Ruoff Chad, Swick Todd J, Doekel Robert, Emsellem Helene A, Feldman Neil T, Rosenberg Russell, Bream Gary, Khayrallah Moise A, Lu Yuan, Black Jed
Stanford University Sleep Medicine Center, Redwood City, CA.
Neurology and Sleep Medicine Consultants of Houston, University of Texas-Houston School of Medicine, Houston, TX.
Sleep. 2016 Jul 1;39(7):1379-87. doi: 10.5665/sleep.5968.
To evaluate the efficacy and safety of oral JZP-110, a second-generation wake-promoting agent with dopaminergic and noradrenergic activity, for treatment of impaired wakefulness and excessive sleepiness in adults with narcolepsy.
This was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 28 centers in the United States. Patients were adults with narcolepsy who had baseline scores ≥ 10 on the Epworth Sleepiness Scale (ESS) and baseline sleep latency ≤ 10 min on the Maintenance of Wakefulness Test (MWT). Patients received a daily placebo (n = 49) or JZP-110 (n = 44) 150 mg/day weeks 1-4 and 300 mg/day weeks 5-12. Primary efficacy endpoints were change from baseline in average MWT sleep latency, and the Clinical Global Impression-Change (CGI-C); secondary endpoints were change from baseline in ESS score and Patient Global Impression-Change.
Improvements were significantly greater with JZP-110 versus placebo on mean MWT sleep latency (4 w, 9.5 versus 1.4 min, P < 0.0001; 12 w, 12.8 versus 2.1 min, P < 0.0001), percentage of patients with CGI-C improvement (4 w, 80% versus 51%, P = 0.0066; 12 w, 86% versus 38%, P < 0.0001), and mean change in ESS (4 w, -5.6 versus -2.4, P = 0.0038; 12 w, -8.5 versus -2.5, P < 0.0001). Three JZP-110-treated patients (6.8%) discontinued due to adverse events (AEs). The most common AEs with JZP-110 versus placebo were insomnia (23% versus 8%), headache (16% versus 10%), nausea (14% versus 6%), diarrhea (11% versus 6%), decreased appetite (14% versus 0%), and anxiety (11% versus 0%).
At doses of 150-300 mg/day, JZP-110 was well tolerated and significantly improved the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy.
Clinicaltrials.gov identifier NCT01681121.
评估口服JZP - 110（一种具有多巴胺能和去甲肾上腺素能活性的第二代促醒药物）治疗发作性睡病成年患者觉醒障碍和过度嗜睡的疗效与安全性。
这是一项2b期、随机、双盲、安慰剂对照、平行组试验，在美国28个中心进行。患者为发作性睡病成年患者，在爱泼华嗜睡量表（ESS）上基线评分≥10分，在清醒维持试验（MWT）中基线睡眠潜伏期≤10分钟。患者在第1 - 4周每日接受安慰剂（n = 49）或JZP - 110（n = 44）150毫克，在第5 - 12周每日接受300毫克。主要疗效终点为MWT平均睡眠潜伏期相对于基线的变化以及临床总体印象变化（CGI - C）；次要终点为ESS评分相对于基线的变化以及患者总体印象变化。
与安慰剂相比，JZP - 110在MWT平均睡眠潜伏期方面改善显著更大（4周时，9.5分钟对1.4分钟，P < 0.0001；12周时，12.8分钟对2.1分钟，P < 0.0001），CGI - C改善的患者百分比更高（4周时，80%对51%，P = 0.0066；12周时，86%对38%，P < 0.0001），以及ESS的平均变化更大（4周时，-5.6对-2.4，P = 0.0038；12周时，-8.5对-2.5，P < 0.0001）。3名接受JZP - 110治疗的患者（6.8%）因不良事件停药。与安慰剂相比，JZP - 110最常见的不良事件为失眠（23%对8%）、头痛（16%对10%）、恶心（14%对6%）、腹泻（11%对6%）、食欲减退（14%对0%）和焦虑（11%对0%）。
在每日150 - 300毫克的剂量下，JZP - 110耐受性良好，显著改善了发作性睡病成年患者的保持清醒能力和过度嗜睡的主观症状。
Clinicaltrials.gov标识符NCT01681121。
