||
Subject analysis set title |
Clinical Toxicity, all Grade
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The adverse events were assessed using the terminology Criteria for adverse Event (CTCAE) version 3.0.
Clinical toxicty at the recommended dose (RAD001, 50mg)
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Subject analysis set title |
Clinical Toxicity, Grade 1-2
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The adverse events were assessed using the terminology Criteria for adverse Event (CTCAE) version 3.0
Clinical toxicity at the recommended dose (RAD001,50mg)
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Subject analysis set title |
Clinial Toxicity, Grade 3-4
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The adverse events were assessed using the terminology Criteria for adverse Event (CTCAE) version 3.0
Clinical toxicity at the recommended dose (RAD001, 50mg)
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Subject analysis set title |
Biological Toxicity, All Grade
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The adverse events were assessed using the terminology Criteria for adverse Event (CTCAE) version 3.0
At recommended dose (RAD001, 50mg)
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Subject analysis set title |
Biological Toxicity, Grade 0-1
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The adverse events were assessed using the terminology Criteria for adverse Event (CTCAE) version 3.0
At the recommended dose (RAD001, 50mg)
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Subject analysis set title |
Biological Toxicity, grade 3-4
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The adverse events were assessed using the terminology Criteria for adverse Event (CTCAE) version 3.0
At the recommended dose RAD001, 50mg
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End point title |
Objective Response Rate [1] | ||||||||||||||
End point description |
All eligible patients will be included in the response rate calculation. Objective response rate was according to RECIST criteria.
The subset that will be assigned a response category (CR, PR, SD or PD) are all patients who have received at least one treatment and have their disease re-evaluated.
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End point type |
Primary
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End point timeframe |
Evaluation at 11 weeks after first administration.
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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: Results of phase II trial will be given as response rates with 95% confidence intervals. |
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| Notes [2] - 5 patients were not included in efficacity analysis, being not evaluable for tumor response. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Clinical Adverse Event at RAD001 50mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
All patients will be evaluable for toxicity from the time of their first treatment with RAD001, carboplatin and paclitaxel. Safety evaluations were conducted at least weekly until 2 weeks after the end of therapy and included assessments of laboratory parameters and clinical adverse reactions. Clinical adverse events were graded according to the NCI-CTCAE grading system version 3.0.
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End point type |
Secondary
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End point timeframe |
From inclusion to 14 days after radiation therapy completion
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Biological Adverse Events at RAD001 50mg | ||||||||||||||||||||||||||||||||||||
End point description |
All patients will be evaluable for toxicity from the time of their first treatment with RAD001, carboplatin and paclitaxel. Safety evaluations were conducted at least weekly until 2 weeks after the end of therapy and included assessments of laboratory parameters and clinical adverse reactions. Clinical adverse events were graded according to the NCI-CTCAE grading system version 3.0.
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End point type |
Secondary
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End point timeframe |
From the randomisation to 14 days after radiation therapy completion
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Effect of CAPRA study in the expression of biomarkers (Ki67 and p-S6K) | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Biopsie specimens obtained before treatment (baseline) and post treatment (Post-CAPRA).
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Attachments |
Untitled (Filename: CAPRA biomarkers in biopsies results.pdf) |
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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 |
From the first dose taken to 14 days after radiation therapy completion
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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 |
15.1
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Reporting groups
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Reporting group title |
Paclitaxel - carboplatin- RAD001 (50mg)
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Reporting group description |
Forty-six patients were evaluable for toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 4% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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15 Feb 2010 |
Precision concerning inclusion and exclusion criteria. |
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14 Apr 2011 |
Prolongation of the trial |
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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 | |||
