This is a pharmacodynamic study in healthy volunteers to determine the effects of a new 5-HT4 agonist on gastric, small bowel and colonic transit.
ATI-7505, is an engineered analog of the 5-HT4 agent, cisapride. The objectives of this study are to compare effects of ATI-7505 and placebo on gastric, small bowel and colonic transit in healthy human volunteers and evaluate the safety and tolerability of ATI-7505. This trial is a double-blind, randomized, placebo-controlled study evaluating the gastrointestinal transit effects of ATI-7505 and placebo. Three different doses (3, 10, 30mg) of ATI-7505 and placebo will be administered in parallel to four independent groups of 12 subjects each. The maximum duration of drug exposure for any subject is 9 days. All participants will undergo a standard 48 hour gastrointestinal transit measurement using scintigraphy with standardized meals during the first 12 hours. The response endpoints (colonic geometric center at 4 h, colonic geometric center at 24 h, colonic geometric center at 48 h, gastric residual at 2 \& 4 h, colonic filling at 6 h and ascending colonic emptying t1/2) will be based on abdominal scintigraphic images following the technetium-99m egg meal and methacrylate-coated, delayed-release capsule containing 111In labeled activated charcoal. Safety and tolerability will be evaluated by serial assessment of vital signs, physical examination, ECG, adverse events, concomitant medications and blood sample analysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
48
Mayo Clinic
Rochester, Minnesota, United States
Colonic geometric center at 24 h
Colonic geometric center determined 24 hours post first camera image following ingestion of study medication with Indium-111 capsule and breakfast with Technetium-99 labeled egg breakfast
Time frame: 24 hours
Ascending colonic emptying t1/2
As measured with scintigraphic method following 111In labeled capsule and 99Tc labeled egg breakfast
Time frame: 24 hours
Gastric emptying of solids (T1/2)
As measured with scintigraphic method following technetium-99m egg meal
Time frame: 4 hours
Colonic filling at 6 h
As measured with scintigraphic method following ingestion of 111In labeled capsule and 99Tc labeled egg breakfast
Time frame: 6 hours
Colonic geometric center at 48 hours
As measured with scintigraphic method following ingestion of In111 capsule and Tc99 labeled breakfast
Time frame: 48 hours
Percent gastric emptying at 1, 2 and 4 hours
As measured with scintigraphic method following ingestion of 99Tc labeled egg breakfast
Time frame: 4 hours
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20 mg ATI-7505 three times daily for 9 days