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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01993186
Recruitment Status : Completed
First Posted : November 25, 2013
Last Update Posted : June 20, 2018
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:
UX007 is more effective than placebo for the reduction of seizures in patients with Glut1 DS, as measured by the reduction from baseline in frequency of generalized or partial-onset seizures, including: Generalized Tonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focal with Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, Complex Partial/Focal, Absence and Simple Partial/Focal Motor seizures

Condition or disease Intervention/treatment Phase
Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) Drug: UX007 (triheptanoin) Drug: Placebo Oil Phase 2

Detailed Description:


UX007G-CL201 is a randomized, double-blind, placebo-controlled, parallel-group, study to assess the safety and efficacy of UX007 in Glut1 DS. The study will enroll pediatric, adolescent, and adult subjects who are currently not on, or not compliant with a ketogenic or other high fat diet. Enrolled subjects are otherwise able to maintain standard of care treatment with 1-3 AEDs throughout the duration of the study.

Beginning with the screening visit, subjects will record seizure frequency during the 6-week Baseline Period. If the subject does not meet the seizure count criteria, the subject will be considered a screen failure and will not be randomized. At the end of the Baseline Period, eligible subjects will be randomized in a 3:1 ratio to either UX007 or placebo. Dosing will be initiated using a 2-week titration schedule until the subject has reached 35% of total daily calories from study drug (~1-4 g/kg/day depending on age). If a subject has not reached the target of 35% of total daily calories by the end of the 2-week titration period, dose titration should continue until the maximum tolerated dose is reached.

Phase 2 study will enroll approximately 40 subjects. After the initial 8-week double-blind Treatment Period, the open-label Extension Period will begin, wherein all subjects will be treated with UX007 through Week 52 of the study. A population-PK analysis at Week 26 will provide data on metabolite levels with all subjects on UX007. Following the Week 26 visit, approximately the first 40 subjects will participate in a 10-week Dose Exploration Period to assess the impact of UX007 dose level on seizure control, other clinical manifestations such as movement disorders and cognitive deficits, and tolerability. At the end of the Dose Exploration Period, the subject will continue in the open-label Extension period, maintained on the UX007 dose (as determined by the Investigator) that provided the maximum improvement in clinical status with acceptable tolerability, and continued on this dose for the duration of the study. Long term safety and maintenance of effect of UX007 will be assessed during the Extension Period.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : April 2014
Actual Primary Completion Date : September 7, 2017
Actual Study Completion Date : September 19, 2017

Arm Intervention/treatment
Experimental: UX007 (triheptanoin)
Oral liquid administered with food 4 times a day to make up to 35% of total caloric intake. 52 weeks.
Drug: UX007 (triheptanoin)
Triheptanoin is a triglyceride composed of three heptanoate (C7 fatty acid) esters. UX007 is manufactured by chemical synthesis from glycerol and heptanoic acid. UX007 (triheptanoin) is a liquid, intended for oral (PO) administration.
Other Names:
  • C7 oil
  • Triheptanoin
  • glycerol triheptanoate
  • glycerol trienanthate
  • 1, 2, 3-trienanthoylglycerol
  • trienanthin
  • 2,3-di(heptanoyloxy)propyl heptanoate

Placebo Comparator: Placebo Oil
Placebo oil matching color and appearance of UX007.
Drug: Placebo Oil

Primary Outcome Measures :
  1. Efficacy of UX007 compared to placebo as measured by reduction from randomization to week 8 in frequency of seizures. Observable generalized and partial-onset seizures measured by diary [ Time Frame: 6 weeks ]
  2. Evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG) [ Time Frame: 52 weeks ]
  3. Efficacy of UX007 compared to placebo as measured by reduction from randomization to week 8 in frequency of absence seizures measured overnight by EEG [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Efficacy of UX007 compared to placebo as measured by Seizure Response Rate, defined as the percentage of subjects with at least a 50% reduction from randomization to week 8 in frequency of seizures. [ Time Frame: 6 weeks ]
  2. Efficacy of UX007 compared to placebo as measured by Change from randomization to week 8 in cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: 6 weeks ]
  3. Efficacy of UX007 compared to placebo as measured by Change from randomization to Week 8 in distance walked as measured by 6 Minute Walk Test (6MWT) [ Time Frame: 6 weeks ]
  4. Efficacy of UX007 compared to placebo as measured by Time to onset of paroxysmal exertional dyskinesia (PED) as measured during 6 minute walk test (6MWT) from randomization to week 8 [ Time Frame: 6 weeks ]
  5. Efficacy of UX007 compared to placebo as measured by Change from baseline in gross motor function using the Gross Motor Function Measure-88 (GMFM-88) [ Time Frame: 6 weeks ]
  6. Evaluate long term efficacy as measured by changes from randomization in frequency of seizures over time through week 52 [ Time Frame: 52 weeks ]
  7. Evaluate the optimal dose to control seizures and impact on other clinical manifestations during the dose exploration period as measured by reduction in seizures [ Time Frame: 52 weeks ]

Other Outcome Measures:
  1. Change from baseline in neurological function using the Columbia Neurological Score (CNS) [ Time Frame: 52 weeks ]
  2. Change from baseline in physician global impression of change in clinical status using the Clinical Global Impression - Severity scale (CGI-S) and Clinical Global Impression - Improvement scale (CGI-I) [ Time Frame: 52 weeks ]
  3. Change from baseline in receptive vocabulary using the Peabody Picture Vocabulary Test (PPVT) [ Time Frame: 52 weeks ]
  4. Change from baseline in patient or caregiver-reported quality of life using Short Form-10™ (SF-10) Health Survey for Children or Short Form-12™ (SF-12) for adults [ Time Frame: 52 weeks ]
  5. Change from baseline in functional disability by caregiver report using the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT) [ Time Frame: 52 weeks ]
  6. Change from baseline in gait, using gait analysis by computerized mat (at select sites). [ Time Frame: 52 weeks ]
  7. Pharmacokinetics (PK) properties of UX007 Plasma Peak [ Time Frame: 52 weeks ]
  8. Pharmacokinetics (PK) properties of UX007 Metabolites [ Time Frame: 52 weeks ]
  9. Beery-Buktenica Developmental Test of Visual Motor Integration: Visual-motor integration measured using a design copy test administered by a clinician (at select sites) [ Time Frame: 52 Weeks ]
  10. Raven's Coloured Progressive Matrices: Spatial understanding and abstract reasoning using picture tests administered by a clinician (at select sites) [ Time Frame: 52 Weeks ]

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Ages Eligible for Study:   1 Year to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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 EEG
  5. Continuing to have seizures despite a prior or current use of at least 1 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 3X 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01993186

United States, Colorado
Children's Hospital Colorado - University of Colorado, Denver, School of Medicine
Aurora, Colorado, United States, 80045
United States, Florida
Miami Children's Hospital
Miami, Florida, United States, 33155
Neurology & Epilepsy Research Center
Orlando, Florida, United States, 32819
United States, New York
Columbia University - Department of Neurology
New York, New York, United States, 10032
Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
Cook Children's Hospital
Fort Worth, Texas, United States, 76104
University of Texas Neurometabolic Clinic
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Australia, Victoria
Melbourne Brain Centre
Heidelberg, Victoria, Australia, 3084
Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP
Paris, Cedex 19, France, 75935
Sheba University Medical Center
Tel Aviv, Israel
Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini"
Genova, Italy
Hospital Sant Joan de Deu
Barcelona, Spain
United Kingdom
Newcastle University
Newcastle Upon Tyne, United Kingdom
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Study Director: Melanie Brandabur, MD Ultragenyx Pharmaceutical

Additional Information:
Responsible Party: Ultragenyx Pharmaceutical Inc Identifier: NCT01993186     History of Changes
Other Study ID Numbers: UX007G-CL201
First Posted: November 25, 2013    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018

Keywords provided by Ultragenyx Pharmaceutical Inc:
Glucose Transporter Type 1 Deficiency Syndrome Glut1

Additional relevant MeSH terms:
Carbohydrate Metabolism, Inborn Errors
Pathologic Processes
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs