A phase 2 clinical trial of a vasopressin V1a receptor antagonist shows improved adaptive behaviors in men with autism spectrum disorder

Sci Transl Med. 2019 May 8;11(491):eaat7838. doi: 10.1126/scitranslmed.aat7838. Epub 2019 May 1.


There are no approved pharmacological therapies to address the core symptoms of autism spectrum disorder (ASD), namely, persistent deficits in social communication and social interaction and the presence of restricted, repetitive patterns of behaviors, interests, or activities. The neuropeptide vasopressin has been implicated in the regulation of social behaviors, and its modulation has emerged as a therapeutic target for ASD. The phase 2 VANILLA clinical trial reported here evaluated balovaptan, an orally administered selective vasopressin V1a receptor antagonist, in 223 men with ASD and intelligence quotient ≥70. The drug was administered daily for 12 weeks and was compared with placebo. Participants were randomized to placebo (n = 75) or one of three balovaptan dose arms (1.5 mg, n = 32; 4 mg, n = 77; 10 mg, n = 39). Balovaptan treatment was not associated with a change from baseline compared with placebo at 12 weeks in the primary efficacy endpoint (Social Responsiveness Scale, 2nd Edition). However, dose-dependent and clinically meaningful improvements on the Vineland-II Adaptive Behavior Scales composite score were observed for participants treated with balovaptan 4 or 10 mg compared with placebo. This was driven principally by improvements in the Vineland-II socialization and communication scores. Balovaptan was well tolerated across all doses, and no drug-related safety concerns were identified. These results support further study of balovaptan as a potential treatment for the socialization and communication deficits in ASD.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / drug effects*
  • Adolescent
  • Adult
  • Antidiuretic Hormone Receptor Antagonists / pharmacology
  • Antidiuretic Hormone Receptor Antagonists / therapeutic use*
  • Autism Spectrum Disorder / drug therapy*
  • Behavior / drug effects*
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Middle Aged
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Quality of Life
  • Receptors, Vasopressin / metabolism*
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*
  • Young Adult


  • AVPR1A protein, human
  • Antidiuretic Hormone Receptor Antagonists
  • Pyridines
  • Receptors, Vasopressin
  • Triazoles
  • Benzodiazepines
  • balovaptan