Clinical Trial Results:
Valproate dose reduction and its clinical evaluation by introducing lamotrigine in Japanese women with epilepsy – single arm, multicenter, and open-label study
Summary
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EudraCT number |
2017-001515-36 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
11 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Oct 2017
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First version publication date |
20 Oct 2017
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Other versions |
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 |
200776
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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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 |
17 Jul 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 |
11 May 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 |
To examine whether the VPA dose can be reduced by additional administration of LTG (up to 200 mg/d if there are no safety concerns) in Japanese pre-menopausal female epilepsy patients aged 15 years or older, whose seizures are well controlled by VPA monotherapy (fixed maintenance dose of 400-1200 mg/d).
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Apr 2014
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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: 33
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Worldwide total number of subjects |
33
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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) |
0
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
27
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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 |
Participants (par.) receiving monotherapy treatment with sodium valproate (VPA) maintenance dose of 400-1200 milligrams/day [mg/d]) due to a history of partial seizures (including secondary generalized seizures) or tonic-clonic seizures, and whose seizures had been controlled for 12 weeks (wk) prior to start of treatment were enrolled in the study. | ||||||||||||||
Pre-assignment
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Screening details |
A total of 33 participants were enrolled into the study and 20 participants completed the study. | ||||||||||||||
Period 1
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Period 1 title |
LTG Escalation Phase
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Escalation Phase: LTG plus VPA | ||||||||||||||
Arm description |
Participants received a fixed maintenance dose of VPA (400-1200 mg/d) along with lamotrigine (LTG) which was gradually escalated to 200 mg/d in accordance with the information of package insert: i.e. 25 mg of LTG was orally administered once every other day for the first 2 weeks and then once daily for the following 2 weeks. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 weeks for once or twice daily administration. If there were safety concerns, the LTG dose was decreased to 100 mg/d at the discretion of the investigator or sub-investigator. If there were still safety concerns despite the dose reduction to 100 mg/d, LTG was discontinued. The total duration of this phase was 8 to18 weeks. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Lamotrigine 25 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg of Lamotrigine tablet was orally administered once every other day for the first two weeks and then once daily for the next 2 weeks.
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Investigational medicinal product name |
Lamotrigine 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg of Lamotrigine tablet was orally administered in dose escalation phase once or twice daily depending on the dose escalation.
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Investigational medicinal product name |
Sodium Valproate 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 100 mg tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate 200 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 200 mg tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate extended release 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 100 mg extended release tablets were administered as per the dosage instruction on package insert by oral route
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Investigational medicinal product name |
Sodium Valproate extended release 200 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 200 mg extended release tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate extended release 400 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 400 mg extended release tablets were administered as per the dosage instruction on package insert by oral route.
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Period 2
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Period 2 title |
VPA Reduction Phase
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Reduction Phase: LTG plus VPA | ||||||||||||||
Arm description |
Participants received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was determined at the discretion of the investigator or sub-investigator: e.g., 1000 mg/d (2 weeks), 800 mg/d (2 weeks), 600 mg/d (2 weeks), 400 mg/d (2 weeks), 300 mg/d OR 1000 mg/d (4 weeks), 600 mg/d (4 weeks), 300 mg/d and when VPA was reduced to less than 300 mg/d, the dose was reduced to 300, 200, 100, and 0 mg/d in 100 mg decrements in steps of at least one week duration. When VPA was concomitantly used, LTG was administered twice daily with 200 mg/d as a maintenance dose. If there were safety concerns during the LTG Escalation Phase, a fixed maintenance dose of 100 to 200 mg/d of LTG was administered twice daily. When VPA was withdrawn (that is, VPA was reduced to 0 mg/d), LTG was required to be increased by 50-100 mg/d. If there were any safety concern, 25 mg increment was also available. The total duration of this phase was 4 to16 weeks. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Lamotrigine 25 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg of Lamotrigine tablet was orally administered once every other day for the first two weeks and then once daily for the next 2 weeks.
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Investigational medicinal product name |
Lamotrigine 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg of Lamotrigine tablet was orally administered in dose escalation phase once or twice daily depending on the dose escalation.
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Investigational medicinal product name |
Sodium Valproate 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 100 mg tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate 200 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 200 mg tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate extended release 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 100 mg extended release tablets were administered as per the dosage instruction on package insert by oral route
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Investigational medicinal product name |
Sodium Valproate extended release 200 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 200 mg extended release tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate extended release 400 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 400 mg extended release tablets were administered as per the dosage instruction on package insert by oral route.
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Period 3
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Period 3 title |
LTG and VPA Maintenance Phase
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Maintenance Phase: LTG plus VPA | ||||||||||||||
Arm description |
Participants received two different treatments. In one group, participants received a fixed maintenance dose of LTG 200 mg/d (or 100 to 200 mg/d if there were safety concerns during the LTG Escalation Phase) and VPA 100 mg/d (or higher if seizures occurred during the VPA Reduction Phase) were administered twice and 1-3 times daily, respectively, for 12 weeks. The frequency of administration was not changed. If seizures occurred, VPA dose could be increased/re-introduced. On the other group, after VPA was withdrawn, LTG dose was escalated up to 300 mg/d with 50-100 mg increment per 1-2 weeks. If there was safety concern or if remaining dose to 300 mg/d was below 50 mg, 25 mg increment was also available. If seizures occurred, LTG dose was increased up to 400 mg/d. If there was safety concern, LTG dose was decreased to 100 mg/d. If there was still safety concern at 100 mg/d, the participants were discontinued from the study. The total duration of this phase was 12 weeks. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Lamotrigine 25 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg of Lamotrigine tablet was orally administered once every other day for the first two weeks and then once daily for the next 2 weeks.
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Investigational medicinal product name |
Lamotrigine 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg of Lamotrigine tablet was orally administered in dose escalation phase once or twice daily depending on the dose escalation.
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Investigational medicinal product name |
Sodium Valproate 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 100 mg tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate 200 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 200 mg tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate extended release 100 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 100 mg extended release tablets were administered as per the dosage instruction on package insert by oral route
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Investigational medicinal product name |
Sodium Valproate extended release 200 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 200 mg extended release tablets were administered as per the dosage instruction on package insert by oral route.
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Investigational medicinal product name |
Sodium Valproate extended release 400 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sodium Valproate 400 mg extended release tablets were administered as per the dosage instruction on package insert by oral route.
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Baseline characteristics reporting groups
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Reporting group title |
LTG Escalation Phase
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Reporting group description |
LTG Escalation Phase | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Escalation Phase: LTG plus VPA
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Reporting group description |
Participants received a fixed maintenance dose of VPA (400-1200 mg/d) along with lamotrigine (LTG) which was gradually escalated to 200 mg/d in accordance with the information of package insert: i.e. 25 mg of LTG was orally administered once every other day for the first 2 weeks and then once daily for the following 2 weeks. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 weeks for once or twice daily administration. If there were safety concerns, the LTG dose was decreased to 100 mg/d at the discretion of the investigator or sub-investigator. If there were still safety concerns despite the dose reduction to 100 mg/d, LTG was discontinued. The total duration of this phase was 8 to18 weeks. | ||
Reporting group title |
Reduction Phase: LTG plus VPA
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Reporting group description |
Participants received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was determined at the discretion of the investigator or sub-investigator: e.g., 1000 mg/d (2 weeks), 800 mg/d (2 weeks), 600 mg/d (2 weeks), 400 mg/d (2 weeks), 300 mg/d OR 1000 mg/d (4 weeks), 600 mg/d (4 weeks), 300 mg/d and when VPA was reduced to less than 300 mg/d, the dose was reduced to 300, 200, 100, and 0 mg/d in 100 mg decrements in steps of at least one week duration. When VPA was concomitantly used, LTG was administered twice daily with 200 mg/d as a maintenance dose. If there were safety concerns during the LTG Escalation Phase, a fixed maintenance dose of 100 to 200 mg/d of LTG was administered twice daily. When VPA was withdrawn (that is, VPA was reduced to 0 mg/d), LTG was required to be increased by 50-100 mg/d. If there were any safety concern, 25 mg increment was also available. The total duration of this phase was 4 to16 weeks. | ||
Reporting group title |
Maintenance Phase: LTG plus VPA
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Reporting group description |
Participants received two different treatments. In one group, participants received a fixed maintenance dose of LTG 200 mg/d (or 100 to 200 mg/d if there were safety concerns during the LTG Escalation Phase) and VPA 100 mg/d (or higher if seizures occurred during the VPA Reduction Phase) were administered twice and 1-3 times daily, respectively, for 12 weeks. The frequency of administration was not changed. If seizures occurred, VPA dose could be increased/re-introduced. On the other group, after VPA was withdrawn, LTG dose was escalated up to 300 mg/d with 50-100 mg increment per 1-2 weeks. If there was safety concern or if remaining dose to 300 mg/d was below 50 mg, 25 mg increment was also available. If seizures occurred, LTG dose was increased up to 400 mg/d. If there was safety concern, LTG dose was decreased to 100 mg/d. If there was still safety concern at 100 mg/d, the participants were discontinued from the study. The total duration of this phase was 12 weeks. | ||
Subject analysis set title |
LTG plus VPA (Phase 1, 2 and 3)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to < 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
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End point title |
Percentage of participants who achieved reduction in daily VPA dose [1] | ||||||||
End point description |
The VPA dose reduction from Baseline is defined as post VPA dose minus the Baseline VPA dose < 0. Baseline VPA dose is the dose at the Baseline visit (Week 0) and the post VPA dose is the last VPA dose during the LTG and VPA Maintenance Phase. Percentage of participants with dose reduction during the LTG and VPA Maintenance Phase is presented. Full analysis set (FAS): comprised of all participants in the Safety Population who provided at least one efficacy data after the first dose of the investigational product during the LTG Escalation Phase.
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End point type |
Primary
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End point timeframe |
Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction Phase
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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: There are no statistical data to report. |
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Notes [2] - FAs population |
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No statistical analyses for this end point |
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End point title |
Percent change in the VPA dose [3] | ||||||||
End point description |
Percent change in VPA dose is calculated as (pre-dose - post-dose) / pre-dose x 100. Pre-dose is the VPA dose at the Baseline visit and post-dose is the last VPA dose during the LTG and VPA Maintenance Phase.
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End point type |
Primary
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End point timeframe |
Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction Phase
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Notes [3] - 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: There are no statistical data to report. |
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Notes [4] - FAS population |
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No statistical analyses for this end point |
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End point title |
Number of days in total that epileptic seizures occurred up to the LTG and VPA Maintenance Phase | ||||||
End point description |
The participants with no seizure, had no record in seizure dairy. Only those participants with more than one seizure were assessed for this Outcome Measure.
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End point type |
Secondary
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End point timeframe |
Baseline and up to 46 weeks
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Notes [5] - FAS population |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in quality of life in epilepsy-31-P (QOLIE-31-P) in participants aged 18 years and older | ||||||||||||
End point description |
QOLIE-31-P is a questionnaire analyzed according to the scoring manual at Baseline, at the end of LTG/VPA Maintenance Phase and withdrawals for the participants aged 18 years and older (n=26, excluding 1 participant withdrawn due to protocol violation). Overall score was calculated as an average of sub scores that were normalized to 0 to 100. QOLIE-31-P has 7 subscale items (energy, mood, daily activities, cognition, medication effect, seizure worry and overall QOL). Higher score presents higher quality of life. Epileptic symptoms generally affect the QOL of participants, and so QOLIE-31-P is world widely used for the QOL assessment of adult participants. Baseline is defined as Day 1 (pre-dose) value. Change from Baseline is calculated as post-dose visit value minus Baseline value. Only those participants available at the indicated phase were analyzed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Baseline and up to 46 weeks
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Notes [6] - FAS population |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in quality of life in epilepsy for adolescents (QOLIE-AD-48) in participants aged 15-17 years | ||||||||||||
End point description |
QOLIE-AD-48 is a questionnaire analyzed according to the scoring manual at Baseline, at the end of the LTG/VPA Maintenance Phase and withdrawals for participants aged 15-17 years (n=6). Particpants who has started by QOLIE-AD-48 were using the same questionnaire even after 18 years old. Overall score was calculated as an average of sub scores that were normalized to 0 to 100. QOLIE-AD-48 has 8 subscale items (epilepsy impact, memory/concentration, physical fuctioning, stigma, social support, school behavior, attitudes towards epilepsy and health perceptions). Higher score presents higher quality of life. Epileptic symptoms generally affect the QOL of participants, and so QOLIE-AD-48 is world widely used for the QOL assessment of non-adult participants. Baseline is defined as Day 1 (pre-dose) value. Change from Baseline is calculated as post-dose visit value minus Baseline value.
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End point type |
Secondary
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End point timeframe |
Baseline and up to 46 weeks
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Notes [7] - FAS population |
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No statistical analyses for this end point |
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End point title |
Percentage of participants who completed or discontinued from the study | ||||||||||
End point description |
Following cases were considered for participants to have completed a part of or whole of the study. For whole period completion: participants who completed the last LTG and VPA Maintenance Phase visit (M5) in the LTG and VPA Maintenance Phase and follow-up examination. For LTG Escalation Phase completion: participants who reached 200 mg/d of LTG (or 100-200 mg/d of LTG if there were safety concerns) within 8-18 weeks of the phase. For VPA Reduction Phase completion: participants who completed the last fixed dose of VPA Reduction Phase visit (0 mg/d) (FR4) of the phase. For LTG and VPA Maintenance Phase completion: participants who completed M5 of the phase. Participants who met any of the withdrawal criteria after the start of investigational product were considered to have discontinued the study. Percentage of participants who completed or discontinued/withdrawn from the study is presented. Enrolled Population: comprised of all participants who had a Baseline (Week 0) visit.
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End point type |
Secondary
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End point timeframe |
Up to 50 weeks
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Notes [8] - Enrolled Population |
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No statistical analyses for this end point |
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End point title |
Number of participants with adverse events (AEs), AEs leading to discontinuation of the investigational product and/or withdrawal from the study, drug-related AEs, deaths and serious adverse events (SAEs) throughout the study | ||||||||||||||||
End point description |
An AE is defined as untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect, based on medical or scientific judgement and all events of possible drug-induced liver injury. Safety Population: comprised of participants who received at least one dose of the investigational product during the LTG Escalation Phase.
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End point type |
Secondary
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End point timeframe |
From the start of study treatment until follow-up (up to 50 weeks)
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Notes [9] - Safety Population |
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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 |
Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
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Adverse event reporting additional description |
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
LTG plus VPA (Phase 1, 2 and 3)
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Reporting group description |
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to < 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |