Clinical Trial Results:
A Phase III Study of M071754 - A Single-Blind Study in Patients With Infantile Spasms
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Summary
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EudraCT number |
2017-000230-62 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
27 Mar 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jul 2017
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First version publication date |
20 Jul 2017
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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 |
EFC12369
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Japan Pharmaceutical Information Center: JapicCTI-142558 | ||
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Sponsors
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Sponsor organisation name |
Alfresa Pharma Corporation
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Sponsor organisation address |
2-2-9 Kokumachi, Chuo-ku, Osaka , Japan, 540-8575
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Public contact |
Executive Officer, Alfresa Pharma Corporation, contact-suishin-1@kaihatsu-alfresa-pharma.com
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Scientific contact |
Executive Officer, Alfresa Pharma Corporation, contact-suishin-1@kaihatsu-alfresa-pharma.com
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Sponsor organisation name |
Sanofi K.K.
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Sponsor organisation address |
3-20-2 Nishi-Shinjuku, Shinjuku-ku, Tokyo , Japan, 163-1488
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, contact-US@sanofi.com
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Jul 2014
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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 |
27 Mar 2014
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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 |
To investigate the efficacy of orally-administered vigabatrin in subjects with infantile spasms, using changes in spasms frequency as an endpoint. Also to investigate the safety and pharmacokinetics.
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jan 2013
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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 |
Japan: 15
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Worldwide total number of subjects |
15
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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) |
15
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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) |
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 9 centers in Japan from 31 January 2013 to 27 March 2014. A total of 15 subjects were screened, out of which 13 were treated with the investigational drug. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
The study consisted of 5 periods: a screening period, a dose adjustment period, a maintenance administration period, a dose tapering period, and a follow-up period. | ||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Single blind | ||||||||||||||||||||
Roles blinded |
Subject | ||||||||||||||||||||
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Arms
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Arm title
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Vigabatrin | ||||||||||||||||||||
Arm description |
Water as Placebo (for Vigabatrin) twice a day for first 3 days in dose adjustment period. From Day 4, subjects received Vigabatrin 50 mg/kg/day to 150 mg/kg/day up to a maximum of 3 g/day, administered during three periods: dose adjustment period (6 days - 8 weeks), followed by maintenance administration period (2 weeks) and then dose tapering period (3 weeks). | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Vigabatrin
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Investigational medicinal product code |
M071754
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Other name |
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Pharmaceutical forms |
Granules for oral solution in sachet
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Routes of administration |
Oral use
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Dosage and administration details |
Dose adjustment period: Vigabatrin started from Day 4 at a dose of 50 mg/kg/day (25 mg/kg/day twice a day) as initial dose; dose increased by 25-50 mg/kg/day on Day 4 after the start of Vigabatrin, if spasms had not disappeared and there was no safety concern. Thereafter, similar dose increments until spasms disappeared or up to a maximum dose of 150 mg/kg/day (75 mg/kg twice a day; up to a maximum of 3 g/day). Maintenance administration period (MAP): subjects receiving appropriate dose in dose adjustment period or who reached a dose of 150 mg/kg/day (75 mg/kg/day twice a day; up to a maximum of 3 g/day) continued in MAP at the same dose for 2 weeks. Dose tapering period: Unless immediate discontinuation of Vigabatrin was required, the dose was tapered by 25-50 mg/kg/day every 3-4 days over a 3 week period.
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Investigational medicinal product name |
Water as Placebo (for Vigabatrin)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Water as Placebo orally twice a day for first 3 days in the dose adjustment period.
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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: A total of 15 subjects were screened, out of which 13 were treated with the investigational drug. Subject Disposition and Baseline Characteristics are presented for the 13 subjects who received investigational drug. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Vigabatrin 50 mg/kg/day (25 mg/kg/day twice a day) to 150 mg/kg/day (75 mg/kg/day twice a day) up to a maximum dose of 3 g/day, administered during three periods: Dose adjustment period (6-8 weeks), followed by a maintenance administration period (2 weeks), followed by Dose tapering period (3 weeks). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Vigabatrin
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Reporting group description |
Water as Placebo (for Vigabatrin) twice a day for first 3 days in dose adjustment period. From Day 4, subjects received Vigabatrin 50 mg/kg/day to 150 mg/kg/day up to a maximum of 3 g/day, administered during three periods: dose adjustment period (6 days - 8 weeks), followed by maintenance administration period (2 weeks) and then dose tapering period (3 weeks). | ||
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End point title |
Percentage of Subjects With Reduction of At Least 50% From Baseline in Frequency of Spasms on Date of Assessment of Primary Endpoint of Spasms [1] | ||||||||
End point description |
Subjects who achieved at least 50% reduction from baseline in frequency of infantile spasms on the date of assessment of primary end point of spasms (defined as two days prior to the maintenance administration start date [Day -2 and Day -1]) were reported in this endpoint. Analysis was performed on efficacy analysis set that included all subjects who were treated with the investigational drug.
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End point type |
Primary
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End point timeframe |
2 days before the start of maintenance period (6 days - 8 weeks)
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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: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Reduction of At Least 50% From Baseline in Frequency of Spasms on Date of Assessment of Frequency of Spasms During Maintenance Administration Period | ||||||||
End point description |
Subjects who achieved at least 50% reduction from baseline in frequency of infantile spasms on the date of assessment of frequency of spasms during the maintenance administration period (defined as a two day period comprising the maintenance administration period end date and the previous day) were reported in this endpoint. Analysis was performed on efficacy analysis set. Number of subjects analyzed=subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
End of 2 days of Maintenance period (3-10 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Disappearance of Spasms on Date of Assessment of Frequency of Spasms during Maintenance Administration Period | ||||||||
End point description |
Subjects whose spasms were disappeared on the date of assessment during the maintenance administration period (defined as a two day period comprising the maintenance administration period end date and the previous day) were reported in this endpoint). Analysis was performed on efficacy analysis set. Number of subjects analyzed=subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
End of 2 days of Maintenance period (3-10 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Complete Disappearance of Infantile Spasms | ||||||||
End point description |
Subjects whose spasms had disappeared on the date of assessment of spasms during the maintenance administration period and whose brainwaves during the maintenance administration period showed no signs of hypsarrhythmia, were reported as complete disappearance presented. Hypsarrhythmia was assessed by the Central Brain wave Assessment Committee. Analysis was performed on efficacy analysis set. Number of subjects analyzed=subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
End of 2 days of Maintenance period (3-10 weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Hypsarrhythmia findings on Maintenance Administration Period End Date Compared With During Screening Period | ||||||||||||||||
End point description |
A contingency table was prepared for evaluation of hypsarrhythmia on the end day of the maintenance administration period and compared with the hypsarrhythmia status at the screening period. Subjects who showed any change in hypsarrhythmia (disappeared, improved, no change, deteriorated) were reported. Analysis was performed on efficacy analysis set. Number of subjects analyzed=subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
End of day of Maintenance period (3-10 weeks)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of Subjects With Comprehensive Evaluation of Efficacy by Principal Investigator or Sub-Investigator Including Impression of Guardians | ||||||||||||
End point description |
The comprehensive evaluation of efficacy of Vigabatrin as "effective or ineffective" by the Principal investigator or sub-investigators including the guardians’ opinion for the subjects was evaluated. Analysis was performed on efficacy analysis set. Number of subjects analyzed=subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
End of day of Maintenance period (3-10 weeks)
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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 |
All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 19) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (time from dose adjustment period until follow up period). Analysis was performed on safety analysis set that included all subjects who were treated with investigational drug.
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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 |
17.0
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Reporting groups
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Reporting group title |
Vigabatrin
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Reporting group description |
Water as Placebo (for Vigabatrin) twice a day for first 3 days in dose adjustment period. From Day 4, subjects received Vigabatrin 50 mg/kg/day to 150 mg/kg/day up to a maximum of 3 g/day, administered during three periods: dose adjustment period (6 days - 8 weeks), followed by maintenance administration period (2 weeks) and then dose tapering period (3 weeks). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
