Safety and Efficacy of AST-120 in Patients With Non-Constipating Irritable Bowel Syndrome

NCT ID: NCT00583128

Last Updated: 2014-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2010-06-30

Brief Summary

The objective of this study is to evaluate the safety and effectiveness of the experimental drug AST-120 in treating patients with non-constipating IBS. The study will test whether or not patients receiving AST-120 experience at least a 50% reduction in the number of days with abdominal pain compared to placebo.

Detailed Description

Patients experiencing non-constipating IBS will be randomized to one of two arms in the study: the experimental drug AST-120 or placebo. Patients will take 2g of AST-120 or placebo three times per day for eight weeks. After the 8 week course, patients will receive an additional 8 weeks single blind treatment, after a one week washout period.

The experimental drug AST-120 is composed of black, odorless spherical carbon particles in 2g sachets (aluminum foil pouches). The placebo consists of microcrystalline cellulose spheres, Celphere CP-305 stained to match the appearance of AST-120, in 2g sachets (aluminum foil pouches). Both AST-120 and placebo are oral (taken by mouth) preparations. Both are tasteless. To take the product, patients will tear open the sachet, drop the contents directly on their tongue and wash it down with 8 ounces of water.

Patients will be expected to participate in up to 10 visits, approximately three by telephone and the remainder of visits are in-clinic. At these visits, patients will undergo a number of tests including: hematology panel, lactose intolerance testing, physical exams, pregnancy tests, evaluations based on the following scales: The Bristol Stool Scale, IBS Severity Scale, IBS Quality of Life, SCL-90R.

Provided the patient has been stable for eight weeks prior to their baseline visit, they will be allowed to take the following medications: drugs that inhibit gastric secretion (histamine blockers, proton pump inhibitors), benzodiazepines and Imidazopyridines (short acting, nonbenzodiazepine hypnotics) for sleep (dose must be consistent with the use of a sleep agent) aspirin at a cardiovascular prophylactic dose (75-150 mg/day) and paracetamol. Antidepressants for non-IBS symptoms are allowed. Loperamide will be permitted as a rescue for diarrhea only when patients are experiencing at least 3 liquid or soft stools in one day. However, Loperamide is prohibited during the two week screening period.

Patients will not be allowed to take the following medications whilst on trial and these therapies must have been discontinued by at least two weeks prior to their baseline visit: probiotics, neuroleptics, antidepressants for IBS symptoms, daytime tranquilizers, prokinetics, spasmolytics, analgesics, other investigational agents and any over-the-counter medications.

Patient will be required to keep a diary during the study

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

AST-120, 2 gram sachets

Group Type: EXPERIMENTAL

AST-120

Intervention Type: DRUG

oral, sachet, 2 grams three times daily for 8 weeks

2

Celphere® CP-305, stained to match appearance of AST-120, in 2g sachets

Group Type: PLACEBO_COMPARATOR

Celphere® CP-305

Intervention Type: DRUG

oral, placebo, sachet, 2 grams three times daily for 8 weeks

Interventions

AST-120

oral, sachet, 2 grams three times daily for 8 weeks

Intervention Type: DRUG

Celphere® CP-305

oral, placebo, sachet, 2 grams three times daily for 8 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body weight ≥ 40 kg;
• Recurrent abdominal pain or discomfort for three or more days per month for the last three months which meets Rome III criteria for non-constipating IBS;
• Patients on a stable diet for at least eight weeks;
• Patients ≥ 50 years of age with a negative screening colonoscopy in the last five years;
• Able and willing to comply with all protocol procedures for the planned duration of the study;
• Able and willing to understand, sign and date an informed consent document, and authorize access to protected health information,
• Females must be postmenopausal, surgically incapable of bearing children, or practicing a reliable method of birth control (intrauterine devices, spermicide and barrier) (Hormonal contraceptives are NOT regarded as adequate for the purpose of this trial.) Partner/spouse sterility may also qualify at the Investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline.

Exclusion Criteria

• Constipating IBS;
• History of untreated lactose intolerance;
• History of colonic or major abdominal surgery (colectomy, for example);
• Active (untreated) Thyroid disease;
• Current diagnosis of major depression or psychosis;
• Known positive stool cultures for Clostridium difficile or other pathogens;
• Any condition necessitating the administration of analgesics (except paracetamol), probiotics, neuroleptics, antidepressants for IBS symptoms, daytime tranquilizers, prokinetics or spasmolytic medications;
• Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling;
• Other major physical or major psychiatric illness within the last six months that in the opinion of the investigator would affect the patient's ability to complete the trial;
• Uncontrolled systemic disease such as diabetes;
• Patients undergoing chemotherapy for the treatment of cancer;
• Known hypersensitivity or contraindication to any component of the test product (study drugs) or diagnostics used;
• Participation in another study within eight (8) weeks prior to the study;
• Unable to attend all visits required by the protocol;
• Female patients must be excluded if they are pregnant, breast feeding, or planning to become pregnant during the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ocera Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Tack, MD

Role: PRINCIPAL_INVESTIGATOR

University of Leuven, Department of Gastroenterology

Locations

Clinical Research Associates

Huntsville, Alabama, United States

Northern California Research

Sacramento, California, United States

Medical Center for Clinical Research

San Diego, California, United States

Madeleine DuPree, MD

Boynton Beach, Florida, United States

Michael Epstein, MD

Annapolis, Maryland, United States

Chevy Chase Clinical Research

Chevy Chase, Maryland, United States

Long Island Gastrointestinal Research Group

Great Neck, New York, United States

LeBauer Research Associates

Greensboro, North Carolina, United States

Peters Medical Research, LLC

High Point, North Carolina, United States

Ohio Gastroenterology and Liver Institute

Cincinnatti, Ohio, United States

Oklahoma Foundation for Digestive Disease

Oklahoma City, Oklahoma, United States

Breco Research LTD

Houston, Texas, United States

Wisconsin Center for Advanced Research

Milwaukee, Wisconsin, United States

Zuid-Oost Limburg Campus St. Jan

Genk, Genk, Belgium

UCL St. Luc

Woluwe, Woluwe, Belgium

AZ St. Lucas Assebroek

Assebroek, , Belgium

UZ Leuven

Leuven, , Belgium

Countries

United States; Belgium

References

Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006 Apr;130(5):1377-90. doi: 10.1053/j.gastro.2006.03.008. No abstract available.

Reference Type: BACKGROUND

PMID: 16678553 (View on PubMed)

Schuster MM. Defining and diagnosing irritable bowel syndrome. Am J Manag Care. 2001 Jul;7(8 Suppl):S246-51.

Reference Type: BACKGROUND

PMID: 11474909 (View on PubMed)

Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006 Aug;55(8):1095-103. doi: 10.1136/gut.2005.077503. Epub 2006 Jan 9.

Reference Type: BACKGROUND

PMID: 16401691 (View on PubMed)

Wood JD. Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies. Gut. 2006 Apr;55(4):445-7. doi: 10.1136/gut.2005.079046.

Reference Type: BACKGROUND

PMID: 16531524 (View on PubMed)

Tack JF, Miner PB Jr, Fischer L, Harris MS. Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome - a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011 Oct;34(8):868-77. doi: 10.1111/j.1365-2036.2011.04818.x. Epub 2011 Aug 24.

Reference Type: RESULT

PMID: 21883322 (View on PubMed)

Other Identifiers

AST014

Identifier Type: -

Identifier Source: org_study_id