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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Conditions
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Gastroparesis

Intervention / Treatment
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* Drug: TC-6499
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One capsule of placebo administered as a single dose. | Drug: Placebo<br> <br> |
| Experimental: 2 mg TC-6499<br>One capsule of 2 mg TC-6499 administered as a single dose. | Drug: TC-6499<br> <br> |
| Experimental: 5 mg TC-6499<br>One capsule of 5 mg TC-6499 administered as a single dose. | Drug: TC-6499<br> <br> |
| Experimental: 10 mg TC-6499<br>One capsule of 10 mg TC-6499 administered as a single dose. | Drug: TC-6499<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in gastric emptying half-time determined for each treatment relative to placebo after single dose administration of study drug in each arm. | Gastric emptying time will be assessed using the oral 13-C-spirulina breath test also known as the Gastric Emptying Breath Test (GEBT) administered following each treatment. | 4 hrs post-GEBT meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent dose excreted as 13-CO2 at specific post-meal time points for each treatment relative to placebo after single dose administration of study drug in each arm. |  | 90 and 120 min post-GEBT meal | 
| The time of maximal rate of 13-CO2 expiration for each treatment relative to placebo after single dose administration of study drug in each arm. |  | 4 hrs post-GEBT meal |