Study of the Effects of ITCA 650 on Gastric Emptying and Interaction of ITCA 650 on 4 Commonly Studied Drugs

Acetaminophen will be use to assess the effect of ITCA 650 on the rate of gastric emptying.

Interactions between ITCA 650 and the medications lisinopril, digoxin, atorvastatin, and
warfarin will also be studied.

Inclusion Criteria:

- Body mass index (BMI) between 19 to 32 kg/m2.

- Glycosylated hemoglobin A1c (HbA1c )<6.5%.

- Normal renal function (eGFR ≥80 mL/min/1.73 m2).

- Women of child bearing potential - use of an additional adequate method of
contraception during the study and until 1 additional menstrual cycle following the
end-of-study (EOS) visit. Adequate methods of contraception for women of child
bearing potential (WOCBP) include: mechanical products (ie, intrauterine device
[IUD]—copper IUD); or barrier methods (eg, diaphragm, condoms, cervical cap) with
spermicide.

Exclusion Criteria:

- History of type 1 or type 2 diabetes.

- History or evidence of myocardial infarction, coronary revascularization (coronary
artery bypass grafting or percutaneous coronary intervention), unstable angina, or
cerebrovascular accident or stroke.

- History of uncontrolled hypertension.

- History or evidence of acute or chronic pancreatitis.

- History of liver disease.

- History of medullary thyroid cancer or a personal or family history of multiple
endocrine neoplasia type 2.

- Poor thyroid, liver, or renal function.

- Weight loss surgery or requires weight loss medications.

- History of malignancy (not including basal or squamous cell carcinoma of the skin
with past 5 years). (Subjects who have been disease free for 5 years may be
included.)

- History of active alcohol or substance abuse.

- Weekly consumption of more than 7 alcoholic beverages for females and 14 alcoholic
beverages for males.

- Excessive in xanthine consumption (more than 5 cups of coffee or equivalent per day).

- Treatment with medications that affect GI motility.

- Any condition that would affect drug transit time or absorption (eg, gastrointestinal
bypass surgery, partial or total gastrectomy, small bowel resection, chronic
diarrhea, vagotomy, chronic gastroesophageal reflux disease, malabsorption,
colostomy, Crohn's disease, ulcerative colitis, or celiac sprue).

- History of hypersensitivity to exenatide.

- Contraindications or warnings according to the specific label(s) for acetaminophen,
atorvastatin, lisinopril, digoxin or warfarin therapy.

- Women that are pregnant, lactating, or planning to become pregnant.

- Concurrent use of anticoagulants, including daily low dose aspirin (81 mg).

- History of or positive results on screening tests for hepatitis B and/or hepatitis C
and/or human immunodeficiency virus (HIV).

- Planned in-patient surgery, dental procedure, or hospitalization during the study.

- Prior or current treatment with any glucagon-like peptide-1 (GLP-1) receptor agonist
(eg, Bydureon™, Byetta®, Victoza®, Tanzeum® or exogenous native GLP-1) or prior
participation in an ITCA 650 clinical trial.

- Use or intended use of any drug or other product that inhibits or induces cytochrome
P450 (CYP)1A2, CYP2C9, CYP2C19, or CYP3A4 within 14 days prior to the first dose of
warfarin or ITCA650 or during the conduct of the study.

- History of thrombophlebitis, thromboembolic disorders, or deep vein thrombophlebitis.

- Fasting triglycerides above upper limit of normal at Screening.

- Any gastrointestinal complaints within 7 days prior to first dosing.

- Taking drugs or natural herbal supplements (such as albuterol, antacids, and St.
John's Wort) with known interactions with atorvastatin, lisinopril, digoxin, or
warfarin from within 7 days prior to Day 1 until EOS

- Consumed or unwilling to refrain from grapefruit, cranberries, grapefruit- or
cranberry-containing products, or Seville oranges from within 7 days prior to Day 1
until EOS.

- Chronic use of analgesics, pain medication, or non-steroidal anti-inflammatory
agents.