Safety and Efficacy Study of Exenatide Once Weekly in Adolescents With Type 2 Diabetes

This Phase 3, double-blind (controlled assessment period), randomized, multicenter,
placebo-controlled parallel study is designed to examine the efficacy and safety of EQW
compared to placebo (PBO) in adolescents with type 2 diabetes for 24 weeks. This study will
assess safety and efficacy of EQW (as monotherapy and adjunctive therapy to oral antidiabetic
agents and/or insulin). At least 40% and not more than 60% of the randomized patients must be
females. At least 40% of patients should be recruited from areas with similar ethnicity and
lifestyle to those of the European Union member states. Long term safety and efficacy of EQW
will subsequently be monitored for 28 weeks in the open-label, uncontrolled extension period
(through Week 52). The study will be terminated at Visit 11 (Week 62/Study Termination) which
will be a follow-up visit occurring 10 weeks after the last dose administration at Visit 10
(Week 52). This study will be conducted in 77 patients with type 2 diabetes treated with diet
and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or
insulin for at least 2 months prior to screening. During the controlled assessment period,
approximately 77 patients will be randomly assigned in a 5:2 ratio to either EQW 2 mg (Group
A) or PBO (Group B), to yield at least 70 evaluable patients: at least 50 patients in the
exenatide and at least 20 patients in the PBO group. Following the 24-week controlled
assessment period, patients assigned to the EQW 2 mg treatment (Group A) will continue to be
treated with EQW 2 mg during the extension period (through Week 52). Patients randomized to
PBO (Group B) will receive EQW 2 mg beginning at the start of the extension period, Week 25
through Week 52. In addition to receiving study medications, all patients will participate in
a lifestyle intervention program encompassing diet and physical activity modifications
following the signing of the informed consent and assent forms (Visit 1 [Week -2]) through
the end of the extension period (Week 52). Following Visit 11 (Week 62/Study Termination),
patients whose height increase is at least 5 mm between Visit 8 (Week 28) and Visit 11 (Week
62/Study Termination) will participate in a long-term safety follow-up period. Patients who
discontinue study medication prior to Visit 11 (Week 62/Study Termination) will also
participate in the Extended Safety Follow-up Period, unless they have a height increase of
less than 5 mm over a 6-month interval at study site visits prior to discontinuation of study
medication. Patients who do not have height assessments at study-site visits over a 6-month
interval prior to discontinuation of study medication will enter the Extended Safety
Follow-up Period. The Extended Safety Follow Up Period will continue for up to 3 years or
until the difference between two 6-month interval visits is less than a 5 mm increase
(whichever comes first). No study medication will be administered during the Extended Safety
Follow-up Period. Blood samples will be collected for calcitonin and carcinoembryonic antigen
(CEA) laboratory measurements.

Each patient must meet the following criteria to be enrolled in this study.

1. Is a child or an adolescent of 10 to <18 years old, at Visit 1 (Screening)

2. Has been diagnosed with type 2 diabetes mellitus per American Diabetes Association
diagnostic criteria

3. HbA1c of 6.5% to 11.0%, inclusive, in patients not taking insulin/SU, and of 6.5% to
12.0%, inclusive, in patients taking insulin/SU, at Visit 1 (Screening)

4. Has a C-peptide of >0.6 ng/L at Visit 1 (Screening)

5. Has been treated with diet and exercise alone or in combination with a stable dose of
an oral antidiabetic agent (e.g., metformin and/or SU) and/or insulin for their type 2
diabetes for at least 2 months prior to Visit 1 (Screening)

6. Has a fasting plasma glucose concentration <280 mg/dL (15.5 mmol/L) at Visit 1
(Screening)

Patients who meet any of the following criteria will be excluded from the study.

1. Has a clinically significant medical condition that could potentially affect study
participation and/or personal well-being, as judged by the Investigator, including but
not limited to the following conditions:

1. Hepatic disease (defined by aspartate or alanine transaminase >3.0 times the
upper limit of normal (ULN)

2. Renal disease or serum creatinine >1.5 mg/dL (132.6 µmol/L) (males) or 1.4 mg/dL
(123.8 µmol/L) (females)

3. Gastrointestinal disease deemed significant by the Investigator

4. Organ transplantation

5. Chronic infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B
virus, or hepatitis C virus)

6. Clinically significant malignant disease (with the exception of basal and
squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening)

2. Has positive antibody titers to glutamic acid decarboxylase (GAD65) or islet cell
antigen (ICA512) at Visit 1 (Screening)

3. Has a personal or family history of elevated calcitonin, calcitonin >100 ng/L,
medullary thyroid carcinoma, or multiple endocrine neoplasia-2

4. Has ever used exenatide (exenatide once weekly [exenatide LAR], exenatide BID, BYETTA,
or any other formulation) or any glucagon-like peptide-1 (GLP-1) receptor agonist
(e.g., liraglutide [Victoza®])

5. Is pregnant