A Dose-Ranging, Randomized, Parallel, Placebo-Controlled Study to Assess the Effect of TAK-954 on Gastrointestinal and Colonic Transit in Patients With Diabetic or Idiopathic Gastroparesis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids
研究概览
简要总结
The purpose of this study is to evaluate the dose-dependent effects of TAK-954 on gastric emptying time of solids in participants with diabetic or idiopathic gastroparesis assessed by scintigraphy.
详细描述
The drug being tested in this study is called TAK-954. TAK-954 is a serotonin (5 HT4) receptor agonist and is being tested to treat people who have diabetic or idiopathic gastroparesis and who previously reported delay in stomach emptying. This study will look at the gastric emptying time of solids in people who take TAK-954 or placebo.
The study will enroll approximately 41 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- TAK-954 0.1 mg
- TAK-954 0.3 mg
- TAK-954 1 mg
- Placebo (dummy inactive solution) - this is a solution that looks like the study drug but has no active ingredient.
This single center trial will be conducted in the United States. The duration of treatment is 3 days and the overall period of evaluation is up to 28 days. The participants will be contacted by telephone (Days 10 to 14) for follow-up assessment. There will be another follow-up phone call for women of childbearing potential (Days 38 to 43).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has diabetes mellitus with symptoms of gastroparesis and previously documented gastric emptying delay or previously documented idiopathic gastroparesis in the last 5 years.
- •Has a body mass index (BMI) greater than or equal to (>=) 16 and less than or equal to (<=) 40 kilogram per square meter (kg/m^2) at the Screening Visit.
排除标准
- •Has glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%).
- •Has other structural diseases/conditions that affect the gastrointestinal (GI) system.
- •Are unable to withdraw drugs known to alter GI transit 48 hours prior to the study.
- •Has clinically significant abnormal baseline safety laboratory values.
- •Has preexisting hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
- •Are without known preexisting hepatic disease who have 1 or more of the following:
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the upper limit of normal (ULN).
- •Bilirubin >1.5 times the ULN unless due to Gilbert's syndrome.
- •International normalized ratio (INR) >1.5 unless on anticoagulation therapy.
- •Has QT intervals with Fridericia correction method (QTcF) interval (>=) 460 millisecond (msec) or with other factors that increase the risk of QT prolongation or arrhythmic events at screening. Note: Participants with bundle branch block and a prolonged QTc interval, or with QTcF between 450 and 460 msec, should be reviewed by the Medical Monitor for potential inclusion.
- •Has second or third degree atrioventricular (AV) block; AV disassociation; >5 beats of non-sustained VT at a rate >120 beats per minute (bpm); Electrocardiogram (ECG) changes consistent with acute myocardial ischemia or infarction.
- •Has cardiac history that includes conditions requiring heart rate control (example, atrial fibrillation, atrial flutter, ventricular tachycardia, or other tachyarrhythmias).
- •Has clinical evidence (including physical examination, ECG, clinical laboratory value and review of the medical history) of significant cardiovascular, respiratory, moderate or severe renal insufficiency (creatinine clearance <=60 mL/min), hematological, neurological, or psychiatric disease, or other disease that interferes with the objectives of the study.
- •If female, are pregnant or lactating or intending to become pregnant before participating in this study, during the study, and 4 to 5 days (5 half-lives) PLUS 30 days after last dose of the study drug; or intending to donate ova during such time period.
- •Are considered by the investigator to be alcoholics not in remission or known substance abusers. Have a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer [354 milliliter per [mL/] 12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce] per day).
研究组 & 干预措施
TAK-954 0.1 mg
TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.
干预措施: TAK-954 (Drug)
Placebo
TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once daily on Days 1 to 3.
干预措施: Placebo (Drug)
TAK-954 0.3 mg
TAK-954 1 mg, 60-minute infusion, IV, once daily for up to 3 days.
干预措施: TAK-954 (Drug)
TAK-954 1 mg
TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.
干预措施: TAK-954 (Drug)
结局指标
主要结局
Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids
时间窗: Predose and at multiple time-points post-dose (up to 9 hours) on Day 2
Half-emptying time (t1/2) of gastric solids is the time for half of the ingested solids or liquids to leave the stomach. Scintigraphy assessments were used to evaluate the gastric emptying of solids following a radio-labelled meal. A negative percent change from baseline indicated improvement.
次要结局
- Ctrough: Observed Plasma Concentration at the End of a Dosing Interval(At multiple time-points post-dose, up to 9 hours on Day 2 and up to 25 hours on Day 3)
- Colonic Filling at Hour 6(6 hours post-radiolabel meal on Day 2)
- Half-emptying Time (T1/2) of Ascending Colon(Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3)
- Cmax: Maximum Observed Plasma Concentration for TAK-954(Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3)
- Colonic Geometric Center(4, 24, and 48 hours post-radiolabeled meal on Day 2)
- AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to t for TAK-954(Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3)