A Study to Evaluate the Efficacy and Safety of Arbaclofen Placarbil (XP19986) as Adjunctive Therapy in Subjects With Gastroesophageal Reflux Disease (GERD)

A Dose-Response Efficacy and Safety Study of Arbaclofen Placarbil (XP19986) as Adjunctive Therapy in Subjects With Gastroesophageal Reflux Disease (GERD) Who Are Incomplete Responders to a Proton Pump Inhibitor (PPI)

The purpose of the study is to evaluate efficacy and safety of arbaclofen placarbil (XP19986) versus placebo as adjunctive therapy in subjects with troublesome GERD symptoms despite therapy with approved doses of a Proton Pump Inhibitor (PPI).

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: arbaclofen placarbil-Cohort 1; Drug: PPI; Drug: arbaclofen placarbil-Cohort 2; Drug: arbaclofen placarbil-Cohort 3; Drug: arbaclofen placarbil-Cohort 4; Drug: Placebo-Cohort 5

• Study Type: Interventional
• Enrollment (Actual): 460
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1H 3R3
    • Toronto, Ontario, Canada, M3N 2V7
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Mesa, Arizona, United States, 85213
    • Mesa, Arizona, United States, 85203
    • Scottsdale, Arizona, United States, 85251
    • Tucson, Arizona, United States, 85715
  • Arkansas
    • Sherwood, Arkansas, United States, 72120
  • California
    • Anaheim, California, United States, 92801
    • Lancaster, California, United States, 93534
    • Mission Hills, California, United States, 91345
    • Sacramento, California, United States, 95821
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92120
    • Stanford, California, United States, 94305
    • Westlake Village, California, United States, 91361
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
    • Lafayette, Colorado, United States, 80026
    • Lakewood, Colorado, United States, 80215
    • Littleton, Colorado, United States, 80120
  • Connecticut
    • Milford, Connecticut, United States, 06460
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • Jupiter, Florida, United States, 33458
    • Pembroke Pines, Florida, United States, 33024
  • Georgia
    • Atlanta, Georgia, United States, 30342
  • Iowa
    • Clive, Iowa, United States, 50325
  • Kentucky
    • Lexington, Kentucky, United States, 40504
    • Madisonville, Kentucky, United States, 42431
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
    • Metairie, Louisiana, United States, 70006
    • Monroe, Louisiana, United States, 71201
    • Shreveport, Louisiana, United States, 71103
  • Maryland
    • Annapolis, Maryland, United States, 21401
    • Hagerstown, Maryland, United States, 21742
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
  • New York
    • Binghamton, New York, United States, 13903
    • Brooklyn, New York, United States, 11214
    • Great Neck, New York, United States, 11021
    • Johnson City, New York, United States, 11042
    • Lake Success, New York, United States, 11042
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
    • Fayetteville, North Carolina, United States, 28304
    • Greensboro, North Carolina, United States, 27403
    • Raleigh, North Carolina, United States, 27612
  • North Dakota
    • Fargo, North Dakota, United States, 58104
  • Ohio
    • Columbus, Ohio, United States, 43215
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
    • Uniontown, Pennsylvania, United States, 15401
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
    • Germantown, Tennessee, United States, 38138
  • Texas
    • Bellaire, Texas, United States, 77401
    • Lake Jackson, Texas, United States, 77566
    • San Antonio, Texas, United States, 78215
    • San Antonio, Texas, United States, 78209
  • Utah
    • Logan, Utah, United States, 84405
    • Ogden, Utah, United States, 84405
    • Salt Lake City, Utah, United States, 84107
  • Virginia
    • Charlottesville, Virginia, United States, 22911
    • Christiansburg, Virginia, United States, 24073
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. confirmed diagnosis of GERD by a gastroenterologist
2. minimum of 3 months of GERD symptoms prior to screening.
3. currently taking an FDA approved dose of PPI therapy for symptomatic GERD for at least 4 weeks prior to screening
4. experienced partial relief of GERD symptoms while receiving approved dose and regimen of PPI therapy
5. experienced GERD symptoms, defined as heartburn (with or without regurgitation or other GERD symptoms) on ≥ 3 days during the week prior to screening

Exclusion Criteria:

1. evidence of erosive esophagitis or erosive gastritis on upper gastrointestinal endoscopy during screening
2. has not experienced any GERD symptom improvement after an adequate course of PPI treatment (at least 2 weeks)
3. unstable or severe medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: arbaclofen placarbil-Cohort 1; arbaclofen placarbil 20 mg QD with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD	Drug: arbaclofen placarbil-Cohort 1; After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 20 mg QD) for 7 weeks including titration and taper periods; Other Names: XP19986; Drug: PPI; Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD; Other Names: Proton Pump Inhibitor
EXPERIMENTAL: arbaclofen placarbil-Cohort 2; arbaclofen placarbil 40 mg QD with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD	Drug: PPI; Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD; Other Names: Proton Pump Inhibitor; Drug: arbaclofen placarbil-Cohort 2; After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 40 mg QD) with for 7 weeks including titration and taper periods; Other Names: XP19986
EXPERIMENTAL: arbaclofen placarbil-Cohort 3; arbaclofen placarbil 20 mg BID with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD	Drug: PPI; Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD; Other Names: Proton Pump Inhibitor; Drug: arbaclofen placarbil-Cohort 3; After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 20 mg BID) for 7 weeks including titration and taper periods; Other Names: XP19986
EXPERIMENTAL: arbaclofen placarbil-Cohort 4; arbaclofen placarbil 30 mg BID with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD	Drug: PPI; Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD; Other Names: Proton Pump Inhibitor; Drug: arbaclofen placarbil-Cohort 4; After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (arbaclofen placarbil 30 mg BID) for 7 weeks including titration and taper periods; Other Names: XP19986
PLACEBO_COMPARATOR: Placebo-Cohort 5; Placebo dose with PPI* * Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD	Drug: PPI; Allowable PPIs : Rabeprazole Sodium 20 mg QD, Esomeprazole Magnesium 20 mg or 40 mg QD, Lansoprazole 15 mg or 30 mg QD, Pantoprazole 20 mg or 40 mg QD, Omeprazole 20 mg or 40 mg QD, Omeprazole/sodium bicarbonate 20 mg or 40 mg QD, Dexlansoprazole 30 mg or 60 mg QD; Other Names: Proton Pump Inhibitor; Drug: Placebo-Cohort 5; After the 4 week screening period, eligible subjects will be randomized to adjunctive study treatment (placebo) for 7 weeks including titration and taper periods; Other Names: XP19986 matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heartburn Episodes	number of episodes	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regurgitation Episodes	number of episodes	6 weeks

Collaborators and Investigators

• Sponsor: XenoPort, Inc.
• Investigators: Study Director: Study Director, XenoPort, Inc.

Publications and helpful links

General Publications

• Vakil NB, Huff FJ, Cundy KC. Randomised clinical trial: arbaclofen placarbil in gastro-oesophageal reflux disease--insights into study design for transient lower sphincter relaxation inhibitors. Aliment Pharmacol Ther. 2013 Jul;38(2):107-17. doi: 10.1111/apt.12363. Epub 2013 May 30.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 15, 2009
• First Posted (ESTIMATE): September 16, 2009

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: GERD
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen; Proton Pump Inhibitors; Arbaclofen placarbil
• Other Study ID Numbers: XP-B-078