A Study Evaluating the Effect of Albiglutide on Gallbladder Emptying in Healthy Subjects
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Albiglutide 50 mg; Placebo; CCK (Kinevac)
Intervention description: Albiglutide 50 mg pen is a single-use fixed dose, fully disposable pen injector system for SC delivery in the abdomen containing 67 mg lyophilized albiglutide and 0.65 mL diluents designed to deliver a dose of 50 mg in a volume of 0.5 mL after reconstitution; Placebo is a single-use fixed dose, fully disposable pen injector system for SC delivery of 0.5 mL injector volume in the abdomen; CCK (Kinevac) will be infused intravenously. Kinevac is supplied in vials containing 5 microgram (mcg)/vial. Infusion prepared aseptically by adding 5 mL of Sterile Water for Injection United States Pharmacopeia (USP) to the vial to create a solution of 1 mcg/mL. Infuse 0.003 mcg/kg dose in 100 mL of Sodium Chloride Injection USP, 0.9%
Intervention MeSH terms: rGLP-1 protein
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cholecystokinin; ultrasonography; Albiglutide; Gallbladder ejection fraction

Summary:

      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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between 18 and 65 years of age

          -  Healthy

          -  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

          -  Male or

          -  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

        Exclusion Criteria:

          -  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