PMID- 33443117
OWN - NLM
STAT- MEDLINE
DCOM- 20210302
LR  - 20211217
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 96
IP  - 7
DP  - 2021 Feb 16
TI  - The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman 
      Syndrome.
PG  - e1024-e1035
LID - 10.1212/WNL.0000000000011409 [doi]
AB  - OBJECTIVE: To evaluate safety and tolerability and exploratory efficacy end 
      points for gaboxadol (OV101) compared with placebo in individuals with Angelman 
      syndrome (AS). METHODS: Gaboxadol is a highly selective orthosteric agonist that 
      activates delta-subunit-containing extrasynaptic gamma-aminobutyric acid type A (GABA(A)) 
      receptors. In a multicenter, double-blind, placebo-controlled, parallel-group 
      trial, adolescent and adult individuals with a molecular diagnosis of AS were 
      randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo 
      morning dose and gaboxadol 15 mg evening dose (qd), gaboxadol 10 mg morning dose 
      and 15 mg evening dose (bid), or placebo morning and evening dose. Safety and 
      tolerability were monitored throughout the study. Prespecified exploratory 
      efficacy end points included adapted Clinical Global Impression-Severity and 
      Clinical Global Impression-Improvement (CGI-I) scales, which documented the 
      clinical severity at baseline and change after treatment, respectively. RESULTS: 
      Eighty-eight individuals were randomized. Of 87 individuals (aged 13-45 years) 
      who received at least 1 dose of study drug, 78 (90%) completed the study. Most 
      adverse events (AEs) were mild to moderate, and no life-threatening AEs were 
      reported. Efficacy of gaboxadol, as measured by CGI-I improvement in an 
      exploratory analysis, was observed in gaboxadol qd vs placebo (p = 0.0006). 
      CONCLUSION: After 12 weeks of treatment, gaboxadol was found to be generally 
      well-tolerated with a favorable safety profile. The efficacy as measured by the 
      AS-adapted CGI-I scale warrants further studies. CLINICALTRIALSGOV IDENTIFIER: 
      NCT02996305. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence 
      that, for individuals with AS, gaboxadol is generally safe and well-tolerated.
CI  - Copyright (c) 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the American Academy of Neurology.
FAU - Bird, Lynne M
AU  - Bird LM
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Ochoa-Lubinoff, Cesar
AU  - Ochoa-Lubinoff C
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Tan, Wen-Hann
AU  - Tan WH
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Heimer, Gali
AU  - Heimer G
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Melmed, Raun D
AU  - Melmed RD
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Rakhit, Amit
AU  - Rakhit A
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Visootsak, Jeannie
AU  - Visootsak J
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - During, Matthew J
AU  - During MJ
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Holcroft, Christina
AU  - Holcroft C
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Burdine, Rebecca D
AU  - Burdine RD
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
FAU - Kolevzon, Alexander
AU  - Kolevzon A
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston. alexander.kolevzon@mssm.edu.
FAU - Thibert, Ronald L
AU  - Thibert RL
AD  - From the University of California, San Diego (L.M.B.); Rady Children's Hospital 
      (L.M.B.), San Diego, CA; Division of Developmental-Behavioral Pediatrics 
      (C.O.-L.), Rush University Medical Center, Chicago, IL; Division of Genetics and 
      Genomics (W.-H.T.), Boston Children's Hospital, Harvard Medical School, MA; 
      Pediatric Neurology Unit (G.H.), Safra Children's Hospital, the Sheba Medical 
      Center, Ramat Gan; The Sackler School of Medicine (G.H.), Tel Aviv University, 
      Israel; Southwest Autism Research and Resource Center (R.D.M.), Phoenix, AZ; Ovid 
      Therapeutics Inc. (A.R., M.J.D.); Neurogene (J.V.), New York, NY; Prometrika, LLC 
      (C.H.), Cambridge, MA; Department of Molecular Biology (R.D.B.), Princeton 
      University, NJ; Seaver Autism Center for Research and Treatment, Department of 
      Psychiatry (A.K.), Icahn School of Medicine at Mount Sinai, New York, NY; and 
      Angelman Syndrome Clinic, Department of Neurology (R.L.T.), Massachusetts General 
      Hospital, Boston.
LA  - eng
SI  - ClinicalTrials.gov/NCT02996305
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20201221
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (GABA Agonists)
RN  - 0 (Isoxazoles)
RN  - K1M5RVL18S (gaboxadol)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Angelman Syndrome/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - GABA Agonists/*administration & dosage
MH  - Humans
MH  - Isoxazoles/*administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC8055330
EDAT- 2021/01/15 06:00
MHDA- 2021/03/03 06:00
PMCR- 2021/02/16
CRDT- 2021/01/14 08:47
PHST- 2020/03/03 00:00 [received]
PHST- 2020/10/12 00:00 [accepted]
PHST- 2021/01/15 06:00 [pubmed]
PHST- 2021/03/03 06:00 [medline]
PHST- 2021/01/14 08:47 [entrez]
PHST- 2021/02/16 00:00 [pmc-release]
AID - WNL.0000000000011409 [pii]
AID - NEUROLOGY2020070516 [pii]
AID - 10.1212/WNL.0000000000011409 [doi]
PST - ppublish
SO  - Neurology. 2021 Feb 16;96(7):e1024-e1035. doi: 10.1212/WNL.0000000000011409. Epub 
      2020 Dec 21.