Safety and Efficacy of AST-120 in Patients With GERD Who Continue to be Symptomatic on a Standard Dose of PPI

This study has been terminated.
(Terminated for lack of enrollment)
Sponsor:
Information provided by (Responsible Party):
Ocera Therapeutics
ClinicalTrials.gov Identifier:
NCT00587275
First received: December 21, 2007
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

The purpose of this project is to test how safe and how well AST-120, an investigational product, works in treating too much acid in the stomach. Patients will be randomly assigned to one of two groups, AST-120 or a placebo for the first four weeks of the study. The patients will be switched to the other group (AST-120 or placebo)for the following four weeks.


Condition Intervention Phase
Gastroesophageal Reflux Disease (GERD)
Drug: AST-120
Drug: Celphere CP-305
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo-Controlled Crossover Study to Assess the Efficacy of AST-120 in Patients With Gastroesophageal Reflux Disease (GERD) Who Continue to be Symptomatic on a Standard Dose of Proton Pump Inhibitor (PPI)

Resource links provided by NLM:


Further study details as provided by Ocera Therapeutics:

Primary Outcome Measures:
  • Reduction in the severity of GERD symptoms in patients receiving AST-120 assessed by comparing the symptom scores on the GSAS. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Safety endpoint is adverse events (AEs)deemed possibly, probably, or definitely related to treatment with investigational product. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Reduction in severity of GERD symptoms in patients receiving AST-120 assessed by patient self assessment using a daily diary. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Percent days without heartburn. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Percent daytime period without heartburn. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Percent change in SF-36 score. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Esophageal bilirubin levels as measured by Bilitec. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Amount of rescue medication (Gelusil) taken per day. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Changes in clinical laboratory tests from baseline. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Prior and concomitant medications. [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature). [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • GI tolerability (diarrhea, constipation, etc). [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 4
Study Start Date: October 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AST-120, 2 gram sachets
Drug: AST-120
Oral, sachet, 2 grams daily for 4 weeks
Placebo Comparator: 2
Celphere CP-305, stained to match appearance of AST-120 in 2g sachets.
Drug: Celphere CP-305
Oral, sachet, 2 grams daily for 4 weeks

Detailed Description:

This is a double-blind, randomized, placebo-controlled, crossover trial where 20 patients with confirmed persistent GERD symptoms (at least twice weekly) after a standard course of PPI, with abnormal bile reflux levels but normal esophageal acid exposure are randomized to initially receive either AST-120 or placebo for a period of 4 weeks after a two week screening period. After a washout period of one week, patients will cross over to the opposite blinded treatment.

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. 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 continue to receive the previously prescribed PPI throughout the duration of the trial. In addition, patients will be allowed up to 6 Gelusil tablets daily as a "rescue medication".

Patients will be expected to participate in approximately 5 in-clinic visits. During these visits, patients will undergo a number of tests including: comprehensive physical, hematology panel, a urine pregnancy test for pre-menopausal females, completion of the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) and Short-Form-36 (SF-36)Quality of Life Form and an upper endoscopy will be performed to determine the extent of esophageal inflammation.

Patients will be allowed to continue on their previously prescribed PPI with no changes and may take up to 6 Gelusil tablets per day. The following therapies must be discontinued and should not be taken during the trial: H2receptor antagonists, NSAIDs, Baclofen and Antacids (OTC or prescription).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body weight 40 to 136 kg (88 to 300 lbs)
  • Recent history of GERD related symptoms (at least twice weekly) confirmed during screening.
  • Recent history of 8 week PPI treatment without significant improvement
  • Abnormal bilirubin level as assessed by Bilitec
  • Normal esophageal pH value (pH<4.0 for <4.2% of the time calculated over a 24 hour period)
  • Platelet count (thrombocytes) >100,000/µL
  • Normal Hgb and Hct levels
  • 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 (hormonal contraceptives, intrauterine devices, spermicide and barrier). 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:

  • Concurrent GI or other pathology which could interfere with the course of the study (e.g., erosive esophagitis, malabsorption, cirrhosis, ascites, bleeding ulcer, diabetes, scleroderma, non-GI myopathy or neuropathy etc.) Note: patients with Barrett's esophagus (short segment defined as < 3 cm) can be included.
  • Patients with cancer or undergoing chemotherapy for the treatment of cancer
  • Patients with a history of upper GI surgery
  • Patients with GERD complications such as stricture of the esophagus
  • Contraindication to continued PPI treatment
  • Patients requiring the concomitant use of NSAIDs for the duration of the study
  • Uncontrolled systemic disease
  • Diagnosis of a psychiatric disorder within the past 2 years and not on a stable dose of medications for at least 6 months
  • Other major physical or psychiatric illness in previous 6 months as determined by the treating physician
  • Known hypersensitivity or contraindication to any component of the test product (study drug) or diagnostics used
  • Participation in another study within eight (8) weeks prior to randomization
  • Unable to attend all visits required by the protocol
  • Pregnant, breast feeding, or planning to become pregnant during the study
  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: NCT00587275

Locations
United States, Arizona
Southern Arizona VA Health Care System and University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85723
Sponsors and Collaborators
Ocera Therapeutics
Investigators
Principal Investigator: Ronnie Fass, MD Southern Arizona VA Health Care System
  More Information

Publications:
Responsible Party: Ocera Therapeutics
ClinicalTrials.gov Identifier: NCT00587275     History of Changes
Other Study ID Numbers: AST013
Study First Received: December 21, 2007
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ocera Therapeutics:
Gastroesophageal Reflux Disease
GERD

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014