A Topical Non Steroidal Anti-inflammatory for Rosacea

治疗红斑痤疮的外用非类固醇抗炎药

• 批准号: 8196282
• 负责人: Braham Shroot
• 金额: $ 100.7万
• 依托单位: SIGNUM BIOSCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196282
• 关键词: American; Anti-Inflammatory Agents; Anti-inflammatory; Award; Cardiotoxicity; Cavia; Cells; Chronic; Clinical; Clinical Research; Clinical Trials; Conduct Clinical Trials; Cream; Cysteine; Cytochrome P450; Dermal; Development; Disease; Drug Formulations; Drug Kinetics; Edema; Ensure; Erythema; Etiology; Event; Face; Flushing; Glucocorticoids; Goals; Hepatic; Homeostasis; IL8 gene; In Vitro; Inflammation; Inflammatory; Interleukin-17; Interleukin-4; Interleukin-6; Investigational Drugs; Lead; Left; Lesion; Life; Lotion; Metronidazole; Miniature Swine; Modeling; Neutrophil Infiltration; Nodule; Non-Rodent Model; Oryctolagus cuniculus; Pathology; Patients; Penetration; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Phase III Clinical Trials; Pregnancy; Procedures; Production; Program Development; Qualifying; Rattus; Redness; Reproduction; Risk; Rosacea; Safety; Site; Skin; Small Business Innovation Research Grant; TNF gene; Telangiectasis; Therapeutic; Therapeutic Agents; Time; Topical application; Toxic effect; Toxicokinetics; Toxicology; Work; analog; analytical method; azelaic acid; clinical application; cytokine; drug candidate; improved; in vivo Model; irritation; manufacturing process; method development; mouse model; novel; patient population; pre-clinical; preclinical efficacy; preclinical safety; reproductive; safety study; skin disorder

DESCRIPTION (provided by applicant): Rosacea is a chronic dermatological condition characterized by flushing, erythema, papules, pustules, inflammatory nodules and telangiectasia. Although disease etiology remains unclear, skin inflammation has been identified as the main contributor to disease pathology. Isoprenylcysteine (IPC) analogs represent a novel class of topical anti-inflammatory compounds being developed as therapeutic agents for rosacea. As part of the Phase II SBIR project, Signum identified a lead investigational new drug (IND)-candidate, SIG990 which demonstrated strong efficacy in in vitro and in vivo models. Through pharmacokinetic and safety pharmacology studies, the preclinical safety profile for SIG990 was established. In the renewal application, we propose to continue SIG990's development path towards clinical application and FDA approval by conducting further safety assessment of drug product toxicity. Upon completion of the proposed aims, Signum will enter SIG990 into the Phase III clinical trials. PUBLIC HEALTH RELEVANCE: Rosacea is a common, chronic skin disorder afflicting people all around the world, including ~16 million Americans. Currently available treatments have yielded mixed results, often leaving patients with significant levels of facial redness and inflammatory lesions. Successful pharmaceutical development of topical IPC analog anti-inflammatories will provide an important additional, and potentially better, therapeutic option for people suffering from rosacea associated redness.

描述（由申请人提供）：酒渣鼻是一种慢性皮肤病学，其特征是潮红，红斑，丘疹，脓疱，炎症结节和telangiectia。尽管疾病的病因尚不清楚，但皮肤炎症已被确定为疾病病理学的主要因素。亚肾上腺素半胱氨酸（IPC）类似物代表了一种新型的局部抗炎化合物，作为酒渣鼻的治疗剂。作为II期SBIR项目的一部分，Signum确定了一种铅研究新药（IND） - 候选剂Sig990，该药物在体外和体内模型中表现出强大的功效。通过药代动力学和安全药理学研究，建立了SIG990的临床前安全性。在续签应用中，我们建议通过对药物毒性进行进一步的安全评估来继续Sig990的临床应用和FDA批准的发展路径。拟议的目标完成后，Signum将进入III期临床试验中的SIG990。 公共卫生相关性：酒渣鼻是一种常见的，慢性皮肤疾病，困扰着世界各地的人们，包括约1600万美国人。目前可用的治疗方法产生了不同的结果，通常会使患者的面部发红和炎症性病变水平很高。局部IPC模拟抗炎药的成功药物开发将为患有酒渣鼻相关的发红的人提供重要的，潜在的更好的治疗选择。