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Effect of ATI-7505 on Gastrointestinal Transit in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT01094821
Recruitment Status : Completed
First Posted : March 29, 2010
Last Update Posted : March 29, 2010
Sponsor:
Collaborator:
ARYx Therapeutics
Information provided by:
Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: ATI-7505 Drug: Placebo Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : January 2005
Actual Primary Completion Date : December 2005
Actual Study Completion Date : December 2005

Arm Intervention/treatment
Experimental: 3 mg ATI-7505
3 mg ATI-7505 three times daily for 9 days followed by transit scintigraphy
Drug: ATI-7505
3 mg three times daily for 9 days

Placebo Comparator: Placebo
Placebo capsule three times daily for 9 days followed by transit scintigraphy
Drug: Placebo
Placebo capsule three times daily for 9 days

Experimental: 10 mg ATI-7505
10 mg ATI-7505 three times daily for 9 days followed by transit scintigraphy
Drug: ATI-7505
10 mg ATI-7505 three times daily for 9 days

Experimental: 20 mg ATI-7505
20 mg ATI-7505 three times daily for 9 days followed by transit scintigraphy
Drug: ATI-7505
20 mg ATI-7505 three times daily for 9 days




Primary Outcome Measures :
  1. Colonic geometric center at 24 h [ Time Frame: 24 hours ]
    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

  2. Ascending colonic emptying t1/2 [ Time Frame: 24 hours ]
    As measured with scintigraphic method following 111In labeled capsule and 99Tc labeled egg breakfast

  3. Gastric emptying of solids (T1/2) [ Time Frame: 4 hours ]
    As measured with scintigraphic method following technetium-99m egg meal


Secondary Outcome Measures :
  1. Colonic filling at 6 h [ Time Frame: 6 hours ]
    As measured with scintigraphic method following ingestion of 111In labeled capsule and 99Tc labeled egg breakfast

  2. Colonic geometric center at 48 hours [ Time Frame: 48 hours ]
    As measured with scintigraphic method following ingestion of In111 capsule and Tc99 labeled breakfast

  3. Percent gastric emptying at 1, 2 and 4 hours [ Time Frame: 4 hours ]
    As measured with scintigraphic method following ingestion of 99Tc labeled egg breakfast



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy volunteers between the ages of 18 to 65 years old (inclusive) with a BMI ≥ 18 and ≤ 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01094821


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
ARYx Therapeutics
Investigators
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Principal Investigator: Michael Camilleri, MD Mayo Clinic

Publications of Results:
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Responsible Party: Michael Camilleri, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01094821     History of Changes
Other Study ID Numbers: IRB 276-05
IND 68,208 ( Other Identifier: FDA issued IND number )
First Posted: March 29, 2010    Key Record Dates
Last Update Posted: March 29, 2010
Last Verified: March 2010

Keywords provided by Mayo Clinic:
Healthy volunteers
ATI-7505
Scintigraphy
Gastrointestinal transit

Additional relevant MeSH terms:
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ATI 7505
Serotonin 5-HT4 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs