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Clinical Trial Results:
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)

Summary
EudraCT number	2015-005536-17
Trial protocol	DE ES FR GB IT
Global end of trial date	09 Oct 2019

Results information
Results version number	v1(current)
This version publication date	24 Apr 2020
First version publication date	24 Apr 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

UX007G-CL301

ISRCTN number

US NCT number

NCT02960217

WHO universal trial number (UTN)

Other trial identifiers

EMA/190573: Unique Product Identifier (UPI)

Sponsor organisation name

Ultragenyx Pharmaceutical Inc.

Sponsor organisation address

60 Leveroni Court, Novato, United States, California 94949

Public contact

Medical Information, Ultragenyx Pharmaceutical Inc, +1 888- 756-8657, medinfo@ultragenyx.com

Scientific contact

Medical Information, Ultragenyx Pharmaceutical Inc, +1 888- 756-8657, medinfo@ultragenyx.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Oct 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Oct 2019

Was the trial ended prematurely?

Yes

Main objective of the trial

Primary Objectives: •Evaluate the efficacy and safety of UX007 in the treatment of disabling paroxysmal movement disorders associated with Glut1 DS

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.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Apr 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 8

Country: Number of subjects enrolled

Germany: 8

Country: Number of subjects enrolled

Spain: 5

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

United States: 15

Country: Number of subjects enrolled

Italy: 5

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

During a 6-week Run-in Period, subjects recorded disabling paroxysmal movement disorder events in a daily electronic Glut1 DS movement disorder diary.

Number of subjects started

Number of subjects completed

Reason: Number of subjects

Randomized not treated: 1

Period 1 title

Maintenance Phase: Treatment Period 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Blinding implementation details

Double-blind conditions were established during this period so that neither the sponsor, subject, or site personnel involved in study conduct knew the identity of a subject’s treatment. After all subjects completed the double-blind period, unblinding of the study occurred.

Are arms mutually exclusive

Yes

Double-Blind UX007 Followed by Placebo

Arm description

Double-Blind Maintenance Phase: Subjects 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.

Arm type

Experimental

Investigational medicinal product name

triheptanoin

Investigational medicinal product code

UX007

Other name

C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

Double-Blind Placebo Followed by UX007

Arm description

Double-Blind Maintenance Phase: Subjects 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.

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

safflower oil

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

Number of subjects in period 1 ^[1]	Double-Blind UX007 Followed by Placebo	Double-Blind Placebo Followed by UX007
Started	22	21
Completed	21	21
Not completed	1	0
Adverse event	1	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: One subject was randomized but did not receive any treatment due to a protocol violation; this subject was not included in any analyses in this study.

Period 2 title

Maintenance Phase: Crossover Washout

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Are arms mutually exclusive

Yes

Double-Blind UX007 Followed by Placebo

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Double-Blind Placebo Followed by UX007

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	Double-Blind UX007 Followed by Placebo	Double-Blind Placebo Followed by UX007
Started	21	21
Completed	21	21

Period 3 title

Maintenance Phase: Treatment Period 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Blinding implementation details

Are arms mutually exclusive

Yes

Double-Blind UX007 Followed by Placebo

Arm description

Arm type

Experimental

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

safflower oil

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

Double-Blind Placebo Followed by UX007

Arm description

Arm type

Experimental

Investigational medicinal product name

triheptanoin

Investigational medicinal product code

UX007

Other name

C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

Number of subjects in period 3	Double-Blind UX007 Followed by Placebo	Double-Blind Placebo Followed by UX007
Started	21	21
Completed	20	18
Not completed	1	3
Consent withdrawn by subject	-	1
Other, not specified	-	1
Adverse event	-	1
Lack of efficacy	1	-

Period 4 title

Open-Label Extension Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Double-Blind UX007 Followed by Placebo-->Open Label UX007

Arm description

Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.

Arm type

Experimental

Investigational medicinal product name

triheptanoin

Investigational medicinal product code

UX007

Other name

C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

Double-Blind Placebo Followed by UX007-->Open Label UX007

Arm description

Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.

Arm type

Experimental

Investigational medicinal product name

triheptanoin

Investigational medicinal product code

UX007

Other name

C7 oil, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3- trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

The total daily dose was divided into 4 equal doses mixed with food or drink (or formula, as appropriate), and administered orally or by gastronomy tube at breakfast, lunch, dinner, and before bed.

Number of subjects in period 4 ^[2]	Double-Blind UX007 Followed by Placebo-->Open Label UX007	Double-Blind Placebo Followed by UX007-->Open Label UX007
Started	20	13
Completed	0	0
Not completed	20	13
Other, not specified	-	1
Adverse event	1	-
Sponsor decision	18	11
Lack of efficacy	1	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 5 subjects completed the double blind period but did not continue in the open label period.

Baseline characteristics

Top of page

Reporting group title

Double-Blind UX007 Followed by Placebo

Reporting group description

Reporting group title

Double-Blind Placebo Followed by UX007

Reporting group description

Reporting group values	Double-Blind UX007 Followed by Placebo	Double-Blind Placebo Followed by UX007	Total
Number of subjects	22	21	43
Age categorical
Units: Subjects
< 18 years old	7	9	16
>= 18 years old	15	12	27
Age continuous
Units: years
arithmetic mean (standard deviation)	23.41 ( 13.156 )	18.37 ( 5.730 )	-
Gender categorical
Units: Subjects
Female	12	12	24
Male	10	9	19
Ethnicity
Units: Subjects
Hispanic or Latino	1	0	1
Not Hispanic or Latino	17	17	34
Unknown or Not Reported	4	4	8
Race
Units: Subjects
Black or African American	0	1	1
White	18	16	34
Missing	4	4	8

End points

Top of page

Reporting group title

Double-Blind UX007 Followed by Placebo

Reporting group description

Reporting group title

Double-Blind Placebo Followed by UX007

Reporting group description

Reporting group title

Double-Blind UX007 Followed by Placebo

Reporting group description

Reporting group title

Double-Blind Placebo Followed by UX007

Reporting group description

Reporting group title

Double-Blind UX007 Followed by Placebo

Reporting group description

Reporting group title

Double-Blind Placebo Followed by UX007

Reporting group description

Reporting group title

Double-Blind UX007 Followed by Placebo-->Open Label UX007

Reporting group description

Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.

Reporting group title

Double-Blind Placebo Followed by UX007-->Open Label UX007

Reporting group description

Subjects had the option of rolling into the Open-Label Extension Phase, to continue UX007 treatment for up to 3 years.

Subject analysis set title

Full Analysis Set: Double-Blind UX007

Subject analysis set type

Full analysis

Subject analysis set description

UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Full Analysis Set: all randomized subjects who received at least 1 dose of study drug.

Subject analysis set title

Full Analysis Set: Double-Blind Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo for 10 weeks. Full Analysis Set: all randomized subjects who received at least 1 dose of study drug.

Subject analysis set title

Safety Analysis Set: Double-Blind UX007

Subject analysis set type

Safety analysis

Subject analysis set description

UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Safety Analysis Set: all randomized subjects who received at least 1 dose of study drug.

Subject analysis set title

Safety Analysis Set: Double-Blind Placebo

Subject analysis set type

Safety analysis

Subject analysis set description

Placebo for 10 weeks. Safety Analysis Set: all randomized subjects who received at least 1 dose of study drug.

Subject analysis set title

Safety Analysis Set: Open-Label UX007

Subject analysis set type

Safety analysis

Subject analysis set description

UX007 treatment continuation for up to 3 years. Safety Analysis Set: all randomized participants who received at least 1 dose of study drug.

Primary: Maintenance Phase Movement Disorder Frequency

Top of page

End point title

Maintenance Phase Movement Disorder Frequency ^[1]

End point 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.

End point type

Primary

End point timeframe

Maintenance Phase (up to Week 22)

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: Statistical analyses are attached as a pdf.

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	43	42
Units: movement disorder events per 4 weeks
median (full range (min-max))	14.26 (0.0 to 112.0)	11.81 (0.5 to 112.0)

Attachments

Untitled (Filename: Statistical Analysis for Maintenance Phase Movement Disorder Frequency.docx)

No statistical analyses for this end point

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

Top of page

End point title

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs ^[2]

End point 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.

End point type

Primary

End point timeframe

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.

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.

End point values	Safety Analysis Set: Double-Blind UX007	Safety Analysis Set: Double-Blind Placebo	Safety Analysis Set: Open-Label UX007
Number of subjects analysed	43	42	33
Units: subjects
TEAEs	40	34	28
Serious TEAEs	2	1	2
Treatment-Related TEAEs	33	19	17
Treatment-Related Serious TEAEs	1	0	0
Grade 3 or 4 TEAEs	4	3	3
Grade 4 TEAEs	0	0	0
Gastrointestinal TEAEs	32	17	18
TEAEs Leading to Treatment Discontinuation	2	1	0
TEAEs Leading to Study Discontinuation	2	1	0
TEAEs Leading to Death	0	0	0

No statistical analyses for this end point

Primary: Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period

Top of page

End point title

Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period ^[3]

End point 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.

End point type

Primary

End point timeframe

Baseline, up to Week 22

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics are presented per protocol.

End point values	Safety Analysis Set: Double-Blind UX007	Safety Analysis Set: Double-Blind Placebo
Number of subjects analysed	40 ^[4]	40 ^[5]
Units: participants
BL: No Events	38	38
PB: No Events	40	39
BL: Suicidal Ideation	1	1
PB: Suicidal Ideation	0	0
BL: Suicidal Behavior	1	1
PB: Suicidal Behavior	0	1
BL: Suicidal Ideation and/or Behavior	2	2
PB: Suicidal Ideation and/or Behavior	0	1
BL: Self-Injurious Behavior, No Suicidal Intent	1	1
PB: Self-Injurious Behavior, No Suicidal Intent	0	1

Notes
[4] - Subjects with a baseline (BL) and postbaseline (PB) assessment
[5] - Subjects with a baseline (BL) and postbaseline (PB) assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10

Top of page

End point title

Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	36 ^[6]	38 ^[7]
Units: meters
least squares mean (standard error)	-15.9 ( 25.63 )	-33.0 ( 24.91 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in 12MWT Distance.docx)

Notes
[6] - subjects with an assessment
[7] - subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10

Top of page

End point 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

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[8]	25 ^[9]
Units: T-score
least squares mean (standard error)	-0.9 ( 0.67 )	-0.9 ( 0.65 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Physical Function Score.docx)

Notes
[8] - adult subjects with an assessment
[9] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[10]	25 ^[11]
Units: T-score
least squares mean (standard error)	2.9 ( 1.40 )	0.9 ( 1.36 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score.docx)

Notes
[10] - adult subjects with an assessment
[11] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[12]	25 ^[13]
Units: T-score
least squares mean (standard error)	0.4 ( 1.24 )	0.7 ( 1.20 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance.docx)

Notes
[12] - adult subjects with an assessment
[13] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[14]	25 ^[15]
Units: T-score
least squares mean (standard error)	4.5 ( 1.64 )	3.7 ( 1.58 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference.docx)

Notes
[14] - adult subjects with an assessment
[15] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[16]	25 ^[17]
Units: T-score
least squares mean (standard error)	2.0 ( 1.29 )	1.2 ( 1.25 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function.docx)

Notes
[16] - adult subjects with an assessment
[17] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[18]	25 ^[19]
Units: T-score
least squares mean (standard error)	-4.1 ( 1.35 )	-2.3 ( 1.32 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities.docx)

Notes
[18] - adult subjects with an assessment
[19] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	23 ^[20]	25 ^[21]
Units: T-score
least squares mean (standard error)	3.1 ( 1.49 )	0.5 ( 1.45 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score.docx)

Notes
[20] - adult subjects with an assessment
[21] - adult subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	16 ^[22]	13 ^[23]
Units: T-score
least squares mean (standard error)	-1.0 ( 1.62 )	0.0 ( 1.73 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Mobility Score.docx)

Notes
[22] - pediatric subjects with an assessment
[23] - pediatric subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	16 ^[24]	13 ^[25]
Units: T-score
least squares mean (standard deviation)	-0.4 ( 1.91 )	1.3 ( 2.11 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Upper Extremity.docx)

Notes
[24] - pediatric subjects with an assessment
[25] - pediatric subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	16 ^[26]	13 ^[27]
Units: T-score
least squares mean (standard error)	-1.8 ( 2.40 )	-0.6 ( 2.64 )

Attachments

Untitled (Filename: Statistical Analysis 2 for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Fatigue.docx)

Notes
[26] - pediatric subjects with an assessment
[27] - pediatric subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	16 ^[28]	13 ^[29]
Units: T-score
least squares mean (standard error)	3.2 ( 1.84 )	1.6 ( 1.96 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Pain Interference.docx)

Notes
[28] - pediatric subjects with an assessment
[29] - pediatric subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10

Top of page

End point title

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	16 ^[30]	13 ^[31]
Units: T-score
least squares mean (standard error)	2.0 ( 1.57 )	-0.0 ( 1.64 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric_Parent-Proxy Form) Peer Relationships.docx)

Notes
[30] - pediatric subjects with an assessment
[31] - pediatric subjects with an assessment

No statistical analyses for this end point

Secondary: Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10

Top of page

End point title

Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

Week 10

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	38	40
Units: score on a scale
least squares mean (standard error)	3.5 ( 0.20 )	3.6 ( 0.20 )

Attachments

Untitled (Filename: Statistical Analysis for Clinical Global Impression - Improvement (CGI-I).docx)

No statistical analyses for this end point

Secondary: Duration of Movement Disorder Events During Maintenance Phase

Top of page

End point title

Duration of Movement Disorder Events During Maintenance Phase

End point 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.

End point type

Secondary

End point timeframe

Maintenance Phase (up to 22 weeks)

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	43	42
Units: hours
arithmetic mean (standard deviation)	0.9 ( 1.98 )	0.7 ( 1.53 )

No statistical analyses for this end point

Secondary: Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10

Top of page

End point title

Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	13	14
Units: units on a scale
least squares mean (standard error)	0.1 ( 0.31 )	0.6 ( 0.29 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP).docx)

No statistical analyses for this end point

Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10

Top of page

End point title

Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10

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. SWMBE assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	13	14
Units: units on a scale
least squares mean (standard error)	-0.2 ( 2.94 )	0.2 ( 2.83 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE).docx)

No statistical analyses for this end point

Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10

Top of page

End point title

Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10

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. 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	13 ^[32]	14 ^[33]
Units: units on a scale
least squares mean (standard error)	0.6 ( 0.77 )	-0.4 ( 0.74 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS).docx)

Notes
[32] - subjects with an assessment
[33] - subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10

Top of page

End point title

Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10

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. 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.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	13 ^[34]	15 ^[35]
Units: units on a scale
least squares mean (standard error)	-2.0 ( 4.74 )	-8.5 ( 4.41 )

Attachments

Untitled (Filename: Statistical Analysis 2 for Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA).docx)

Notes
[34] - subjects with an assessment
[35] - subjects with an assessment

No statistical analyses for this end point

Secondary: Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10

Top of page

End point title

Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10

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. PALFTMS assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function.

End point type

Secondary

End point timeframe

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

End point values	Full Analysis Set: Double-Blind UX007	Full Analysis Set: Double-Blind Placebo
Number of subjects analysed	13 ^[36]	15 ^[37]
Units: units on a scale
least squares mean (standard error)	-0.1 ( 1.12 )	0.9 ( 1.04 )

Attachments

Untitled (Filename: Statistical Analysis for Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS).docx)

Notes
[36] - subjects with an assessment
[37] - subjects with an assessment

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

DB UX007

Reporting group description

Double-Blind Maintenance Phase: Subjects received UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks.

Reporting group title

OL UX007

Reporting group description

Open-Label Extension Phase: Subjects continued UX007 treatment for up to 3 years.

Reporting group title

DB Placebo

Reporting group description

Double-Blind Maintenance Phase: Subjects received placebo for 10 weeks.

Serious adverse events	DB UX007	OL UX007	DB Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 43 (4.65%)	2 / 33 (6.06%)	1 / 42 (2.38%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Injury, poisoning and procedural complications
Head Injury
subjects affected / exposed	1 / 43 (2.33%)	0 / 33 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Movement Disorder
subjects affected / exposed	1 / 43 (2.33%)	1 / 33 (3.03%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychomotor Hyperactivity
subjects affected / exposed	0 / 43 (0.00%)	0 / 33 (0.00%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Limb Asymmetry
subjects affected / exposed	0 / 43 (0.00%)	1 / 33 (3.03%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	DB UX007	OL UX007	DB Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	36 / 43 (83.72%)	22 / 33 (66.67%)	26 / 42 (61.90%)
Investigations
Blood Ketone Body Increased
subjects affected / exposed	3 / 43 (6.98%)	0 / 33 (0.00%)	2 / 42 (4.76%)
occurrences all number	3	0	2
Weight Increased
subjects affected / exposed	3 / 43 (6.98%)	2 / 33 (6.06%)	1 / 42 (2.38%)
occurrences all number	3	2	1
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 43 (2.33%)	2 / 33 (6.06%)	2 / 42 (4.76%)
occurrences all number	1	2	2
Dyskinesia
subjects affected / exposed	3 / 43 (6.98%)	3 / 33 (9.09%)	2 / 42 (4.76%)
occurrences all number	3	4	2
Headache
subjects affected / exposed	7 / 43 (16.28%)	6 / 33 (18.18%)	6 / 42 (14.29%)
occurrences all number	15	17	12
General disorders and administration site conditions
Fatigue
subjects affected / exposed	3 / 43 (6.98%)	3 / 33 (9.09%)	5 / 42 (11.90%)
occurrences all number	3	5	5
Gait Disturbance
subjects affected / exposed	0 / 43 (0.00%)	2 / 33 (6.06%)	1 / 42 (2.38%)
occurrences all number	0	2	1
Pyrexia
subjects affected / exposed	4 / 43 (9.30%)	2 / 33 (6.06%)	1 / 42 (2.38%)
occurrences all number	5	2	1
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	4 / 43 (9.30%)	0 / 33 (0.00%)	0 / 42 (0.00%)
occurrences all number	10	0	0
Abdominal Pain
subjects affected / exposed	6 / 43 (13.95%)	5 / 33 (15.15%)	1 / 42 (2.38%)
occurrences all number	9	6	1
Abdominal Pain Upper
subjects affected / exposed	14 / 43 (32.56%)	7 / 33 (21.21%)	6 / 42 (14.29%)
occurrences all number	35	22	11
Anal Incontinence
subjects affected / exposed	3 / 43 (6.98%)	0 / 33 (0.00%)	0 / 42 (0.00%)
occurrences all number	4	0	0
Constipation
subjects affected / exposed	1 / 43 (2.33%)	3 / 33 (9.09%)	1 / 42 (2.38%)
occurrences all number	1	5	1
Diarrhoea
subjects affected / exposed	22 / 43 (51.16%)	9 / 33 (27.27%)	5 / 42 (11.90%)
occurrences all number	50	46	12
Nausea
subjects affected / exposed	7 / 43 (16.28%)	4 / 33 (12.12%)	5 / 42 (11.90%)
occurrences all number	10	6	7
Vomiting
subjects affected / exposed	13 / 43 (30.23%)	8 / 33 (24.24%)	8 / 42 (19.05%)
occurrences all number	23	14	11
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 43 (4.65%)	3 / 33 (9.09%)	0 / 42 (0.00%)
occurrences all number	2	4	0
Oropharyngeal Pain
subjects affected / exposed	4 / 43 (9.30%)	1 / 33 (3.03%)	3 / 42 (7.14%)
occurrences all number	4	1	3
Psychiatric disorders
Aggression
subjects affected / exposed	4 / 43 (9.30%)	0 / 33 (0.00%)	0 / 42 (0.00%)
occurrences all number	4	0	0
Infections and infestations
Gastroenteritis
subjects affected / exposed	3 / 43 (6.98%)	1 / 33 (3.03%)	0 / 42 (0.00%)
occurrences all number	3	1	0
Gastroenteritis Viral
subjects affected / exposed	0 / 43 (0.00%)	2 / 33 (6.06%)	1 / 42 (2.38%)
occurrences all number	0	2	1
Influenza
subjects affected / exposed	3 / 43 (6.98%)	2 / 33 (6.06%)	0 / 42 (0.00%)
occurrences all number	3	3	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	5 / 43 (11.63%)	2 / 33 (6.06%)	2 / 42 (4.76%)
occurrences all number	7	4	2
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	5 / 43 (11.63%)	1 / 33 (3.03%)	1 / 42 (2.38%)
occurrences all number	5	1	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

05 Sep 2018

• Section 4.6 was included to define subgroups for analysis. Section 8.8.1 and Appendix A were updated with the statistical methods for analyses of the subgroups defined in Section 4.6. • Revised Section 5.8 to define PROMIS final T scores from the PROMIS online scoring system. • Revised SAP to align with changes to the Protocol made in Amendment 3.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: 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)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Maintenance Phase Movement Disorder Frequency

Primary: Maintenance Phase Movement Disorder Frequency

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

Primary: Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period

Primary: Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period

Secondary: Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10

Secondary: Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10

Secondary: Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10

Secondary: Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10

Secondary: Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10

Secondary: Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10

Secondary: Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10

Secondary: Duration of Movement Disorder Events During Maintenance Phase

Secondary: Duration of Movement Disorder Events During Maintenance Phase

Secondary: Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10

Secondary: Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10

Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10

Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10

Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10

Secondary: Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10

Secondary: Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10

Secondary: Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10

Secondary: Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10

Secondary: Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
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)