A Study Evaluating the Effect of Albiglutide on Gallbladder Emptying in Healthy Subjects

NCT ID: NCT02496221

Last Updated: 2018-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-11
• Study Completion Date: 2015-10-13

Brief 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).

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Albiglutide 50 mg

Intervention Type: DRUG

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

Intervention Type: DRUG

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)

Intervention Type: DRUG

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%

Interventions

Albiglutide 50 mg

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

Intervention Type: DRUG

Placebo

Placebo is a single-use fixed dose, fully disposable pen injector system for SC delivery of 0.5 mL injector volume in the abdomen

Intervention Type: DRUG

CCK (Kinevac)

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 Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Baltimore, Maryland, United States

Countries

United States

References

Shaddinger BC, Young MA, Billiard J, Collins DA, Hussaini A, Nino A. Effect of Albiglutide on Cholecystokinin-Induced Gallbladder Emptying in Healthy Individuals: A Randomized Crossover Study. J Clin Pharmacol. 2017 Oct;57(10):1322-1329. doi: 10.1002/jcph.940. Epub 2017 May 19.

Reference Type: DERIVED

PMID: 28543352 (View on PubMed)

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

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Other Identifiers

201834

Identifier Type: -

Identifier Source: org_study_id