|Principal Investigator: Andrew Gawron|
|Keywords: reflux , proton pump inhibitors , gastrointestinal reflux disorder , Bravo , pathological acid reflux||Department: Gastroenterology|
|IRB Number: 00117324|
|Specialty: Gastroenterology, Gastroenterology, Gastroenterology, Gastroenterology|
|Sub Specialties: Esophageal Diseases, Gastroesophageal Reflux Disease (GERD), Endoscopy|
|Recruitment Status: Recruiting|
The objective of this study is to evaluate the safety and efficacy of IW-3718administered to patients with GERD who continue to have persistent symptoms, such asheartburn and regurgitation, while receiving once-daily (QD), standard-dose PPIs.
Patient has signed an ICF before any study-specific procedures are performed.
Patient is an ambulatory male or female (if female, nonpregnant) and is at least 18 years old at the Screening Visit.
Patient has a diagnosis of GERD and reports experiencing GERD symptoms (heartburn or regurgitation) on average ≥ 4 days per week over the last 8 weeks before the Screening Visit.
Patient has been receiving standard-labeled dose, QD, PPI therapy (treatment that, according to the Investigator’s judgment, could not be further improved by changing the brand or timing of PPI administration) for a minimum of 8 weeks before the Screening Visit. Patients should be on a PPI dose and schedule that is consistent with the approved labeling. Patients who have their PPI modified during the Screening Period may be re-screened after 8 weeks of standard-labeled dose, QD, PPI therapy provided they have not previously entered the Pretreatment Period.
Up to 96 hours of pH monitoring (with a Bravo device) during the Screening Period (while the patient continues taking their PPI) demonstrates evidence of pathological acid reflux (pH is < 4 for ≥ 4.2% of the recording time) during at least 1 of the 24-hour time intervals of pH testing with the Bravo device as confirmed by centralized review of pH monitoring.
During the last 7 days before randomization patient reports an average heartburn severity (HS, maximum of Items #1 and #2 on mRESQ-eD) of ≥ 2 (mild) and has a daily HS ≥ 3 (moderate) for at least 2 of those days.
Female patients must be postmenopausal for ≥1 year, surgically sterile (ie, bilateral oophorectomy, hysterectomy, or tubal sterilization [tie, clip, band, or burn]); or must agree to completely abstain from heterosexual intercourse; or, if heterosexually active, must agree to use 1 of the following methods of birth control from the date she signs the ICF until 24 hours after their final dose of study drug:
Progesterone implant or an intrauterine device (IUD)
Combination of 2 highly effective birth control methods (eg, diaphragm with spermicide plus a condom, condom with spermicide plus a diaphragm or cervical cap, hormonal contraceptive [eg, oral and transdermal patch] plus a barrier method, partner with vasectomy [conducted ≥60 days before the Screening Visit or confirmed via sperm analysis] plus a hormone or barrier method).
Females of childbearing potential must have a negative urine or serum pregnancy test at the Screening Visit and at the Randomization Visit prior to dosing. Positive urine test results will be confirmed by a serum pregnancy test.
Patient agrees not to make any changes to their usual diet or exercise regimen during the study
Patient is able to successfully use the eDiary, and has adequately completed the eDiary questions on at least 5 days each week and the weekly questions at least once during the 14 days before the start of the Treatment Period.
Patient is compliant with QD PPI dosing during the 14 days before the start of the Treatment Period. Patients are considered compliant if, as reported in the eDiary, they take their PPI on at least 5 days each week.
Patient is fluent and literate in at least one of the languages to be used for PRO assessments.
For patients who are receiving supplementation of a fat-soluble vitamin in order to correct or avoid a fat-soluble vitamin deficiency, the patient is willing to take the vitamin supplement at least 4 hours before taking study medication.
Patient has a history of complete lack of GERD symptom response to PPIs.
Patient reports epigastric pain or epigastric burning as his or her predominant symptom at the Screening Visit.
Patient has a diagnosis of gastroparesis per gastric emptying study, or a history of bowel obstruction, or is at risk for a bowel obstruction (e.g., patient has an organic gastrointestinal [GI] motility disorders or a history of major GI surgery).
Patient has a history of serum triglyceride concentrations > 500 mg/dL on a fasting specimen, or has serum triglyceride concentrations > 500 mg/dL on a fasting specimen at Screening or any time during the Pretreatment Period.
Patient has a history of hypertriglyceridemia-induced pancreatitis.
In the Investigator's opinion, patient is susceptible to a deficiency of fat-soluble vitamins (especially vitamin D deficiency; e.g., the patient has osteoporosis or osteomalacia) and will be put at risk by receiving colesevelam for 8 weeks.
Patient has an active swallowing disorder that would compromise their ability to swallow the study medication.
Patient has any alarm symptoms including, but not limited to, GI bleeding, anemia, vomiting, or unexpected weight loss at any time during the Screening or Pretreatment Periods.
Patient has undergone surgery that meets any of the following criteria:
Surgery of the GI tract (including gastric banding) other than an appendectomy, cholecystectomy, or minor oral or rectal surgery (e.g., tonsillectomy, hemorrhoidectomy, rectocele repair) at any time before the Screening Visit
An appendectomy during the 3 months before the Screening Visit, or a cholecystectomy during the 6 months before the Screening Visit, or minor oral or rectal surgery during the 30 days before the Screening Visit
Non-GI surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit
Thoracic surgery during the 6 months before the Screening Visit
Other major non-GI surgery during the 30 days before the Screening Visit
Patient has previously undergone thoracic or abdominal radiotherapy.
Patient has large (>5 cm) hiatal hernia.
EGD, conducted during the Screening Period, reveals that the patient has long-segment Barrett’s esophagus (greater than 3 centimeters) or definite dysplastic changes in the esophagus, peptic ulcer disease, active GI bleeding, presence of symptomatic esophageal strictures, presence of esophageal or fundic varices, erosive gastritis, or eosinophilic, herpetic or Candida esophagitis.
Patient has Gilbert’s disease, Crohn’s disease, diabetes mellitus (defined as A1C >6.5%), Zollinger-Ellison syndrome, pancreatitis, cholecystitis, or systemic sclerosis.
Patient has elevated (defined as > 1.5 times the upper limit of normal by the laboratory) levels of serum bilirubin at Screening or any time during the Pretreatment Period.
Patient has a history of clinically significant hypersensitivity or allergies to any of the excipients contained in the study medication (active or placebo).
Patient has a history of cancer (resected basal cell or squamous cell carcinoma is acceptable). Note: patients with a history of cancer are allowed provided that the malignancy has been in complete remission for at least 5 years before the Screening Visit. A complete remission is defined as the disappearance of all signs of cancer in response to treatment.
Patient has active substance abuse or history of chronic substance abuse (including alcoholism but not including nicotine) within 12 months before the Screening Visit or is positive for any of the following at the Screening Visit unless legally prescribed for anything but gastrointestinal pain: amphetamines, benzodiazepines, opiates, barbiturates, cocaine, or phencyclidine.
Note: Marijuana use, whether prescribed or not, is prohibited from 30 days before screening through the duration of the study. Use of illicit drugs is not allowed during the study.
Patient has any clinically significant finding on a physical exam, 12-lead electrocardiogram (ECG), or clinical laboratory test after signing the ICF but before receiving the first dose of study medication. (Note: The Investigator will determine if a particular finding is clinically significant. In making this determination, the Investigator will consider whether the particular finding could prevent the patient from performing any of the protocol-specified assessments, could represent a condition that would exclude the patient from the study, could represent a safety concern if the patient participates in the study, or could confound the study-specified assessments of safety or efficacy.)
Patient reports using a prohibited medication during the Screening or Pretreatment Periods, or is not willing or able to abide by the restrictions regarding use of prohibited medications as defined in Appendix 4.
Patient has received an investigational drug during the 30 days before the Screening Visit, or is planning to receive another investigational drug or use an investigational device at any time during the study.
Patient has an acute or chronic condition that, in the Investigator's opinion, would limit the patient's ability to complete or participate in this clinical study.
Patient has previously entered the Treatment Period of an IW-3718 study.
Patient has previously entered the Pretreatment Period of this study. (Note: patients who failed the Pretreatment Period due to abnormal laboratory findings or timing issues may be re-screened.)
Patient is enrolled in this study at another clinical study site; is an employee of the Institution or Ironwood Pharmaceuticals; or is a first-degree family member, significant other, or relative residing with an employee of the Institution or Ironwood Pharmaceuticals.