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.
Mov Disord
; 39(8): 1386-1396, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38725190
ABSTRACT
BACKGROUND:
Paroxysmal movement disorders are common in Glut1 deficiency syndrome (Glut1DS). Not all patients respond to or tolerate ketogenic diets.OBJECTIVES:
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.METHODS:
UX007G-CL301 was a randomized, double-blind, placebo-controlled, phase 3 crossover study. After a 6-week run-in, eligible patients were randomized 11 to the first sequence (triheptanoin/placebo or placebo/triheptanoin) titration plus maintenance, followed by washout and the opposite sequence titration plus maintenance. The placebo (safflower oil) matched the appearance, taste, and smell of triheptanoin. Open-label triheptanoin was administered in the extension. The frequency of disabling paroxysmal movement disorder events per 4 weeks (recorded by diary during maintenance; primary endpoint) was assessed by Wilcoxon rank-sum test.RESULTS:
Forty-three patients (children, n = 16; adults, n = 27) were randomized and treated. There was no difference between triheptanoin and placebo in the mean (interquartile range) number of disabling paroxysmal movement disorder events (14.3 [4.7-38.3] vs. 11.8; [3.2-28.7]; Hodges-Lehmann estimated median difference 1.46; 95% confidence interval, -1.12 to 4.36; P = 0.2684). Treatment-emergent adverse events were mild/moderate in severity and included diarrhea, vomiting, upper abdominal pain, headache, and nausea. Two patients discontinued the study because of non-serious adverse events that were predominantly gastrointestinal. The study was closed early during the open-label extension because of lack of effectiveness. Seven patients continued to receive triheptanoin compassionately.CONCLUSION:
There were no significant differences between the triheptanoin and placebo groups in the frequency of disabling movement disorder events during the double-blind maintenance period. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Errores Innatos del Metabolismo de los Carbohidratos
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Estudios Cruzados
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Mov Disord
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos