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

Primary Purpose

Gastroesophageal Reflux Disease (GERD)

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

AST-120

Celphere CP-305

About this trial

This is an interventional treatment trial for Gastroesophageal Reflux Disease (GERD) focused on measuring Gastroesophageal Reflux Disease, GERD

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Southern Arizona VA Health Care System and University of Arizona Health Sciences Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

AST-120, 2 gram sachets

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

Outcomes

Primary Outcome Measures

Reduction in the severity of GERD symptoms in patients receiving AST-120 assessed by comparing the symptom scores on the GSAS.

Safety endpoint is adverse events (AEs)deemed possibly, probably, or definitely related to treatment with investigational product.

Secondary Outcome Measures

Reduction in severity of GERD symptoms in patients receiving AST-120 assessed by patient self assessment using a daily diary.

Percent days without heartburn.

Percent daytime period without heartburn.

Percent change in SF-36 score.

Esophageal bilirubin levels as measured by Bilitec.

Amount of rescue medication (Gelusil) taken per day.

Changes in clinical laboratory tests from baseline.

Prior and concomitant medications.

Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature).

GI tolerability (diarrhea, constipation, etc).

Full Information

NCT ID

NCT00587275

First Posted

December 21, 2007

Last Updated

June 2, 2014

Sponsor

Ocera Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT00587275

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2014

Overall Recruitment Status

Terminated

Why Stopped

Terminated for lack of enrollment

Study Start Date

October 2007 (undefined)

Primary Completion Date

June 2008 (Actual)

Study Completion Date

June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ocera Therapeutics

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastroesophageal Reflux Disease (GERD)

Keywords

Gastroesophageal Reflux Disease, GERD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

AST-120, 2 gram sachets

Arm Title

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

AST-120

Intervention Description

Oral, sachet, 2 grams daily for 4 weeks

Intervention Type

Drug

Intervention Name(s)

Celphere CP-305

Intervention Description

Oral, sachet, 2 grams daily for 4 weeks

Primary Outcome Measure Information:

Title

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

Title

Safety endpoint is adverse events (AEs)deemed possibly, probably, or definitely related to treatment with investigational product.

Time Frame

8 weeks

Secondary Outcome Measure Information:

Title

Reduction in severity of GERD symptoms in patients receiving AST-120 assessed by patient self assessment using a daily diary.

Time Frame

8 weeks

Title

Percent days without heartburn.

Time Frame

8 weeks

Title

Percent daytime period without heartburn.

Time Frame

8 weeks

Title

Percent change in SF-36 score.

Time Frame

8 weeks

Title

Esophageal bilirubin levels as measured by Bilitec.

Time Frame

8 weeks

Title

Amount of rescue medication (Gelusil) taken per day.

Time Frame

8 weeks

Title

Changes in clinical laboratory tests from baseline.

Time Frame

8 weeks

Title

Prior and concomitant medications.

Time Frame

8 weeks

Title

Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature).

Time Frame

8 weeks

Title

GI tolerability (diarrhea, constipation, etc).

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ronnie Fass, MD

Organizational Affiliation

Southern Arizona VA Health Care System

Official's Role

Principal Investigator

Facility Information:

Facility Name

Southern Arizona VA Health Care System and University of Arizona Health Sciences Center

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85723

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

16482234

Citation

Xu XR, Li ZS, Zou DW, Xu GM, Ye P, Sun ZX, Wang Q, Zeng YJ. Role of duodenogastroesophageal reflux in the pathogenesis of esophageal mucosal injury and gastroesophageal reflux symptoms. Can J Gastroenterol. 2006 Feb;20(2):91-4. doi: 10.1155/2006/498142.

Results Reference

background

PubMed Identifier

16303036

Citation

Fennerty MB. Review article: alternative approaches to the long-term management of GERD. Aliment Pharmacol Ther. 2005 Dec;22 Suppl 3:39-44. doi: 10.1111/j.1365-2036.2005.02711.x.

Results Reference

background

PubMed Identifier

16011666

Citation

Fass R, Shapiro M, Dekel R, Sewell J. Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease--where next? Aliment Pharmacol Ther. 2005 Jul 15;22(2):79-94. doi: 10.1111/j.1365-2036.2005.02531.x.

Results Reference

background

Citation

Fukuda Y, Takazoe M, Sugita A, et al. The treatment with an oral spherical adsorptive carbon (AST-120) improves anal fistula, PDAI and CDAI scores - A randomized double-blind placebo controlled trial. Abstract #765 presented at Digestive Disease Week meeting, Los Angeles, CA May 24, 2006

Results Reference

background

Citation

Yamazaki Z, Fujimori T, Yoshimoto T, et al. Effect of Oral Adsorbent on Animal Models of Hepatic Failure 92(2):331-335, 1980

Results Reference

background

PubMed Identifier

11142579

Citation

Araki Y, Tsujikawa T, Andoh A, Sasaki M, Fujiyama Y, Bamba T. Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen. Dig Liver Dis. 2000 Nov;32(8):691-8. doi: 10.1016/s1590-8658(00)80332-1.

Results Reference

background

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

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