deudextromethorphan/quinidine ultra-low dose (AVP-786) / Otsuka, Sun Pharma - LARVOL DELTA

Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=241 | Terminated | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Nov 2026 ➔ Jun 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2026 ➔ Jun 2024; The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.

Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders • Dementia

Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=1197 | Terminated | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Jan 2025 ➔ Sep 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2025 ➔ Sep 2024; The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.

Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=184 | Terminated | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Mar 2026 ➔ Jun 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Jun 2024; The AVP-786 program was discontinued, the recruitment was stopped and all participants are no longer being examined or receiving intervention.

Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders • Dementia

Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=1197 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia

Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=241 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting | N=750 ➔ 241

Enrollment change • Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=183 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting | N=750 ➔ 183

Enrollment change • Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia

Otsuka to Terminate Development of AVP-786 (Businesswire) - "Otsuka Pharmaceutical Co., Ltd...announce termination of development of the novel compound AVP-786, which was in development as a potential treatment for patients with agitation associated with dementia due to Alzheimer's disease...After a detailed analysis of results from the completed trial, Otsuka and OPDC have decided to terminate the development of this drug candidate."

Discontinued • Alzheimer's Disease • CNS Disorders • Dementia

Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Jul 2025 ➔ Jan 2025 | Trial primary completion date: Jul 2025 ➔ Jan 2025

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=601 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Dementia

Otsuka Announces Phase 3 Topline Results of AVP-786 in the Treatment of Agitation Associated With Dementia Due to Alzheimer’s Disease (Businesswire) - P3 | N=601 | NCT03393520 | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | "...Otsuka Pharmaceutical...announce topline results of the phase 3 clinical trial of AVP-786 in the treatment of agitation associated with dementia due to Alzheimer’s disease...A statistically significant difference was not achieved on the primary efficacy endpoint, mean change from baseline to week 12 in the Cohen-Mansfield Agitation Inventory (CMAI) total score between AVP-786 and placebo. There was one treatment-emergent adverse event, a fall, that appeared with an incidence rate of more than 5% in patients treated with AVP-786 and greater than placebo; 16 (8.6%) in AVP-786 high dose, 18 (9.1%) in AVP-786 low dose and 6 (2.8%) placebo....Otsuka intends to submit the trial results for scientific publication at a later date."

P3 data: top line • Alzheimer's Disease

Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=750 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Dec 2024 ➔ Nov 2026 | Trial primary completion date: Dec 2024 ➔ Aug 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=750 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Dec 2024 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=601 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2024 ➔ Dec 2023

Enrollment closed • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Negative Symptoms of Schizophrenia (clinicaltrials.gov) - P2/3 | N=136 | Terminated | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | N=370 ➔ 136 | Trial completion date: Nov 2024 ➔ May 2023 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2024 ➔ May 2023; Based on the Interim Analysis outcome and recommendation by the DMC, Otsuka approved termination of the study based on futility.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Psychiatry • Schizophrenia

Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial primary completion date: Oct 2023 ➔ Jul 2025

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Oct 2023 ➔ Jul 2025

Trial completion date • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Apr 2023 ➔ Apr 2024 | Trial primary completion date: Mar 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Aug 2023 ➔ Apr 2023 | Trial primary completion date: Jul 2023 ➔ Mar 2023

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Promising candidates from drug clinical trials: Implications for clinical treatment of Alzheimer's disease in China. (PubMed, Front Neurol) - "The research and development pipeline now focuses on disease-modifying therapies such as gantenerumab, aducanumab, ALZ-801, ALZT-OP1, donanemab, lecanemab, simufilam, NE3107, semaglutide, and GV-971, which could put an end to the situation where Alzheimer's patients in China have no effective treatment alternatives. The reuse of drugs or combinations currently under investigation for the psychiatric treatment of Alzheimer's disease, including AXS-05, AVP-786, nabilone, brexpiprazole, methylphenidate, and pimavanserin, could provide physicians with additional treatment options. Although most of these drugs have not been explored in China yet, due to the current development trend in this field in China, it is expected that China will be involved in research on these drugs in the future."

Journal • Review • Alzheimer's Disease • CNS Disorders • Psychiatry

Clinical Application and Synthesis Methods of Deuterated Drugs. (PubMed, Curr Med Chem) - "In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide...In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase Ⅲ clinical studies, and some solid deuterium compounds have entered phase I and Ⅱclinical trials...In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs."

Journal • Huntington's Disease • Movement Disorders

Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Neurobehavioral Disinhibition Including Aggression, Agitation, and Irritability in Patients With Traumatic Brain Injury (clinicaltrials.gov) - P2 | N=168 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Mental Retardation • Vascular Neurology

Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents. (PubMed, Front Pharmacol) - "Esketamine for treatment-resistant major depression and brexanolone for post-partum depression are two exceptions from the monoaminergic model, although their use is still limited by high costs, unique way of administration (only intravenously for brexanolone), physicians' reluctance to prescribe new drugs, and patients' reticence to use them. Glutamatergic neurotransmission is explored based on the positive results obtained by intranasal esketamine, with subanesthetic intravenous doses of ketamine, and D-cycloserine, traxoprodil, MK-0657, AXS-05, AVP-786, combinations of cycloserine and lurasidone, or dextromethorphan and quinidine, explored as therapeutic options for mono- or bipolar depression. Sestrin modulators, cholinergic receptor modulators, or onabotulinumtoxinA have also been investigated for potential antidepressant activity. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost 7 decades of..."

Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

Assessment of the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Agitation in Patients With Dementia of the Alzheimer's Type (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Jul 2022 ➔ Aug 2023 | Trial primary completion date: Jul 2022 ➔ Jul 2023

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Negative Symptoms of Schizophrenia (clinicaltrials.gov) - P2/3 | N=370 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Aug 2022 ➔ Nov 2024 | Trial primary completion date: Jul 2022 ➔ Oct 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Concert Pharmaceuticals Reports 2021 Financial Results and Provides Company Update (Businesswire) - “Partnered Program: AVP-786 for Neurological Disorders: AVP-786 Late-Stage Trials to Complete in Third Quarter of 2022: AVP-786 Phase 3 trial in Alzheimer’s Agitation is projected to complete in July 2022; AVP-786 Phase 2/3 trial in Negative Symptoms of Schizophrenia is projected to complete in August 2022.”

Trial completion date • Alzheimer's Disease • CNS Disorders • Schizophrenia