A Pilot Study Investigating Bioequivalence Between a Single Dose of Formulation 2 and Formulation 3 of MEDI0382

This is a randomized, open label, cross-over, two-period, pilot study in healthy adult
subjects to evaluate the bioequivalence between formulation 2 and formulation 3 of MEDI0382
after a single subcutaneous (SC) dose. The study will be conducted at a single US center.
Each subject will be randomized to receive a single 100 μg (or equimolar equivalent) SC dose
of both formulation 2 and 3 of MEDI0382 on two different in-house periods separated by a
washout period of 7 days. Formulation 3 of MEDI0382 has not been administered to humans
previously.

Subjects will receive the same absolute amount of MEDI0382, when dosed with either
formulation 2 or formulation 3. Formulations of MEDI0382 will be administered via SC
injection in the abdomen of subjects. Subjects will be in the study for a maximum of 59 days,
which includes a screening period of up to 21 days. On Day 1, subjects will admitted to the
clinic and will be randomized to receive formulation 2 and formulation 3 in one of two
sequences; subjects randomized to sequence 1 will receive formulation 2 on Day 1 and
formulation 3 on Day 10 and subjects randomized to sequence 2 will receive formulation 3 on
Day 1 and formulation 2 on Day 10.

On Day 3, subjects will be discharged from the clinic and a 7-day washout period will follow.
Subjects will return to the clinic on Day 10 to receive the second dose of investigational
product and will remain in-house for 3 days. After discharge on Day 12, subjects will return
on Day 38 for the end of study visit. Blood samples for PK analyses of MEDI0382
concentrations will be taken predose and at 11 time points up to 48 hours after dosing (Days
3 and 12). Bedside plasma glucose levels will be monitored before meals and at bedtime during
Days 1 and 10 and will be measured prior to breakfast on Days 2 and 11.

Inclusion Criteria:

1. Healthy subjects age 18 through 45 years at the time of screening.

2. Provision of signed and dated written informed consent prior to study-specific
procedures.

3. Body mass index 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 ECG, vital signs, and blood and urinary laboratory
assessments.

5. Female subjects of childbearing potential must have a negative pregnancy test at
screening and randomization and must not be lactating.

6. Females of childbearing potential who are sexually active with a nonsterilized male
partner must use at least one highly effective method of contraception (see Section
10.2 for definition of females of childbearing potential and for a description of
highly effective methods of contraception) from screening and must agree to continue
using such precautions through to the end of the study. It is strongly recommended for
the male partner of a female subject to also use a male condom plus spermicide
throughout this period. Cessation of contraception after this point should be
discussed with a responsible physician. Periodic abstinence, the rhythm method, and
the withdrawal method are not acceptable methods of contraception.

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 the interpretation of the
results of the study

2. Impaired renal function, defined as s-creatinine ≥ 130 µmol/L

3. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2

4. Blood pressure 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. Any clinically significant abnormal ECG, as judged by the investigator

6. Active hepatitis B, measured by positive tests of surface antigen HBsAg and/or active
hepatitis C, measured by positive hepatitis C virus antibody tests

7. Positive human immunodeficiency virus antibodies

8. Known or suspected allergy to MEDI0382, any component of the formulation, or related
products

9. Use of any prescription or nonprescription medication, except for paracetamol,
hormonal contraceptives, and vitamins within the last 72 hours prior to check-in

10. History of alcoholism or drug abuse during the last 12 months

11. Smoking of cigarettes or other tobacco products

12. Habitual excessive consumption of methylxanthine-containing (theophylline, caffeine or
theobromine) beverages and foods (coffee, tea, soft drinks such as red bull, cola,
chocolate) as judged by the investigator

13. Blood donation within the last 3 months

14. Participation in any other trial investigating other products or involving blood
sampling within the past 30 days

15. Potentially noncompliant or uncooperative, as judged by the investigator

16. Substance dependence likely to impact subject safety or compliance with study
procedures

17. Psychiatric illness such that subjects have been committed to an institution by way of
official or judicial order

18. Involvement of any AstraZeneca, MedImmune, the contract research organization, or the
study site employee or their close relatives