Effect of Ileal Bile Acid Transporter Inhibitor in Functional Constipation

NCT01038687 | Completed Phase 2 Results

• 2 other identifiers: 09-006618UL1RR024150
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Functional Constipation

Keywords

functional constipation; bile acid

Outcome Measures

Primary Outcomes (1)

• Colonic Transit at 24 Hours

  Subjects ingested a Technetium-99m sulfur colloid radiolabeled meal and Indium-111 absorbed on to activated charcoal particles and delivered to the colon by an oral methacrylate-coated capsule. Colonic transit was measured by quantification of radioactive counts via abdominal scintiscans. Overall colonic transit was computed as the colonic geometric center (GC), which is the weighted average of counts in the different colonic regions (ascending, transverse, descending, rectosigmoid and stool), respectively numbered 1 to 5. At any time point, the GC equals the proportion of counts in each colonic region multiplied by its weighting factor: (%ACx1+%TCx2+%DCx3+%RSx4+%stoolx5)/100. As such, a higher GC reflects faster colonic transit. A GC of 1 implies all the isotope is in the ascending colon and a GC of 5 implies all the isotope is in the stool.

  24 hours post-radiolabeled meal

Secondary Outcomes (8)

• Colonic Filling

  6 hours post-radiolabeled meal

• Gastric Emptying , T1/2

  post-treatment, approximately 12-14 days

• Ascending Colon Emptying t 1/2

  post-treatment, approximately 12-14 days

• Colonic Transit at 8 Hours

  8 hours post-radiolabeled meal

• Colonic Transit at 48 Hours

  48 hours post-radiolabeled meal

Study Arms (3)

A3309 15 mg

EXPERIMENTAL

Patients randomized to this arm received one oral tablet daily of 15 mg A3309 for a period of 14 consecutive days.

Drug: A3309

A3309 20 mg

EXPERIMENTAL

Patients randomized to this arm received one oral tablet daily of 20 mg A3309 for a period of 14 consecutive days.

Drug: A3309

Placebo

PLACEBO COMPARATOR

Patients randomized to this arm received one oral tablet daily of a matching placebo for a period of 14 consecutive days.

Drug: placebo

Interventions

A3309 DRUG

A3390, a bile acid transport inhibitor was provided in either 15 mg or 20 mg oral tablets

Also known as: Elobixibat

A3309 15 mg; A3309 20 mg

placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females aged 18 to 65 years old inclusive
• A diagnosis of functional constipation as defined by two or more of the following:
• fewer than three spontaneous complete bowel movements per week
• hard or lumpy stools more than 25 % of the time
• straining during a bowel movement more than 25 % of the time
• 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.
• 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.
• Able to provide written informed consent prior to any study procedures being performed

You may not qualify if:

• Female patients who are pregnant or breast feeding
• 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.
• 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.
• 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.
• Patients who are considered by the PI to be alcoholics not in remission or known substance abusers.
• Patients who have participated in another clinical study in the past 30 days.

Sponsors & Collaborators

• Michael Camilleri, MD: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Wong BS, Camilleri M, McKinzie S, Burton D, Graffner H, Zinsmeister AR. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am J Gastroenterol. 2011 Dec;106(12):2154-64. doi: 10.1038/ajg.2011.285. Epub 2011 Aug 30.

  PMID: 21876564 RESULT

• Rudling M, Camilleri M, Graffner H, Holst JJ, Rikner L. Specific inhibition of bile acid transport alters plasma lipids and GLP-1. BMC Cardiovasc Disord. 2015 Jul 22;15:75. doi: 10.1186/s12872-015-0070-9.

  PMID: 26197999 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

elobixibat

Results Point of Contact

• Title: Michael Camilleri, MD
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-266-2305

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 22, 2009
• First Posted: December 24, 2009
• Study Start: January 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: September 4, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-09

Locations

US (1)