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

Gastroparesis, also referred to as delayed gastric emptying, is a debilitating, chronic disorder that slows or stops the passage of food from the stomach to the small intestine. The purpose of this study is to test whether TC-6499 is safe and effective at reducing 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 (actual = 23 randomized subjects and 21 completing all 4 arms of the crossover).

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