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

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).


Eligibility Criteria:
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