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.
Public Health Relevance Statement: PROJECT NARRATIVE There are more than 22 million individuals in the United States with a substance use disorder (SUD). Current pharmacotherapies are inadequate resulting in an unmet need. In this SBIR, Consegna Pharma Inc. plans to develop a novel SUD therapeutic, a long-acting injectable ketamine, that is expected to address these inadequacies and provide better therapeutic outcomes, aid in a more permanent recovery, reduce cravings, improve retention and compliance, and, in addition to treating opioid SUDs, also provide a breakthrough therapy for non-opioid SUDs such as cannabis and stimulants.
Project Terms: After Care; After-Treatment; post treatment; Aftercare; Mental disorders; Mental health disorders; Psychiatric Disease; Psychiatric Disorder; mental illness; psychiatric illness; psychological disorder; Chronic Disease; Chronic Illness; chronic disorder; Clinical Trials; Delayed-Action Preparations; slow release drug; time release medication; Drug abuse; abuse of drugs; abuses drugs; Pharmacotherapy; Drug Therapy; drug treatment; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Investigational Drugs; Investigational New Drugs; Future; Goals; Hospitals; In Vitro; Ketamine; Marketing; Neuronal Plasticity; CNS plasticity; central nervous system plasticity; neural plasticity; neuroplastic; neuroplasticity; Overdose; Legal patent; Patents; Patients; Drug Kinetics; Pharmacokinetics; Plasma; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; Polymers; polymer; polymeric; Sprague-Dawley Rats; Rattus; Common Rat Strains; Rat; Rats Mammals; Recurrence; Recurrent; Relapse; Research; Safety; Sales; medical specialties; Specialty; Post-Traumatic Stress Disorders; PTSD; Post-Traumatic Neuroses; Posttraumatic Neuroses; post-trauma stress disorder; posttrauma stress disorder; traumatic neurosis; Substance Use Disorder; substance use and disorder; Technology; Time; Translating; United States; Measures; Drug Delivery; Drug Delivery Systems; Dissociation; Injectable; Schedule; BDNF; Brain-Derived Neurotrophic Factor; improved; Clinical; Encapsulated; Phase; Medical; co-occurring disorders; dual diagnosis; Link; Individual; Recovery; Withdrawal; Licensing; Opiates; Opioid; non-narcotic analgesic; non-opiate analgesic; non-opioid; non-opioid therapeutics; nonnarcotic analgesics; nonopiate analgesic; nonopioid; nonopioid analgesics; non-opioid analgesic; Therapeutic; Sedation procedure; sedation; Patient Noncompliance; Non-adherent patient; Nonadherent patient; Patient Non Compliance; Patient Non-Adherence; Patient Nonadherence; Knowledge; programs; non-compliance; non-compliant; noncompliance; noncompliant; drug craving; American; particle; Proxy; Toxic effect; Toxicities; novel; payment; drug seeking behavior; Intoxication; Modeling; Sampling; craving; Cannabis; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; pharmaceutical; Pharmacologic Substance; Rotarod Assay; Rotarod Method; Rotarod Test; Rotarod Performance Test; clinical depression; major depression; major depression disorder; Major Depressive Disorder; Patient Compliance; patient adherence; patient cooperation; therapy compliance; therapy cooperation; treatment compliance; compliance behavior; Address; Dose; Drug Addiction; Chemical Dependence; Drug Dependence; Drug Dependency; Adherence; Data; in vivo; Collection; therapy outcome; therapeutic outcome; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; patient oriented outcomes; Pharmacological Treatment; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Therapeutic Effect; Development; developmental; Emergency Care; ED care; ER care; Emergency Department care; Emergency Room care; Emergency health care; Emergency healthcare; Emergency medical care; cost; designing; design; Outcome; Prevalence; innovate; innovative; innovation; Abstinence; addictive disorder; addiction; commercialization; commercial scale manufacturing; manufacturing ramp-up; scale up batch; scale up production; upscale manufacturing; manufacturing scale-up; cannabis use disorder; marijuana use and disorder; marijuana use disorder; behavior study; behavioral study; Formulation; improved outcome; medication misuse; drug misuse; Injections; synthetic opiate; synthetic opioid; side effect; substance use treatment; therapeutically effective; validate efficacy; efficacy validation; Stimulant; abuse liability; abuse potential; pre-Investigational New Drug meeting; Pre IND FDA meeting; Pre-IND mtg; pre-IND consultation; pre-IND discussion; pre-IND meeting; manufacture
