Effect of Ileal Bile Acid Transporter Inhibitor in Functional Constipation

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01038687
First received: December 22, 2009
Last updated: July 31, 2012
Last verified: July 2012
  Purpose

This is a single-center, randomized, parallel group, double-blind, placebo-controlled, dose response, pharmacodynamic and pharmacokinetic study evaluating the effects of A3309 on gastric, intestinal and colonic transit in patients with functional constipation.


Condition Intervention Phase
Functional Constipation
Drug: A3309
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of A3309, an Ileal Bile Acid Transport Inhibitor, on Gastrointestinal and Colonic Motor Functions in Female Patients With Functional Constipation

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Colonic geometric center at 24 h as measured by scintigraphy. [ Time Frame: 24 h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Colonic filling at 6 h measured by scintigraphy. [ Time Frame: 6 h ] [ Designated as safety issue: No ]
  • Small bowel transit time, T10% measured by scintigraphy [ Time Frame: day 1 ] [ Designated as safety issue: No ]
  • T1/2 of ascending colon emptying measured by scintigraphy. [ Time Frame: first 48 h ] [ Designated as safety issue: No ]
  • Colonic geometric center at 48 h measured by scintigraphy. [ Time Frame: 48h ] [ Designated as safety issue: No ]
  • Gastric emptying , T1/2 measured by scintigraphy [ Time Frame: day 1 ] [ Designated as safety issue: No ]
  • Stool frequency and consistency based on the Bowel Pattern Diary. [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) characteristics for each dose of A3309. [ Time Frame: 8h ] [ Designated as safety issue: No ]
  • Safety and tolerability of A3309 administered as an oral tablet. [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: January 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A3309 15 mg
Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days.
Drug: A3309
A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets
Other Name: Elobixibat
Experimental: A3309 20 mg
Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days.
Drug: A3309
A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets
Other Name: Elobixibat
Placebo Comparator: Placebo
Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days.
Drug: placebo
placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  1. Females aged 18 to 65 years old inclusive
  2. A diagnosis of functional constipation as defined by two or more of the following:

    1. fewer than three spontaneous complete bowel movements per week
    2. hard or lumpy stools more than 25 % of the time
    3. straining during a bowel movement more than 25 % of the time
  3. A normal rectal exam result on file within the past 2 years or performed at screen to exclude the possibility of an evacuation disorder. Examination must exclude findings suggestive of an evacuation disorder such as high sphincter tone at rest, failure of perineal descent and spasm, tenderness or paradoxical contraction of the puborectalis muscles.
  4. Females of child-bearing potential (those who have not experienced a bilateral tubal ligation, hysterectomy or menopause) must use an acceptable method of contraception during the study. Acceptable methods are surgical sterilization, hormonal methods such as oral contraceptives, Norplant and Depo-Provera, double barrier method such as a condom and spermicide, and an IUD.

    Abstinent females may participate if they agree to use the double barrier method should they become sexually active during the study.

  5. Able to provide written informed consent prior to any study procedures being performed

EXCLUSION CRITERIA

  1. Female patients who are pregnant or breast feeding
  2. Structural or metabolic diseases/conditions that affect the gastrointestinal system or functional gastrointestinal disorders other than constipation. The long version BDQ will be used to confirm patients have constipation.
  3. Unable to withdraw all medications 48 hours prior to Visit 1; any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids. prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants and SNRIs; analgesic drugs including opiates, NSAIDs, and COX-2 inhibitors (Note: Tylenol is permitted), GABAergic agents and benzodiazepines.

    Note: All other concomitant medications will be reviewed on a case by case basis by the study physicians.

  4. Clinical evidence (including but not limited to a clinically significant abnormal physical exam, ECG or laboratory test result in the past medical record) or current clinically significant abnormal physical exam or laboratory test result that could indicate significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other diseases that interfere with the objectives of the study. If a laboratory test result is abnormal and clinically significant, it may be repeated once at the discretion of the PI. If the laboratory test result remains abnormal and clinically significant, the patient will be discontinued from the study and referred to a primary care physician for further evaluation.
  5. Patients who are considered by the PI to be alcoholics not in remission or known substance abusers.
  6. Patients who have participated in another clinical study in the past 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01038687

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Michael Camilleri, MD Mayo Clinic
  More Information

Publications:
Responsible Party: Michael Camilleri, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01038687     History of Changes
Other Study ID Numbers: 09-006618, UL1RR024150
Study First Received: December 22, 2009
Last Updated: July 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
functional constipation
bile acid

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Bile Acids and Salts
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014