A Randomized, Double-blind, Single-dose, Placebo Controlled, 2-way Cross-over Study Evaluating Effect of Albiglutide on Cholecystokinin-induced Gallbladder Emptying in Fasting Healthy Subjects
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Maximum Absolute Value of Gallbladder Ejection Fraction (Emax GEF) During Cholecystokinin (CCK) Infusion, as a Measure of Maximum Effect
研究概览
简要总结
Albiglutide, a novel analogue of glucagon-like peptide-1 (GLP-1), has been developed and approved for the treatment of type 2 diabetes mellitus. The primary objective of this study is to assess if a single dose of albiglutide can affect cholecystokinin-induced gallbladder emptying. To make this assessment, each study participant will receive a dose of albiglutide and a dose of placebo followed by cholecystokinin (CCK) infusion and ultrasound measurement of the gallbladder.
The study will be comprised of two periods and 20 subjects. The screening visit will occur within 42 days of the start of Treatment Period 1. The Treatment Periods will be separated by a washout period of a minimum of 42 days. Subjects will return for a follow-up visit after 28 days following the last dose of albiglutide or placebo. The total duration of a subject's participation from Screening to Follow-up will be approximately 17.5 weeks.
This study is a post marketing commitment to the United States Food and Drug Administration (USFDA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- 是
入选标准
- •Between 18 and 65 years of age
- •Have venous access sufficient to allow for intravenous (IV) infusion and blood sampling as per protocol
- •Subject's body mass index (BMI) is >=18 kilogram (kg)/meter(m)^2 and <=30 kg/m^2
- •Female: if she is not pregnant (as confirmed by a test at screening and at other timepoints), not lactating, and at least one of the following conditions applies: a) cannot bear children OR b) agrees to follow contraception requirements defined in the protocol
- •Capable of giving signed informed consent
排除标准
- •Alanine aminotransferase (ALT) >1.5x Upper limit of normal (ULN)
- •Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities
- •QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 milliseconds (msec)
- •Systolic blood pressure is >=140 millimetre (mm) mercury (Hg) at Screening
- •Diastolic blood pressure is >=90 mm Hg at Screening
- •Heart rate is >100 beats/min at Screening
- •Fasting triglyceride level >300 milligram/decilitre at Screening
- •History of cholecystitis or other gallbladder disease
- •History of gallstones, biliary motility dysfunction, or any condition rendering the subject unsuitable for ultrasonography assessments
- •Prior cholecystectomy or any other gallbladder or biliary ducts procedure, prior ileal or gastric surgery, or any other medical procedure that precluded gallbladder emptying
- •History of significant cardiovascular or pulmonary dysfunction prior to screening
- •History of thyroid dysfunction
- •History of intestinal obstruction, ileus, lap-band, gastrointestinal surgery or any other procedures that in the opinion of the investigator could influence gastric emptying (e.g., gastrectomy, gastric bypass)
- •History of acute or chronic pancreatitis
- •History of abdominal pain of unknown cause
- •History of severe gastrointestinal disease, including gastroparesis, inflammatory bowel disease, Crohn's disease, or irritable bowel syndrome
- •Personal or family history of multiple endocrine neoplasia type 2
- •Personal or family history of medullary carcinoma of the thyroid
- •Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days
- •Current or past use of medications that may have significantly affected gastrointestinal and/or gallbladder motility or pancreatic or hepatobiliary systems
- •History of regular alcohol consumption within 6 months of the study
- •Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 3 months prior to screening
- •Subject has a history of significant weight loss or is currently attempting weight loss
- •History of sensitivity or contraindication to any of the study medications or components thereof or a history of drug or other allergy
- •Subject has previously received any GLP-1 mimetic compound (e.g., exenatide, liraglutide, lixisenatide, dulaglutide)
- •A biliary pathology as assessed by ultrasound
- •An abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone at screening
- •An abnormal amylase or lipase test at screening
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result
- •A positive pre-study drug/alcohol screen
- •A positive test for Human immunodeficiency virus (HIV) antibody
- •A screening ultrasound which demonstrates inadequate imaging of gallbladder, main pancreatic duct, or common duct
- •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56-day period
- •The subject participated in a clinical trial and received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
- •Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
研究组 & 干预措施
Albiglutide / Placebo or Placebo / Albiglutide
In treatment period 1, subjects will receive Albiglutide 50 mg or Placebo subcutaneously (SC) after fasting overnight for at least 10 hours according to randomization schedule on Day 1. Subject will also receive CCK (Kinevac) infusion intravenously for a period of 50 minutes after fasting overnight for at least 10 hours on Day 4. After washout period of a minimum of 42 days in treatment period 2, subjects will receive same treatment according to randomization schedule in a cross-over fashion
干预措施: Albiglutide 50 mg (Drug)
Albiglutide / Placebo or Placebo / Albiglutide
In treatment period 1, subjects will receive Albiglutide 50 mg or Placebo subcutaneously (SC) after fasting overnight for at least 10 hours according to randomization schedule on Day 1. Subject will also receive CCK (Kinevac) infusion intravenously for a period of 50 minutes after fasting overnight for at least 10 hours on Day 4. After washout period of a minimum of 42 days in treatment period 2, subjects will receive same treatment according to randomization schedule in a cross-over fashion
干预措施: Placebo (Drug)
Albiglutide / Placebo or Placebo / Albiglutide
In treatment period 1, subjects will receive Albiglutide 50 mg or Placebo subcutaneously (SC) after fasting overnight for at least 10 hours according to randomization schedule on Day 1. Subject will also receive CCK (Kinevac) infusion intravenously for a period of 50 minutes after fasting overnight for at least 10 hours on Day 4. After washout period of a minimum of 42 days in treatment period 2, subjects will receive same treatment according to randomization schedule in a cross-over fashion
干预措施: CCK (Kinevac) (Drug)
结局指标
主要结局
Maximum Absolute Value of Gallbladder Ejection Fraction (Emax GEF) During Cholecystokinin (CCK) Infusion, as a Measure of Maximum Effect
时间窗: Day 4 in each treatment period
Gallbladder ejection fraction (EF) is defined as the reduction in gallbladder volume at any time point from Baseline divided by baseline gallbladder volume and multiplied by 100. Baseline gallbladder volume is the average of the 3 gallbladder volume measurements prior to CCK infusion on Day 4, for each treatment period. Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion). Adjusted mean and its standard error have been presented.
Area Under the Effect Curve for Gallbladder Ejection Fraction (AUEC GEF)
时间窗: Day 4 in each treatment period
Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion). Adjusted mean and its standard error have been presented.
Time at Which the Maximum Effect (Emax GEF) Occurred (TEMAXEF) During the CCK Infusion
时间窗: Day 4 in each treatment period
Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion).
Maximum Gallbladder Ejection Fraction Value During CCK Infusion
时间窗: Day 1 and Day 4 in each treatment period
Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion).
Area Under the Effect Curve for Gallbladder Volume (AUEC VL)
时间窗: Day 4 in each treatment period
Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion). Adjusted mean and its standard error is presented.
Maximum Absolute Change From Baseline in Value of Gallbladder Volume (Emax VL) During CCK Infusion, as a Measure of Maximum Effect
时间窗: Day 4 in each treatment period
Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion). Baseline gallbladder volume is the average of the 3 gallbladder volume measurements prior to CCK infusion on Day 4, for each treatment period. Adjusted mean and its standard error are presented.
Time at Which the Maximum Effect (Emax VL) Occurred (TEmax VL) During the CCK Infusion
时间窗: Day 4 in each treatment period
Gallbladder ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion).
Maximum Change From Baseline in Main Pancreatic Duct Diameter During CCK Infusion
时间窗: Day 4 in each treatment period
Pancreatic duct ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion). Baseline is the average of the three diameter assessments at -15, -10, and -5 minutes relative to start of CCK infusion on Day 4. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value. Adjusted mean and its standard error are presented. Baseline was calculated as the value at the indicated time point minus the Baseline value. Only those participants available at the indicated time points were analyzed.
Maximum Change From Baseline in Common Bile Duct Diameter During CCK Infusion
时间窗: Day 4 in each treatment period
Common bile duct ultrasonography was done at Day 1 (-15, -10, and -5 minutes \[min\] relative to start of albiglutide/placebo injection) and Day 4 (\[prior to CCK infusion\] -15, -10, -5 min, followed by \[during CCK infusion\] every 5 min between 0 and 50 min, then \[after CCK infusion\] at 60, 70, and 80 min, relative to the start of CCK infusion). Baseline is the average of the three diameter assessments at -15, -10, and -5 minutes relative to start of CCK infusion on Day 4. Change from Baseline was calculated as the value at the indicated time point minus the Baseline value. Adjusted mean and its standard error have been presented.
次要结局
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Day -1, Baseline Day 1(Pre-dose), Day 2, Day 3, and 15 minutes (-15 min) prior to dosing and 80 min post dosing on Day 4 in each treatment period and Follow-up (assessed up to a total of approximately 12 weeks))
- Change From Baseline in Heart Rate(Day -1, Baseline Day 1(Pre-dose), Day 2, Day 3, and 15 minutes (-15 min) prior to dosing and 80 min post dosing on Day 4 in each treatment period and Follow-up (a total of approximately 12 weeks))
- Number of Participants With Clinical Chemistry and Hematology Abnormalities of Potential Clinical Importance(Day -1 in each treatment period and Follow-up (at approximately Week 12))
- Change From Baseline in Electrocardiogram (ECG) Parameters(Baseline (Day -1) and Day 4 in each treatment period, and at Follow-up (at approximately Week 12))
- Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event(From Day -1 in treatment period 1 and up to Follow-up Visit (a total of approximately 12 weeks))
- Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick(Day -1 and Follow-up (assessed up to a total of approximately 12 weeks))