Effects of Intranasal Administration of a Single Dose of Oxytocin Using a Novel Device in Adults With Autism Spectrum Disorder

A Randomized, Placebo Controlled, Double-blind, 3-period Cross-over Study in Adult Patients With Autism Spectrum Disorders Evaluating Cognitive Response After Single- Dose Oxytocin 8 or 24 IU Intranasal Administration Using the OptiNose Bi-directional Nose-to-brain Device

Oxytocin (OT) is a small, naturally occurring peptide currently in clinical use to stimulate lactation in breastfeeding women. The intranasal administration of OT has recently attracted attention as a potential novel treatment in several psychiatric disorders in autism. However, given the anatomy of the nasal cavity, the current design of nasal sprays would be expected to provide an inadequate delivery of medication to the areas of the nasal cavity where direct transport into the brain via the olfactory nerve could potentially occur. OptiNose has developed an intranasal delivery device that provides improved reproducibility of nasal delivery, improved deposition to the upper posterior regions of the nasal cavity where the olfactory nerve innervates the nasal cavity.

The primary objective of this study is to identify any differences between a single dose of 8 international units (IU) oxytocin, 24 IU oxytocin, and placebo delivered intranasally with the optimised OptiNose device in volunteers with Autism Spectrum Disorder. This will be measured in terms of performance on cognitive tests and physiological markers.

Inclusion Criteria:

• Male subjects between the ages of 18 and 35, both inclusive, with a confirmed diagnosis of autism spectrum disorder (ASD) diagnosis.
• Subjects must be in good general health, as determined by the investigator.
• Subject's pre-study physical examination, vital signs and electrocardiogram (ECG) must not show any clinically significant abnormalities as determined by the investigator.
• Subjects must be able to communicate well with the Investigator, to understand and comply with the requirements of the study, and to understand the oral and written patient information
• Provision of a signed, written informed consent.

Exclusion Criteria:

• Subjects showing major septal deviation or a significantly altered nasal epithelium.
• Subjects with evidence of previous nasal disease, surgery, and dependence on inhaled drugs.
• Subjects with current significant nasal congestion due to common colds.
• Subjects with a clinically relevant history of significant hepatic, renal, endocrine, cardiac, nervous, pulmonary, haematological or metabolic disorder.
• Psychiatric co-morbidity that requires intervention (e.g., psychosis spectrum disorders, suicide intent)
• Systemic illness requiring treatment within 2 weeks prior to Study Day 1.
• History of significant drug or alcohol abuse (as per WHO Alcohol use disorder identification test and drug use disorder identification test criteria) Subjects with a positive screen for alcohol or drugs of abuse at screening/admission will be excluded from participation in the study.
• Abnormal laboratory values which is deemed clinically significant by investigator.
• Full scale IQ < 75 (due to the prerequisite ability to complete self report measures).
• Known allergic reactions or hypersensitivity to any component of the study medication in the nasal spray, such as propyl parahydroxybenzoate (E216), methyl parahydroxybenzoate (E218) and chlorobutanol hemihydrate.
• Participation in any (other) clinical trial with an investigational medicinal product or medical device within 3 months prior to randomisation.
• Other unspecified reasons that, in the opinion of the investigator or the sponsor make the subject unsuitable for enrollment.