Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Adaptive Study to Assess the Safety and Efficacy of UX007 in Subjects with Glucose Transporter Type 1 Deficiency Syndrome
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Summary
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EudraCT number |
2013-003771-35 |
Trial protocol |
IT GB FR HU ES DK |
Global end of trial date |
20 Sep 2017
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Results information
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Results version number |
v2(current) |
This version publication date |
04 Jul 2020
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First version publication date |
27 Feb 2019
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Other versions |
v1 |
Version creation reason |
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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 |
UX007G-CL201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01993186 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ultragenyx Pharmaceutical Inc.
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Sponsor organisation address |
60 Leveroni Court, Novato, United States, California 94949
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Public contact |
Medical Information, Ultragenyx Pharmaceutical Inc., +1 888- 756-8657, medinfo@ultragenyx.com
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Scientific contact |
Medical Information, Ultragenyx Pharmaceutical Inc., +1 888- 756-8657, medinfo@ultragenyx.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Sep 2017
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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 |
20 Sep 2017
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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 objectives of the study are to evaluate the efficacy of UX007 compared to placebo as measured by the reduction from randomization to week 8 in frequency of seizures and to evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG).
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Protection of trial subjects |
The trial was designed, conducted, recorded, and reported in accordance with the principles established by the 18th World Medical Association General Assembly (Helsinki, 1964) and subsequent amendments and clarifications adopted by the General Assemblies. The investigators made every effort to ensure that the study was conducted in full conformance with Helsinki principles, international Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines, current Food and Drug Administration
(FDA) regulations, EU Clinical Trial Directive 2001/20/EC, and local ethical and regulatory requirements. Each investigator was thoroughly familiar with the appropriate administration and potential risks of administration of the study drug, as described in the protocol and Investigator’s Brochure, prior to the initiation of the study. The method of obtaining and documenting informed consent and the contents of the informed consent form (ICF) complied with ICH GCP guidelines, the requirements of 21 CFR Part 50,
“Protection of Human Subjects,” the Health Insurance Portability and Accountability Act regulations, and all other applicable regulatory requirements. Investigators were responsible for preparing the ICF and submitting it to the Sponsor for approval prior to submission to the Institutional Review Board (IRB). All ICFs were written in regional language and contained the minimum elements for consent as mandated by the ICH guidelines. An IRB-approved ICF was provided by the Sponsor prior to initiation of the study.
Investigators obtained signed written informed consent from each potential study subject prior to the conduct of any study procedures and after the methods, objectives, requirements, and potential risks of the study were fully explained to each potential subject. Consent for participation could be withdrawn at any time for any reason by the subject.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Feb 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 5
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
Australia: 4
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Country: Number of subjects enrolled |
Israel: 3
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Country: Number of subjects enrolled |
United States: 18
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Worldwide total number of subjects |
36
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EEA total number of subjects |
11
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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) |
15
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Adolescents (12-17 years) |
13
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Adults (18-64 years) |
8
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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 |
- | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Beginning with the Screening visit, subjects recorded seizure frequency during a 6-week Baseline Period. If the subject did not meet the seizure count criteria, the subject was considered a screen failure and was not randomized. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Double-Blind Placebo-Controlled Period
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||||||||||||||||||||
Blinding implementation details |
The investigator and site personnel remained blinded to the randomization code during the study. Treatment assignment for an individual subject would be unblinded by the Investigator only in an emergency, and only if knowledge of the treatment assignment were urgently needed for the clinical management or welfare of the subject.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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UX007 | |||||||||||||||||||||||||||
Arm description |
Subjects randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
triheptanoin
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Investigational medicinal product code |
UX007
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Other name |
C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3-trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
Treatment was mixed with food (or formula, if appropriate) and administered orally (PO) or by gastronomy tube at least four times per day (breakfast, lunch, dinner, and before bed).
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Subjects randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
placebo
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Investigational medicinal product code |
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Other name |
safflower oil
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
Treatment was mixed with food (or formula, if appropriate) and administered PO or by gastronomy tube at least four times per day (breakfast, lunch, dinner, and before bed).
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Period 2
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Period 2 title |
Open-Label Extension Period
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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UX007 | |||||||||||||||||||||||||||
Arm description |
Following completion of the Week 8 study visit, subjects continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
triheptanoin
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Investigational medicinal product code |
UX007
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Other name |
C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3-trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
Treatment was mixed with food (or formula, if appropriate) and administered PO or by gastronomy tube at least four times per day (breakfast, lunch, dinner, and before bed).
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Following completion of the Week 8 study visit, placebo subjects continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
triheptanoin
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Investigational medicinal product code |
UX007
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Other name |
C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3-trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
Treatment was mixed with food (or formula, if appropriate) and administered PO or by gastronomy tube at least four times per day (breakfast, lunch, dinner, and before bed).
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Baseline characteristics reporting groups
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Reporting group title |
UX007
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Reporting group description |
Subjects randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
UX007
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Reporting group description |
Subjects randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | ||
Reporting group title |
UX007
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Reporting group description |
Following completion of the Week 8 study visit, subjects continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52). | ||
Reporting group title |
Placebo
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Reporting group description |
Following completion of the Week 8 study visit, placebo subjects continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52). | ||
Subject analysis set title |
Efficacy Analysis Set – 6MWT: UX007
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of subjects taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) 6MWT assessment performed.
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Subject analysis set title |
Efficacy Analysis Set - 6MWT: Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of subjects taking placebo during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) 6MWT assessment performed.
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Subject analysis set title |
Efficacy Analysis Set - GMFM-88: UX007
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of subjects taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) GMFM-88 assessment performed.
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Subject analysis set title |
Efficacy Analysis Set - GMFM-88: Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of subjects taking placebo during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) GMFM-88 assessment performed.
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Subject analysis set title |
Efficacy Analysis Set: UX007
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All randomized subjects who received at least one dose of investigational product.
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Subject analysis set title |
Efficacy Analysis Set: Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All randomized subjects who received at least one dose of investigational product.
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Subject analysis set title |
Safety Analysis Set: UX007
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received at least one dose of investigational product.
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Subject analysis set title |
Safety Analysis Set: Placebo
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received at least one dose of investigational product.
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Subject analysis set title |
Efficacy Analysis Set - CANTAB: UX007
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of subjects taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) CANTAB assessment performed.
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Subject analysis set title |
Efficacy Analysis Set - CANTAB: Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of subjects taking placebo during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) CANTAB assessment performed.
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End point title |
Percent Reduction from Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate) | ||||||||||||
End point description |
Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by electroencephalography (EEG). Seizure types include: generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor and absence seizures. A negative value indicates an increase in frequency.
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End point type |
Primary
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End point timeframe |
Baseline, Week 8
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Statistical analysis description |
Non-parametric post-hoc analysis: Hodges-Lehmann estimate of the location shift with 90% CI and Wilcoxon Rank Sum test p-value, based on Wilcoxon rank-sum test
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Comparison groups |
Efficacy Analysis Set: Placebo v Efficacy Analysis Set: UX007
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Number of subjects included in analysis |
36
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.5812 | ||||||||||||
Method |
Wilcoxon rank-sum test | ||||||||||||
Parameter type |
Hodges-Lehmann estimate | ||||||||||||
Point estimate |
13.45
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
-38.63 | ||||||||||||
upper limit |
80.95 | ||||||||||||
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End point title |
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period [1] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. An SAE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
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End point type |
Primary
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End point timeframe |
Weeks 0 to 8
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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: Descriptive statistics are presented per protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period [2] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence, whether or not considered drug related. An SAE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
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End point type |
Primary
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End point timeframe |
Weeks 9 to 52 plus 30 days
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| Notes [2] - 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: Descriptive statistics are presented per protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | ||||||||||||
End point description |
Observable generalized and partial-onset seizures measured for 6 weeks by diary. Seizure types include: generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory and simple partial/focal psychological. A negative value indicates an increase in frequency.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| Notes [3] - observable seizures subjects [4] - observable seizures subjects |
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Statistical analysis description |
Non-parametric post-hoc analysis: Hodges-Lehmann estimate of the location shift with 90% CI and Wilcoxon Rank Sum test p-value, based on Wilcoxon rank-sum test
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Comparison groups |
Efficacy Analysis Set: UX007 v Efficacy Analysis Set: Placebo
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Number of subjects included in analysis |
27
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.8197 | ||||||||||||
Method |
Wilcoxon rank-sum test | ||||||||||||
Parameter type |
Hodges-Lehmann estimate | ||||||||||||
Point estimate |
0
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
-51.23 | ||||||||||||
upper limit |
84.25 | ||||||||||||
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End point title |
Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate) | ||||||||||||
End point description |
Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| Notes [5] - absence seizure subjects [6] - absence seizure subjects |
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Statistical analysis description |
Non-parametric post-hoc analysis: Hodges-Lehmann estimate of the location shift with 90% CI and Wilcoxon Rank Sum test p-value, based on Wilcoxon rank-sum test
|
||||||||||||
Comparison groups |
Efficacy Analysis Set: UX007 v Efficacy Analysis Set: Placebo
|
||||||||||||
Number of subjects included in analysis |
23
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.7276 | ||||||||||||
Method |
Wilcoxon rank-sum test | ||||||||||||
Parameter type |
Hodges-Lehmann estimate | ||||||||||||
Point estimate |
0
|
||||||||||||
Confidence interval |
|||||||||||||
level |
90% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0 | ||||||||||||
upper limit |
37.5 | ||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures | ||||||||||||
End point description |
Seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of total seizures. Includes observable generalized and partial-onset seizures measured for 6 weeks by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures | ||||||||||||
End point description |
Observable seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of observable seizures. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
| Notes [7] - Subjects with observable seizures. [8] - Subjects with observable seizures. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Subjects With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures | ||||||||||||
End point description |
Absence seizure response, at least 50% reduction from baseline in frequency of absence seizures measured overnight by EEG, is defined as percent reduction in absence seizure frequency greater than or equal to 50%. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
| Notes [9] - Subjects with absence seizures. [10] - Subjects with absence seizures. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||
End point title |
Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | |||||||||||||||||||||
End point description |
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. RTI Simple choice reaction time standard deviation (RTISRTSD) assesses the cognitive domain of attention, with scores on a continuous range from 0 to 5000; lower scores indicate better function. RTI median simple choice reaction time (RTIMDSRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. RTI median 5-choice reaction time (RTIMDFRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. GEE statistical model.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, Week 8
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
RTISRTSD | |||||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
36
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.486 [11] | |||||||||||||||||||||
Method |
GEE model | |||||||||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||||||||
Point estimate |
-2.384
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
90% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-114.44 | |||||||||||||||||||||
upper limit |
109.67 | |||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||
Dispersion value |
68.1231
|
|||||||||||||||||||||
| Notes [11] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
||||||||||||||||||||||
Statistical analysis title |
RTIMDSRT | |||||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
36
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.8849 [12] | |||||||||||||||||||||
Method |
GEE model | |||||||||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||||||||
Point estimate |
63.669
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
90% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-23.6 | |||||||||||||||||||||
upper limit |
150.94 | |||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||
Dispersion value |
53.0537
|
|||||||||||||||||||||
| Notes [12] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
||||||||||||||||||||||
Statistical analysis title |
RTIMDFRT | |||||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
|||||||||||||||||||||
Number of subjects included in analysis |
36
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||
P-value |
= 0.1463 [13] | |||||||||||||||||||||
Method |
GEE model | |||||||||||||||||||||
Parameter type |
Least squares mean difference | |||||||||||||||||||||
Point estimate |
-63.835
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
90% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-163.59 | |||||||||||||||||||||
upper limit |
35.93 | |||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||
Dispersion value |
60.6496
|
|||||||||||||||||||||
| Notes [13] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE | ||||||||||||||||||
End point description |
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PAL total errors adjusted (PALTEA) assesses the cognitive domain of episodic memory/new learning, with scores on a discrete, ordinal scale from 0 to 137; lower scores indicate better function. PAL first trial memory score (PALFTMS) assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function. GEE statistical model.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
PALTEA | ||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
36
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.9378 [14] | ||||||||||||||||||
Method |
GEE model | ||||||||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||||||||
Point estimate |
17.768
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
90% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-1.26 | ||||||||||||||||||
upper limit |
36.79 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
11.5659
|
||||||||||||||||||
| Notes [14] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
|||||||||||||||||||
Statistical analysis title |
PALFTMS | ||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
36
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.5959 [15] | ||||||||||||||||||
Method |
GEE model | ||||||||||||||||||
Parameter type |
Least squares mean difference | ||||||||||||||||||
Point estimate |
-0.531
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
90% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-4.13 | ||||||||||||||||||
upper limit |
3.06 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
2.1853
|
||||||||||||||||||
| Notes [15] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
|||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE | ||||||||||||
End point description |
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SSP Span Length (SSPSLF) assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function. GEE statistical model.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
SSPSLF | ||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: Placebo v Efficacy Analysis Set - CANTAB: UX007
|
||||||||||||
Number of subjects included in analysis |
36
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.4522 [16] | ||||||||||||
Method |
GEE model | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
0.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
90% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.76 | ||||||||||||
upper limit |
0.88 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.4988
|
||||||||||||
| Notes [16] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
|||||||||||||
|
|||||||||||||||||||
End point title |
Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE | ||||||||||||||||||
End point description |
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWM between errors (SWMBE48) assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function. SWM strategy (SWMS68) assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function. GEE statistical model.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
SWMBE48 | ||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
36
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.3017 [17] | ||||||||||||||||||
Method |
GEE model | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-1.237
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
90% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-5.15 | ||||||||||||||||||
upper limit |
2.68 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
2.381
|
||||||||||||||||||
| Notes [17] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
|||||||||||||||||||
Statistical analysis title |
SWMS68 | ||||||||||||||||||
Comparison groups |
Efficacy Analysis Set - CANTAB: UX007 v Efficacy Analysis Set - CANTAB: Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
36
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.5235 [18] | ||||||||||||||||||
Method |
GEE model | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
0.038
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
90% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-1.03 | ||||||||||||||||||
upper limit |
1.11 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.6495
|
||||||||||||||||||
| Notes [18] - One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment. |
|||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT) | ||||||||||||
End point description |
Subjects were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
6MWT distance traveled | ||||||||||||
Comparison groups |
Efficacy Analysis Set – 6MWT: UX007 v Efficacy Analysis Set - 6MWT: Placebo
|
||||||||||||
Number of subjects included in analysis |
34
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.6205 [19] | ||||||||||||
Method |
GEE model | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
-6.897
|
||||||||||||
Confidence interval |
|||||||||||||
level |
90% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-43.874 | ||||||||||||
upper limit |
30.08 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
22.4806
|
||||||||||||
| Notes [19] - One-sided p-value. Additional model covariates include the corresponding baseline value, visit and the interaction between visit and treatment. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT | ||||||||||||
End point description |
Subjects were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. The percent of predicted normal distance walked was determined based on published normative data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
6MWT distance traveled (percent predicted) | ||||||||||||
Comparison groups |
Efficacy Analysis Set – 6MWT: UX007 v Efficacy Analysis Set - 6MWT: Placebo
|
||||||||||||
Number of subjects included in analysis |
34
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.6476 [20] | ||||||||||||
Method |
GEE model | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
-1.354
|
||||||||||||
Confidence interval |
|||||||||||||
level |
90% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-7.236 | ||||||||||||
upper limit |
4.527 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
3.5759
|
||||||||||||
| Notes [20] - One-sided p-value. Additional model covariates include the corresponding baseline value, visit and the interaction between visit and treatment. |
|||||||||||||
|
|||||||||||||||||||
End point title |
Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8 | ||||||||||||||||||
End point description |
For the 6MWT, subjects were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. PED occurring during the 6MWT was assessed. (PED is characterized by transient abnormal, involuntary movements primarily affecting the legs and feet, and typically precipitated by prolonged exertion.)
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 4, Week 8
|
||||||||||||||||||
|
|||||||||||||||||||
| Notes [21] - subjects with at least 1 PED [22] - subjects with at least 1 PED |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score | ||||||||||||
End point description |
The GMFM-88 is a standardized observational measure of abilities that includes the following 5 domains: lying/rolling, sitting, crawling/kneeling, standing, and walking/running/jumping. The GMFM-88 scores include the following:
• Lying & Rolling Score, Range 0–100%, higher is better
• Sitting Score, Range 0–100%, higher is better
• Crawling & Kneeling Score, Range 0–100%, higher is better
• Standing Score, Range 0–100%, higher is better
• Walking, Running & Jumping Score, Range 0–100%, higher is better
• Total Score = (Sum of 5 Above Scores) / 5, Range 0–100%, higher is better.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 8
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
GMFM-88 UX007-Placebo | ||||||||||||
Comparison groups |
Efficacy Analysis Set - GMFM-88: UX007 v Efficacy Analysis Set - GMFM-88: Placebo
|
||||||||||||
Number of subjects included in analysis |
32
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.3435 [23] | ||||||||||||
Method |
GEE model | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
1.568
|
||||||||||||
Confidence interval |
|||||||||||||
level |
90% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.83 | ||||||||||||
upper limit |
7.97 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
3.8899
|
||||||||||||
| Notes [23] - One-sided p-value. Additional model covariates include baseline GMFM-88 total score, visit and the interaction between visit and treatment. |
|||||||||||||
|
|||||||||||||||||||
End point title |
Percent Reduction from Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate) | ||||||||||||||||||
End point description |
Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake
(3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 26, Week 31
|
||||||||||||||||||
|
|||||||||||||||||||
| Notes [24] - n=subjects with an assessment at given time point. [25] - n=subjects with an assessment at given time point. |
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | ||||||||||||||||||||||||
End point description |
Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, Week 31, Week 36, and Week 52
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| Notes [26] - n=subjects with observable seizures and an assessment at given time point. [27] - n=subjects with observable seizures and an assessment at given time point. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate) | ||||||||||||||||||
End point description |
Absence seizures measured overnight by EEG. The absence seizure frequency from EEG (normalized to a 24-hour rate) is defined as Absence Seizure Frequency=Total number of absence seizures/Number of hours observed×24. Seizure types include: absence awake (≥10 sec), absence sleep (≥10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, Week 31
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| Notes [28] - n=subjects with absence seizures and an assessment at given time point. [29] - n=subjects with absence seizures and an assessment at given time point. |
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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 |
Placebo-controlled period from first dose of study drug through Week 8. Extension period: Week 9 up to Week 52 plus 30 days.
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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 |
20.0
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Reporting groups
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Reporting group title |
Placebo Controlled Period / Placebo
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Reporting group description |
Subjects randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Controlled Period / UX007
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Reporting group description |
Subjects randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Extension Period / UX007
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Reporting group description |
Following completion of the Week 8 study visit, placebo and UX007 subjects continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Oct 2013 |
1. Study Sites. The number of study sites was increased.
2. Number of Subjects Planned was increased.
3. Study Procedures and Assessments were modified.
4. Primary Efficacy Hypothesis was modified.
5. The primary objective language was modified.
6. Inclusion Criteria was modified.
7. Treatment Administration: A recommended dose titration schedule was inserted. In addition, dose administration guidelines were modified.
8. Drug Concentration Measurements for population PK assessments were modified.
9. Suicidal Ideation and Behavior Assessments were modified.
10. Statistical Methods plans were modified. |
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20 May 2014 |
1. Number of Subjects Planned was revised.
2. Primary Efficacy Hypothesis was modified.
3. Study Objectives were modified or added to Section 6 in order to align study objectives with modifications to study design and endpoints.
4. Overall Study Design and Plan was modified.
5. Inclusion Criteria was modified.
6. Study Procedures and Assessments were modified
7. Efficacy Measures were changed.
8. Drug Concentration Measurements were modified.
9. Statistical Analysis & Determination of Sample Size was updated. |
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09 Dec 2014 |
1. The adaptive study design component of the protocol was eliminated.
2. Inclusion criteria were updated, changed, and/or removed.
3. The primary and secondary objectives of the study were updated and the primary and secondary endpoints were updated to reflect the changes to the objectives to include a more robust evaluation of triheptanoin in patients with absence seizures.
4. The randomization was changed from 1:1 to 3:1 (UX007: placebo).
5. An EEG assessment was added at the Screening Visit.
6. Removal of Subjects from Therapy or Assessment was updated to clarify the conditions under which subjects either will be removed or may be removed from study participation. |
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30 Nov 2015 |
1. Edited Inclusion Criteria.
2. Updated the list of excluded medications.
3. Primary objective changed to ‘Evaluate the efficacy of UX007 compared to placebo as measured by the reduction from randomization to week 8 in frequency of seizures’.
4. The EEG at Screening for patients with absence seizures only was required for ~3 hours, not overnight.
5. The Erythrocyte Glucose Uptake Assay was removed from the protocol.
6. Plasma level sample collection range for the population PK study at Week 26 was changed from 30 – 180 minutes to 60 and 180 minutes. |
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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 | |||
