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

Phase 2

Terminated

Conditions: Gastroesophageal Reflux Disease (GERD)

Interventions: Drug: AST-120
Drug: Celphere CP-305

Registration Number: NCT00587275

Lead Sponsor: Ocera Therapeutics

Brief Summary: 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.

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	AST-120	AST-120, 2 gram sachets
2	Celphere CP-305	Celphere CP-305, stained to match appearance of AST-120 in 2g sachets.

Primary Outcome Measures

Name	Time	Method
Reduction in the severity of GERD symptoms in patients receiving AST-120 assessed by comparing the symptom scores on the GSAS.	8 weeks
Safety endpoint is adverse events (AEs)deemed possibly, probably, or definitely related to treatment with investigational product.	8 weeks

Secondary Outcome Measures

Name	Time	Method
Changes in clinical laboratory tests from baseline.	8 weeks
Prior and concomitant medications.	8 weeks
Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature).	8 weeks
GI tolerability (diarrhea, constipation, etc).	8 weeks
Reduction in severity of GERD symptoms in patients receiving AST-120 assessed by patient self assessment using a daily diary.	8 weeks
Percent days without heartburn.	8 weeks
Percent daytime period without heartburn.	8 weeks
Percent change in SF-36 score.	8 weeks
Esophageal bilirubin levels as measured by Bilitec.	8 weeks
Amount of rescue medication (Gelusil) taken per day.	8 weeks