Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents with Autism Spectrum Disorder: Design of Two Phase III Studies (SIGN Trials)

Abstract

There are currently no approved pharmacological treatments to improve social reciprocity and limit repetitive and rigid behaviors in autism spectrum disorder (ASD). We describe the design of two Phase III studies evaluating the efficacy/safety of bumetanide oral liquid formulation in ASD. These are international, multicenter, randomized, double-blind, placebo-controlled studies in children and adolescents with ASD aged 7 to 17 years (n = 200; study 1), or younger children with ASD aged 2 to 6 years (n = 200; study 2). The primary endpoint of each is change in Childhood Autism Rating Scale 2 total raw score after 6 months. These studies could contribute to the first pharmacological treatment to improve social reciprocity and limit repetitive and rigid behaviors in children and adolescents with ASD.

Keywords: Autism spectrum disorder; Bumetanide; Pediatrics; Randomized controlled trial.

Fig. 1

Study design. BID twice daily, ECG electrocardiogram. ^aBumetanide oral liquid formulation; dose adapted by body weight. Patients < 25 kg will receive bumetanide 0.02 mg/kg BID (0.04 ml/kg oral liquid formulation BID); patients ≥ 25 kg will receive bumetanide 0.5 mg BID (1 ml oral liquid formulation BID); ^bPatients < 25 kg will receive placebo oral solution of 0.04 ml/kg BID; patients ≥ 25 kg will receive placebo oral solution 1 ml BID