Clinical trial NCT00583128: Safety and Efficacy of AST-120 in Patients With Non-Constipating Irritable Bowel Syndrome
Official title: A Double-Blind, Randomized, Placebo-Controlled Multicenter Study to Assess the Safety and Efficacy of AST-120 in Patients With Non-Constipating Irritable Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: IBS
Irritable Bowel Syndrome
Lead sponsor: Ocera Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-12-31
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Percent of patients who achieve at least a 50% reduction in the number of days with abdominal pain during the final 2 weeks of the double-blind treatment course.
timeFrame: Eight weeks
measure: Safety endpoint is adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product during the double-blind treatment course.
timeFrame: 8 weeks
Secondary outcomes:
measure: Percent change in the IBS QOL score.
timeFrame: Eight weeks
measure: Percent change in HADS score.
timeFrame: 8 weeks
measure: Percent change in Bristol Scale score.
timeFrame: 8 weeks
measure: Percent change in individual items in the IBS Symptom Severity questionnaire.
timeFrame: 8 weeks
measure: Durability of effect after the first eight weeks of treatment.
timeFrame: 8 weeks
measure: Change in clinical laboratory tests from Baseline to Week 8 and to Week 18.
timeFrame: 8 weeks
measure: Any adverse event occurring after Week 8.
timeFrame: 8 weeks
measure: Physical examinations, vital signs (blood pressure, heart rate, respiration and temperature).
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clinical Research Associates
state: Alabama
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: Boynton Beach
country: United States
facility: Madeleine DuPree, MD
state: Florida
city: Annapolis
country: United States
facility: Michael Epstein, MD
state: Maryland
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group
state: New York
city: Greensboro
country: United States
facility: LeBauer Research Associates
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research, LLC
state: North Carolina
city: Cincinnatti
country: United States
facility: Ohio Gastroenterology and Liver Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Digestive Disease
state: Oklahoma
city: Houston
country: United States
facility: Breco Research LTD
state: Texas
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
city: Assebroek
country: Belgium
facility: AZ St. Lucas Assebroek
city: Genk
country: Belgium
facility: Zuid-Oost Limburg Campus St. Jan
city: Leuven
country: Belgium
facility: UZ Leuven
city: Woluwe
country: Belgium
facility: UCL St. Luc
Study officials:
affiliation: University of Leuven, Department of Gastroenterology
name: Jan Tack, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Schuster MM. Defining and diagnosing irritable bowel syndrome. Am J Manag Care. 2001 Jul;7(8 Suppl):S246-51.
citation: 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.
citation: 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.
citation: 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.