Long-acting injectable ketamine for improved substance use disorder (SUD) treatment without dissociative effects.

长效注射氯胺酮，用于改善物质使用障碍 (SUD) 治疗，且不会产生解离效应。

• 批准号: 10744308
• 负责人: Lawrence J Zana
• 金额: $ 32.65万
• 依托单位: CONSEGNA PHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2024-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10744308
• 关键词: Abstinence; Address; Adherence; Aftercare; American; Brain-Derived Neurotrophic Factor; Cannabis; Chronic Disease; Clinical; Clinical Trials; Collection; Data; Delayed-Action Preparations; Development; Dissociation; Dose; Drug Addiction; Drug Delivery Systems; Drug Kinetics; Drug abuse; Emergency Care; Encapsulated; Formulation; Future; Goals; Hospitals; In Vitro; Individual; Injectable; Injections; Intoxication; Investigational Drugs; Ketamine; Knowledge; Legal patent; Licensing; Link; Major Depressive Disorder; Marketing; Measures; Medical; Mental disorders; Modeling; Neuronal Plasticity; Opioid; Outcome; Overdose; Patient Noncompliance; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacological Treatment; Pharmacotherapy; Phase; Plasma; Polymers; Post-Traumatic Stress Disorders; Prevalence; Proxy; Rattus; Recovery; Recurrence; Relapse; Research; Rotarod Performance Test; Safety; Sales; Sampling; Schedule; Sedation procedure; Small Business Innovation Research Grant; Sprague-Dawley Rats; Stimulant; Substance Use Disorder; Technology; Therapeutic; Therapeutic Effect; Time; Toxic effect; Translating; United States; Withdrawal; abuse liability; addiction; behavioral study; commercialization; compliance behavior; cost; craving; design; drug craving; drug misuse; drug seeking behavior; dual diagnosis; efficacy validation; improved; improved outcome; in vivo; innovation; manufacture; manufacturing scale-up; marijuana use disorder; medical specialties; non-compliance; non-opioid analgesic; novel; particle; payment; pre-Investigational New Drug meeting; programs; side effect; substance use treatment; synthetic opioid; therapeutically effective; therapy outcome

PROJECT SUMMARY / ABSTRACT There are more than 22 million individuals in the United States with a substance use disorder (SUD). SUDs are a collection of chronic disorders often characterized by drug-seeking behavior manifesting as a cycle of substance intoxication and binging, followed by withdrawal, and craving states that contribute to compulsive relapses, often driven by non-compliance with treatment medications. Despite decades of research into SUD causes and treatment, more than 108,000 Americans died from drug overdoses in 2021, most involving opioids. Existing pharmacological SUD treatments merely act as a substitute for the misused drug or temporarily improve abstinence but do not reduce the cravings associated with SUD. Despite the overwhelming addiction crisis, few therapies exist, and those that are available have low efficacy. Novel pharmacological treatments are urgently needed. Recent research has suggested that psychoplastogenic compounds (PCs) can reduce drug dependence. This drug abuse cessation is linked to the induction of neuritogenesis and increased neuroplasticity, a hallmark of PCs. As a PC, ketamine promises to be a better SUD pharmacotherapy that can reduce cravings, promote permanent recovery, and treat non-opioid SUDs; however, currently available formulations have several adverse side effects including sedation, dissociative effects, and abuse liability. CP110 encapsulates ketamine in polymer microparticles that slowly release the drug over time as the polymer degrades. This slow release at low levels over time will reduce side effects. The monthly administration will reduce non-adherence and improve retention and provide better patient outcomes. The long-term goal is to develop a new SUD pharmacotherapeutic that will improve abstinence, treat non-compliant patients, reduce cravings, and effectively treat those SUDs that have no effective pharmacological treatments. Our hypothesis is that delivering ketamine at a low level over time will offer a better safety profile than currently available ketamine formulations while improving adherence. Releasing ketamine at low levels will also lengthen the time of neuroplasticity enhancement that is believed to provide more permanent recovery. The Specific Aims are as follows: 1) Validate ketamine release over 28-days in rats, and 2) Validate efficacy of CP110 and demonstrate reduced dissociation in rats. The objective of this project is to continue development of CP110, a novel, long- acting injectable (LAI) ketamine formulation that maintains therapeutic levels for 28-days by validating in vivo pharmacokinetics and demonstrating reduced dissociation. In Phase II, we will conduct an investigational new drug (IND) enabling studies required for an FDA application. Hence, the studies proposed here are important precedents to support a future clinical program for CP110. Market approval for CP110 could address the $2.7 billion global SUD market and fulfill the unmet medical need of an improved SUD therapeutic to provide better therapeutic outcomes for patients.

项目摘要/摘要