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DEFINITIONS
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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01993186
Registration number
NCT01993186
Ethics application status
Date submitted
31/10/2013
Date registered
25/11/2013
Date last updated
19/06/2020
Titles & IDs
Public title
Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
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Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Study to Assess the Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome
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Secondary ID [1]
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UX007G-CL201
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
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Condition category
Condition code
Metabolic and Endocrine
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Metabolic disorders
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Metabolic and Endocrine
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Other metabolic disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - UX007
Treatment: Drugs - Placebo
Experimental: UX007 - Participants randomized to receive UX007 enter 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 continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Placebo Comparator: Placebo - Participants randomized to receive placebo enter 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 continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Treatment: Drugs: UX007
oral liquid
Treatment: Drugs: Placebo
oral liquid
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Week 8
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Primary outcome [2]
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
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Assessment method [2]
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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.
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Timepoint [2]
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Weeks 0 to 8
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Primary outcome [3]
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Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
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Assessment method [3]
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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.
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Timepoint [3]
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Weeks 9 to 52 plus 30 days
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Secondary outcome [1]
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Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Week 8
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Secondary outcome [2]
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Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline, Week 8
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Secondary outcome [3]
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Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures
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Assessment method [3]
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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).
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Timepoint [3]
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Baseline, Week 8
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Secondary outcome [4]
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Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline, Week 8
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Secondary outcome [5]
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Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures
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Assessment method [5]
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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).
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Timepoint [5]
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Baseline, Week 8
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Secondary outcome [6]
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Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline, Week 8
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Secondary outcome [7]
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Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline, Week 8
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Secondary outcome [8]
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Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline, Week 8
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Secondary outcome [9]
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Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE
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Assessment method [9]
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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.
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Timepoint [9]
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Baseline, Week 8
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Secondary outcome [10]
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Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)
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Assessment method [10]
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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.
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Timepoint [10]
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Baseline, Week 8
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Secondary outcome [11]
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Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT
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Assessment method [11]
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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.
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Timepoint [11]
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Baseline, Week 8
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Secondary outcome [12]
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Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8
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Assessment method [12]
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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.)
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Timepoint [12]
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Baseline, Week 4, Week 8
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Secondary outcome [13]
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Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score
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Assessment method [13]
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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.
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Timepoint [13]
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Baseline, Week 8
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Secondary outcome [14]
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Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)
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Assessment method [14]
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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.
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Timepoint [14]
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Baseline, Week 26, Week 31
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Secondary outcome [15]
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Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
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Assessment method [15]
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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.
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Timepoint [15]
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Baseline, Week 26, Week 31, Week 36, Week 52
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Secondary outcome [16]
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Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)
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Assessment method [16]
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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.
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Timepoint [16]
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Baseline, Week 26, Week 31
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Eligibility
Key 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.
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Minimum age
1
Year
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Maximum age
100
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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)
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
28/02/2014
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
20/09/2017
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Sample size
Target
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Accrual to date
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Final
36
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Melbourne Brain Centre - Heidelberg
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Recruitment postcode(s) [1]
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3084 - Heidelberg
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Colorado
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United States of America
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State/province [2]
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Florida
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Country [3]
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United States of America
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State/province [3]
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New York
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Country [4]
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United States of America
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State/province [4]
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Texas
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Country [5]
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United States of America
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State/province [5]
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Washington
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Country [6]
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France
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State/province [6]
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Cedex 19
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Country [7]
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Israel
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State/province [7]
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Tel Aviv
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Country [8]
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Italy
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State/province [8]
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Genova
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Country [9]
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Spain
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State/province [9]
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Barcelona
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Country [10]
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United Kingdom
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State/province [10]
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Newcastle Upon Tyne
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Ultragenyx Pharmaceutical Inc
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01993186
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Medical Director
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Address
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Ultragenyx Pharmaceutical Inc
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01993186
Download to PDF