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Safety of L1-79 in Autism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02947048
Recruitment Status : Completed
First Posted : October 27, 2016
Last Update Posted : February 10, 2020
Sponsor:
Collaborator:
Yamo Pharmaceuticals LLC
Information provided by (Responsible Party):
F Peter Halas, Yamo Pharmaceuticals LLC

Tracking Information
First Submitted Date  ICMJE May 25, 2016
First Posted Date  ICMJE October 27, 2016
Last Update Posted Date February 10, 2020
Study Start Date  ICMJE October 2016
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
Adverse event frequency [ Time Frame: 56 days ]
Adverse events will be solicited over 56 days from the start of treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
  • Change from baseline in CGI [ Time Frame: Week 0 and weekly for first 28 days, and at day 56. ]
    The attending physicians assessment as quantified by the Clinical Global Impressions Scale completed at baseline and weekly through 56 days of treatment and follow-up.
  • Change from Baseline in Vineland Adaptive Behavior Scales - 2nd Edition [ Time Frame: Day 0 and at days 28 and 56. ]
    Changes from baseline in Communication and Socialization domain of Vineland Adaptive Behavior Scale 2nd edition (VABS II)
  • Change from Baseline in the Autism Diagnostic Observation Schedule (ADOS) [ Time Frame: Day 0 and at days 28 and 56. ]
    Changes from baseline in the Autism Diagnostic Observation Schedule (ADOS) total and domain scores.
  • Change from baseline in Aberrant Behavior Checklist - Community [ Time Frame: Week 0 and weekly for first 28 days, and at day 56. ]
    Weekly Changes from baseline in the Aberrant Behavior Checklist-Community (ABC-C) domains of irritability, social withdrawal and lethargy, hyperactivity, inappropriate speech and stereotypical behavior.
  • Change from baseline in the Social Responsiveness Scale - 2nd edition (SRS-2) [ Time Frame: Week 0 and weekly for first 28 days, and at day 56. ]
    Weekly changes from baseline in overall and subdomains of the Social Responsiveness Scale (SRS).
  • Changes from baseline in the Repetitive Behavior Scale - Revised (RBS-R). [ Time Frame: Week 0 and weekly for first 28 days, and at day 56. ]
    Weekly changes from baseline in the overall and subdomains of the Repetitive Behavior Scale - Revised (RBS-R).
  • Plasma concentrations of L1-79 [ Time Frame: Week 0 and weekly for 28 days; random sampling times will be employed ]
    Blood will be collected from assigned patients in each dose group at baseline visit one hour after dose and again at each clinic visit at random times after dose for determination of L1-79 concentrations
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
  • Change from baseline in CGI [ Time Frame: Week 0 and weekly for 56 days ]
    The attending physicians assessment as quantified by the Clinical Global Impressions Scale completed at baseline and weekly through 56 days of treatment and follow-up.
  • Plasma concentrations of L1-79 [ Time Frame: Week 0 and weekly for 28 days; before and one hour after dosing ]
    Blood will be collected from assigned patients in each dose group at baseline and at each clinic visit before and 1 hour after dosing for determination of L1-79 concentrations
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of L1-79 in Autism
Official Title  ICMJE A Phase 2 Safety Study of L1-79 for the Treatment of Autism
Brief Summary 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 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Autism
Intervention  ICMJE
  • Drug: L1-79
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: 100 mg open
    open-label lead-in 100 mg L1-79 t.i.d.
    Intervention: Drug: L1-79
  • Experimental: 100 mg blinded
    blinded and randomized 100 mg L1-79 t.i.d.
    Intervention: Drug: L1-79
  • Experimental: 200 mg open
    open-label lead-in 200 mg L1-79 t.i.d.
    Intervention: Drug: L1-79
  • Experimental: 200 mg blinded
    blinded and randomized 200 mg L1-79 t.i.d.
    Intervention: Drug: L1-79
  • Placebo Comparator: Placebo
    placebo t.i.d.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2018)
42
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2016)
40
Actual Study Completion Date  ICMJE February 1, 2018
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males who are not sexually active
  2. 13 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 13 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02947048
Other Study ID Numbers  ICMJE HT 02-121
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party F Peter Halas, Yamo Pharmaceuticals LLC
Study Sponsor  ICMJE F Peter Halas
Collaborators  ICMJE Yamo Pharmaceuticals LLC
Investigators  ICMJE
Study Director: John Rothman, PhD Yamo Pharmaceuticals
PRS Account Yamo Pharmaceuticals LLC
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP