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

NCT02496221 | Completed Phase 4 Results

• 1 other identifier: 201834
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

Cholecystokinin; ultrasonography; Albiglutide; Gallbladder ejection fraction

Outcome Measures

Primary Outcomes (9)

• Maximum Absolute Value of Gallbladder Ejection Fraction (Emax GEF) During Cholecystokinin (CCK) Infusion, as a Measure of Maximum Effect

  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.

  Day 4 in each treatment period

• Area Under the Effect Curve for Gallbladder Ejection Fraction (AUEC GEF)

  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.

  Day 4 in each treatment period

• Time at Which the Maximum Effect (Emax GEF) Occurred (TEMAXEF) During the CCK Infusion

  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).

  Day 4 in each treatment period

• Maximum Gallbladder Ejection Fraction Value During CCK Infusion

  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).

  Day 1 and Day 4 in each treatment period

• Area Under the Effect Curve for Gallbladder Volume (AUEC VL)

  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.

  Day 4 in each treatment period

• Maximum Absolute Change From Baseline in Value of Gallbladder Volume (Emax VL) During CCK Infusion, as a Measure of Maximum Effect

  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.

  Day 4 in each treatment period

• Time at Which the Maximum Effect (Emax VL) Occurred (TEmax VL) During the CCK Infusion

  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).

  Day 4 in each treatment period

• Maximum Change From Baseline in Main Pancreatic Duct Diameter During CCK Infusion

  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.

  Day 4 in each treatment period

• Maximum Change From Baseline in Common Bile Duct Diameter During CCK Infusion

  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.

  Day 4 in each treatment period

Secondary Outcomes (6)

• 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)

Study Arms (1)

Albiglutide / Placebo or Placebo / Albiglutide

EXPERIMENTAL

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

Drug: Albiglutide 50 mg; Drug: Placebo; Drug: CCK (Kinevac)

Interventions

Albiglutide 50 mg 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

Albiglutide / Placebo or Placebo / Albiglutide

Placebo 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

Albiglutide / Placebo or Placebo / Albiglutide

CCK (Kinevac) 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%

Albiglutide / Placebo or Placebo / Albiglutide

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• 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.

  PMID: 28543352 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rGLP-1 protein; Sincalide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cholecystokinin; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2015
• First Posted: July 14, 2015
• Study Start: June 11, 2015
• Primary Completion: October 13, 2015
• Study Completion: October 13, 2015
• Last Updated: April 5, 2018
• Results First Posted: July 21, 2016

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)