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

This study is currently recruiting participants.
Verified March 2014 by Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc Identifier:
First received: October 31, 2013
Last updated: March 27, 2014
Last verified: March 2014


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 between Weeks 2 and 8 of treatment.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Adaptive Study to Assess the Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome

Resource links provided by NLM:

Further study details as provided by Ultragenyx Pharmaceutical Inc:

Primary Outcome Measures:
  • Evaluate the efficacy of UX007 compared to placebo, between Weeks 2 and 8 of treatment, as measured by the reduction from baseline in frequency of generalized or partial-onset seizures [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG) [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Seizure response rate, defined as the percentage of subjects with at least 50% reduction from baseline in generalized or partial-onset seizures [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in frequency of seizure activity as measured by electroencephalography (EEG) abnormalities [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in distance walked as measured by 6 Minute Walk Test (6MWT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to onset of paroxysmal exertional dyskinesia (PED) as measured during 6 minute walk test (6MWT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in gross motor function using the Gross Motor Function Measure-88 (GMFM-88) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change from baseline in neurological function using the Columbia Neurological Score (CNS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in receptive vocabulary using the Peabody Picture Vocabulary Test (PPVT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in patient or caregiver-reported quality of life using Short Form-10™ (SF-10) Health Survey for Children [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in gait, using gait analysis by computerized mat [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) properties of UX007 Plasma Peak [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    PK blood draws will be collected at screening, randomization and weeks 8, 26 and 52 (or early termination) and analyzed by a central lab. AUC and Cmax will be measured and descriptive statistics will be calculated for the plasma UX007 concentrations.

  • Pharmacokinetics (PK) properties of UX007 Metabolites [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    PK blood draws will be collected at screening, randomization, weeks 8, 26, 52 (or early termination) and analyzed by a central lab. AUC and Cmax will be measured and descriptive statistics will be calculated for the Plasma levels of UX007 metabolites: C4 ketone (BHB), C5 ketones (beta-hydroxypentanoate [BHP] and beta-ketopentanoate [BKP]), and heptanoate.

Estimated Enrollment: 50
Study Start Date: January 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:


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

Beginning with the screening visit, subjects will record seizure frequency during the 6-week Baseline Period.. At the end of the Baseline Period, subjects will be randomized and dosing will be initiated using a 2-week titration schedule until the subject has reached 35% of total daily calories from study drug.

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. Long term safety and persistence of effect of UX007 will be assessed during this Extension Period. Subjects who complete treatment through Week 52 may have the option to continue UX007 treatment, if warranted, in a separate open-label extension study.


Ages Eligible for Study:   3 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of Glut1 DS confirmed by SLC2A1 mutation
  • Males and females, aged 3 - 17 years (inclusive) at the time of informed consent
  • Average of at least 5 observable seizures (generalized [except absence] or partial-onset [simple partial motor, complex partial, or secondarily generalized] seizures) per month over the last 6 months, by subject or caregiver report
  • At least 4 observable seizures (generalized [except absence] or partial-onset seizures) per month during the Baseline Period, with no 3-week seizure-free period during the Baseline Period
  • Continuing to have seizures despite a prior or current use of at least 1 AED
  • Allowed to be on 1 - 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
  • Not on, or not fully compliant with a prescribed diet plan (e.g. ketogenic diet) comprised of at least 50% total daily caloric intake from fat during previous 60 days (confirmed by 3-day diet diary at Screening), or at any time during the course of the trial
  • Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening
  • Naïve to triheptanoin

Exclusion Criteria:

  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X the upper limit of normal at Screening
  • History of, or current suicidal ideation, behavior and/or attempts
  • Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
  • 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
  • Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment
  • 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)
  Contacts and Locations
Please refer to this study by its identifier: NCT01993186

Contact: Julia Martinisi 415.483.8815
Contact: Leigh Stott 415-483-8857

United States, California
Children's Hospital of Los Angeles Not yet recruiting
Los Angeles, California, United States, 20027
Contact: Vanessa Guzman    323-361-4910   
Principal Investigator: Divya Vats, MD         
United States, Colorado
Children's Hospital Colorado - University of Colorado, Denver, School of Medicine Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Nanastasia Welnick    720-777-8608   
Principal Investigator: Abigail Collins, MD         
United States, Florida
Neurology & Epilepsy Research Center Recruiting
Orlando, Florida, United States, 32819
Contact: Barbara Peters    407-293-1122 ext 222   
Principal Investigator: Ronald Davis, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago - Epilepsy Center Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Diana Umanzor    312-227-4517   
Principal Investigator: Srishti Nangia, MD         
United States, New York
Columbia University - Department of Neurology Recruiting
New York, New York, United States, 10032
Contact: Kristen Engelstad    212-305-6834   
Contact: Jonathan Marra    212-305-2461   
Principal Investigator: Darryl De Vivo, MD         
United States, Texas
Cook Children's Hospital Not yet recruiting
Fort Worth, Texas, United States, 76104
Contact: Juli A Ramirez    682-885-7860   
Principal Investigator: Adrian R Lacy, MD         
University of Texas Neurometabolic Clinic Recruiting
Houston, Texas, United States, 77030
Contact: Mary Kay Koenig, MD    713-500-7147      
Principal Investigator: Mary Kay Koenig, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Laurie Guidry    206-987-0058   
Principal Investigator: Russell Saneto, DO, PhD         
Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP Not yet recruiting
Paris, Cedex 19, France, 75935
Contact: Stéphane Auvin, MD, PhD    +33 140 035 724   
Principal Investigator: Stéphane Auvin, MD, PhD         
Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini" Not yet recruiting
Genova, Italy
Contact: Pasquale Striano, MD    +39 (0)10 56362758   
Principal Investigator: Pasquale Striano, MD         
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
  More Information

Additional Information:
No publications provided

Responsible Party: Ultragenyx Pharmaceutical Inc Identifier: NCT01993186     History of Changes
Other Study ID Numbers: UX007G-CL201
Study First Received: October 31, 2013
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration
Italy: The Italian Medicines Agency (AIFA)

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

Additional relevant MeSH terms:
Cryoprotective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions processed this record on April 16, 2014