Gelotte Cathy K, Vakil Amy M, Zimmerman Brenda A, Zannikos Peter, Mishra Rajesh, Eichenbaum Gary, Kuffner Edwin K, Flores Christopher M
Johnson & Johnson Consumer, Inc., Fort Washington, PA, USA.
Johnson & Johnson, Inc., New Brunswick, NJ, USA.
Regul Toxicol Pharmacol. 2023 Aug 23:105480. doi: 10.1016/j.yrtph.2023.105480.
JNJ-10450232 (NTM-006) is a non-opioid, non-NSAID analgesic and antipyretic compound with structural similarity to acetaminophen. Preclinical models show comparable analgesia relative to acetaminophen and no evidence of hepatotoxicity associated with overdose. Moreover, it was safe and generally well tolerated in a First-in-Human Study. This single-dose, single-center, inpatient, randomized, double-blind study in moderate-to-severe acute pain following third molar extraction compared efficacy and safety of 250 mg and 1000 mg JNJ-10450232 (NTM-006), 1000 mg acetaminophen, and placebo during the 24 h following administration. While onset of action of 1000 mg JNJ-10450232 (NTM-006) was relatively slower compared with acetaminophen, its duration of action was sustained up to 24 h being superior beginning 7 h after administration. No clinically important differences among treatment groups in nature or severity of adverse events were observed and no serious adverse events were reported. Increased bilirubin, potentially due to UGT1A1 inhibition and ingestion of blood from oral surgery, was the most commonly reported adverse event and the only event reported by ≥ 5% of subjects across treatment groups. These data support further evaluation of JNJ-10450232 (NTM-006) for the treatment of moderate-to-severe pain. CLINICALTRIALS.GOV ID: NCT02209181.
JNJ-10450232(NTM-006)是一种非阿片类、非甾体抗炎药的镇痛和解热化合物,其结构与对乙酰氨基酚相似。临床前模型显示,其镇痛效果与对乙酰氨基酚相当,且无过量用药导致肝毒性的证据。此外,在一项首次人体研究中,它安全且耐受性良好。这项单剂量、单中心、住院、随机、双盲研究,比较了250毫克和1000毫克JNJ-10450232(NTM-006)、1000毫克对乙酰氨基酚和安慰剂在拔除第三磨牙后中度至重度急性疼痛患者给药后24小时内的疗效和安全性。虽然1000毫克JNJ-10450232(NTM-006)的起效相对比对乙酰氨基酚慢,但其作用持续时间长达24小时,从给药后7小时开始效果更佳。各治疗组在不良事件的性质或严重程度上未观察到临床重要差异,也未报告严重不良事件。胆红素升高可能是由于UGT1A1抑制和口腔手术中摄入血液所致,是最常报告的不良事件,也是各治疗组中≥5%受试者报告的唯一事件。这些数据支持对JNJ-10450232(NTM-006)治疗中度至重度疼痛进行进一步评估。临床试验注册号:NCT02209181。