Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

• Sponsor: Ultragenyx Pharmaceutical Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02960217
• Collaborator: (none)
• Enrollment: 44
• Locations: 12
• Arms: 2
• Actual Duration (Months): 29.7
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of the study was to evaluate the efficacy and safety of UX007 in the treatment of disabling paroxysmal movement disorders associated with Glut1 DS.

Condition or Disease	Intervention/Treatment	Phase
Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)	Drug: UX007; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
• Actual Study Start Date: Apr 19, 2017
• Actual Primary Completion Date: Oct 9, 2019
• Actual Study Completion Date: Oct 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Double-Blind UX007 Followed by Placebo Participants will first receive UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they will then receive placebo for 10 weeks. Participants will have the option of rolling into the open label Extension Period, to continue UX007 treatment for up to 3 years.	Drug: UX007; liquid for oral (PO) administration; Drug: Placebo; liquid safflower oil for PO administration
Experimental: Double Blind Placebo Followed by UX007 Participants will first receive Placebo for 10 weeks. After a washout period of 2 weeks, they will then receive UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Participants will have the option of rolling into the open label Extension Period, to continue UX007 treatment for up to 3 years.	Drug: UX007; liquid for oral (PO) administration; Drug: Placebo; liquid safflower oil for PO administration

Outcome Measures

Primary Outcome Measures

1. Maintenance Phase Movement Disorder Frequency [Maintenance Phase (up to Week 22)]

   The frequency of paroxysmal movement disorders captured as disabling movement disorder events (normalized to a 4-week rate) observed during the Maintenance Phase in participants treated with UX007 versus placebo, as recorded by the subject/caregiver in an event-based daily Glut1 DS symptom diary.

2. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs [From first dose of study drug through 30-35 days after final dose. Mean (SD) treatment duration was 65.7 (12.06) and 68.3 (7.04) days for double-blind UX007 and placebo, and 305.0 (122.71) days for open-label UX007.]

   An Adverse Event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. Serious adverse events (SAE) was defined as an AE that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); a congenital anomaly/birth defect; other important medical event. All reported AEs with with a start date that occurred or worsened in severity on or after the first dose of study drug in the corresponding treatment period and before the first dose of study drug in the next treatment period were defined as TEAEs. AEs were graded as 1=mild, 2=moderate, 3=severe, 4=life=threatening, 5=death.

3. Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period [Baseline, up to Week 22]

   The C-SSRS is a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, and self-injurious behavior with no suicidal intent (yes or no responses). Positive responses (i.e., 'Yes') to C-SSRS questions correspond to events in these categories with the exception of the category 'No events'. Suicidal ideation includes the following subcategories: passive; active-nonspecific; active-method/no intent/no plan; active-intent/with or without method/no plan; active-method/intent/plan. Suicidal behavior includes the following subcategories: suicide attempt; interrupted attempt; aborted attempt; preparatory actions toward immanent suicidal behaviors; completed suicide. Suicidal ideation and/or suicidal behavior category includes participants with positive responses in the category suicidal ideation and/or suicidal behavior.

Secondary Outcome Measures

1. Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   Walking capacity and endurance, as determined by the distance in meters walked in 12 minutes during the 12MWT.

2. Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Physical Function Mobility Domain, increases in score indicate greater mobility.

3. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Fatigue Domain, decreases in score indicate less fatigue.

4. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Sleep Disturbance Domain, decreases in score indicate less sleep disturbance.

5. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases in scores indicate less pain interference.

6. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. The Cognitive Function Domain measures cognitive function impairment. Decreases in score indicate less cognitive function impairment.

7. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Social Roles and Activities Domain, decreases in score indicate worse /less or decrease of performance in social roles and activities.

8. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Anxiety Domain, decreases in scores indicate less anxiety.

9. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

   The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Mobility Domain, decreases in score indicate less mobility.

10. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Upper Extremity Domain, decreases in score indicate less upper extremity movement.

11. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Fatigue Domain, decreases in score indicate less fatigue.

12. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases in score indicate less pain interference.

13. Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Peer Relationships Domain, decreases in score indicate worse functioning in peer relationships.

14. Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10 [Week 10]

    Participant/caregiver global impression of change in clinical status using the CGI-I. The CGI-I is a 7-point scale that assesses how much the participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much better; 2=much better; 3=a little better; 4=no change; 5=a little worse; 6=much worse; 7=very much worse.

15. Duration of Movement Disorder Events During Maintenance Phase [Maintenance Phase (up to 22 weeks)]

    Duration of disabling paroxysmal movement disorder events observed during the Maintenance Period of treatment, as recorded by the subject/caregiver in an event-based daily electronic Glut1 DS symptom diary.

16. Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    Cognitive function as measured by the CANTAB. 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 assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function.

17. Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWMBE assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function.

18. Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWMS assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function.

19. Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. 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.

20. Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10 [Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

    CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PALFTMS assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation

2. Males and females, aged ≥6 years old at the time of informed consent

3. At least 8 disabling paroxysmal movement disorder events in the 12 weeks prior to the Screening, by subject or caregiver report or At least 6 disabling paroxysmal movement disorder events in any 6 consecutive week period, over the last 12 week period prior to the Screening, by subject or caregiver report

4. At least 4 disabling paroxysmal movement disorder events in 6 week Run-in Period, reported in the daily electronic Glut1 DS symptom diary

5. ≥80% compliance with daily electronic Glut1 DS symptom diary completion during the Run in Period

6. Not on ketogenic diet (KD), modified KD, or ketosis-inducing modified-fat diet for at least 3 months prior to Screening

7. Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening

8. Provide written or verbal assent (if possible) and written informed consent by the patient(if an adult), or by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures

9. Must, in the opinion of the Investigator, be willing and able to complete key aspects of the study and be likely to complete the 22-week, placebo-controlled, treatment period

10. Patient (or caregiver) must, in the opinion of the Investigator, be able to comply with accurate completion of the study daily electronic Glut1 DS symptom diary

11. Females of child-bearing potential must have a negative urine pregnancy test at Screening and Baseline and be willing to have additional pregnancy tests during the study. Females considered not to be of child-bearing potential include those who have not experienced menarche, are post-menopausal (defined as having no menses for at least 12 months without an alternative medical cause) or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.

12. Participants of child-bearing potential or fertile males with partners of child-bearing potential who are sexually active must consent to use a highly effective method of contraception as determined by the site Investigator from the period following the signing of the informed consent through 30 days after last dose of study drug

Exclusion Criteria:

1. Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the Investigator, places the subject at increased risk for adverse effects

2. Prior use of triheptanoin within 30 days prior to Screening

3. History of, or current suicidal ideation, behavior and/or attempts per Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or Baseline

4. Pregnant and/or breastfeeding an infant at Screening or Baseline

5. Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives (medium chain triglyceride [MCT] oil, barbiturates, pancreatic lipase inhibitors, KetoCal or other KD supplements, and/or KD])

6. Glut1 DS treatment regimen, including antiepileptic drugs (AEDs), should be stable for at least 30 days prior to Screening

7. Use of any investigational product (drug, medical food, or supplement, including MCT oil, including coconut oil) within 30 days prior to Screening

8. Has a concurrent disease or condition, or laboratory abnormality that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns

9. Feeding or nutrition that, in the opinion of the dietitian, potentially affects consistent administration of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Children's Hospital	Aurora	Colorado	United States	80045
2	Nicklaus Children's Hospital	Miami	Florida	United States	33155
3	Center for Rare Neurological Diseases	Norcross	Georgia	United States	30093
4	Columbia University Medical Center	New York	New York	United States	10032
5	Hopital Robert Debre	Paris		France	75019
6	University of Essen	Essen		Germany	45122
7	Klinikum der Universitat München	München		Germany	81377
8	Universitaetklinikum Tuebingen	Tuebingen		Germany	72076
9	IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino	Pavia		Italy	27100
10	Hospital Vall d'Hebron	Barcelona		Spain	08035
11	Leonard Wolfson Experimental Neurology Centre	London		United Kingdom	WC1N3BG
12	Sheffield Children's NHS Foundation Trust	Sheffield		United Kingdom	S102TH

Sponsors and Collaborators

• Ultragenyx Pharmaceutical Inc

Investigators

• Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Study Documents (Full-Text)

• Study Protocol - Jul 10, 2018
• Statistical Analysis Plan - Sep 5, 2018

More Information

Additional Information:

• Company Website

Publications

None provided.

• Responsible Party: Ultragenyx Pharmaceutical Inc
• ClinicalTrials.gov Identifier: NCT02960217
• Other Study ID Numbers: UX007G-CL301
• First Posted: Nov 9, 2016
• Last Update Posted: Jun 16, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Movement Disorders; Carbohydrate Metabolism, Inborn Errors; Syndrome

Study Results

Participant Flow

Pre-assignment Detail	During a 6-week Run-in Period, participants recorded disabling paroxysmal movement disorder events in a daily electronic Glut1 DS movement disorder diary. One participant was randomized but did not receive any treatment due to a protocol violation; this participant was not included in any analysis population.

Arm/Group Title	Double-Blind UX007 Followed by Placebo	Double-Blind Placebo Followed by UX007
Arm/Group Description	Double-Blind Maintenance Phase: Participants received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks. Participants had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for up to 3 years.	Double-Blind Maintenance Phase: Participants received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Participants had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for up to 3 years.
Period Title: Maintenance Phase: Treatment Period 1
STARTED	22	21
COMPLETED	21	21
NOT COMPLETED	1	0
Period Title: Maintenance Phase: Treatment Period 1
STARTED	21	21
COMPLETED	21	21
NOT COMPLETED	0	0
Period Title: Maintenance Phase: Treatment Period 1
STARTED	21	21
COMPLETED	20	18
NOT COMPLETED	1	3
Period Title: Maintenance Phase: Treatment Period 1
STARTED	20	13
COMPLETED	0	0
NOT COMPLETED	20	13

Baseline Characteristics

Arm/Group Title	Double-Blind UX007 Followed by Placebo	Double-Blind Placebo Followed by UX007	Total
Arm/Group Description	Double-Blind Maintenance Period: Participants received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they then received placebo for 10 weeks. Participants had the option of rolling into the Open-Label Extension Period, to continue UX007 treatment for up to 3 years.	Double-Blind Maintenance Period: Participants received placebo for 10 weeks. After a washout period of 2 weeks, they then received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Participants had the option of rolling into the Open-Label Extension Period, to continue UX007 treatment for up to 3 years.	Total of all reporting groups
Overall Participants	22	21	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.41 (13.156)	18.37 (5.730)	20.95 (10.425)
Age, Customized (Count of Participants)
< 18 years old	7 31.8%	9 42.9%	16 37.2%
>/= 18 years old	15 68.2%	12 57.1%	27 62.8%
Sex: Female, Male (Count of Participants)
Female	12 54.5%	12 57.1%	24 55.8%
Male	10 45.5%	9 42.9%	19 44.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.5%	0 0%	1 2.3%
Not Hispanic or Latino	17 77.3%	17 81%	34 79.1%
Unknown or Not Reported	4 18.2%	4 19%	8 18.6%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	0 0%	1 4.8%	1 2.3%
White	18 81.8%	16 76.2%	34 79.1%
Missing	4 18.2%	4 19%	8 18.6%

Outcome Measures

1. Primary Outcome

Title	Maintenance Phase Movement Disorder Frequency
Description	The frequency of paroxysmal movement disorders captured as disabling movement disorder events (normalized to a 4-week rate) observed during the Maintenance Phase in participants treated with UX007 versus placebo, as recorded by the subject/caregiver in an event-based daily Glut1 DS symptom diary.
Time Frame	Maintenance Phase (up to Week 22)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	43	42
Median (Full Range) [movement disorder events per 4 weeks]	14.26	11.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments	Participants completing both UX007 treatment period and placebo period (n=42). Per protocol, when the normality assumption is not met (p value for Wilk-Shapiro test < 0.05), Wilcoxon rank-sum test will be considered as the primary analysis to assess treatment difference in movement disorder event frequency.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2684
	Comments	Hodges-Lehmann estimate of the location shift with 95% confidence interval (CI) and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate (Median Diff.)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95%; -1.12 to 4.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Wilk-Shapiro test for normality
	Comments

2. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
Description	An Adverse Event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. Serious adverse events (SAE) was defined as an AE that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); a congenital anomaly/birth defect; other important medical event. All reported AEs with with a start date that occurred or worsened in severity on or after the first dose of study drug in the corresponding treatment period and before the first dose of study drug in the next treatment period were defined as TEAEs. AEs were graded as 1=mild, 2=moderate, 3=severe, 4=life=threatening, 5=death.
Time Frame	From first dose of study drug through 30-35 days after final dose. Mean (SD) treatment duration was 65.7 (12.06) and 68.3 (7.04) days for double-blind UX007 and placebo, and 305.0 (122.71) days for open-label UX007.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo	Open-Label UX007
Arm/Group Description	Double-Blind Maintenance Phase: Participants received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Double-Blind Maintenance Phase: Participants received placebo for 10 weeks.	Open-Label Extension Phase: Participants continued UX007 treatment for up to 3 years.
Measure Participants	43	42	33
TEAEs	40 181.8%	34 161.9%	28 65.1%
Serious TEAEs	2 9.1%	1 4.8%	2 4.7%
Treatment-Related TEAEs	33 150%	19 90.5%	17 39.5%
Treatment-Related Serious TEAEs	1 4.5%	0 0%	0 0%
Grade 3 or 4 TEAEs	4 18.2%	3 14.3%	3 7%
Grade 4 TEAEs	0 0%	0 0%	0 0%
Gastrointestinal TEAEs	32 145.5%	17 81%	18 41.9%
TEAEs Leading to Treatment Discontinuation	2 9.1%	1 4.8%	0 0%
TEAEs Leading to Study Discontinuation	2 9.1%	1 4.8%	0 0%
TEAEs Leading to Death	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period
Description	The C-SSRS is a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, and self-injurious behavior with no suicidal intent (yes or no responses). Positive responses (i.e., 'Yes') to C-SSRS questions correspond to events in these categories with the exception of the category 'No events'. Suicidal ideation includes the following subcategories: passive; active-nonspecific; active-method/no intent/no plan; active-intent/with or without method/no plan; active-method/intent/plan. Suicidal behavior includes the following subcategories: suicide attempt; interrupted attempt; aborted attempt; preparatory actions toward immanent suicidal behaviors; completed suicide. Suicidal ideation and/or suicidal behavior category includes participants with positive responses in the category suicidal ideation and/or suicidal behavior.
Time Frame	Baseline, up to Week 22

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants with a baseline (BL) and postbaseline (PB) assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	40	40
BL: No Events	38 172.7%	38 181%
PB: No Events	40 181.8%	39 185.7%
BL: Suicidal Ideation	1 4.5%	1 4.8%
PB: Suicidal Ideation	0 0%	0 0%
BL: Suicidal Behavior	1 4.5%	1 4.8%
PB: Suicidal Behavior	0 0%	1 4.8%
BL: Suicidal Ideation and/or Behavior	2 9.1%	2 9.5%
PB: Suicidal Ideation and/or Behavior	0 0%	1 4.8%
BL: Self-Injurious Behavior, No Suicidal Intent	1 4.5%	1 4.8%
PB: Self-Injurious Behavior, No Suicidal Intent	0 0%	1 4.8%

4. Secondary Outcome

Title	Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10
Description	Walking capacity and endurance, as determined by the distance in meters walked in 12 minutes during the 12MWT.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	36	38
Least Squares Mean (Standard Error) [meters]	-15.9 (25.63)	-33.0 (24.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments	Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=34).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6419
	Comments	Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate (Median Diff.)
	Estimated Value	25.00
	Confidence Interval	(2-Sided) 95%; -62.5 to 91.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

5. Secondary Outcome

Title	Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Physical Function Mobility Domain, increases in score indicate greater mobility.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	-0.9 (0.67)	-0.9 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9513
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -2.0 to 1.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.91
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8214
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

6. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Fatigue Domain, decreases in score indicate less fatigue.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	2.9 (1.40)	0.9 (1.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1572
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -0.8 to 4.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.32
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8451
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

7. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Sleep Disturbance Domain, decreases in score indicate less sleep disturbance.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	0.4 (1.24)	0.7 (1.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8345
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -3.8 to 3.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.66
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2894
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

8. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases in scores indicate less pain interference.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	4.5 (1.64)	3.7 (1.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments	Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=21).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4898
	Comments	Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate (Median Diff.)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -5.4 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. The Cognitive Function Domain measures cognitive function impairment. Decreases in score indicate less cognitive function impairment.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	2.0 (1.29)	1.2 (1.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5853
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -2.2 to 3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.42
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1066
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

10. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Social Roles and Activities Domain, decreases in score indicate worse /less or decrease of performance in social roles and activities.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	-4.1 (1.35)	-2.3 (1.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1875
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -4.6 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.33
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2034
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

11. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Anxiety Domain, decreases in scores indicate less anxiety.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized adult participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	23	25
Least Squares Mean (Standard Error) [T-score]	3.1 (1.49)	0.5 (1.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1138
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -0.7 to 5.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.56
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1478
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

12. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Mobility Domain, decreases in score indicate less mobility.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	16	13
Least Squares Mean (Standard Error) [T-score]	-1.0 (1.62)	0.0 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5505
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -4.6 to 2.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.62
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4459
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

13. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Upper Extremity Domain, decreases in score indicate less upper extremity movement.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	16	13
Least Squares Mean (Standard Error) [T-score]	-0.4 (1.91)	1.3 (2.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5544
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -8.1 to 4.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.84
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1104
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

14. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Fatigue Domain, decreases in score indicate less fatigue.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	16	13
Least Squares Mean (Standard Error) [T-score]	-1.8 (2.40)	-0.6 (2.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7145
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -8.5 to 6.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8255
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

15. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Pain Interference Domain, decreases in score indicate less pain interference.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	16	13
Least Squares Mean (Standard Error) [T-score]	3.2 (1.84)	1.6 (1.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4176
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -2.5 to 5.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.82
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6557
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

16. Secondary Outcome

Title	Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10
Description	The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013; NIH 2015) via parent/proxy. It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Peer Relationships Domain, decreases in score indicate worse functioning in peer relationships.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized pediatric participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	16	13
Least Squares Mean (Standard Error) [T-score]	2.0 (1.57)	-0.0 (1.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0935
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for participant within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -0.4 to 4.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7267
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

17. Secondary Outcome

Title	Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10
Description	Participant/caregiver global impression of change in clinical status using the CGI-I. The CGI-I is a 7-point scale that assesses how much the participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much better; 2=much better; 3=a little better; 4=no change; 5=a little worse; 6=much worse; 7=very much worse.
Time Frame	Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	38	40
Least Squares Mean (Standard Error) [score on a scale]	3.5 (0.20)	3.6 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8329
	Comments	Based on an ANCOVA model including covariate for study baseline CGI-S score, fixed effects for treatment sequence, treatment group, period, and a random effect for subject within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2348
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

18. Secondary Outcome

Title	Duration of Movement Disorder Events During Maintenance Phase
Description	Duration of disabling paroxysmal movement disorder events observed during the Maintenance Period of treatment, as recorded by the subject/caregiver in an event-based daily electronic Glut1 DS symptom diary.
Time Frame	Maintenance Phase (up to 22 weeks)

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants (or parent/proxy) who received at least 1 dose of study drug.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	43	42
Mean (Standard Deviation) [hours]	0.9 (1.98)	0.7 (1.53)

19. Secondary Outcome

Title	Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10
Description	Cognitive function as measured by the CANTAB. 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 assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	13	14
Least Squares Mean (Standard Error) [units on a scale]	0.1 (0.31)	0.6 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0315
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments	Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=13).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2425
	Comments	Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate (Median Diff.)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWMBE assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	13	14
Least Squares Mean (Standard Error) [units on a scale]	-0.2 (2.94)	0.2 (2.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0072
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments	Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=12).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate (Median Diff.)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -14.5 to 13.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWMS assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	13	14
Least Squares Mean (Standard Error) [units on a scale]	0.6 (0.77)	-0.4 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1076
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for subject within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 2.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7698
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

22. Secondary Outcome

Title	Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. 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.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants (or parent/proxy) who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	13	15
Least Squares Mean (Standard Error) [units on a scale]	-2.0 (4.74)	-8.5 (4.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0138
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments	Number of participants in this analysis completed both UX007 treatment period and placebo treatment period (n=13).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3907
	Comments	Hodges-Lehmann estimate of the location shift with 95% CI and Wilcoxon Rank Sum test p-value are based on Wilcoxon rank-sum test.
	Method	Wilcoxon Rank Sum test
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate (Median Diff.)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -3.5 to 20.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PALFTMS assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function.
Time Frame	Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized participants (or parent/proxy) who received at least 1 dose of study drug. Participants who had an assessment.

Arm/Group Title	Double-Blind UX007	Double-Blind Placebo
Arm/Group Description	UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.	Placebo for 10 weeks.
Measure Participants	13	15
Least Squares Mean (Standard Error) [units on a scale]	-0.1 (1.12)	0.9 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5233
	Comments	Based on an ANCOVA model including covariate for period baseline value, fixed effects for treatment sequence, treatment group, period, and a random effect for subject within the sequence.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -4.4 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.51
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-Blind UX007, Double-Blind Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6918
	Comments
	Method	Wilk-Shapiro Test for Normality
	Comments

Adverse Events

Time Frame	From first dose of study drug through 30-35 days after final dose. Mean (SD) treatment duration was 65.7 (12.06) and 68.3 (7.04) days for double-blind UX007 and placebo, respectively, and 305.0 (122.71) days for open-label UX007.
Arm/Group Title	DB UX007		DB Placebo		OL UX007
Arm/Group Description	Double-Blind Maintenance Phase: Participants received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.		Double-Blind Maintenance Phase: Participants received placebo for 10 weeks.		Open-Label Extension Phase: Participants continued UX007 treatment (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for up to 3 years.
All Cause Mortality
	DB UX007		DB Placebo		OL UX007
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/42 (0%)		0/33 (0%)
Serious Adverse Events
	DB UX007		DB Placebo		OL UX007
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/43 (4.7%)		1/42 (2.4%)		2/33 (6.1%)
Injury, poisoning and procedural complications
Head Injury	1/43 (2.3%)		0/42 (0%)		0/33 (0%)
Musculoskeletal and connective tissue disorders
Limb Asymmetry	0/43 (0%)		0/42 (0%)		1/33 (3%)
Nervous system disorders
Movement Disorder	1/43 (2.3%)		0/42 (0%)		1/33 (3%)
Psychomotor Hyperactivity	0/43 (0%)		1/42 (2.4%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	DB UX007		DB Placebo		OL UX007
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/43 (83.7%)		26/42 (61.9%)		22/33 (66.7%)
Gastrointestinal disorders
Abdominal Discomfort	4/43 (9.3%)		0/42 (0%)		0/33 (0%)
Abdominal Pain	6/43 (14%)		1/42 (2.4%)		5/33 (15.2%)
Abdominal Pain Upper	14/43 (32.6%)		6/42 (14.3%)		7/33 (21.2%)
Anal Incontinence	3/43 (7%)		0/42 (0%)		0/33 (0%)
Constipation	1/43 (2.3%)		1/42 (2.4%)		3/33 (9.1%)
Diarrhoea	22/43 (51.2%)		5/42 (11.9%)		9/33 (27.3%)
Nausea	7/43 (16.3%)		5/42 (11.9%)		4/33 (12.1%)
Vomiting	13/43 (30.2%)		8/42 (19%)		8/33 (24.2%)
General disorders
Fatigue	3/43 (7%)		5/42 (11.9%)		3/33 (9.1%)
Gait Disturbance	0/43 (0%)		1/42 (2.4%)		2/33 (6.1%)
Pyrexia	4/43 (9.3%)		1/42 (2.4%)		2/33 (6.1%)
Infections and infestations
Gastroenteritis	3/43 (7%)		0/42 (0%)		1/33 (3%)
Gastroenteritis Viral	0/43 (0%)		1/42 (2.4%)		2/33 (6.1%)
Influenza	3/43 (7%)		0/42 (0%)		2/33 (6.1%)
Viral Upper Respiratory Tract Infection	5/43 (11.6%)		2/42 (4.8%)		2/33 (6.1%)
Investigations
Blood Ketone Body Increased	3/43 (7%)		2/42 (4.8%)		0/33 (0%)
Weight Increased	3/43 (7%)		1/42 (2.4%)		2/33 (6.1%)
Metabolism and nutrition disorders
Decreased Appetite	5/43 (11.6%)		1/42 (2.4%)		1/33 (3%)
Nervous system disorders
Dizziness	1/43 (2.3%)		2/42 (4.8%)		2/33 (6.1%)
Dyskinesia	3/43 (7%)		2/42 (4.8%)		3/33 (9.1%)
Headache	7/43 (16.3%)		6/42 (14.3%)		6/33 (18.2%)
Psychiatric disorders
Aggression	4/43 (9.3%)		0/42 (0%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/43 (4.7%)		0/42 (0%)		3/33 (9.1%)
Oropharyngeal Pain	4/43 (9.3%)		3/42 (7.1%)		1/33 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.