Study Evaluating the Effect of TC-6499 on Gastric Emptying Time in Diabetic Subjects With Gastroparesis

This is a 4-way crossover study to assess the effect of TC-6499 on gastric emptying time in
diabetic subjects with gastroparesis. The length of study participation for a subject is up
to 50 days. During screening, eligible subjects will complete an oral 13-C-spirulina breath
test also known as the Gastric Emptying Breath Test (GEBT). During the treatment period,
subjects will complete 4 overnight drug assessment visits (treatment arms) where they will
receive a randomized single dose of study drug and the GEBT. Each overnight visit will be
separated by approximately 7 days. At least 18 subjects will be randomized and complete all
4 dosing arms.

Inclusion Criteria:

- A diagnosis of gastroparesis or symptoms consistent with gastroparesis for at least 6
months (and Gastroparesis Cardinal Symptoms Index total score >22)

- Gastroparesis confirmed using the GEBT

- Type 1 or Type 2 diabetes with a Hemoglobin A1c ≤ 10%

- Fasting blood glucose (finger stick) ≤ 275 mg/dL prior to each GEBT

- Body Mass Index (BMI) ≤ 40

- Willingness to remain in clinical research facility for the protocol-required days of
treatment and study procedures

- Willingness to use a double barrier method of birth control (except post-menopausal
females)

- Able to understand study procedures and provide written informed consent

Exclusion Criteria:

- History of abdominal surgery including gastric banding procedure

- Chronic parenteral feeding or feeding through a gastrostomy or jejunostomy tube

- Persistent daily vomiting

- A history of eating disorder

- Recent history of poor control of diabetes

- Acute severe gastroenteritis

- Have implanted or use any type of gastric electric stimulator

- Use of opiates, anticholinergic medications, GLP-1 mimetics or amylin analogs

- Use of medications potentially influencing upper gastrointestinal motility or
appetite

- Allergies or intolerance to egg, wheat, milk, or algae

- Pregnant or lactating females

- Presence of a clinically significant medical condition at any time during the study

- Presence of clinically significant abnormalities in laboratory findings, physical
exam findings or vital signs

- Participated in an investigational drug study within 30 days of screening