A Study Comparing the Effect of Albiglutide With Exenatide on Regional Brain Activity Related to Nausea in Healthy Subjects

An Exploratory Randomized, 2-Part, Single-blind, 2-Period Crossover Study Comparing the Effect of Albiglutide With Exenatide on Regional Brain Activity Related to Nausea in Healthy Volunteers

The drug effects will be studied after a single dose of 50 milligram (mg) albiglutide and a single dose of 10 microgram exenatide, to gain insight into the central mechanisms of nausea associated with Glucagon-like peptide-1 receptor (GLP-1R) agonists. This study will explore the potential differences at the expected time of maximum concentration (Cmax) between a long-acting (albiglutide) and short-acting (exenatide) GLP-1R agonist in brain activation of healthy volunteers assessed by magnetic resonance imaging (MRI). This is a phase IV, 2-part, 2-period crossover (session), single dose, randomized, single blind (blinded to both the subject and the imaging evaluators analysing the MRI data), placebo- and active-controlled study in adult healthy volunteers who are susceptible to motion sickness. Part A and Part B are the same in design, both consisting of a screening stage, a dosing/assessment stage, and a follow-up visit. Data from Part A will inform progression, methods, and analysis plan for Part B. Each sequence includes three scanning visits: albiglutide plus scan, exenatide plus scan and an off-therapy -natural history scan with a 6-9 week washout period between the dosing scans. A total of 24 to 28 subjects will be randomized in the study (Part A and Part B). The cross over design is divided into 2 sessions and schedule is as follow, on Day 1 (either Session 1 (S1) or Session 2 (S2) per, if randomized) subject will under go an off-therapy MRI scan, on Day 5 subject will receive a single dose of 50 mg albiglutide or albiglutide placebo, and Day 8 subject will receive a single dose of 10 microgram exenatide or saline placebo followed by a post-dose MRI scan. At each session subject will receive only one active drug (albiglutide or exenatide).

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Albiglutide 50mg; Drug: Albiglutide matching placebo; Drug: Exenatide 10microgram; Drug: Exenatide placebo (saline)

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
• Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
• Pure right-handed based on Edinburgh Handedness Inventory
• Motion Sickness Susceptibility Questionnaire (MSSQ) Screening score >60 and mock fMRI nausea rating >=2
• A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator (in consultation with the Medical Monitor, if necessary) decides and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or ability to interpret study results.
• Subject's body mass index (BMI) is >=19 (kilogram per square meter)kg/m^2 and =<30 kg/m^2
• Male OR
• Female: eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test at screening and at other timepoints), not lactating, and at least one of the following conditions applies: a. Non-reproductive potential defined as pre-menopausal females who are having documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented Bilateral Oophorectomy OR Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause to confirm (refer to laboratory reference ranges for confirmatory levels)]. b. Reproductive potential and agrees to follow one of the options listed for avoiding pregnancy in females of reproductive potential (FRP) requirements from 30 days prior to the first dose of study medication and for the duration of study including the completion of the follow-up visit. The options are, Contraceptive subdermal implant or Intrauterine device or intrauterine system or Combined estrogen and progestogen oral contraceptive or Injectable progestogen or Contraceptive vaginal ring or Percutaneous contraceptive patches or Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. The documentation on male sterility can come from the site personnel's: review of subject's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions.

Exclusion Criteria:

• Severe nausea (with or without vomiting) in the last three months or any event of unexplained nausea (with or without vomiting) as reported by the subject in the last 14 days before screening.
• History of vestibular or balance disorders as determined by the Investigator.
• History of smoking cigarettes or using tobacco products or any nicotine-containing products (including nicotine patches) within 3 months of screening.
• Use of eyeglasses during functional MRI (fMRI). Subjects requiring visual correction to participate in visual task that cannot be corrected with contact lenses.
• Alanine amino transferase (ALT) >1.5xupper 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 msec
• Systolic blood pressure is >=140 millimeter of Mercury (mm Hg) at Screening; repeat blood pressures should be taken if the subject's systolic blood pressure is >=140 mm Hg and if the results are consistently >=140 mm Hg, then the subject will be excluded and advised to consult a physician
• Diastolic blood pressure is >=90 mm Hg at Screening; repeat blood pressures should be taken if the subject's diastolic blood pressure is >=90 mm Hg and if the results are consistently >=90 mm Hg, then the subject should be excluded and advised to consult a physician
• Mean resting heart rate is >100 beats/minutes (mins) out of 3 consecutive measures taken 10 mins apart at Screening
• History of intestinal obstruction, ileus, gastrointestinal surgery or any other medical condition or procedure (e.g., gastrectomy, gastric bypass, lap-band) that may impair gastrointestinal motility
• History of significant cardiovascular or pulmonary dysfunction prior to screening
• History of acute or chronic pancreatitis
• History of severe gastrointestinal disease, including gastroparesis, inflammatory bowel disease, Crohn's disease, or irritable bowel syndrome
• History of any significant psychiatric illness (e.g., schizophrenia, bipolar affective disorder, bulimia or anorexia nervosa) that in the opinion of the Investigator would interfere with participation in the study.
• History and/or evidence of any other Central Nervous System (CNS) disorder that in the opinion of the Investigator would interfere with participation in the study (e.g., epilepsy, brain tumour, brain surgery).
• History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral contusion, spinal cord compression) or seizures.
• 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 (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• Received within 7 days prior to screening or unable to refrain from taking for the duration of each part of study, medications that might; modify gastric myoelectical activity or gastrointestinal motility as prokinetic (e.g., erythromycin), anti-emetic agents (e.g., metoclopromide), narcotic analgesics (e.g., morphine), anticholinergic drugs (e.g., domperidone), anti-acid (e.g., pump inhibitors, H2 blockers) and laxative agents or
• stimulate or inhibit CNS (e.g., modafinil, dexamphetamine, methylphenidate, bromopheniramine, chlorpheniramine, clemastine, diphenhydramine, hyrdoxyzine)
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Is unwilling to abstain from alcohol for 24 hours before dosing and before each MRI scanning visit
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• Subject has a history of significant weight loss (>5% reported change within 3 months prior to screening) or is currently attempting weight loss
• History of hypersensitivity to albiglutide, exenatide, or any product components
• Personal or family history of multiple endocrine neoplasia type 2, or medullary carcinoma of the thyroid
• Subject has any known condition(s) that may be contraindicated or interfere with the completion of MRI scanning such as implants (e.g., pacemaker, cochlear), a medical or electronic device (e.g., metallic joint prostheses, metal pins, screws, plates, stents or surgical staples), or claustrophobia.
• An abnormal (i.e., outside the normal reference range) thyroid function test assessed by thyroid stimulating hormone and Free T4 at screening.
• An abnormal amylase or lipase test at screening
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or at screening
• A positive pre-study drug/alcohol screen
• A positive test for human immunodeficiency virus (HIV) antibody
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56-day period
• Subject has previously received any Glucagon-like peptide-1 receptor (GLP-1R) agonist at any time (e.g., albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide)
• Subject has previously received dipeptidyl peptidase 4 (DPP-IV) inhibitor (sitagliptin, saxagliptin, linagliptin, alogliptin) within 30 days from screening
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 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 investigational products within 12 months prior to the first dosing day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: With Off therapy MRI in S1:Albiglutide-S1 & Exenatide-S2; In session 1, eligible subject will undergo off-therapy MRI scan Subject will receive single dose each of 50 mg albiglutide on Day 5 and exenatide placebo on Day 8 followed by a post-dose MRI. In session 2, subject will receive single dose each of albiglutide placebo on Day 1 (Week 9) and 10 microgram exenatide on Day 4 followed by a post-dose MRI scan. There will be 6-9 week washout period between Session 1 and Session 2	Drug: Albiglutide 50mg; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. A 50 mg pen contains 67 mg lyophilized albiglutide and 0.65 mL diluents. It will be injected subcutaneously (SC) in the upper arm.; Drug: Albiglutide matching placebo; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide 10microgram; It is provided as a sterile solution containing 250 microgram/mL exenatide. One dose of 10 microgram is equivalent to 0.04 ml. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide placebo (saline); It is provided as a sterile saline. It will be injected subcutaneously (SC) in the upper arm
Experimental: Without Off therapy MRI in S1:Albiglutide-S1 & Exenatide-S2; In session 1, eligible subject will receive single dose each of 50 mg albiglutide on Day 1 and exenatide placebo on Day 4 followed by a post-dose MRI scan. In session 2, Day 1 (Week 9) subject will undergo off-therapy MRI scan. Subject will receive single dose each of albiglutide placebo on Day 5 and 10 microgram of exenatide on Day 8 followed by a post-dose MRI scan. There will be 6-9 week washout period between Session 1 and Session 2	Drug: Albiglutide 50mg; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. A 50 mg pen contains 67 mg lyophilized albiglutide and 0.65 mL diluents. It will be injected subcutaneously (SC) in the upper arm.; Drug: Albiglutide matching placebo; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide 10microgram; It is provided as a sterile solution containing 250 microgram/mL exenatide. One dose of 10 microgram is equivalent to 0.04 ml. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide placebo (saline); It is provided as a sterile saline. It will be injected subcutaneously (SC) in the upper arm
Experimental: With Off therapy MRI in S1:Exenatide-S1 & Albiglutide-S2; In session 1, Day 1 subject will undergo off-therapy MRI scan Subject will receive single dose each of albiglutide placebo on Day 5 and 10 microgram of exenatide on Day 8 followed by a post-dose MRI scan In session 2, eligible subject will receive single dose each of 50 mg albiglutide on Day 1 (Week 9) and exenatide placebo Day 4 followed by a post-dose MRI scan. There will be 6-9 week washout period between Session 1 and Session 2	Drug: Albiglutide 50mg; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. A 50 mg pen contains 67 mg lyophilized albiglutide and 0.65 mL diluents. It will be injected subcutaneously (SC) in the upper arm.; Drug: Albiglutide matching placebo; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide 10microgram; It is provided as a sterile solution containing 250 microgram/mL exenatide. One dose of 10 microgram is equivalent to 0.04 ml. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide placebo (saline); It is provided as a sterile saline. It will be injected subcutaneously (SC) in the upper arm
Experimental: Without Off therapy MRI in S1: Exenatide-S1 & Albiglutide-S2; In session 1, subject will receive single dose each of albiglutide placebo on Day 1 and 10 microgram exenatide on Day 4 followed by a post-dose MRI scan. In session 2, subject will undergo off-therapy MRI scan on Day 1 (Week 9). Subject will receive single dose each of 50 mg albiglutide on Day 5 and exenatide placebo on Day 8 followed by a post-dose MRI scan.. There will be 6-9 week washout period between Session 1 and Session 2	Drug: Albiglutide 50mg; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. A 50 mg pen contains 67 mg lyophilized albiglutide and 0.65 mL diluents. It will be injected subcutaneously (SC) in the upper arm.; Drug: Albiglutide matching placebo; It is provided as a single use fixed dose disposable pen injector (0.5 mL) system for SC delivery. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide 10microgram; It is provided as a sterile solution containing 250 microgram/mL exenatide. One dose of 10 microgram is equivalent to 0.04 ml. It will be injected subcutaneously (SC) in the upper arm; Drug: Exenatide placebo (saline); It is provided as a sterile saline. It will be injected subcutaneously (SC) in the upper arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Oxygen Level Dependent (BOLD) Signal by Functional Magnetic Resonance Imaging (fMRI) Visual Nauseogenic Task	BOLD signal fMRI Visual Nauseogenic Task data were to be collected at indicated time-points. The seed-to-voxel driven approach included a priori seed Regions of interest (ROIs) placed in brain areas subserving nausea-related processing included regions like interoceptive/sensory (insula, Dorsal anterior cingulate cortex [dACC]), emotional/affective (amygdala, Pregenual anterior cingulate cortex [pgACC]), and cognitive/evaluative (dorsolateral prefrontal cortex [dlPFC]/ Occipitofrontal Circumference [OFC]) brain areas, primary visual (V1) and extrastriate cortices. The primary endpoints of this exploratory study involved combining data from Part A and Part B. The purpose of Part A was decision making for Part B. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was to be reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Regional Cerebral Blood Flow (rCBF) by Functional MRI (fMRI)-Arterial Spin Labeling (ASL)	Pseudo-Continuous Arterial spin labeling (pCASL) data were planned to be analyzed to assess rCBF within the brain during using functional MRI scans. Quality control of imaging data were planned to be performed by visual inspection with adequate data denoted by mean rCBF values over the gray matter within a previously defined normal range (i.e., 40-60 millimeter [mm]/100 gram [g] tissue/ minute [min]). In addition, all data were planned to undergo motion and physiological noise correction. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Glutamate Concentration in Nausea-associated Brain Regions by Magnetic Resonance Spectroscopy (MRS)	Glutamine/Glutamate (Glx) was planned to be analyzed using proton-density weighted magnetic resonance spectroscopy (1H-MRS). 1H-MRS analysis assessed regional differences in Glx concentrations, normalized as a ratio with creatine. MRS quantification of metabolites of interest were based on frequency domain analysis using a Linear Combination of Model spectra (LCModel). Cramer-Rao lower bounds (CRLBs), as reported from the LCModel analysis, were planned to be used to assess the reliability of the major metabolites and adequate Signal to noise ratio (SNR). CRLBs values less than 40% were further planned to be analyzed. Metabolite maps for each participant, and each session were planned to be calculated. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Gama-aminobutyric Acid (GABA) Concentration in Nausea-associated Brain Regions by MRS	GABA concentrations was planned to be analyzed using proton-density weighted 1H-MRS. 1H-MRS analysis assessed regional differences GABA concentrations, normalized as a ratio with creatine. MRS quantification of metabolites of interest were based on frequency domain analysis using a LC Model. CRLBs, as reported from the LC Model analysis, were planned to be used to assess the reliability of the major metabolites and adequate SNR. CRLBs values less than 40% were further planned to be analyzed. Metabolite maps for each participant, and each session were planned to be calculated. Placebo was used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate Variability Using Autonomic Response Measures by MRI	Heart rate variability was to be evaluated using autonomic response measure. All peripheral autonomic physiological signals were planned to be collected at 400 Hz using Chart Data Acquisition Software (ADInstruments) on a laptop equipped with a 16-channel Powerlab DAQ System (ADInstruments). Heart rate variability was to be reported as recorded by chart data acquisition software. Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Number of Participants With Abnormal Electrocardiogram (ECG) Intervals Using Autonomic Response Measures by MRI	ECGs intervals were to be evaluated for the participant during the scanning session using autonomic response measures. ECG signal were planned to be collected with an MRI-compatible participant Monitoring system (Biopac 150, Biopac Systems Inc.) through MRI-compatible electrodes (VerMed, Bellows Falls) placed on the chest. Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Number of Participants With Abnormal Respiratory Rate Using Autonomic Response Measures by MRI	Number of participants with abnormal respiratory rate are reported during imaging session was to be evaluated using autonomic response measures. All peripheral autonomic physiological signals were planned to be collected at 400 Hz using Chart Data Acquisition Software (ADInstruments) on a laptop equipped with a 16-channel Powerlab DAQ System (ADInstruments). Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Number of Participants With Skin Conductance Level Using Autonomic Response Measures by MRI	Skin conductance level was to planned to be evaluated with MRI-compatible bipolar Silver (Ag)/Silver chloride (AgCl) finger electrodes placed on the palmar aspect of the second and fourth fingers of the non-dominant (left) hand, prior to the MRI session. All peripheral autonomic physiological signals were planned to be collected at 400 Hz using Chart Data Acquisition Software (ADInstruments) on a laptop equipped with a 16-channel Powerlab DAQ System (ADInstruments). Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Number of Participants With Abnormal Heart Rate for Session 1	Data of participants with abnormal heart rate (measured during site visits by sphygmomanometer) were reported. Participants with low and high heart rate has been presented. Potential clinical concern value for heart rate is < 50 beats per minute to > 120 beats per minute. Safety Population comprised of all participants who received at least one dose of the study treatment.	Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: -2 hour pre-MRI, 0.5 and 1 hour post-MRI
Number of Participants With Abnormal Heart Rate for Session 2	Data of participants with abnormal heart rate (measured during site visits by sphygmomanometer) were reported. Participants with low and high heart rate has been presented. Potential clinical concern value for heart rate is < 50 beats per minute to > 120 beats per minute.	Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: -2 hour pre-MRI, 0.5 and 1 hour post-MRI
Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Session 1	SBP and DBP were measured in supine position after 5 minutes rest. Data for Session 1 and 2 and for Pre and Post MRI has been presented. Potential clinical concern value for SBP is <100 millimeters of mercury (mmHg) and >170 mmHg. Potential clinical concern value for DBP is <50 mmHg and >110 mmHg.	Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: 0.5 and 1 hour post-MRI
Number of Participants With Abnormal SBP and DBP for Session 2	SBP and DBP were measured in supine position after 5 minutes rest. Data for Session 1 and 2 and for Pre and Post MRI has been presented. Potential clinical concern value for SBP is <100 millimeters of mercury (mmHg) and >170 mmHg. Potential clinical concern value for DBP is <50 mmHg and >110 mmHg.	Day 1: pre-MRI, 0.5 hour post-MRI; Day 4: -2 hours pre-MRI, 0.5 and 1 hour post MRI; Day 5; Day 8: 0.5 and 1 hour post-MRI
Number of Participants With Abnormal Clinical Chemistry Parameters	Clinical chemistry parameters included assessment of blood urea nitrogen (BUN), creatinine, epidermal growth factor receptor (eGRF), potassium, sodium, calcium, Aspartate transaminase (AST), Alanine transaminase (AST), Alkaline phosphatase, total and direct bilirubin, total protein and albumin.	Up to Week 11
Number of Participants With Abnormal Hematology Parameters	Hematology parameters included assessment of platelet count, red blood cell (RBC) count, hemoglobin, hemotocrit, RBC indices including mean corpuscular volume and mean corpuscular hemoglobin (MCH), and White blood cells (WBC) count with differential count including, neutrophils, lymphocytes, monocytes, eosinophils and basophils.	Up to Week 11
Number of Participants With Abnormal Urinalysis	Urinalysis parameters included assessment of specific gravity, microscopic analysis, and potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method.	Up to Week 11
Number of Participants With Abnormal Glycemic Parameters	Glycemic parameters included assessment of capillary blood glucose and fasting plasma glucose.	Up to Week 11
Number of Participants With Non-serious Adverse Events (AE) With Incidence > = 2 % and Serious AEs (SAE)	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Data of participants with non-serious AEs ( with incidence >= 2%) and SAEs has been presented. Placebo was included to maintain the single blind only; similar to double dummy.	Up to Week 13
Nausea Ratings Scale to Rate Nausea Sensation Using Autonomic Response Measures by MRI	Nausea ratings were planned to be collected during motion sickness provocation using a 0-4 numerical rating scale (NRS), where 1 is rated as minimal nausea experienced and 4 as severe nausea was experienced. Participants were asked to press buttons on a MRI compatible button-box to rate nausea from 0 to 4. Placebo was planned to be used to enable albiglutide and exenatide to be dosed at different times relative to MRI due to differences in Tmax, while preserving single-blind (similar to double dummy), hence data was reported in albiglutide, exenatide and off-therapy arms only.	Up to Week 11
Gastrointestinal (GI) Visual Analogue Scale (VAS) for Assessment of Nausea for Session 1	Participant completed VAS to record their perception of stomach fullness, hunger, nausea, bloating and abdominal pain. The VAS was represented by lines, 100 millimeter in length, anchored with words describing the most negative rating on the left and the most positive rating on the right. Scores ranged from 0 mm to 100 mm. Scores of 0 mm are worst (most negative rating on the left) and scores of 100 mm are best (most positive rating on the right). NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.	Day 1 (Pre-MRI and 0.5 hour post-MRI); Day 4 (Pre-MRI and 0.5 hour post-MRI); and Day 8 (Pre-MRI and 0.5 hour post-MRI)
GI VAS for Assessment of Nausea for Session 2	Participant completed VAS to record their perception of stomach fullness, hunger, nausea, bloating and abdominal pain. The VAS was represented by lines, 100 millimeter in length, anchored with words describing the most negative rating on the left and the most positive rating on the right. Scores ranged from 0 mm to 100 mm. Scores of 0 mm are worst (most negative rating on the left) and scores of 100 mm are best (most positive rating on the right). NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.	Day 1 (Pre-MRI and 0.5 hour post-MRI); Day 4 (Pre-MRI and 0.5 hour post-MRI); and Day 8 (Pre-MRI and 0.5 hour post-MRI)
Motion Sickness Assessment Questionnaire (MSAQ) for Assessment of Nausea for Session 1	Participant completed MSAQ to quantify the severity of different dimensions of nausea induced by motion sickness. There were total 16 items: 4 related to gastro-intestinal (GI), 5 related to central (C), 3 related to peripheral (P) and 4 related to sopite-related (SR). All items were scored individually on a scale of 1-9 where 1 means 'not at all severe' and 9 means 'severe', with higher score indicates more severity. Individual 16 items with their scores are presented. NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.	Day 1 0.5 hour post-MRI; Day 4 0.5 hour post-MRI; and Day 8 0.5 hour post-MRI
MSAQ for Assessment of Nausea for Session 2	Participant completed MSAQ to quantify the severity of different dimensions of nausea induced by motion sickness. There were total 16 items: 4 related to gastro-intestinal (GI), 5 related to central (C), 3 related to peripheral (P) and 4 related to sopite-related (SR). All items were scored individually on a scale of 1-9 where 1 means 'not at all severe' and 9 means 'severe', with higher score indicates more severity. Individual 16 items with their scores are presented. NA indicates that data were not available as standard deviation could not be calculated due to low number of participants.	Day 1 0.5 hour post-MRI; Day 4 0.5 hour post-MRI; and Day 8 0.5 hour post-MRI

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: The General Hospital Corporation d/b/a Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2016
• Primary Completion (Actual): August 10, 2017
• Study Completion (Actual): September 7, 2017

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (Estimate): June 16, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 8, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Nausea; Magnetic resonance imaging; Gastrointestinal; Glucagon like peptide
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide; rGLP-1 protein; Glucagon-Like Peptide 1
• Other Study ID Numbers: 201840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO