Safety of L1-79 in Adolescent and Adult Males With Autism

This is a five-arm designed to assess the safety of L1-79 that incorporates 15 prospectively randomized, placebo controlled patients and 5 open label patients at either 100 tid (three times daily) or 200 tid dosing for 28 days. The open label patients will be assessed for the purpose of understanding PK/PD and to determine if there are any EKG changes associated with the administration of L1-79. Additional safety information will be provided by the 30 patients randomized 2:1 active:placebo.

Protocol Number: HT 02-121

Protocol Title: Phase 2 Safety Study of L1-79 for the Treatment of Autism Study Phase: 2

The first cohort of 20 patients to be enrolled will all receive L1-79 100 mg t.i.d., and will be comprised of 3 groups of patients. The first group of patients to receive 100 mg will differ from the others in that they will get blood samples drawn for PK analysis and EKGs will be taken. The safety and PK data from this group will be submitted for FDA review and acceptance before the 200 mg t.i.d. cohort will be enrolled. The remaining 15 patients in this cohort will be randomized to receive either L1-79 100 mg t.i.d. or placebo on a 2:1 basis (2 L1-79 patients for each placebo patient). While the FDA is reviewing the data from the first 5 patients all 100 mg t.i.d. patients will continue to be treated.

The second cohort is identical to the first. The initial 5 patients to be enrolled will differ from the others in that they will get blood samples drawn for PK analysis and EKGs will be taken. The remaining 15 patients in this cohort will be randomized to receive either L1-79 200 mg t.i.d. or placebo on a 2:1 active:placebo.

Sample Size: N=40

* Group 1 (n=5) open100mg L1-79 (1x100mg capsule+1 placebo capsule)
* Group 2 (n=10) blind100mg L1-79 (1x100mg capsule+1 placebo capsule)
* Group 3 (n=5) open200 mg L1-79 (2x100 mg capsules)
* Group 4 (n=10) blind200 mg L1-79 (2x100 mg capsules)
* Group 5 (n=10) Placebo (2 placebo capsules) All Groups will receive the assigned study drug three-times daily

Study Population: Male subjects with autism between the ages of 13 and 21 years of age who meet the entry criteria and who are able to complete standardized measures allowing them to participate in this study.

Evaluation Schedule: Subjects will be evaluated within one week prior to study accession, and weekly throughout the dosing period, and again 4 weeks after the cessation of treatment. The Assigned Dosage Groups (Groups 1 and 3) will have PK blood draws and EKG the randomized group will not have.

Safety Measures: All Groups will have regularly scheduled complete history and physical examination that includes orthostatic blood pressure measurements, vital signs, CBC, differential, platelet counts, urine analysis, and serum analytes including: total protein, albumin, glucose, BUN, creatinine, direct and total bilirubin, alkaline phosphatase, phosphorous, calcium, AST, ALT, sodium, potassium, chloride, bicarbonate, T4, TSH, and adverse events assessments. The Assigned Groups (1 and 3) will also have electrocardiograms taken at the study screening visit and weekly throughout the treatment interval.

Eligibility Criteria:
Inclusion Criteria:

1. Males who are not sexually active
2. 12 and 21 years of age
3. Signed informed consent
4. Normal clinical laboratory values
5. DSM-5 compliant diagnosis of autism spectrum disorder, confirmed by the Autistic Diagnosis Interview Review (ADIR), and by the Autism Diagnosis Observation Schedule (ADOS) score consistent with a diagnosis of autism
6. No more than one concomitant medication for the treatment of autism, on a stable for at least 2 weeks prior to enrollment and no planned changes in psychosocial interventions during the trial
7. No medications for any other pathology

Exclusion Criteria:

1. Any co-morbidities, including Fragile-X syndrome, epilepsy, Retts syndrome, ADHD, or other disease or syndrome aside from autism that requires treatment
2. Any other psychiatric disorder, or out of range lab values
3. DSM-5 diagnosis of schizophrenia, schizoaffective disorder, alcohol use disorder
4. Active medical problems: unstable seizures (\>2 in past month)
5. Concomitant physical illness