Triheptanoin (Dojolvi) - for the treatment of adult and pediatric patients with long-chain fatty acid oxidation disorders Search Page - Drug and Health Product Register * Skip to main content * Skip to "About this site"Language selection * FrançaisGovernment of CanadaSearch and menus * Search and menusSearchSearch websiteSearchTopics menu * Jobs * Immigration * Travel * Business * Benefits
triheptanoin - Dojolvi - Long-chain fatty acid oxidation disorders Skip to main contentAboutCollaboration/OutreachPatient/CommunityCareersContactMy CADTHFRReportsResourcesProvide InputSubmit a RequestNews & EventsWhat Does The Evidence Say About...SearchBreadcrumbHome Reimbursement Reviews triheptanoinCopied to clipboard triheptanoin( Last Updated : December 24, 2021)Reimbursement ReviewAbout disordersManufacturer: Ultragenyx Canada IncBrand Name: DojolviProject Line: Reimbursement ReviewProject Number: SR0684-000NOC Status at Filing: Post NOCDetailsManufacturer Requested Reimbursement Criteria1: Ultragenyx is requesting triheptanoin be reimbursed for the treatment of adult and pediatric patients with long-chain fatty acid oxidation disorders (LC-FAOD)Submission Type: InitialFee Schedule: Schedule
Triheptanoin (Dojolvi) - To treat molecularly long-chain fatty acid oxidation disorders Drug Approval Package: DOJOLVI * Skip to main page content * Skip to search * Skip to topics menu * Skip to common linksHHS U.S. Department of Health and Human Services U.S. Food and Drug Administration * Follow FDA * En EspañolSearch FDASubmit search * Popular Content * Home * Food * Drugs * Medical
Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study. Brain energy deficiency occurs at the early stage of Huntington disease (HD). Triheptanoin, a drug that targets the Krebs cycle, can restore a normal brain energetic profile in patients with HD. In this study, we aimed at assessing its efficacy on clinical and neuroimaging structural measures in HD. We conducted a 6-month bicentric (Paris, Leiden) double-blind randomized controlled trial followed by a 6-month open-label phase, between June 2015 and December 2019. We enrolled 107 patients at the early stage of HD-total motor score (TMS) of the UHDRS between 5 and 40. Participants received triheptanoin 1 g/kg/day or placebo (ratio 1/1). The primary outcome
Triheptanoin Did Not Show Benefit versus Placebo for the Treatment of Paroxysmal Movement Disorders in Glut1 Deficiency Syndrome: Results of a Randomized Phase 3 Study. Paroxysmal movement disorders are common in Glut1 deficiency syndrome (Glut1DS). Not all patients respond to or tolerate ketogenic diets. The objective was to evaluate the effectiveness and safety of triheptanoin in reducing the frequency of disabling movement disorders in patients with Glut1DS not receiving a ketogenic diet. UX007G-CL301 was a randomized, double-blind, placebo-controlled, phase 3 crossover study. After a 6-week run-in, eligible patients were randomized 1:1 to the first sequence (triheptanoin/placebo or placebo/triheptanoin) titration plus maintenance, followed by washout and the opposite sequence titration plus
A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome. This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS). UX007G-CL201 was a randomized, double-blind , placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52. The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction
No effect of triheptanoin in patients with phosphofructokinase deficiency. Phosphofructokinase deficiency (PFKD) is a rare disorder of glycogen metabolism. The lack of phosphofructokinase activity blocks the oxidative pathway from glucose and glycogen to pyruvate. Patients suffer from myopathy, exercise intolerance, and myoglobinuria. Currently, there is no specific treatment for PFKD. We hypothesized that 2 weeks treatment with triheptanoin could improve oxidative metabolism during exercise by bypassing the blocked pyruvate generation in PFKD. The study was a randomized, double-blind, placebo-controlled crossover study. Three genetically verified patients completed two treatment periods of 14 days each with triheptanoin (0.3-1 g × kg × day) or placebo liquid. Primary outcomes were heart rate
Triheptanoin (UX-007) for glucose transporter type 1 deficiency syndrome (de vivo disease) – first line Triheptanoin (UX-007) for glucose transporter type 1 deficiency syndrome (de vivo disease) – first line - NIHR * About * Our Team * Our Stakeholders * Horizon Scanning * Pipeline Analysis * Imagine Series * Data Science & AI * Get Involved * Devices, Diagnostics All Outputs * Search All Tech Briefings * Latest Dashboards * Triheptanoin (UX-007) for glucose transporter type 1 deficiency syndrome (de vivo disease) – first line Interventions: Triheptanoin (UX007; Dojolvi) Indications: Glucose transporter type 1 deficiency syndrome Therapeutic Areas: Endocrine Nutritional and Metabolic Disorders Year: 2017 Glucose transporter type 1 deficiency
The Pharmacokinetics of Triheptanoin and Its Metabolites in Healthy Subjects and Patients With Long-Chain Fatty Acid Oxidation Disorders. Long-chain fatty acid oxidation disorders (LC-FAODs) are a group of life-threatening autosomal recessive disorders caused by defects in nuclear genes encoding mitochondrial enzymes involved in the conversion of dietary long-chain fatty acids into energy . Triheptanoin is an odd-carbon, medium-chain triglyceride consisting of 3 fatty acids with 7 carbons each on a glycerol backbone developed to treat adult and pediatric patients with LC-FAODs. The pharmacokinetics of triheptanoin and circulating metabolites were explored in healthy subjects and patients with LC-FAODs using noncompartmental analyses. Systemic exposure to triheptanoin following an oral
Open-label long-term treatment of add-on triheptanoin in adults with drug-resistant epilepsy. To investigate feasibility, safety, and tolerability of long-term (48 weeks) add-on treatment with triheptanoin (UX007), the triglyceride of heptanoate, in adults with drug-resistant epilepsy. This extension study was offered to adult participants with drug-resistant epilepsy who completed a 12-week randomized controlled trial of add-on medium-chain triglycerides (MCT) vs triheptanoin. Participants were asked to titrate triheptanoin to their maximum tolerated dose over 3 weeks, followed by 48-week maintenance before tapering or treatment extension. The primary aims were to assess retention and safety of the triheptanoin treatment, and secondary aims to assess the tolerated doses and changes in seizure
Concerning "Triheptanoin vs trioctanoin for long-chain fatty acid oxidation disorders: A double blinded, randomized controlled trial" by Gillingham et al.
Triheptanoin alters [U-13C6]-glucose incorporation into glycolytic intermediates and increases TCA cycling by normalizing the activities of pyruvate dehydrogenase and oxoglutarate dehydrogenase in a chronic epilepsy mouse model. Triheptanoin is anticonvulsant in several seizure models. Here, we investigated changes in glucose metabolism by triheptanoin interictally in incorporation of C in several glycolytic intermediates compared to control mice suggesting glucose utilization may be impaired and/or glycogenolysis increased in the untreated interictal hippocampus. Triheptanoin prevented the interictal reductions of C incorporation in most glycolytic intermediates, suggesting it increased glucose utilization or - as an additional astrocytic fuel - it decreased glycogen
Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy. To investigate the feasibility, safety, and tolerability of add-on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment-refractory epilepsy. After an 8-week prospective baseline period, people with drug-resistant epilepsy were randomized in a double-blind fashion to receive triheptanoin or MCTs. Treatment was titrated over 3 weeks to a maximum of 100 mL/d to be distributed over 3 meals and mixed into food, followed by 12-week maintenance before tapering. The primary aims were to assess the following: (a) safety by comparing the number of intervention-related adverse
No effect of triheptanoin on exercise performance in McArdle disease. To study if treatment with triheptanoin, a 7-carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen-dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxidation. We hypothesized that triheptanoin metabolism generates substrates for the TCA, which potentially boosts fat oxidation and improves exercise tolerance in McArdle disease. Double-blind, placebo-controlled, crossover study in patients with McArdle disease completing two treatment periods of 14 days each with a triheptanoin or placebo diet (1 g/kg/day). Primary outcome was change in mean heart rate during 20 min submaximal exercise on a cycle
Triheptanoin Protects Motor Neurons and Delays the Onset of Motor Symptoms in a Mouse Model of Amyotrophic Lateral Sclerosis. There is increasing evidence that energy metabolism is disturbed in Amyotrophic Lateral Sclerosis (ALS) patients and animal models. Treatment with triheptanoin, the triglyceride of heptanoate, is a promising approach to provide alternative fuel to improve oxidative phosphorylation and aid ATP generation. Heptanoate can be metabolized to propionyl-CoA, which after carboxylation can produce succinyl-CoA and thereby re-fill the tricarboxylic acid (TCA) cycle (anaplerosis). Here we tested the hypothesis that treatment with triheptanoin prevents motor neuron loss and delays the onset of disease symptoms in female mice overexpressing the mutant human SOD1G93A (hSOD1G93A) gene
A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome. Adult polyglucosan body disease (APBD) is a progressive neurometabolic disorder caused by a deficiency of glycogen branching enzyme. We tested the efficacy of triheptanoin as a therapy for patients with APBD based on the hypothesis that decreased glycogen degradation leads to brain energy deficit. This was a two-site, randomized crossover trial of 23 patients (age 35-73 years; 63% men) who received triheptanoin or vegetable oil as placebo. The trial took place over 1 year and was followed by a 4-year open-label phase. Generalized linear mixed models were used to analyze this study. At baseline, using the 6-min walk test, patients could walk a mean of 389 ± 164 m
Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial. Observational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium-chain triglyceride (MCT) treatment of long-chain fatty acid oxidation disorders (LC-FAODs ) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven-carbon fatty acid triglyceride, to trioctanoin (C8), an eight-carbon fatty acid triglyceride, in patients with LC-FAODs. A double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase
A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood Based on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations. We conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Each treatment period consisted of a 12-week fixed-dose phase, separated by a 4-week washout period. The primary outcome was the total number of paroxysmal events. Secondary outcomes included the number of paroxysmal motor-epileptic events; a composite