A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose Ranging Study to Evaluate the Efficacy and Safety of 2 Dose Regimens of Intravenous TAK-954 for the Prophylaxis and Treatment of Postoperative Gastrointestinal Dysfunction in Patients Undergoing Large- and Small-Bowel Resection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 209
- 试验地点
- 25
- 主要终点
- Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator
研究概览
简要总结
The main aim of this study is to check for side effects from TAK-954 and whether it speeds up the recovery of gastrointestinal function after small-bowel or large-bowel resection surgery.
Participants will be treated with TAK-954 before surgery and up to 10 days after surgery.
详细描述
The drug being tested in this study is called TAK-954. In this study TAK-954 is being administered presurgery to evaluate if it can enhance the recovery of GI function postsurgery in participants undergoing open or laparoscopic-assisted partial small- or large-bowel resection. In addition, some participants will also receive TAK-954 postoperatively to evaluate if there is an additional benefit when this drug is administered both pre and post-surgery.
The study will enroll approximately 180 participants. Participants will be equally randomized into one of the three remaining parallel treatment arms- which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).
All participants will be given intravenous infusion preoperation and daily postoperation until return of upper and lower GI function or for up to 10 days.
This multi-center trial will be conducted in the United States and Germany. The overall time to participate in this study is up to 100 days. Participants will be treated with the study drug for up to 10 days after surgery or until return of GI function post-surgery (whichever occurs first).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is scheduled to undergo a laparoscopic-assisted or open partial small- or large-bowel resection.
- •Participant's American Society of Anesthesiologists (ASA) physical status classification is ASA 1 to 3.
排除标准
- •Has significant mechanical bowel obstruction that is not expected to resolve after the surgery, short bowel syndrome, pre-existing clinically significant GI motility disorder (example, gastroparesis, scleroderma, chronic intestinal pseudo-obstruction), uncontrolled diabetes (glycosylated hemoglobin [HbA1c] greater than [>] 10 percent [%]), has an active gastric pacemaker, or requires parenteral nutrition.
- •Had previous major abdominal surgery (example, gastrectomy, gastric bypass, gastric sleeve, lap banding, Whipple, pancreatic resection, total/subtotal colectomy, hemicolectomy, extensive bowel resection).
- •Had a history of radiation therapy to the abdomen or pelvis.
- •Scheduled to undergo any of the following surgeries: low anterior resection, total or subtotal colectomy, colostomy, ileostomy or reversal of stoma, or has a diagnosis that requires rectal resection (eg, tumors in the anorectum) and will likely require lower anterior resection surgery. Participants with planned surgery for which there is no anticipated significant rectal resection and is, therefore, likely to preserve anorectal function and continence postsurgery, will likely be eligible for inclusion in the study if they meet all the study inclusion/exclusion criteria (eg, participants with lesions not involving the rectum [sigmoid colon and above]).
- •Has pre-existing hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
- •Has received alvimopan, erythromycin, prucalopride, metoclopramide, domperidone, cisapride, mosapride, renzapride, or azithromycin in the 24 hours prior to starting study drug.
- •Participant has known COVID-19 infection, or suspected COVID-19 infection.
- •Scheduled for abdominal surgery that is classified as emergency.
研究组 & 干预措施
Placebo
TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.
干预措施: TAK-954 Placebo (Drug)
TAK-954 0.1 mg/100 mL
TAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.
干预措施: TAK-954 (Drug)
TAK-954 0.5 mg/100 mL
TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.
干预措施: TAK-954 (Drug)
TAK-954 0.1 mg/100 mL + Placebo
TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
干预措施: TAK-954 Placebo (Drug)
TAK-954 0.1 mg/100 mL + Placebo
TAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
干预措施: TAK-954 (Drug)
TAK-954 0.5 mg/100 mL + Placebo
TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
干预措施: TAK-954 Placebo (Drug)
TAK-954 0.5 mg/100 mL + Placebo
TAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
干预措施: TAK-954 (Drug)
结局指标
主要结局
Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator
时间窗: Day 1 (surgery) up to Day 10 postsurgery
The time from end of surgery to tolerance of solid food, without first occurrence of vomiting or clinically significant nausea for 1 calendar day after a solid meal (upper GI function) and first spontaneous bowel movement (lower GI function), whichever occurred later up to 10 days postsurgery was observed. Kaplan-Meier survival analysis method was used.
次要结局
- Time From the End of Surgery to Discharge From Hospital(Day 1 (surgery) up to Day 24)
- Time From End of Surgery to First Spontaneous Bowel Movement as Assessed by the Investigator(Day 1 (surgery) up to Day 10 postsurgery)
- Percentage of Participants With Postoperative Gastrointestinal Dysfunction (POGD) >= 5 Days as Assessed by the Investigator(Day 1 (surgery) up to Day 10)
- Time From End of Surgery to Tolerance of Solid Food as Assessed by the Investigator(Day 1 (surgery) up to Day 10 postsurgery)
- Percentage of Participants Requiring Insertion of Nasogastric (NG) Tube Postsurgery(Day 1 (surgery) up to Day 24 postsurgery (10 days of treatment period postsurgery plus 14-day observation period post last dose for recurrence of symptoms))
- Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator(Day 1 (surgery) up to Day 24)
- Time From the End of Surgery Until the Discharge Order is Written(Day 1 (surgery) up to Day 24)
- Time From End of Surgery to First Flatus(Day 1 (surgery) up to first flatus (up to Day 10 postsurgery))
- Observed Plasma Concentration of TAK-954 at the End of Infusion on Day 1(Day 1 (surgery): postinfusion)