DeMicco Michael, Barrow Laura, Hickey Bernadette, Shailubhai Kunwar, Griffin Patrick
Anaheim Clinical Trials, Anaheim, CA, USA.
Synergy Pharmaceuticals Inc., New York, NY, USA.
Therap Adv Gastroenterol. 2017 Nov;10(11):837-851. doi: 10.1177/1756283X17734697. Epub 2017 Oct 25.
Plecanatide, with the exception of a single amino acid replacement, is identical to human uroguanylin and is approved in the United States for adults with chronic idiopathic constipation (CIC). This double-blind, placebo-controlled, phase III study evaluated the efficacy and safety of plecanatide placebo in CIC.
Adults meeting modified Rome III CIC criteria were randomized to plecanatide 3 mg ( = 443), 6 mg ( = 449), or placebo ( = 445). Patients recorded bowel movement (BM) characteristics [including spontaneous BMs (SBMs) and complete SBMs (CSBMs)] and rated CIC symptoms in daily electronic diaries. The primary endpoint was the percentage of durable overall CSBM responders (weekly responders for ⩾9 of 12 treatment weeks, including ⩾3 of the last 4 weeks). Weekly responders had ⩾3 CSBMs/week and an increase of ⩾1 CSBM from baseline for the same week.
A significantly greater percentage of durable overall CSBM responders resulted with each plecanatide dose compared with placebo (3 mg = 20.1%; 6 mg = 20.0%; placebo = 12.8%; = 0.004 each dose). Over the 12 weeks, plecanatide significantly improved stool consistency and stool frequency. Significant increases in mean weekly SBMs and CSBMs began in week 1 and were maintained through week 12 in plecanatide-treated patients. Adverse events were mostly mild/moderate, with diarrhea being the most common (3 mg = 3.2%; 6 mg = 4.5%; placebo = 1.3%).
Plecanatide resulted in a significantly greater percentage of durable overall CSBM responders and improved stool frequency and secondary endpoints. Plecanatide was well tolerated; the most common AE, diarrhea, occurred in a small number of patients.[ClinicalTrials.gov identifier: NCT02122471].
普卡那肽除了有一个氨基酸替换外，与人类尿鸟苷素相同，在美国已被批准用于治疗成人慢性特发性便秘（CIC）。这项双盲、安慰剂对照的III期研究评估了普卡那肽与安慰剂在CIC中的疗效和安全性。
符合改良罗马III型CIC标准的成人被随机分为普卡那肽3毫克组（n = 443）、6毫克组（n = 449）或安慰剂组（n = 445）。患者在每日电子日记中记录排便（BM）特征[包括自发排便（SBM）和完全自发排便（CSBM）]并对CIC症状进行评分。主要终点是持久总体CSBM应答者的百分比（12个治疗周中至少9周的每周应答者，包括最后4周中的至少3周）。每周应答者每周有至少3次CSBM，且与同一周的基线相比CSBM增加至少1次。
与安慰剂相比，各普卡那肽剂量组的持久总体CSBM应答者百分比显著更高（3毫克组 = 20.1%；6毫克组 = 20.0%；安慰剂组 = 12.8%；各剂量组P = 0.004）。在12周内，普卡那肽显著改善了大便稠度和大便频率。在接受普卡那肽治疗的患者中，平均每周SBM和CSBM从第1周开始显著增加，并持续到第12周。不良事件大多为轻度/中度，腹泻最为常见（3毫克组 = 3.2%；6毫克组 = 4.5%；安慰剂组 = 1.3%）。
普卡那肽使持久总体CSBM应答者的百分比显著更高，并改善了大便频率和次要终点。普卡那肽耐受性良好；最常见的不良事件腹泻发生在少数患者中。[ClinicalTrials.gov标识符：NCT02122471]
