Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

• ClinicalTrials.gov Identifier: NCT01993186
• Recruitment Status: Completed
• First Posted: November 25, 2013
• Results First Posted: May 29, 2020
• Last Update Posted: June 19, 2020
• Sponsor: Ultragenyx Pharmaceutical Inc
• Information provided by (Responsible Party): Ultragenyx Pharmaceutical Inc

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
• Interventions: Drug: UX007; Drug: Placebo
• Enrollment: 36

Participant Flow

Recruitment Details
Pre-assignment Details	Beginning with the Screening visit, participants recorded seizure frequency during a 6-week Baseline Period. If the participant did not meet the seizure count criteria, the participant was considered a screen failure and was not randomized.

Arm/Group Title	UX007	Placebo
Arm/Group Description	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Period Title: Double-Blind Placebo-Controlled Period
Started	25	11
Completed	23	11
Not Completed	2	0
Reason Not Completed
Protocol Violation	1	0
Withdrawal by Subject	1	0
Period Title: Open-Label Extension Period
Started	23	11
Completed	16	5
Not Completed	7	6
Reason Not Completed
Other, Not Specified	0	1
Adverse Event	1	0
Principal Investigator Decision	1	0
Withdrawal by Subject	4	5
Subject Non-Compliance	1	0

Baseline Characteristics

Arm/Group Title		UX007	Placebo	Total
Arm/Group Description		Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Total of all reporting groups
Overall Number of Baseline Participants		25	11	36
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	25 participants	11 participants	36 participants
		13.86 (5.107)	15.24 (13.795)	14.28 (8.525)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	25 participants	11 participants	36 participants
2 years to < 12 years		8 32.0%	7 63.6%	15 41.7%
12 years to < 18 years		12 48.0%	1 9.1%	13 36.1%
18 years to < 65 years		5 20.0%	3 27.3%	8 22.2%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	11 participants	36 participants
	Female	15 60.0%	7 63.6%	22 61.1%
	Male	10 40.0%	4 36.4%	14 38.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	25 participants	11 participants	36 participants
	Hispanic or Latino	2 8.0%	1 9.1%	3 8.3%
	Not Hispanic or Latino	21 84.0%	9 81.8%	30 83.3%
	Unknown or Not Reported	2 8.0%	1 9.1%	3 8.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	25 participants	11 participants	36 participants
American Indian or Alaska Native		0 0.0%	1 9.1%	1 2.8%
Asian		1 4.0%	0 0.0%	1 2.8%
Black or African American		0 0.0%	1 9.1%	1 2.8%
Native Hawaiian or other Pacific Islander		0 0.0%	0 0.0%	0 0.0%
White		23 92.0%	9 81.8%	32 88.9%
Other (Not Specified)		1 4.0%	0 0.0%	1 2.8%
Total Seizure Frequency Per 4 Weeks [1]; Median (Full Range); Unit of measure: Seizures per 4 weeks
	Number Analyzed	25 participants	11 participants	36 participants
		96.6; (0 to 10250)	2.1; (0 to 1176)	35.7; (0 to 10250)
		[1] Measure Description: Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from electroencephalography (EEG) include absence awake (>=10sec), absence sleep (>=10sec), indeterminate absence awake (3-10sec), and indeterminate absence sleep (3-10sec).

Outcome Measures

1. Primary Outcome

Title	Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Description	Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Median (Full Range); Unit of Measure: percent reduction of seizures per 4 wks
	12.6; (-651 to 100)	0.0; (-1021 to 100)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	Non-parametric post-hoc analysis: Hodges-Lehmann estimate of the location shift with 90% confidence interval (CI) and Wilcoxon Rank Sum test p-value, based on Wilcoxon rank-sum test
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5812
	Comments	[Not Specified]
	Method	Wilcoxon rank-sum test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate
	Estimated Value	13.45
	Confidence Interval	(2-Sided) 90%; -38.63 to 80.95
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
Description	An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
Time Frame	Weeks 0 to 8

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all participants who received at least one dose of investigational product.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Measure Type: Count of Participants; Unit of Measure: Participants
TEAE	22 88.0%	9 81.8%
Serious TEAE	1 4.0%	0 0.0%
Grade 3 or 4 TEAE	2 8.0%	0 0.0%
TEAE Leading to Study Discontinuation	0 0.0%	0 0.0%
TEAE Leading to Death	0 0.0%	0 0.0%
Gastrointestinal TEAE	18 72.0%	5 45.5%
Related TEAE	18 72.0%	5 45.5%
Related Serious TEAE	0 0.0%	0 0.0%
Related Gastrointestinal TEAE	17 68.0%	4 36.4%
UX007 Emergent AE	22 88.0%	0 0.0%
Serious UX007 Emergent AE	1 4.0%	0 0.0%

3. Primary Outcome

Title	Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
Description	An AE was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
Time Frame	Weeks 9 to 52 plus 30 days

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all participants who received at least one dose of investigational product.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	23	11
Measure Type: Count of Participants; Unit of Measure: Participants
TEAE	21 91.3%	11 100.0%
Serious TEAE	2 8.7%	0 0.0%
Grade 3 or 4 TEAE	1 4.3%	0 0.0%
TEAE Leading to Study Discontinuation	1 4.3%	0 0.0%
TEAE Leading to Death	0 0.0%	0 0.0%
Gastrointestinal TEAE	15 65.2%	10 90.9%
Related TEAE	19 82.6%	8 72.7%
Related Serious TEAE	0 0.0%	0 0.0%
Related Gastrointestinal TEAE	13 56.5%	8 72.7%
UX007 Emergent AE	21 91.3%	11 100.0%
Serious UX007 Emergent AE	2 8.7%	0 0.0%

4. Secondary Outcome

Title	Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
Description	Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with observable seizures.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	17	10
Median (Full Range); Unit of Measure: percent reduction in seizures per 4 wks
	0.0; (-651 to 84)	0.0; (-1021 to 75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	Non-parametric post-hoc analysis: Hodges-Lehmann estimate of the location shift with 90% CI and Wilcoxon Rank Sum test p-value, based on Wilcoxon rank-sum test
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8197
	Comments	[Not Specified]
	Method	Wilcoxon rank-sum test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate
	Estimated Value	0
	Confidence Interval	(2-Sided) 90%; -51.23 to 84.25
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)
Description	Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with absence seizures.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	17	6
Median (Full Range); Unit of Measure: percent reduction in seizures per 4 wks
	0.0; (-2400 to 100)	0.0; (0 to 100)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	Non-parametric post-hoc analysis: Hodges-Lehmann estimate of the location shift with 90% CI and Wilcoxon Rank Sum test p-value, based on Wilcoxon rank-sum test
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7276
	Comments	[Not Specified]
	Method	Wilcoxon rank-sum test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hodges-Lehmann estimate
	Estimated Value	0
	Confidence Interval	(2-Sided) 90%; 0 to 37.5
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures
Description	Seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of total seizures. Includes observable generalized and partial-onset seizures measured for 6 weeks by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Measure Type: Number; Unit of Measure: percentage of participants
	20.0	36.4

7. Secondary Outcome

Title	Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures
Description	Observable seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of observable seizures. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with observable seizures.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	17	10
Measure Type: Number; Unit of Measure: percentage of participants
	5.9	30.0

8. Secondary Outcome

Title	Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures
Description	Absence seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of absence seizures. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with absence seizures.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	17	6
Measure Type: Number; Unit of Measure: percentage of participants
	23.5	16.7

9. Secondary Outcome

Title	Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. RTI Simple choice reaction time standard deviation (RTISRTSD) assesses the cognitive domain of attention, with scores on a continuous range from 0 to 5000; lower scores indicate better function. RTI median simple choice reaction time (RTIMDSRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. RTI median 5-choice reaction time (RTIMDFRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. GEE statistical model.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set, CANTAB: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) CANTAB assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
RTISRTSD	41.698 (42.3539)	44.082 (53.3552)
RTIMDSRT	15.512 (15.9204)	-48.157 (48.8781)
RTIMDFRT	-14.723 (14.1862)	49.112 (58.4722)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	RTISRTSD
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.486
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-2.384
	Confidence Interval	(2-Sided) 90%; -114.44 to 109.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 68.1231
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	RTIMDSRT
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8849
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	63.669
	Confidence Interval	(2-Sided) 90%; -23.6 to 150.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 53.0537
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	RTIMDFRT
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1463
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-63.835
	Confidence Interval	(2-Sided) 90%; -163.59 to 35.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 60.6496
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PAL total errors adjusted (PALTEA) assesses the cognitive domain of episodic memory/new learning, with scores on a discrete, ordinal scale from 0 to 137; lower scores indicate better function. PAL first trial memory score (PALFTMS) assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function. GEE statistical model.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set, CANTAB: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) CANTAB assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
PALTEA	-10.082 (2.4784)	-27.849 (11.3061)
PALFTMS	2.574 (0.6833)	3.105 (2.0766)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	PALTEA
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9378
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	17.768
	Confidence Interval	(2-Sided) 90%; -1.26 to 36.79
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.5659
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	PALFTMS
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5959
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.531
	Confidence Interval	(2-Sided) 90%; -4.13 to 3.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.1853
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SSP Span Length (SSPSLF) assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function. GEE statistical model.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set, CANTAB: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) CANTAB assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	0.019 (0.2387)	-0.041 (0.4246)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	SSPSLF
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4522
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 90%; -0.76 to 0.88
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4988
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE
Description	CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWM between errors (SWMBE48) assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function. SWM strategy (SWMS68) assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function. GEE statistical model.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set, CANTAB: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) CANTAB assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	25	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
SWMBE48	1.003 (1.4582)	2.240 (1.8036)
SWMS68	0.060 (0.4794)	0.022 (0.4279)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	SWMBE48
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3017
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.237
	Confidence Interval	(2-Sided) 90%; -5.15 to 2.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.381
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	SWMS68
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5235
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline CANTAB score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.038
	Confidence Interval	(2-Sided) 90%; -1.03 to 1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6495
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)
Description	Participants were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set - 6MWT: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) 6MWT assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	23	11
Least Squares Mean (Standard Error); Unit of Measure: meters
	-10.336 (14.8614)	-3.439 (16.1506)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	6MWT distance traveled
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6205
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline value, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-6.897
	Confidence Interval	(2-Sided) 90%; -43.874 to 30.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 22.4806
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT
Description	Participants were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. The percent of predicted normal distance walked was determined based on published normative data.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set - 6MWT: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) 6MWT assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	23	11
Least Squares Mean (Standard Error); Unit of Measure: percent of predicted distance
	-1.338 (2.4752)	0.016 (2.6398)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	6MWT distance traveled (percent predicted)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6476
	Comments	One-sided p-value. Additional model covariates include the corresponding baseline value, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-1.354
	Confidence Interval	(2-Sided) 90%; -7.236 to 4.527
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.5759
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8
Description	For the 6MWT, subjects were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. PED occurring during the 6MWT was assessed. (PED is characterized by transient abnormal, involuntary movements primarily affecting the legs and feet, and typically precipitated by prolonged exertion.)
Time Frame	Baseline, Week 4, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set - 6MWT: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) 6MWT assessment performed. Participants with at least 1 PED.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	3	0
Mean (Standard Deviation); Unit of Measure: minutes
Week 4	4.7 (4.73)
Week 8	1.8 (1.30)

16. Secondary Outcome

Title	Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score
Description	The GMFM-88 is a standardized observational measure of abilities that includes the following 5 domains: lying/rolling, sitting, crawling/kneeling, standing, and walking/running/jumping. The GMFM-88 scores include the following: Lying & Rolling Score, Range 0-100%, higher is better; Sitting Score, Range 0-100%, higher is better; Crawling & Kneeling Score, Range 0-100%, higher is better; Standing Score, Range 0-100%, higher is better; Walking, Running & Jumping Score, Range 0-100%, higher is better; Total Score = (Sum of 5 Above Scores) / 5, Range 0-100%, higher is better.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set - GMFM-88: Subset of participants taking UX007 during the treatment period in the efficacy analysis set who had a baseline and at least 1 post baseline (Week 4 or Week 8) GMFM-88 assessment performed.

Arm/Group Title	UX007	Placebo
Arm/Group Description:	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed	21	11
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	3.209 (2.3669)	1.642 (2.6690)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007, Placebo
	Comments	GMFM-88 UX007-Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3435
	Comments	One-sided p-value. Additional model covariates include baseline GMFM-88 total score, visit and the interaction between visit and treatment.
	Method	GEE model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.568
	Confidence Interval	(2-Sided) 90%; -4.83 to 7.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.8899
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Description	Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame	Baseline, Week 26, Week 31

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with an assessment at given time point.

Arm/Group Title		UX007	Placebo
Arm/Group Description:		Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed		22	11
Median (Full Range); Unit of Measure: percent reduction of seizures per 4 wks
Week 26	Number Analyzed	22 participants	11 participants
		7.8; (-409 to 100)	0.0; (-207 to 94)
Week 31	Number Analyzed	19 participants	8 participants
		42.7; (-267 to 100)	5.3; (-681 to 75)

18. Secondary Outcome

Title	Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
Description	Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
Time Frame	Baseline, Week 26, Week 31, Week 36, Week 52

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with observable seizures and an assessment at given time point.

Arm/Group Title		UX007	Placebo
Arm/Group Description:		Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed		15	10
Median (Full Range); Unit of Measure: percent reduction in seizures per 4 wks
Week 26	Number Analyzed	15 participants	10 participants
		0.0; (-260 to 88)	-27.7; (-207 to 74)
Week 31	Number Analyzed	12 participants	7 participants
		23.6; (-267 to 100)	0.0; (-681 to 67)
Week 36	Number Analyzed	12 participants	7 participants
		42.5; (-438 to 100)	-49.8; (-400 to 77)
Week 52	Number Analyzed	12 participants	6 participants
		31.0; (-222 to 100)	-10.3; (-358 to 85)

19. Secondary Outcome

Title	Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)
Description	Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame	Baseline, Week 26, Week 31

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with absence seizures and an assessment at given time point.

Arm/Group Title		UX007	Placebo
Arm/Group Description:		Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Overall Number of Participants Analyzed		14	4
Median (Full Range); Unit of Measure: percent reduction in seizures per 4 wks
Week 26	Number Analyzed	14 participants	4 participants
		0.0; (-3135 to 100)	0.0; (0 to 94)
Week 31	Number Analyzed	12 participants	3 participants
		0.0; (-3905 to 100)	0.0; (0 to 75)

Adverse Events

Time Frame	Placebo-controlled period from first dose of study drug through Week 8. Extension period: Week 9 up to Week 52 plus 30 days.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo Controlled Period / UX007	Placebo Controlled Period / Placebo	Extension Period / UX007
Arm/Group Description	Participants randomized to receive UX007 entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period.	Participants randomized to receive placebo entered a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period.	Following completion of the Week 8 study visit, placebo and UX007 participants continued treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
All-Cause Mortality
	Placebo Controlled Period / UX007	Placebo Controlled Period / Placebo	Extension Period / UX007
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/25 (0.00%)	0/11 (0.00%)	0/34 (0.00%)
Serious Adverse Events
	Placebo Controlled Period / UX007	Placebo Controlled Period / Placebo	Extension Period / UX007
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/25 (4.00%)	0/11 (0.00%)	2/34 (5.88%)
Injury, poisoning and procedural complications
Subcutaneous Haematoma † 1	0/25 (0.00%)	0/11 (0.00%)	1/34 (2.94%)
Nervous system disorders
Seizure † 1	0/25 (0.00%)	0/11 (0.00%)	1/34 (2.94%)
Status Epilepticus † 1	1/25 (4.00%)	0/11 (0.00%)	2/34 (5.88%)
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo Controlled Period / UX007	Placebo Controlled Period / Placebo	Extension Period / UX007
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	21/25 (84.00%)	9/11 (81.82%)	31/34 (91.18%)
Gastrointestinal disorders
Abdominal Discomfort † 1	2/25 (8.00%)	0/11 (0.00%)	0/34 (0.00%)
Abdominal Pain † 1	7/25 (28.00%)	1/11 (9.09%)	3/34 (8.82%)
Abdominal Pain Upper † 1	7/25 (28.00%)	0/11 (0.00%)	5/34 (14.71%)
Breath Odour † 1	0/25 (0.00%)	0/11 (0.00%)	2/34 (5.88%)
Constipation † 1	2/25 (8.00%)	0/11 (0.00%)	5/34 (14.71%)
Diarrhoea † 1	9/25 (36.00%)	3/11 (27.27%)	18/34 (52.94%)
Flatulence † 1	1/25 (4.00%)	1/11 (9.09%)	2/34 (5.88%)
Nausea † 1	5/25 (20.00%)	0/11 (0.00%)	5/34 (14.71%)
Vomiting † 1	11/25 (44.00%)	2/11 (18.18%)	15/34 (44.12%)
General disorders
Pyrexia † 1	2/25 (8.00%)	0/11 (0.00%)	6/34 (17.65%)
Infections and infestations
Gastroenteritis Viral † 1	1/25 (4.00%)	0/11 (0.00%)	2/34 (5.88%)
Otitis Media Acute † 1	0/25 (0.00%)	1/11 (9.09%)	0/34 (0.00%)
Sinusitis † 1	1/25 (4.00%)	0/11 (0.00%)	2/34 (5.88%)
Upper Respiratory Tract Infection † 1	0/25 (0.00%)	2/11 (18.18%)	2/34 (5.88%)
Viral Upper Respiratory Tract Infection † 1	3/25 (12.00%)	1/11 (9.09%)	6/34 (17.65%)
Injury, poisoning and procedural complications
Contusion † 1	0/25 (0.00%)	1/11 (9.09%)	2/34 (5.88%)
Fall † 1	0/25 (0.00%)	1/11 (9.09%)	2/34 (5.88%)
Head Injury † 1	0/25 (0.00%)	1/11 (9.09%)	2/34 (5.88%)
Ligament Sprain † 1	0/25 (0.00%)	1/11 (9.09%)	0/34 (0.00%)
Lip Injury † 1	0/25 (0.00%)	1/11 (9.09%)	0/34 (0.00%)
Investigations
Weight Increased † 1	3/25 (12.00%)	1/11 (9.09%)	1/34 (2.94%)
Metabolism and nutrition disorders
Decreased Appetite † 1	1/25 (4.00%)	1/11 (9.09%)	5/34 (14.71%)
Musculoskeletal and connective tissue disorders
Back Pain † 1	0/25 (0.00%)	1/11 (9.09%)	1/34 (2.94%)
Nervous system disorders
Clonic Convulsion † 1	0/25 (0.00%)	1/11 (9.09%)	0/34 (0.00%)
Dizziness † 1	2/25 (8.00%)	0/11 (0.00%)	1/34 (2.94%)
Headache † 1	3/25 (12.00%)	0/11 (0.00%)	3/34 (8.82%)
Seizure † 1	0/25 (0.00%)	0/11 (0.00%)	2/34 (5.88%)
Psychiatric disorders
Abnormal Behaviour † 1	0/25 (0.00%)	0/11 (0.00%)	3/34 (8.82%)
Agitation † 1	1/25 (4.00%)	0/11 (0.00%)	2/34 (5.88%)
Insomnia † 1	0/25 (0.00%)	0/11 (0.00%)	2/34 (5.88%)
Reproductive system and breast disorders
Dysmenorrhoea † 1	0/25 (0.00%)	0/11 (0.00%)	2/34 (5.88%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/25 (0.00%)	0/11 (0.00%)	3/34 (8.82%)
Oropharyngeal Pain † 1	0/25 (0.00%)	0/11 (0.00%)	2/34 (5.88%)
Skin and subcutaneous tissue disorders
Acne † 1	2/25 (8.00%)	0/11 (0.00%)	0/34 (0.00%)
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc
• Phone: 1-888-756-8657
• EMail: medinfo@ultragenyx.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Striano P, Auvin S, Collins A, Horvath R, Scheffer IE, Tzadok M, Miller I, Kay Koenig M, Lacy A, Davis R, Garcia-Cazorla A, Saneto RP, Brandabur M, Blair S, Koutsoukos T, De Vivo D. A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome. Epilepsia. 2022 Jul;63(7):1748-1760. doi: 10.1111/epi.17263. Epub 2022 May 21.

• Responsible Party: Ultragenyx Pharmaceutical Inc
• ClinicalTrials.gov Identifier: NCT01993186
• Other Study ID Numbers: UX007G-CL201
• First Submitted: October 31, 2013
• First Posted: November 25, 2013
• Results First Submitted: May 12, 2020
• Results First Posted: May 29, 2020
• Last Update Posted: June 19, 2020