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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
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
Hide 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
Arm/Group Title UX007 Placebo Total
Hide 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
Hide 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).
1.Primary Outcome
Title Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product.
Arm/Group Title UX007 Placebo
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all participants who received at least one dose of investigational product.
Arm/Group Title UX007 Placebo
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all participants who received at least one dose of investigational product.
Arm/Group Title UX007 Placebo
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product.
Arm/Group Title UX007 Placebo
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
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
Hide 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%) 
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8657
EMail: medinfo@ultragenyx.com
Layout table for additonal information
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