An Exploratory Clinical Study of a Low-dose Buprenorphine Patch for the Treatment of Autism Spectrum Disorders

This study evaluates the safety and efficacy of low-dose buprenorphine in patients with ASD by using standard ASD symptom assessment methods (e.g., SRS-2 and ABC) as well as AI-assisted analyses utilizing exploratory gaze patterns in conjunction with fMRI and electroencephalogram measurements to assess changes in brain functional status.

The study aims to assess the safety and efficacy of buprenorphine in patients with autism spectrum disorders (ASD) in very low, lower, and higher dose groups and to explore the sensitivity and specificity of ophthalmoscopy for evaluating the efficacy of ASD treatment. Combined neuroimaging techniques to examine the effects of buprenorphine on neurologic function in ASD.

In this study, changes in functional brain status will be assessed by using standard ASD symptom assessment methods (e.g., SRS and ABC) as well as algorithms utilizing AI's exploratory gaze patterns in conjunction with functional magnetic resonance and electroencephalography imaging to evaluate changes in the functional brain state of the very low-dose group (5 mg 1/9 at follow-up only), the lower-dose group (5 mg 1/9/week) and the higher-dose group (5 mg 1/3/week) buprenorphine safety and efficacy in patients with ASD. This study will validate the results of previous studies based on humans and rodents and is expected to develop an effective drug for treating the core symptoms of ASD with significant social and economic benefits.

This is a randomized, three-arm, double-blind study in male/female subjects with ASD with a treatment duration of 56 days. Items to be evaluated include efficacy on ASD symptoms, safety, Day57's buprenorphine drug concentration in plasma, and changes in oculomotor, functional magnetic resonance, and electroencephalographic data before and after treatment. The effective dose is estimated based on the results of preclinical studies of buprenorphine in ASD model mice, using a dose of one-third or one-ninth of the available 5-mg buprenorphine transdermal patch.

Eligibility Criteria:
Inclusion Criteria:

* Sex: male/female;
* Age:6-18 years at the time of randomization;
* Clinical diagnosis in accordance with the DSM-5 diagnosis of ASD;
* Diagnosis of ASD using the K-SADS-PL-C DSM-5 and CARS;
* A severity score of ≥ 4 on the CGI scale;
* Subjects must be able to participate and deemed suitable for participation in the study, at the investigator's discretion, and be able to follow the study evaluation schedule;
* The parent or guardian agrees to accompany the subject to all clinical visits and to provide information about the subject's behavior and symptoms, and must agree to supervise the subject's compliance with protocol-specified procedures and the use of study drug doses;
* The parent or guardian is willing and able to give written informed consent in accordance with local requirements. When the subject is capable of making the decision to consent to participation in the study, the subject is likewise willing and able to provide written informed consent in accordance with local requirements.

Exclusion Criteria:

1. Neurologic/Psychiatric Disorders

   * Concurrent comorbidity with any other mental disorder (other than ADHD) as diagnosed by the K-SADS-PL-C DSM-5;
   * Neurologic disorders or prior head trauma resulting in coma;
   * Unstable or uncontrollable clinically significant psychiatric and/or neurological disorders that may interfere with safety or efficacy outcome;
   * Unstable or uncontrolled irritability in the judgment of the investigator;
   * Any suicide attempts in the opinion of the investigator at the time of screening that he/she is at risk for suicidal behavior or in his/her medical history;
   * A history of seizures within the past 6 months;
   * A history of alcohol or other substance abuse/dependence.
2. Cardiovascular Disease

   * Current cardiovascular disease not effectively controlled in the opinion of the investigator;
   * Clinically significant abnormalities (e.g., twice consecutive measurements) as confirmed by ECG at screening, including, but not limited to: QTc: ≥450 milliseconds, absence of predominant sinus rhythm, and second or third degree a-v block.
3. Diseases of other organ systems

   * Accompanying other diseases or conditions (pulmonary, gastrointestinal, hepatic, renal, metabolic, immune system, or obesity) that may interfere or whose treatment may interfere with the conduct of the study; or where, in the opinion of the Investigator, discontinuation of the Prohibited Substance may pose an unacceptable risk to the subject.
   * Evidence of gastrointestinal bleeding, e.g., active gastric ulcer;
   * History of coagulopathy, bleeding disorders or blood disorders;
4. Other exclusion criteria

   * Marked respiratory depression;
   * Acute or severe bronchial asthma;
   * Known or suspected paralytic bowel obstruction;
   * Allergic to buprenorphine;
   * Participation in a drug study within 30 days prior to randomization or within 5 times the half-life of the molecule to be studied, whichever is longer; or drug study; or participation in a study testing a medical device within 30 days prior to randomization, or the device is still in action. active;
   * History of blood loss greater than 250 mL within 3 months prior to screening;
   * Medications permitted since 4 weeks prior to screening that have NOT been clearified and stable, and medications permitted for the treatment of epilepsy since 3 months prior to screening that have NOT been clearified and stable.
   * Usage of a prohibited medication within 2 weeks prior to the screening visit (and ensuring at least 4 weeks of washout time prior to the baseline assessment) or usage of a prohibited medication within 5 times of half-life prior to the randomization (whichever is longer).