ketamine prolonged release formulation / Ketabon - LARVOL DELTA

Sleep quality and daytime sleepiness/sedation during treatment with oral prolonged-release KET01 ketamine: combined Results of the KET01-02 and KET01-03 trials (ECNP 2024) - "Background: Sub-anesthetic doses of ketamine and esketamine exert rapid antidepressant effects. A single 240 mg KET01 dose exerts no acute negative effects on alertness and daytime sleepiness while repeated KET01 administration is not associated with a negative effect on sleep quality after 3 weeks. KET01 at an antidepressant dose appears better tolerated than intranasal esketamine in terms of daytime sleepiness/drowsiness. Obtained data support the use of KET01 as an oral antidepressant devoid of negative effects on sleep quality, daytime sleepiness and drowsiness."

CNS Disorders • Depression • Psychiatry • Sleep Disorder

Acute tolerability of antidepressant dose of oral prolonged-release ketamine (KET01) in patients with treatment-resistant depression and healthy volunteers (ECNP 2024) - "Background: Ketamine and esketamine exert rapid antidepressant effects. At antidepressant doses, KET01 (240 mg) exerts no dissociation or negative effects on hemodynamic parameters and appears to be better tolerated than intranasal esketamine (84 mg). The lower peak concentration of the parent compound after KET01 than after esketamine may explain the lack of dissociative and hemodynamic effects which are presumed to be mediated via NMDA-receptor antagonism. The high peak concentrations of the metabolites norketamine and hydroxynorketamine (which have antidepressant properties in animal models) may explain why KET01 can exert antidepressant effects without causing dissociation."

Clinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

Comparison of Tolerability, Safety, and Pharmacokinetics of Antidepressant Doses of Oral Ketamine Prolonged Release Tablets (KET01) and Intranasal Esketamine: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Trial (ASCP 2024) - "An antidepressant dose of intranasal esketamine was associated with a high rate of dissociation and effects on heart rate and blood pressure, while an antidepressant dose of KET01 had a low incidence of such findings. Our results challenge the notion that NMDAR inhibition is necessary for the antidepressant efficacy of ketamine. The advantageous tolerability profile of KET01 suggests that prolonged-release oral ketamine has the potential to be developed for use without medical supervision."

Clinical • PK/PD data • CNS Disorders

Oral Prolonged-Release Adjunctive Ketamine (KET01): Phase 2 Trial in Treatment-Resistant Depression and Phase 1 Trial Comparing Tolerability with Intranasal Esketamine (ASCP 2024) - "The program demonstrates rapid and clinically relevant reduction of depressive symptoms in patients with TRD after treatment with 240 mg/day KET01 with only minimal signs of dissociative symptoms, suggesting a low degree of NMDAR inhibition. The findings challenge the view that NMDAR inhibition is necessary for antidepressant efficacy of ketamine-based medications. The low level of dissociative symptoms during treatment with KET01 is advantageous compared to other currently used ketamine-based depression treatments."

P1 data • P2 data • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Randomized Placebo-Controlled Double-Blind Phase 2 Trial of Adjunctive KET01 (Oral Prolonged-Release Ketamine) for Treatment-Resistant Depression (ASCP 2024) - "This study demonstrated a rapid and clinically relevant reduction of depressive symptoms after treatment with 240 mg/day KET01 with only minimal signs of dissociative and cardiovascular symptoms, suggesting a low degree of NMDAR inhibition. This is in line with challenges to the view that NMDAR inhibition should be necessary for antidepressant efficacy of ketamine-based medications (2). Learning Objectives To learn how oral prolonged-release ketamine can provide rapid and sustained improvement in TRD."

Clinical • P2 data • CNS Disorders • Depression • Mood Disorders • Psychiatry

Rapid reduction of depressive symptoms with minimal dissociation: results from the KET01-02 and KET01-03 trials with oral prolonged-release (PR) ketamine KET01 (EPA 2024) - "Oral 240 mg/day KET01 induces a rapid, and clinically relevant reduction of depressive symptoms with only minimal signs of dissociation, potentially due to lower ketamine levels and increased norketamine and hydroxynorketamine levels compared to intravenous administration. Our results suggest that KET01 may be an efficacious and safe take-at-home adjunct treatment for TRD."

CNS Disorders • Depression • Psychiatry

HMNC Brain Health and Develco Pharma Partner to Initiate Ketamine Study Targeting Treatment-Resistant Depression (TRD) (GlobeNewswire) - "HMNC Brain Health...will advance the development of an investigational oral prolonged- release formulation of ketamine targeting treatment-resistant depression (TRD) with a clinical phase-II-study that will commence in Q4 2021. HMNC and Swiss-based Develco Pharma have created a joint venture and formed the company Ketabon, which will initiate a Contract Research Organization (CRO)-led proof-of-concept study. The study will be managed by SCOPE, an internationally renowned CRO headquartered in Germany....Data from the Ketabon project trial is likely to be reported in Q1 2023. An investigator-initiated phase II proof-of-concept ketamine study is ongoing at the renowned Psychiatric University Clinic Zurich and should lead to first data as early as Q1, 2022."

New P2 trial • P2 data • Trial status • CNS Disorders • Depression