Completion of IND-package for a novel, non-narcotic painkiller

完成新型非麻醉止痛药的 IND 包装

• 批准号: 9889914
• 负责人: Ajay S Yekkirala
• 金额: $ 177.66万
• 依托单位: BLUE THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9889914
• 关键词: Absence of pain sensation; Adverse effects; Agonist; Analgesics; Animals; Award; Back; Canis familiaris; Cardiotoxicity; Caring; Categories; Cessation of life; Characteristics; Chemistry; Clinical; Clinical Trials; Constipation; Consult; Coupled; Cyclic GMP; Dependence; Development; Dose; Dose-Limiting; Drug Kinetics; Exhibits; Formulation; Frequencies; Funding; Future; Genetic; Goals; Health; Human; Hydrocodone; In Vitro; Industrialization; Intravenous; Kilogram; Lead; Ligands; Lung; Metabolic; Morphine; Mus; Narcotics; No-Observed-Adverse-Effect Level; Opioid; Opioid Analgesics; Opioid Receptor; Opioid agonist; Oral; Organ; Outcome; Oxycodone; Pain; Pain management; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Pharmacology Study; Phase; Phase I Clinical Trials; Physical Dependence; Postoperative Pain; Pre-Clinical Model; Preparation; Privatization; Process; Property; Rattus; Rodent; Safety; Small Business Innovation Research Grant; Testing; Therapeutic; Toxic effect; Toxicology; Treatment Efficacy; United States; Ventilatory Depression; Work; chronic pain; clinical pain; commercialization; drug seeking behavior; effective therapy; first-in-human; in vivo; lead candidate; manufacturing process; metabolic profile; novel; opioid abuse; opioid overdose; pain model; preclinical development; prescription opioid; prescription opioid abuse; programs; scale up; side effect; small molecule

Project Summary Opioids like morphine and hydrocodone are generally the most effective therapeutics for treatment of moderate to severe pain. However, their use is limited by serious side effects - tolerance, constipation, respiratory depression, physical dependence and high addictive potential. The frequency of clinical pain, coupled with a lack of alternative therapeutic options has led to a national health crisis centered on prescription opioid abuse. Alternative pain relievers with the analgesic potency of conventional opioids, but devoid of narcotic side effects are an immediate need. The goal of this project is to develop and commercialize an alternative to conventional opioid analgesics with reduced side effects and without the addictive properties common to mu-opioid agonists. Our lead molecule, Blue181 is a highly selective agonist for a novel CNS target that is a potent analgesic without apparent addictive potential, tolerance, or physical dependence. We started the pre-clinical development of Blue181 using a combination of federal and private funds to scale up and develop an industrial synthetic process for generating large amounts of Blue181 and shown that Blue181 does not produce respiratory depression, reduction of GI transit, inhibition of hERG in the therapeutic range, or genetic toxicity. We also have a preliminary understanding of the pharmacokinetic profile of Blue181. We will now finish all the remaining IND-enabling studies targeting an initial indication of IV postoperative pain for Blue181. We will continue our efforts on developing an FDA-compliant process for preparation of Blue181 in the kilogram scale that would be amenable for later cGMP synthesis and prepare a CMC package for IND filing. We will also perform studies to further delineate the PK and metabolic profile of Blue181 and determine the no- observable-adverse-effects-level (NOAEL) in the toxicity species. Finally, we will finish safety pharmacology studies (pulmonary toxicity and cardiotoxicity) and GLP toxicity in two species. At the end of the project period, Blue181 will be an IND-ready asset and can be advanced into Phase 1 human trials.

项目总结