Ulcerative colitis MedDRA version: 19.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
Product Code: APD334
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not yet available
Current Sponsor code: APD334
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
Arena Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women of age 18 to 70 years, inclusive 2. Able to give signed informed consent 3. Willing and able to comply with the study requirements 4. Considered to be in stable health in the opinion of the investigator, as determined by: • A pre-study physical examination with no clinically significant abnormalities unrelated to ulcerative colitis • Vital signs (VS) at screening: pulse rate = 55 bpm, systolic blood pressure (SBP) = 90, and diastolic blood pressure (DBP) = 55 • Liver function tests (ALT/AST, bilirubin and alkaline phosphatase) 8 years duration or left-sided colitis of > 12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (if not, the patient should undergo a colonoscopy in lieu of a flexible proctosigmoidoscopy during screening). 9. Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least one of the following agents below as defined in Section 4.2 of the protocol: • Oral 5-aminosalicylates (5-ASAs) • Corticosteroids • Immunosuppressives • TNFa antagonists • Integrin antagonists 10. May be receiving a therapeutic dose of the following drugs: a. Oral 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to randomization b. Oral corticosteroid therapy (prednisone at a stable dose = 20 mg/day, budesonide at a stable dose = 9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to screening if corticosteroids have just been initiated c. Azathioprine or 6-mercaptopurine provided that the dose has been stable for the 8 weeks immediately prior to screening. (These immunosuppressive agents must be discontinued at the time of randomization.) d. Probiotics (e.g., Culturelle, Saccharomyces boulardii) provided that the dose ha
Exclusion criteria
Exclusion criteria: 1. Evidence of abdominal abscess or toxic megacolon at the initial screening visit 2. Previous extensive colonic resection (subtotal or total colectomy) 3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine 4. Within 30 days prior to randomization, receipt of any of the following for the treatment of underlying disease: a. Non-biologic therapies (eg, cyclosporine, tacrolimus, tofacitinib, thalidomide) other than those specifically listed in Section 6.12.1 of the protocol. b. A non-biologic investigational therapy c. An approved non-biologic therapy in an investigational protocol 5. Within 60 days prior to randomization, receipt of any of the following: a. Infliximab, adalimumab, golimumab, certolizumab, vedolizumab b. Any other investigational or approved biologic agent 6. Any prior exposure to natalizumab, efalizumab, or rituximab 7. Previous treatment with more than 2 biologic agents 8. Use of topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug 9. Evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to randomization 10. Currently require or are anticipated to require surgical intervention for UC during the study 11. Current evidence of adenomatous colonic polyps that have not been removed 12. Current evidence of colonic mucosal dysplasia 13. Diagnosis of Crohn’s colitis or indeterminate colitis 14. Infection with the Hepatitis B or C virus 15. Active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following: a. History of tuberculosis (that has not been acceptably treated) b. A positive diagnostic tuberculosis (TB) test within one month of randomization defined as: i. a positive QuantiFERON® test or 2 successive indeterminate QuantiFERON tests OR ii. a tuberculin skin test reaction =5 mm. c. Chest X-ray within 12 months of randomization in which active or latent pulmonary tuberculosis cannot be excluded 16. Any known history of congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus [HIV] infection [ELISA and Western blot] test result, organ transplantation) 17. Clinically significant extra-intestinal infection (e.g., pneumonia, pyelonephritis) within 30 days prior to randomization 18. Prior participation in any study of APD334 19. History of any clinically significant medical condition that, in the investigator's opinion, would preclude participation in the study 20. Recent history (within 6 months of screening visit) of cardio or cerebrovascular disease, ACS, MI, unstable angina, CVA, TIA at screening 21. Any surgical procedure requiring general anesthesia within 30 days prior to randomization or plans to undergo major surgery during the study period 22. History of retinal macular edema 23. History of or signs and symptoms of progressive multifocal leukoencephalopathy (PML) as assessed by the PML Checklist 24. History of cardiac arrhythmia, conduction system disease (including AV node dysfunction, 2nd or 3rd degree heart block, and sick sinus syndrome), or use of Class 1a and Class III anti-arrhythmic agents, or baseline QTc = 500 msec. 25. FEV1 or FVC < 80% of predicted values (i.e., abnormal) 26. Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 4 weeks of screening 27.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of treatment with APD334 in inducing clinical remission at 12 weeks;Secondary Objective: • To determine the effect of treatment with APD334 in inducing clinical response at 12 weeks • To determine the effect of treatment with APD334 on endoscopic improvement at 12 weeks;Primary end point(s): • The proportion of patients achieving clinical remission [defined as individual subscores of the 3-component Mayo Clinic score as follows: an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1, a rectal bleeding score of 0, and a stool frequency score of 0 or 1 with a decrease of = 1 point from baseline subscore] at Week 12;Timepoint(s) of evaluation of this end point: Screening and Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Screening and Week 12;Secondary end point(s): • The proportion of patients who achieve clinical response [defined as a decrease in 3-component Mayo Clinic score of = 2 points and a decrease of = 30% with either a decrease of rectal bleeding of = 1 or rectal bleeding score of 0 or 1] at Week 12 • The proportion of patients who achieve endoscopic improvement [defined as Mayo endoscopic subscore (using findings of flexible proctosigmoidoscopy) of = 1 point] at Week 12 | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Israel, Latvia, Lithuania, New Zealand, Poland, Romania, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactJoerg Willers
Arena Pharmaceuticals, Inc.
Outcome results
None listed