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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
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%
GSK Investigational Site
Baltimore, Maryland, United States
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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Day 4 in each treatment period
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Baseline is defined as Day 1 (pre-dose) visit. SBP and DBP were measured in a semi-supine position after 5 minutes of rest, at each indicated time point. Assessments were performed on Day -1, Day 1 (pre-dose), Day 2, Day 3 and 15 minutes (-15 min) prior to dosing and 80 min post dosing on Day 4. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants available at the indicated time points (represented by n=X,X in the category titles) were analyzed.
Time frame: 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
Baseline is defined as Day 1 (pre-dose) visit. Heart rate was measured in a semi-supine position after 5 minutes of rest, at each indicated time point. Assessments were performed on Day -1, Day 2, Day 3 and 15 minutes (-15 min) prior to dosing and 80 min post dosing on Day 4. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants available at the indicated time points (represented by n=X,X in the category titles) were analyzed.
Time frame: 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
The following parameters were measured through blood sampling. Hematology: Hematocrit, Hemoglobin, Lymphocytes, Neutrophil Count, Platelet Count, While Blood Cell Count (WBC); Clinical Chemistry: Albumin, Calcium, Creatinine, Glucose, Magnesium, Phosphorus, Potassium, Sodium, Total carbon dioxide; Liver Function Tests: Alanine transaminase (ALT), Aspartate transaminase, Alkaline Phosphatase, Total Bilirubin, Total Bilirubin + ALT. Values were considered to be of potential clinical importance if they had a 'low' or 'high' flag with respect to a pre-defined clinical concern range. Only participants starting each period (represented by n=X) with a particular treatment were analyzed. The follow-up time point is not restricted to a treatment or treatment period.
Time frame: Day -1 in each treatment period and Follow-up (at approximately Week 12)
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Change From Baseline in Electrocardiogram (ECG) Parameters
Single 12-lead ECG was obtained in a semi-supine position after 5 minutes of rest at each indicated time point using an ECG machine that automatically calculated the heart rate and measured the PR, QRS, QT, and QT corrected by Fridericia's formula (QTcF) intervals. Change from Baseline was calculated as value at indicated time point minus Baseline value.
Time frame: 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
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalised ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgement. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time frame: 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
Urine dipstick test was carried out on Day -1 and at Follow-up. Urinalysis parameters assessed were glucose, ketones, nitrite and protein. Dipstick results were categorized as Normal (glucose), Negative or Trace (ketones), and Negative (nitrite and protein). Only participants available at the indicated time points (as represented by n=X, X, X in the category titles) were analyzed. The resultant fields with no available data have been represented by 'NA'.
Time frame: Day -1 and Follow-up (assessed up to a total of approximately 12 weeks)