This is a randomized, open label, cross-over study in healthy adult subjects to investigate cotadutide exposure after subcutaneous injection at 3 different anatomical sites. The study will be conducted at a single US center. Each subject will be randomized to receive a single SC dose of 100 μg cotadutide via a pen device according to 6 sequences of dosing. Each SC injection will be administered by a health care provider at a different injection site (arm, thigh, or abdomen) in each period. SC injection in the abdomen will be used as the reference treatment to determine the relative PK of cotadutide 100 μg SC injections in the arm and thigh. Each SC injection of cotadutide will be separated by 7 days washout. Blood samples for PK analyses of cotadutide will be taken pre dose and at 11 time points up to 48 hours after dosing (Days 3, 10, and 17).

Inclusion Criteria:

1. Healthy subjects aged 18 through 60 years (inclusive) at the time of screening.
2. Electronic and/or written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
3. BMI between 19 and 30 kg/m2 (inclusive) at screening.
4. Good general health as judged by the investigator, based on medical history, physical examination including 12 lead electrocardiogram (ECG), vital signs, and blood and urinary laboratory assessments.
5. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of investigational product, and must not be breastfeeding.
6. Female subjects of childbearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of investigational product. As applicable, at least one method must be in effect prior to receiving the first dose of investigational product.

Exclusion Criteria:

1. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate, or affect interpretation of subject safety or study results.
2. Inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper GI tract, which may affect gastric emptying or could affect the interpretation of safety and tolerability data.
3. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; eGFR will be determined by the chronic kidney disease - epidemiology collaboration (CKD-EPI) equation.
4. BP and heart rate in supine position outside the ranges of 90 140 mmHg systolic, 50-90 mmHg diastolic and heart rate 40-100 beats/min following a 10 minute rest period.
5. Active hepatitis B, measured by positive tests of surface antigen HBsAg and/or active hepatitis C, measured by positive hepatitis C virus antibody tests.
6. Positive human immunodeficiency virus (HIV) antibodies.
7. Subjects with a history of acute or chronic pancreatitis.
8. Subjects with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and subjects with a screening/baseline serum calcitonin ≥ 50 ng/L.
9. Signs or symptoms of severe hepatic impairment AND any of the following laboratory values at screening: Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN), alanine transaminase (ALT) ≥ 3 × ULN, or total bilirubin (TBL) ≥ 2 × ULN. Alternatively, AST ≥ 5 × ULN, ALT ≥ 5 × ULN, or TBL ≥ 2 × ULN regardless of signs and symptoms. An isolated increase in TBL in subjects with known Gilbert's syndrome is not a reason for exclusion.
10. Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis.
11. History of neoplastic disease within 5 years prior to screening except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
12. Known or suspected allergy to cotadutide, any component of the formulation, or related products.
13. Use of any prescription or nonprescription medication, with the exception of permitted concomitant medications, within the last 72 hours prior to Day 1.
14. History of alcoholism or drug abuse during the last 12 months.
15. Current smoker of cigarettes or other tobacco products.
16. Habitual excessive consumption of methylxanthine containing (theophylline, caffeine, or theobromine) beverages and foods (eg, coffee, tea, red bull, cola, chocolate) as judged by the investigator.
17. Blood donation within the last 3 months.
18. Participation in any other study investigating other products or involving blood sampling within the past 30 days.
19. Potentially noncompliant or uncooperative, as judged by the investigator.
20. Substance dependence likely to impact subject safety or compliance with study procedures, to include a positive test result for drugs of abuse and/or alcohol at screening or prior to administration of investigational product on Day 1.
21. Psychiatric illness such that subjects have been committed to an institution by way of official or judicial order.
22. Involvement of any AstraZeneca, MedImmune, the contract research organization, or the study center employee or their close relatives.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.