Clinical Trial Results:
A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase alfa Enzyme Replacement Therapy in Children and Adolescents with Type 3 Gaucher Disease
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Summary
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EudraCT number |
2012-003427-38 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
15 Mar 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Dec 2018
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First version publication date |
01 Dec 2018
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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 |
HGT-GCB-068
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01685216 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Shire
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Sponsor organisation address |
300 Shire Way, Lexington, United States, MA 02421
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Public contact |
Study Director, Shire, ClinicalTransparency@shire.com
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Scientific contact |
Study Director, Shire, ClinicalTransparency@shire.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-000556-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 |
15 Mar 2015
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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 |
15 Mar 2015
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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 |
The primary objective of this trial was to explore the efficacy and safety of velaglucerase alfa enzyme replacement therapy (ERT) in children and adolescents with type 3 Gaucher disease.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice (GCP) and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Sep 2012
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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 |
Egypt: 4
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Country: Number of subjects enrolled |
India: 1
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Country: Number of subjects enrolled |
Tunisia: 1
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Worldwide total number of subjects |
6
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EEA total number of subjects |
0
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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) |
5
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Adolescents (12-17 years) |
1
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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 |
The study was conducted at 6 centers in Egypt, India, and Tunisia between 14 Sep 2012 (first subject first visit) and 15 Mar 2015 (last subject last visit). | ||||||
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Pre-assignment
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Screening details |
A total of 7 subjects were enrolled, of them 6 subjects received treatment. | ||||||
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Pre-assignment period milestones
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Number of subjects started |
6 | ||||||
Number of subjects completed |
6 | ||||||
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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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Velaglucerase alfa | ||||||
Arm description |
Subjects received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Gene-Activated Human Glucocerebrosidase 400U/vial
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Investigational medicinal product code |
GA-GCB
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Other name |
VELAGLUCERASE ALFA
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received an intravenous (IV) infusion of velaglucerase alfa every other week for 1 year.
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Baseline characteristics reporting groups
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Reporting group title |
Velaglucerase alfa
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Reporting group description |
Subjects received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Velaglucerase alfa
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Reporting group description |
Subjects received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. | ||
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End point title |
Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration [1] | ||||||||||
End point description |
Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased. The intent-to-treat (ITT) population included all subjects who received at least 1 study drug infusion (full or partial). In the below table, the number of subjects analyzed signifies subjects who were evaluable for this measure
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End point type |
Primary
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End point timeframe |
Baseline, Week 53 or end of study
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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: Per protocol, only descriptive statistics were collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Change From Baseline to 12 Months (Week 53) in Platelet Count | ||||||||||
End point description |
Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased. The ITT population included all subjects who received at least 1 study drug infusion (full or partial). In the below table, the number of subjects analyzed signifies subjects who were evaluable for this measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 53
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI) | ||||||||||
End point description |
Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the subject, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the subject identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased. The ITT population included all subjects who received at least 1 study drug infusion (full or partial). In the below table, the number of subjects analyzed signifies subjects who were evaluable for this measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 51 or end of study
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI) | ||||||||||
End point description |
Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the subject, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the subject identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased. The ITT population included all subjects who received at least 1 study drug infusion (full or partial). In the below table, the number of subjects analyzed signifies subjects who were evaluable for this measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 51
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Subjects With Abnormal Neurological Status During the Study | ||||||||
End point description |
Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each subject. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given subject at baseline performed the neurological examinations scheduled for that subject during the treatment phase and at the end of study visit. The ITT population included all subjects who received at least 1 study drug infusion (full or partial).
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 13, 25, 37, and 53 or end of study
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects who Experienced a Treatment-Emergent Adverse Event | ||||||||||||
End point description |
Adverse events (AEs) were monitored continuously throughout the study from the time the subject or subjects parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the subject’s last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the subject’s last study infusion. An infusion-related reaction is defined as an AE that 1) began either during or within 12 hours after the start of the infusion, and 2) was judged as possibly or probably related to study medication. The safety analysis population, included all subjects who received at least 1 study drug infusion (full or partial).
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End point type |
Secondary
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End point timeframe |
From start of study drug administration to follow-up (up to 57 weeks)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subject who Developed Anti-Velaglucerase Alfa Antibodies During the Study | ||||||||||||||||
End point description |
Subjects provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer). The ITT population included all subjects who received at least 1 study drug infusion (full or partial).
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 13, 25, 37 and 53
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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 start of study drug administration to follow-up (up to 57 weeks)
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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 |
14.0
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Reporting groups
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Reporting group title |
Velaglucerase alfa
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Reporting group description |
Subjects received an intravenous (IV) infusion of velaglucerase alfa at 60 U/kg, every other week for 1 year, then were followed for 1 month. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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01 Dec 2010 |
- The patients were to have anemia at screening and at least 1 of 3 additional criteria (at least moderate splenomegaly, thrombocytopenia, or a readily palpable enlarged liver).
- Change in the liver and spleen endpoints to indicate that the organ volumes would be determined by magnetic resonance imaging (MRI), not ultrasound, unless sedation would be required to perform the MRI and the investigator deemed that this would pose an unwarranted risk to the patient.
- Change in immunoassay methods for evaluation of anti-velaglucerase alfa antibodies: Serum samples will be collected for evaluation of anti-velaglucerase alfa antibodies. Analysis of anti-velaglucerase alfa antibodies will be conducted using validated 3-tier immunoassay methods (screening, confirmatory, and titer) and the anti-velaglucerase alfa antibody positive samples will be further tested for the presence of neutralizing antibodies (NAb). |
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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 | |||
