Phase 4 Multicenter Assessment of Eluxadoline in the Treatment of Irritable Bowel Syndrome with Diarrhea (IBS-D) - Relief GMO-US-GI-0429
A Phase 4 Multicenter, Multinational, Prospective, Randomized, Placebo-Controlled, Double-Blinded Parallel Group Study to Assess Efficacy of Eluxadoline in the Treatment of Irritable Bowel Syndrome with Diarrhea (IBS-D) in Patients who Report Inadequate Control of IBS-D Symptoms with Prior Loperamide Use (RELIEF).
1. Patient is an adult aged 18 to 80 years (male or female), inclusive, at Screening.
2. Patient has a diagnosis of IBS-D, defined by the Rome III criteria as loose (mushy) or watery stools ≥25% and hard or lumpy stools ≤25% of bowel movements.
3. Patient has had a colonoscopy performed within 5 years prior to Screening if they are at least 50 years of age, OR if they meet any of the following alarm features: a) Patient has documented weight loss within the past 6 months; or b) Patient has nocturnal symptoms; or c) Patient has a familial history of colon cancer; or d) Patient has blood mixed with their stool (excluding any blood from hemorrhoids)
4. Patient has an average WAP score in the past 24 hours of >3.0 (on a 0 to 10 scale) over the week prior to randomization.
5. Patient has an average daily stool consistency score (BSS) of ≥5.5 and at least 5 days with a BSS score ≥5 on a 1-7 scale during the week prior to randomization.
6. Patient reports use of loperamide in the 12 months prior to Screening for IBS-D symptoms and that loperamide did not provide adequate control of IBS-D symptoms.
7. Patient has completed the ePRO diary on at least 5 of the 7 days during the week prior to randomization AND at least 10 of the 14 days during the 2 weeks prior to randomization. Patients have 3 weeks to meet these criteria.
8. Patient is willing to be compliant with study procedures including completing the daily ePRO diary during the screening and pretreatment period and throughout the study.
9. Patient has not used any loperamide rescue medication within 14 days prior to randomization.
10. Patient is not planning to change his/her usual diet and lifestyle during the course of the study. Patients on stable doses of antidepressants (i.e., for the 3 months prior to screening) will be allowed to participate in the study. Medications taken for the treatment of allergies, chronic medical conditions, and migraine headaches can be taken during this study (with the exception of opioids for acute treatment of migraines). Patients must be on a stable dose of medication for chronic migraines or preventive therapy for at least 1 month at screening. As-needed use of benzodiazepines for anxiety is permitted during the study.
11. Female patients must be:
a) Postmenopausal, defined as 52 years or older and amenorrheic for at least 2 years at Screening; or
b) Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy); or
c) Abstinent; or
d) If sexually active, be practicing an effective method of birth control such as hormonal prescription oral contraceptives, progesterone implants or injections, contraceptive patch, intrauterine device, or male partner with a vasectomy. A double barrier method of birth control such as condoms, diaphragms, or cervical caps with spermicidal foam, cream, or gel may be used as a method of birth control. Women of childbearing potential must have a negative serum beta human chorionic gonadotropin pregnancy test at Screening and a negative urine pregnancy test at baseline before the first dose of study drug is taken.
12. Patient must sign an informed consent form (ICF) before the initiation of any study-related procedures indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.
- Patient has a diagnosis of IBS with a subtype of constipation IBS, mixed IBS, or unsubtyped IBS by the Rome III criteria.
- Patient has a history of inflammatory or immue-mediated GI disorders including inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis), microscopic colitis, or celiac disease.
- Patient has a history of diverticulitis within 3 months prior to screening.
- Patient has a documented history of lactose intolerance.
- Patient has a documented history of bile-acid malabsorption.
- Patient has a history of chronic or severe constipation or intestinal obstruction, stricture, toxic megacolon, Gi perferation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (e.g., aortoiliac disease.
- Patient has any of the following surgical history:
- Cholecystecomy or previously documented agenesis of gallbladder; or
- Major gastric, hepatic, pancreatic, or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed).NOTE: For the purposes of this study, lapraroscopic surgeries without complication are considered minor and non-exclusionary, provide the condition for which the surgery was performed was not exclusionary.
- Patient has a history of cholecystitis within 6 months before screening.
- Patient has a history of pancreatitis or structual diseases of the pancrease, including known or suspected pancreatic duct obstruction.
- Patient has a history of known or suspected biliary duct obstruction or spincter of Oddi disease or dysfunction, excluding a history of gallstones.
- Patient has an elevated serum lipase >2 times upper limit of mormal (ULN) at screening.
- Patient has a history or current evidence of laxative abuse within 5 years prior to screening.
- Patient has documented evidence of cirrhosis (Child-Pugh classification A, B, or C).
- Patient has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the ULN or total bilirubin >3 mg/dL (>51.3 µmol/L), with the exception of Gilbert's syndrome, at screening.
- Patient has a history of cardiovascular events, including stroke, syocardial infaction, congestive heart failure, or transient ischemic attack within 6 months prior to screening.
- Patient has an unstable renal, hepatic, metabolic, or hematologic condition.
- Patient has a history of malignancy within 5 years before screening (except squamous and basal cell carcinomas and cervical carcinoma in situ).
- Patient has a history of human immunodeficiency virus infection.
- Patient has a history of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision-defined substance dependency, excluding nicotine and caffeine, within 2 years prior to screening.
- Patient has a history of alcohol abuse, alcohol addiction, and alcoholism or drinks more than 3 alcoholic beverages per day.
- Patient has uncontrolled hypertension, defined as systolic blood pressure >180 mm Hg or a diastolic blood pressure >100 mm Hg at the time of randomization.
- Patient has abnormal thyroid function test as confirmed by thyroid-stimulating hormone <0.3 mcIU/mL or ≥5 mcIU/mL at screening. However, patients who are clinically euthyroid due to thyroid supplementation are candidates for the study.
- Patient has evidence of anemia as confirmed by hemoglobin <10 g/dL for women and <12 g/dL for men at screening.
- Patient has used 5-HT3 antagonists (e.g., alosetron or ondansetron) within 14 days of screening.
- Patient has used aspirin or aspirin-containing medications (>325 mg of aspirin per day) or nonsteroidal anti-inflammatory drugs, when taken specifically for the symptoms of IBS, within 14 days of randomization.
- Patient has current (within 14 days of randomization) or expected use of any narcotic or opioid-containing agents, tramadol, docusate, enemas, GI preparations (including antacids containing aluminum or magnesium, antidiarrheal agents [except loperamide rescue medication after randomization]), antinausea agents, antispasmodic agents, bismuth, or prokinetic agents.
- Patient has current (within 28 days of randomization) use of rifaximin or other antibiotics (with the exception of topical antibiotics or a 1-day course with an antibiotic). Expected use of rifaximin or other antibiotics during the course of the study that is known at the time of randomization (e.g., for planned elective surgery) is also prohibited. However, a patient will be allowed to remain in the study should unplanned used of antibiotics other than rifaximin occur after the patient has been randomly assigned to study drug.
- Patient is unable to swallow solid oral dosage forms whole with the aid of liquid (patients may not chew, divide, dissolve, or crush the study drug).
- Patient has known allergies or hypersensitivity to opioids.
- Patient has received an investigational drug or used an investigational medical device within 30 days prior to randomization, or is currently enrolled in an investigational study.
- Patient has an elective surgery planned or expects to need elective surgery at any time during the study. An elective procedure scheduled after the patient has been randomly assigned to study drug will not be considered a protocol violation.
- Patient is pregnant or breastfeeding.
- Patient has any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirement.
- Patient is an employee of the investigator or study site with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
Candace Hefner 937-429-2422 Ext. 109