Clinical trial NCT01094821: Effect of ATI-7505 on Gastrointestinal Transit in Healthy Volunteers
Official title: A Double Blind, Randomized, Placebo Controlled, Parallel Group Study to Investigate the Effect of ATI-7505 on Gastric Emptying and Small Bowel and Colonic Transit in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Keywords: Healthy volunteers
ATI-7505
Scintigraphy
Gastrointestinal transit
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: ARYx Therapeutics
First posted: 2010-03-29
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Healthy volunteers between the ages of 18 to 65 years old (inclusive) with a BMI \&#8805; 18 and \&#8804; 32
2. PR, QRS and QT intervals within normal limits on screening ECG. Specifically, PR \< 220 msec, QRS \< 140 msec, QTc \< 450 msec
3. Are able and willing to understand study requirements, follow instructions, attend all required study visits (especially during 48 hrs of scintigraphic scan), undergo all planned tests (including drawing of blood samples and consumption of standardized study meals)
4. Are able and willing to sign IRB-approved, written informed consent to participate in this study
5. Have had negative urine screen and clinical history (prior 2 years) for drugs of abuse at screening visit
6. Women with no child bearing potential, as defined by at least 1 year post-menopausal (absence of vaginal bleeding or spotting) or surgically sterile. Men will have a sterile sexual partner or will, starting at time of study drug administration a minimum of 1 month after study drug administration, be willing to use an approved method of contraception (which may include use of a condom with spermicide or use by partner of oral, implantable or injectable contraceptives, IUD, diaphragm with spermicide)

Exclusion Criteria

1. Inability to understand study requirements or follow study procedures (especially entire 48 h of scintigraphy examination), attend all required study visits, undergo all planned tests (including drawing of blood samples and consumption of study meals)
2. Any out of range laboratory value at screening that has not been reviewed, approved and documented as not clinically significant (NCS) by the Principal Investigator.
3. Use of alcohol within 24 h of randomization visit (Visit 2) and through completion of the study
4. History of untoward effects of metoclopramide
5. Any clinically significant abnormality on screening ECG.
6. Any other condition or clinically significant abnormal findings on the physical examination, medical history, or clinical laboratory results during screening that, in the opinion of the Principal Investigator, would make the subject unsuitable for the study or put them at additional risk)
7. Known allergy, hypersensitivity or sensitivity to cisapride
8. Pregnancy or lactation
9. History of alcohol or other substance abuse within the past two years
10. Received treatment with any other investigational drug within the preceding 30 days or 5 half-lives, whichever is greater
11. Major surgery within 3 months of study entry and any surgery within 2 weeks of study entry unless approved by the Principal Investigator and Sponsor?s Medical Monitor
12. Any documented history of irregular intestinal transit including but not limited to gastro-esophageal reflux disease (GERD), gastroparesis of any kind, irritable bowel syndrome, inflammatory bowel disease and chronic constipation or diarrhea under the care of a physician and/or requiring daily medication
13. Any history of gastrointestinal tract or abdominal surgery, except tubal ligation, hysterectomy, appendectomy, cholecystectomy or hemorrhoid surgery \> 3 months prior to screening
14. More than three positive (i.e., ?yes?) responses on screening bowel symptom questionnaire

Primary outcomes:
measure: Colonic geometric center at 24 h
timeFrame: 24 hours
measure: Ascending colonic emptying t1/2
timeFrame: 24 hours
measure: Gastric emptying of solids (T1/2)
timeFrame: 4 hours
Secondary outcomes:
measure: Colonic filling at 6 h
timeFrame: 6 hours
measure: Colonic geometric center at 48 hours
timeFrame: 48 hours
measure: Percent gastric emptying at 1, 2 and 4 hours
timeFrame: 4 hours
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Camilleri M, Vazquez-Roque MI, Burton D, Ford T, McKinzie S, Zinsmeister AR, Druzgala P. Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans. Neurogastroenterol Motil. 2007 Jan;19(1):30-8. doi: 10.1111/j.1365-2982.2006.00865.x.