Plecanatide safe, effective for chronic constipation
Two new studies suggest that the peptide plecanatide is safe and effective in the treatment of chronic idiopathic constipation. The drug had a low rate of diarrhea, about 7.1%.
The research, presented in two posters at the annual meeting of the American College of Gastroenterology, includes a pooled efficacy and safety analysis from two previous phase III clinical trials, as well as an open-label extension study.
Though there is no way to be sure in the absence of head-to-head studies, plecanatide could have a better tolerability profile than the existing constipation drugs like lubiprostone (Amitiza) and linaclotide (Linzess).
“Many patents are still very dissatisfied” with existing drugs, said Satish Rao, MD, PhD, director of the Digestive Health Center at the Medical College of Georgia, Augusta, who presented one of the posters.
The drug is a derivative of uroguanylin, a peptide found in the gastrointestinal tract. Like the native peptide, plecanatide stimulates digestive fluid movement in the proximal small intestine, which in turn encourages regular bowel function. “I think because it is so much closer to the innate uroguanylin molecule, it will have better tolerability,” said Dr. Rao in an interview.
The open-label study followed 2,370 patients who received 3-mg or 6-mg doses of plecanatide once daily for up to 72 weeks. The most common adverse events were diarrhea (7.1%) and urinary tract infection (2.2%), and these were the only adverse events that occurred at a frequency above 2%.
开放标签研究随访了2,370例每日接受3 mg或6 mg plecanatide治疗长达72周的患者。最常见的不良事件包括腹泻（7.1%）和尿路感染（2.2%），这是仅有的发生率超过2%之不良事件。
About 5% of patients discontinued due to adverse events, 3.1% because of diarrhea. Patients were also asked to score their satisfaction with the drug and their willingness to continue on it, and the median values to those answers corresponded to quite satisfied and quite likely to continue.
The other study was a pooled analysis of two previously presented double-blind, placebo-controlled phase III trials of plecanatide. These studies included 2,791 patients with chronic idiopathic constipation who were treated over the course of 12 weeks, with 3- and 6-mg doses. Both groups showed significant improvements in the rate of durable overall complete spontaneous bowel movements: 20.5% in the 3-mg group and 19.8% in the 6-mg group, compared with 11.5% in the placebo group (less than .001 for both comparisons).
另外一项研究是合并分析了此前报告的两项双盲安慰剂对照plecanatide III期试验结果。这两项研究纳入2,791例慢性特发性便秘患者，他们接受为期12周3 mg或6 mg剂量药物治疗。两组患者可耐受的总完全自发性排便率均有显著改善：3 mg和6 mg组分别为20.5%和19.8%，而安慰剂组为11.5%（P<0.001）。
Patients experienced improvements as early as the first week of treatment (31.6% in the 3-mg group versus 16.1% in placebo, P less than .001), and improvements were maintained through the end of the treatment period. There were also significant improvements in secondary endpoints, including stool consistency, straining, and bloating.
Adverse events occurred in 30.6% of subjects taking the 3-mg dose and 31.1% of those taking 6 mg, compared with 28.7% in the placebo group. As with the long-term study, the most common adverse event was diarrhea (4.6% in 3 mg and 5.1% in 6 mg, compared with 1.3% in placebo). Of those in the 3-mg group, 4.1% discontinued, as did 4.5% in the 6-mg group, and 2.2% in the placebo group.
3 mg和6 mg剂量组患者的不良事件发生率分别为30.6%和31.1%，而安慰剂组为28.7%。与长期研究结果相同，最常见的不良事件为腹泻（3 mg和6 mg剂量组分别为4.6%和5.1%，安慰剂组为1.3%）。3 mg和6 mg剂量组患者停药率分别为4.1%和4.5%，安慰剂组为2.2%。
“I think these are very exciting results. They clearly show a benefit of plecanatide in patients with chronic constipation. These are really methodologically rigorous, large clinical trials that should provide doctors and patients with confidence that the drug will provide benefits,” commented William D. Chey, MD, a professor of medicine at the University of Michigan, Ann Arbor.
密歇根大学安娜堡分校医学教授William D. Chey博士评论指出：我认为这是非常令人兴奋的结果，结果明确显示plecanatide可使慢性便秘患者获益。这些研究方法学严谨的大规模临床试验，能够让医师和患者相信该药物将会给患者带来益处。
Plecanatide is also being developed for irritable bowel syndrome with constipation, and has finished recruitment for two phase III clinical trials, which Synergy expects to report on later this year.