Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Conditions
Keywords
Glucose Transporter Type 1 Deficiency Syndrome Glut1
Brief summary
The primary objectives of the study are to evaluate the efficacy of UX007 compared to placebo as measured by the reduction from randomization to Week 8 in frequency of seizures and to evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG).
Interventions
DRUGUX007
oral liquid
DRUGPlacebo
oral liquid
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation 2. Males and females at least 1 of age at the time of informed consent 3. Average of at least 2 observable seizures (generalized or partial-onset \[simple partial motor, complex partial, absence, or secondarily generalized seizures) in 4 weeks over the last 24 weeks, by subject or caregiver report 4. At least 2 observable seizures (generalized or partial-onset \[simple partial motor, complex partial, or secondarily generalized seizures) in 4 weeks during the Baseline Period, with no 3-week seizure-free period during the Baseline Period OR absence seizures documented on Screening electroencephalogram (EEG) 5. Continuing to have seizures despite a prior or current use of at least 1 antiepileptic drug (AED) 6. Allowed to be on up to 3 concomitant AEDs that must have been stable in dose at least 2 weeks prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8-week, placebo-controlled Treatment Period 7. Not on, or not fully compliant with a prescribed diet plan (e.g. KD) 8. Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening 9. Provide written or verbal assent (if possible) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures 10. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizures diary, and likely to complete the 8 week, placebo-controlled, Treatment Period 11. Females of childbearing potential must have a negative pregnancy test at Screening, be willing to use an acceptable method of contraception, and have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not reached menarche, had total hysterectomy, have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening.
Exclusion criteria
1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 3 times the upper limit of normal at Screening 2. Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the investigator, places the subject at increased risk for adverse effects 3. Prior use of triheptanoin within 30 days prior to Screening 4. History of, or current suicidal ideation, behavior and/or attempts 5. Pregnant and/or breastfeeding an infant at Screening 6. Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives 7. Use of any investigational product (drug or supplement, including medium chain triglyceride \[MCT\] oil) within 30 days prior to Screening, or at any time during the study 8. Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment 9. Has a concurrent disease or condition, or laboratory abnormality that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns (e.g., diabetes mellitus, other concurrent neurological or psychiatric disorders)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate) | Baseline, Week 8 | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Weeks 0 to 8 | 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. |
| Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Weeks 9 to 52 plus 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures | Baseline, Week 8 | 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. |
| Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures | Baseline, Week 8 | 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). |
| Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | Baseline, Week 8 | 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. |
| Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE | Baseline, Week 8 | 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. |
| Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE | Baseline, Week 8 | 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. |
| Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE | Baseline, Week 8 | 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. |
| Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Baseline, Week 8 | 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. |
| Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT | Baseline, Week 8 | 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 (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8 | Baseline, Week 4, Week 8 | 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.) |
| Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score | Baseline, Week 8 | 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. |
| Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate) | Baseline, Week 26, Week 31 | 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. |
| Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Baseline, Week 26, Week 31, Week 36, Week 52 | 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. |
| Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate) | Baseline, Week 26, Week 31 | 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. |
| Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT) | Baseline, Week 8 | 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. |
| Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate) | Baseline, Week 8 | 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. |
| Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures | Baseline, Week 8 | 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). |
Countries
Australia, France, Israel, Italy, Spain, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| UX007 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). | 25 |
| Placebo 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). | 11 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Placebo-Controlled Period | Protocol Violation | 1 | 0 |
| Double-Blind Placebo-Controlled Period | Withdrawal by Subject | 1 | 0 |
| Open-Label Extension Period | Adverse Event | 1 | 0 |
| Open-Label Extension Period | Other, Not Specified | 0 | 1 |
| Open-Label Extension Period | Principal Investigator Decision | 1 | 0 |
| Open-Label Extension Period | Subject Non-Compliance | 1 | 0 |
| Open-Label Extension Period | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | UX007 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 13.86 years STANDARD_DEVIATION 5.107 | 15.24 years STANDARD_DEVIATION 13.795 | 14.28 years STANDARD_DEVIATION 8.525 |
| Age, Customized 12 years to < 18 years | 12 Participants | 1 Participants | 13 Participants |
| Age, Customized 18 years to < 65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Customized 2 years to < 12 years | 8 Participants | 7 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 9 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other (Not Specified) | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 9 Participants | 32 Participants |
| Sex: Female, Male Female | 15 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 14 Participants |
| Total Seizure Frequency Per 4 Weeks | 96.6 seizures per 4 weeks | 2.1 seizures per 4 weeks | 35.7 seizures per 4 weeks |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 11 | 0 / 34 |
| other Total, other adverse events | 21 / 25 | 9 / 11 | 31 / 34 |
| serious Total, serious adverse events | 1 / 25 | 0 / 11 | 2 / 34 |
Outcome results
Primary
Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
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
Population: Safety Analysis Set: all participants who received at least one dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Serious UX007 Emergent AE | 2 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | TEAE | 21 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Serious TEAE | 2 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Grade 3 or 4 TEAE | 1 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | TEAE Leading to Study Discontinuation | 1 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | TEAE Leading to Death | 0 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Gastrointestinal TEAE | 15 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Related TEAE | 19 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Related Serious TEAE | 0 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Related Gastrointestinal TEAE | 13 Participants |
| UX007 | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | UX007 Emergent AE | 21 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | UX007 Emergent AE | 11 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Gastrointestinal TEAE | 10 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | TEAE | 11 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Related Gastrointestinal TEAE | 8 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Serious TEAE | 0 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Related TEAE | 8 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Grade 3 or 4 TEAE | 0 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Serious UX007 Emergent AE | 0 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | TEAE Leading to Study Discontinuation | 0 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | Related Serious TEAE | 0 Participants |
| Placebo | Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period | TEAE Leading to Death | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
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
Population: Safety Analysis Set: all participants who received at least one dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Serious TEAE | 1 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Related TEAE | 18 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | TEAE Leading to Study Discontinuation | 0 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Related Serious TEAE | 0 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | TEAE | 22 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Related Gastrointestinal TEAE | 17 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | TEAE Leading to Death | 0 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | UX007 Emergent AE | 22 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Grade 3 or 4 TEAE | 2 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Serious UX007 Emergent AE | 1 Participants |
| UX007 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Gastrointestinal TEAE | 18 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Serious UX007 Emergent AE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Grade 3 or 4 TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | TEAE Leading to Study Discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | TEAE Leading to Death | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Gastrointestinal TEAE | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Related TEAE | 5 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Related Serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | Related Gastrointestinal TEAE | 4 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | UX007 Emergent AE | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period | TEAE | 9 Participants |
Primary
Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007 | Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate) | 12.6 percent reduction of seizures per 4 wks |
| Placebo | Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate) | 0.0 percent reduction of seizures per 4 wks |
Comparison: 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 testp-value: 0.581290% CI: [-38.63, 80.95]Wilcoxon rank-sum test
Secondary
Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | RTISRTSD | 41.698 score on a scale | Standard Error 42.3539 |
| UX007 | Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | RTIMDSRT | 15.512 score on a scale | Standard Error 15.9204 |
| UX007 | Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | RTIMDFRT | -14.723 score on a scale | Standard Error 14.1862 |
| Placebo | Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | RTISRTSD | 44.082 score on a scale | Standard Error 53.3552 |
| Placebo | Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | RTIMDSRT | -48.157 score on a scale | Standard Error 48.8781 |
| Placebo | Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE) | RTIMDFRT | 49.112 score on a scale | Standard Error 58.4722 |
Comparison: RTISRTSDp-value: 0.48690% CI: [-114.44, 109.67]GEE model
Comparison: RTIMDSRTp-value: 0.884990% CI: [-23.6, 150.94]GEE model
Comparison: RTIMDFRTp-value: 0.146390% CI: [-163.59, 35.93]GEE model
Secondary
Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE | PALTEA | -10.082 score on a scale | Standard Error 2.4784 |
| UX007 | Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE | PALFTMS | 2.574 score on a scale | Standard Error 0.6833 |
| Placebo | Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE | PALTEA | -27.849 score on a scale | Standard Error 11.3061 |
| Placebo | Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE | PALFTMS | 3.105 score on a scale | Standard Error 2.0766 |
Comparison: PALTEAp-value: 0.937890% CI: [-1.26, 36.79]GEE model
Comparison: PALFTMSp-value: 0.595990% CI: [-4.13, 3.06]GEE model
Secondary
Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE | 0.019 score on a scale | Standard Error 0.2387 |
| Placebo | Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE | -0.041 score on a scale | Standard Error 0.4246 |
Comparison: SSPSLFp-value: 0.452290% CI: [-0.76, 0.88]GEE model
Secondary
Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE | SWMBE48 | 1.003 score on a scale | Standard Error 1.4582 |
| UX007 | Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE | SWMS68 | 0.060 score on a scale | Standard Error 0.4794 |
| Placebo | Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE | SWMBE48 | 2.240 score on a scale | Standard Error 1.8036 |
| Placebo | Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE | SWMS68 | 0.022 score on a scale | Standard Error 0.4279 |
Comparison: SWMBE48p-value: 0.301790% CI: [-5.15, 2.68]GEE model
Comparison: SWMS68p-value: 0.523590% CI: [-1.03, 1.11]GEE model
Secondary
Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT) | -10.336 meters | Standard Error 14.8614 |
| Placebo | Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT) | -3.439 meters | Standard Error 16.1506 |
Comparison: 6MWT distance traveledp-value: 0.620590% CI: [-43.874, 30.08]GEE model
Secondary
Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT | -1.338 percent of predicted distance | Standard Error 2.4752 |
| Placebo | Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT | 0.016 percent of predicted distance | Standard Error 2.6398 |
Comparison: 6MWT distance traveled (percent predicted)p-value: 0.647690% CI: [-7.236, 4.527]GEE model
Secondary
Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| UX007 | Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score | 3.209 score on a scale | Standard Error 2.3669 |
| Placebo | Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score | 1.642 score on a scale | Standard Error 2.669 |
Comparison: GMFM-88 UX007-Placebop-value: 0.343590% CI: [-4.83, 7.97]GEE model
Secondary
Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with absence seizures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UX007 | Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures | 23.5 percentage of participants |
| Placebo | Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures | 16.7 percentage of participants |
Secondary
Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with observable seizures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UX007 | Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures | 5.9 percentage of participants |
| Placebo | Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures | 30.0 percentage of participants |
Secondary
Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UX007 | Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures | 20.0 percentage of participants |
| Placebo | Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures | 36.4 percentage of participants |
Secondary
Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate) | Week 26 | 0.0 percent reduction in seizures per 4 wks |
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate) | Week 31 | 0.0 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate) | Week 26 | 0.0 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate) | Week 31 | 0.0 percent reduction in seizures per 4 wks |
Secondary
Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 26 | 0.0 percent reduction in seizures per 4 wks |
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 31 | 23.6 percent reduction in seizures per 4 wks |
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 36 | 42.5 percent reduction in seizures per 4 wks |
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 52 | 31.0 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 52 | -10.3 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 26 | -27.7 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 36 | -49.8 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | Week 31 | 0.0 percent reduction in seizures per 4 wks |
Secondary
Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate) | Week 26 | 7.8 percent reduction of seizures per 4 wks |
| UX007 | Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate) | Week 31 | 42.7 percent reduction of seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate) | Week 26 | 0.0 percent reduction of seizures per 4 wks |
| Placebo | Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate) | Week 31 | 5.3 percent reduction of seizures per 4 wks |
Secondary
Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with absence seizures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007 | Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate) | 0.0 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate) | 0.0 percent reduction in seizures per 4 wks |
Comparison: 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 testp-value: 0.727690% CI: [0, 37.5]Wilcoxon rank-sum test
Secondary
Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
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
Population: Efficacy Analysis Set: all randomized participants who received at least one dose of investigational product. Participants with observable seizures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UX007 | Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | 0.0 percent reduction in seizures per 4 wks |
| Placebo | Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate) | 0.0 percent reduction in seizures per 4 wks |
Comparison: 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 testp-value: 0.819790% CI: [-51.23, 84.25]Wilcoxon rank-sum test
Secondary
Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UX007 | Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8 | Week 4 | 4.7 minutes | Standard Deviation 4.73 |
| UX007 | Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8 | Week 8 | 1.8 minutes | Standard Deviation 1.3 |