Delving into the Latest Updates on TKP-1002 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

antipsychotics(EUSA Pharma), antipsychotics(Talisker Pharma), antipsychotics(University of Liege)

+ [1]

Target

D4 receptor

Mechanism

D4 receptor antagonists(Dopamine D4 receptor antagonists)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Schizophrenia

Originator Organization

University of Liege

Active Organization-

Inactive Organization

Jazz Pharmaceuticals (EUSA Pharma USA), Inc.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

The dorsolateral prefrontal cortex (DLPFC) - cerebellum circuit has been implicated in the pathogenesis of negative symptoms of schizophrenia (SZ). Both areas are considered separate targets for repetitive transcranial magnetic stimulation (rTMS) treatment, showing potential for improving negative symptoms. However, there is still a lack of research that targets both DLPFC and cerebellum simultaneously. In this study, we will explore the efficacy and safety of dual-target rTMS based on the DLPFC-cerebellum circuit in the treatment of negative symptoms in SZ.

Methods:

The study is a multicenter randomized, double-blind, and sham-controlled trial. First-episode schizophrenia is treated with adjunctive 1 Hz rTMS to the right DLPFC and intermittent theta burst stimulation (iTBS) to the cerebellum delivered sequentially in 20 sessions (active group) or a sham condition (sham group) along with antipsychotics. Clinical symptoms are assessed using the Positive and Negative Symptom Scale (PANSS) at baseline (T0), at the middle of the TMS intervention (after 10 sessions, T1), at the end of the intervention (after 20 sessions, T2), and at a 4-week follow-up after the intervention concludes (T3). Subjects will undergo magnetic resonance imaging (MRI) scans twice: once at baseline (T0) and again at the end of TMS intervention (T2). Comparisons of improvements in negative symptoms are conducted between the active and sham groups. Alterations in functional connectivity (FC) are also compared between both groups. Pearson or Spearman correlation analysis is performed to estimate the relationship between FC alteration and clinical symptom remission (PANSS negative subscale reduction scores and response rates, etc) depending on whether the data follows a normal distribution. In addition, potential neuroimaging biomarkers based on MRI associated with TMS treatment will be explored.

Discussion:

Positive results from this double-blind, sham-controlled, randomized study may optimize the TMS treatment strategy for SZ, particularly in managing negative symptoms. Clinicians can select TMS with increased confidence as a safe adjunctive treatment option. Furthermore, the findings of this trial may offer preliminary insights into the potential neuroimaging therapeutic mechanisms of TMS interventions targeting the prefrontal-cerebellar circuit.Trial registration: ClinicalTrials.govNCT04853485Primary sponsor: Jijun WANG (J. Wang), Principal Investigator: jijunwang27@163.com.

01 Mar 2025·NEUROPHARMACOLOGY

Efficacy and safety of evenamide, a glutamate modulator, added to a second-generation antipsychotic in inadequately/poorly responding patients with chronic schizophrenia: Results from a randomized, double-blind, placebo-controlled, phase 3, international clinical trial

Article

Author: Hartman, Richard ; Roy, Arjun ; Sansi, Francesca ; Turolla, Alessio ; Chinellato, Giovanni ; Anand, Ravi

BACKGROUND:

Evenamide, a glutamate modulator, is currently in phase 3 of development as add-on treatment to antipsychotics in patients with inadequate response or treatment-resistant schizophrenia. This study was designed to determine if patients with chronic schizophrenia inadequately responding to a second-generation antipsychotic would benefit from add-on treatment with evenamide at a dose of 30 mg bid.

METHODS:

Study 008A was a prospective, 4-week, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of oral doses of evenamide of 30 mg bid in patients with chronic schizophrenia treated at stable therapeutic doses of a second-generation antipsychotic. Outpatients aged ≥18 years, both males and females, with a diagnosis of schizophrenia (DSM-V), who had been receiving antipsychotics for at least 2 years at stable doses, but still symptomatic (PANSS 70-85, CGI-S 4-6, predominant positive symptoms), were eligible for the study. Patients were randomised equally to evenamide 30 mg or placebo, given bid, after completing a 21-day screening period. The primary outcome (change from baseline in PANSS total score) was assessed weekly, with the primary endpoint at 4 weeks.

RESULTS:

A total of 291 patients were enrolled, of which 11 (3·8%) discontinued prematurely, overall. Add-on treatment with evenamide was associated to a statistically significant (the absolute difference of the two treatment groups for the PANSS Total at Day 29, primary efficacy endpoint, was = 2·5 [p-value<0.05] that is associated with a Cohen's d effect size = 0·33) and clinically meaningful benefit compared to placebo across all efficacy measures, and was well tolerated.

CONCLUSION:

The demonstration of statistically significant and clinically meaningful benefit of evenamide, a glutamate modulator, as add-on treatment in patients with chronic schizophrenia inadequately responding to their second-generation antipsychotic may represent a new treatment paradigm for this population.

01 Feb 2025·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Direct effects of antipsychotics on potassium channels

Review

Author: Park, Won Sun ; Mun, Seo-Yeong ; Zhuang, Wenwen

Schizophrenia (SCZ) and bipolar disorder (BD) and are severe psychiatric conditions that contribute to disability and increased healthcare costs globally. Although first-, second-, and third-generation antipsychotics are available for treating BD and SCZ, most have various side effects unrelated to their unique functions. Many antipsychotics affect K⁺ channels (Kv, K_Ca, Kir, K_2P, and other channels), which change the functions of various organs. This review summarizes the biological actions of antipsychotics, including off-target side effects involving K⁺ channels.

100 Deals associated with TKP-1002

Login to view more data