ecopipam (PSYRX 101) / Paragon Biosci - LARVOL DELTA

Safety and Effect of 12-Month Ecopipam Treatment in Pediatric Patients with Tourette Syndrome. (PubMed, Mov Disord Clin Pract) - "Twelve months of ecopipam dosing was well tolerated during this study and no new adverse events were detected. Compared to baseline, significantly reduced TS symptom severity and improved QOL were observed in children and adolescents."

Journal • CNS Disorders • Depression • Developmental Disorders • Infectious Disease • Mood Disorders • Movement Disorders • Pediatrics • Psychiatry • Tic Disorders • Tourette Syndrome

Determining Clinically Meaningful Improvement in Children and Adolescents with Tourette Syndrome Receiving Pharmacotherapy. (PubMed, J Child Adolesc Psychopharmacol) - "Materials and Analyses used data from two clinical trials of ecopipam (a randomized controlled trial and its open-label extension)...Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was a generally appropriate minimum threshold to define clinically meaningful improvement in this population. Findings offer an objective threshold for classifying clinically meaningful improvement in children and adolescents receiving pharmacotherapy for TS in clinical practice."

Journal • Movement Disorders • Pediatrics • Tic Disorders • Tourette Syndrome

EBS-101-TD-391: A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Emalex Biosciences Inc. | Trial primary completion date: Nov 2024 ➔ Dec 2026

Trial primary completion date • Movement Disorders • Tourette Syndrome

D1AMOND: Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (clinicaltrials.gov) - P3 | N=216 | Completed | Sponsor: Emalex Biosciences Inc. | Active, not recruiting ➔ Completed

Trial completion • Tourette Syndrome

Ecopipam Induced Hyperkalemia in an 18-Year-Old Male (NKF-SCM 2025) - "This case emphasizes the need for ongoing safety monitoring in the use of any investigational medication and identifies a potentially novel adverse effect associated with ecopipam.Conclusion This case highlights a novel adverse effect of ecopipam, an investigational Tourette Syndrome treatment, causing hyperkalemia due to renal tubular dysfunction. Monitoring renal function and serum potassium is crucial to mitigate risks, emphasizing the need for thorough safety assessments in clinical trials."

CNS Disorders • Congenital Adrenal Hyperplasia • Developmental Disorders • Endocrine Disorders • Hypotension • Movement Disorders • Nephrology • Psychiatry • Renal Disease • Tourette Syndrome

Changes in Metabolic Parameters and Determination of Minimal Clinically Important Difference in YGTSS-TTS Using Data From the Randomized Phase 2b and Open-Label Extension Studies of Ecopipam For Tourette Syndrome (AAN 2025) - "Ecopipam did not adversely affect parameters associated with an increased risk of metabolic syndrome. ROC analysis suggested that ≥25% reduction in YGTSS-TTS is an appropriate minimum threshold to define clinically meaningful improvement (MCID) in this patient population."

Clinical • P2b data • Metabolic Disorders • Movement Disorders • Tourette Syndrome

The Effect of Ecopipam and its Metabolites on Cardiac Repolarization, QTcF (AAN 2025) - "Design/A randomized, double-blind, placebo-controlled, 4-way crossover study with single doses of ecopipam 179.2 mg, ecopipam 537.6 mg, placebo, and open-label moxifloxacin 400 mg was conducted. A 10 msec increase in ΔΔQTcF can be ruled out at ecopipam 179.2 mg, the therapeutic dose. A 10 msec increase in ΔΔQTcF interval cannot be ruled out at the high clinical drug exposure (ecopipam 179.2 mg + a general UGT inhibitor), but the effect is small. After a 537.6 mg ecopipam dose, increases in the ΔΔQTcF interval up to 20.4 msec are predicted."

Tourette Syndrome • CYP3A4 • UGT1A9

SNX19 Interacts with Caveolin-1 and Flotillin-1 to Regulate D1R Endocytosis and Signaling. (PubMed, Biomedicines) - "In mouse RPTCs transfected with wild-type (WT) Snx19, fenoldopam (FEN), a D1-like receptor agonist, increased the colocalization of SNX19 with caveolin-1 and flotillin-1. FEN also increased the co-immunoprecipitation of SNX19 with caveolin-1 and flotillin-1, effects that were prevented by SCH39166, a D1-like receptor antagonist...Nocodazole, a microtubule depolymerization inhibitor, interfered with the FEN-mediated increase in the colocalization between SNX19 and D1R. SNX19 contains caveolin-1 and flotillin-1 binding motifs, which play an important role in D1R endocytosis and signaling."

Journal • CAV1 • FLOT1 • SNX

Food-effect Study of Ecopipam Pharmacokinetics (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Emalex Biosciences Inc. | Active, not recruiting ➔ Completed

Trial completion

D1 dopamine receptor antagonists as a new therapeutic strategy to treat autistic-like behaviours in lysosomal storage disorders. (PubMed, Mol Psychiatry) - "Neither risperidone nor methylphenidate improves ALBs in the MPS-IIIA mouse model, with the former showing increased cataleptic (extrapyramidal-like) side effects compared to littermate wild-type animals. In contrast, ecopipam, a D1 antagonist already used in the clinic for other neuropsychiatric disorders, rescues ALBs, cognition, D1 hyperactivity, and does not worsen neurodegenerative signs. These results align with recent evidence highlighting the clinical relevance of D1 antagonists for neuropsychiatric disorders and pave the way for their use in managing psychotic symptoms in neurodegenerative disorders such as dementia with Lewy bodies."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Hunter Syndrome • Inflammation • Lewy Body Disease • Lysosomal Storage Diseases • Mental Retardation • Metabolic Disorders • Psychiatry • Rare Diseases • Sleep Disorder • DRD2

Safety and Efficacy of Ecopipam in Patients with Tourette Syndrome: A Systematic Review and Meta-analysis. (PubMed, CNS Drugs) - "Ecopipam is effective in reducing the severity of tics in subjects with TS and has a good safety profile. However, only a limited number of studies were included in the review, with some having small sample sizes and short duration of follow-up."

Journal • Retrospective data • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Movement Disorders • Psychiatry • Tourette Syndrome

Food-effect Study of Ecopipam Pharmacokinetics (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: Emalex Biosciences Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Emerging therapeutic approaches for Tourette syndrome and other tic disorders - a systematic review of current clinical trials. (PubMed, Eur Child Adolesc Psychiatry) - "Potential candidates include the dopamine D1 antagonist ecopipam, the phosphodiesterase inhibitor gemlapodect, and cannabis-based therapies. Despite the range of research activities underway, the overall landscape remains limited. In this report we will discuss the findings, current developments, and relevant aspects concerning future research including clinical, scientific, and patient perspectives."

Journal • Review • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry • Tic Disorders • Tourette Syndrome • Transplantation

D1AMOND: Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (clinicaltrials.gov) - P3 | N=196 | Active, not recruiting | Sponsor: Emalex Biosciences Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Tourette Syndrome

Central administration of galanin-like peptide (GALP) causes short-term orexigenic effects in broilers: Mediatory role of NPY1 and D1 receptors. (PubMed, Neurosci Lett) - "However, the orexigenic effects of GALP were stimulated following the co-administration of SCH39166A + GALP (P < 0.05). These findings indicate that NPY1 and D1 receptors can mediate GALP-induced hyperphagia in broilers."

Journal • GAL

Food-effect Study of Ecopipam Pharmacokinetics (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Emalex Biosciences Inc.

New P1 trial

Dopamine D1-Like Receptor-Mediated Insurmountable Blockade of the Reinforcing Effects of Cocaine in Rats. (PubMed, J Pharmacol Exp Ther) - "Significance Statement Dopamine D1-like (D1R) agonists decrease maximal cocaine self-administration, whereas D2-like (D2R) agonists shift the cocaine self-administration dose-effect function leftward with mechanisms for those different effects unclear. The present study demonstrates blockade by the selective D1R antagonist SCH-39166 of decreases in maximal cocaine self-administration at doses that blocked other D1R-mediated effects but not effects of cocaine, suggesting fundamentally distinct roles of the dopamine D1-like and D2-like receptors in cocaine reinforcement and development of D1R agonists as potential treatments for cocaine-use disorder."

Journal • Preclinical • Psychiatry

An Anchor-Based Method to Establish Clinically Meaningful Changes in YGTSS-TTS Using Data From the Pooled D1AMOND Clinical Studies of Ecopipam, a Selective D1 Receptor Antagonist, in Tourette's Disorder (AACAP 2024) - "We identified a range of values on the YGTSS-TTS indicating meaningful clinical benefit. While analytic methods were not prespecified in the study protocols, the use of CGI-S as an anchor measure provides evidence that a ≥25% improvement on the YGTSS-TTS in children and adolescents with TD is an appropriate threshold for clinically meaningful improvement. Similar analyses underway with other anchor measures will reveal the cutoff for YGTSS-TTS improvement associated with these clinical outcomes.TD, R"

Clinical • Tourette Syndrome

Persistent Tic Disorders: Practical Tips on When, What, and How to Treat (AACAP 2024) - "Although haloperidol, pimozide, and aripiprazole are the only FDA-approved medications labeled for treatment of Tourette's disorder in the United States, these are associated with intolerable adverse effects...Topiramate, clonazepam, deutetrabenazine, or baclofen can be used off-label, and there are compounds under investigation, such as ecopipam. Pragmatic approaches to pharmacotherapy for tic disorders involve disentangling and prioritizing target symptoms. Developing a systematic evaluation and hierarchical method is essential.TICD, PDS, TREAT"

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiovascular • CNS Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Psychiatry • Tic Disorders • Tourette Syndrome

Effect of Ecopipam, a Selective Dopamine-1 Receptor Antagonist, on Tic Characteristics as Assessed by the YGTSS: Results from a Phase IIb Randomized, Double-blind, Placebo-controlled Clinical Trial in Tourette Syndrome (MDS Congress 2024) - "Ecopipam significantly reduced both motor and phonic tics. Of the 5 motor tic characteristics, only complexity was not significantly reduced. Of phonic tic characteristics, only complexity was significantly reduced."

Clinical • P2b data • CNS Disorders • Insomnia • Pain • Sleep Disorder • Tourette Syndrome

Ecopipam does not adversely affect Metabolic Parameters in Pediatric Subjects with Tourette Syndrome: Results from a Phase 2b with 12-month Open Label Extension Study (MDS Congress 2024) - "In both the 12-week P2b study and the 12-month OLE study, ecopipam, a selective D1 receptor antagonist, significantly improved the YGTSS-TTS without adversely affecting weight, BMI, HgbA1c, lipids, or BP. There is no evidence that ecopipam increases the risk of metabolic syndrome."

Clinical • P2b data • CNS Disorders • Insomnia • Pain • Sleep Disorder • Tourette Syndrome

Safety and Tolerability of Ecopipam in Tourette Syndrome (TS) with Psychiatric Comorbidities. (MDS Congress 2024) - "In the phase IIb trial of children with TS, ecopipam significantly reduced the YGTSS-TTS while not affecting measures of common psychiatric comorbidities."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Insomnia • Mood Disorders • Obsessive-Compulsive Disorder • Pain • Psychiatry • Sleep Disorder • Tourette Syndrome

EBS-101-HV-106: Drug Interaction Study (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Emalex Biosciences Inc. | Recruiting ➔ Completed

Trial completion

Pharmacological characterization of sex differences in the effects of dopaminergic drugs on effort-based decision making in rats. (PubMed, Psychopharmacology (Berl)) - "The neural and behavioral effects of TBZ differed across sexes, emphasizing the importance of conducting studies in male and female rats. This research has implications for understanding the effort-related motivational dysfunctions seen in psychopathology."

Journal • Preclinical • CNS Disorders • Fatigue • Mental Retardation • Psychiatry • FOS

Ecopipam Treatment of Tourette's Syndrome in Subjects 7-17 Years (clinicaltrials.gov) - P2 | N=40 | Completed | Sponsor: Emalex Biosciences Inc. | Unknown status ➔ Completed

Trial completion • Tourette Syndrome