Maintenance of remission of ulcerative colitis
Conditions
Interventions
Product Name: OPC-6535
Product Code: OPC-6535
Pharmaceutical Form: Tablet
Current Sponsor code: OPC-6535
Other descriptive name: 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl] pyridine-2-carboxylic acid
Conce
Sponsors
Otsuka Maryland Research Institute, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, 18 to 80 years of age, inclusive, who provide written, informed consent prior to any study-related procedures and who are, in the opinion of the Investigator, likely to comply with all the requirements of the study. 2. Subjects with a prior diagnosis of ulcerative colitis, established by colonoscopy. 3. Subjects currently in remission, defined as rectal bleeding (RB) score of 0 and flexible sigmoidoscopy (FS) score of 0 (screening flexible sigmoidoscopy or colonoscopy). 4. Subjects who have undergone treatment for a flare of ulcerative colitis, with symptomatic onset of remission occurring no more than 52 weeks from the Screening Period. 5. If subjects are taking sulfasalazine or 5-ASA products prior to entry, the dose must be stable for at least 6 weeks prior to the Screening Period. NOTE: During the study, use of these drugs will be discontinued 6. Subjects having undergone colonoscopy with pan-colonic surveillance biopsies negative for dysplasia within 1 year of the Screening Visit if at increased risk of colorectal cancer (= 8 year history of ulcerative colitis). [Colonoscopy with pan-colonic surveillance biopsies for dysplasia will be substituted for flexible sigmoidoscopy during Screening if this inclusion criterion is not met.] 7. Female or male subjects who are surgically sterilized or who are prepared to and agree to practice a double-barrier form of birth control from the Screening Period through 30 days (females) and 90 days (males), respectively, from the last dose of study medication. Females who are more than 12 months post-menopausal are also eligible to participate in the study. [See Section 5.4 for a description of acceptable forms of birth control.] Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects who have active disease, defined as a RB = 1 or FS = 1 during the Screening Period. 2. Subjects who have any other clinically significant disease(s) or condition/procedure(s) which, in the opinion of the Investigator, could compromise the subject’s involvement in the study and/or interfere with the absorption of the study drug or the overall interpretation of the data. 3. Subjects who have had major gastrointestinal surgery including, but not limited to, a colostomy, an ileostomy or previous colonic surgery other than appendectomy. 4. Subjects who have used oral or intravenous corticosteroids or intrarectal topical agents (corticosteroid or 5-ASA enemas, suppositories, foams) within 6 weeks of the Screening Period. 5. Subjects who have used azathioprine, 6-mercaptopurine or methotrexate within 6 weeks of the screening period or other immunosuppressive agents including, but not limited to IL-10, IL-11, FK-506 [tacrolimus], mycophenalate, cyclosporin, anti-TNF-a or a monoclonal antibody within 8 weeks of the Screening Period. 6. Subjects who have a history or evidence of an active malignancy within the previous 5 years (surgically-treated basal cell, squamous cell or in-situ cervical carcinomas permissible), an intra-abdominal abscess, a toxic megacolon, or a clinical instability resulting from any other cause. 7. Subjects with a known or suspected history of sclerosing cholangitis. 8. Subjects with partial bowel obstruction, as documented by proximal small bowel dilatation during the Screening Period. 9. Female subjects who are pregnant or lactating. 10. Female subjects who are likely to undergo an in vitro fertilization (IVF ) procedure from the Screening Period through 30 days after the last dose of study medication, OR male subjects likely to participate in an IVF procedure from the Screening Period through 90 days after the last dose of study medication. 11. Subjects with compromised hepatic function, characterized by ALT and/or AST levels twice (2x) the upper normal limit and/or a serum bilirubin > 1.7 mg/dL (unless the subject has been diagnosed with Gilbert’s syndrome) based on clinical laboratory results. 12. Subjects with compromised renal function, characterized by serum creatinine levels 1.5 times the upper normal limit 13. Subjects with a platelet count 750,000/mm3 based on clinical laboratory results. 14. Subjects with severe anemia, defined as hemoglobin of 1.2 based on clinical laboratory results. 17. Subjects with a neutrophil count of 325 mg aspirin/day or chronic (> 7 consecutive days) NSAID or COX-2 inhibitor use within 7 days of the Screening Period. 19. Subjects who have used antibiotics, other than topical antibiotics, within 14 days of the Screening Period. [NOTE: Oral antibiotic use will be permitted after randomization for up to 7 consecutive days for non-serious infections at the discretion of the investigator. See table 4.1-1] 20. Subjects taking warfarin (phenprocoumon) within 7 days of the Screening Period, or who are likely to take warfarin (phenprocoumon). 21. (Intentionally left blank) 22. Subjects taking pharmaceutical nicotine within 14 days of the Screening Period, or who are likely to take pharmaceutical nicotine. 23. Subjects with a his
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study will compare the safety and efficacy of 25 mg QD and 50 mg QD of OPC-6535 to 800 mg BID of Asacol® in the maintenance of remission in subjects with ulcerative colitis. The primary efficacy measure is time to treatment failure, defined as (1) relapse of ulcerative colitis or (2) discontinuation from the study for any other reason. Relapse is defined as either (RB = 1 and FS =1) or the need for other medication for treatment of an acute flare, as judged by the principal investigator. OPC-6535 25 mg QD and OPC-6535 50 mg QD will be compared to Asacol®. 800 mg BID for noninferiority and then for superiority—for a treatment duration of 26 weeks.;Secondary Objective: Efficacy: 1.Time to relapse for a treatment duration of 26 weeks. 2.Proportion of randomized subjects at Week 26&52 who are not treatment failures 3.Time to treatment failure for a treatment duration of 26&52 weeks. 4.Proportion of randomized subjects at Week 52 with endoscopic relapse 5.Change from baseline in health related quality of life at Weeks 26 and 52, based on the Inflammatory Bowel Disease Questionnaire. 6.At Weeks 26&52, the proportion of randomized subjects who are not treatment failures and the times to treatment failure in 3 treatment groups. 7.Changes from baseline in the stool frequency, bleeding, bowel urgency, abdominal pain and general well being scores. Safety: Vital signs, ECGs, laboratory studies (including hematology, clinical chemistry, and urinalysis), and adverse events. Pharmacokinetics: OPC-6535 plasma concentrations. ;Primary end point(s): Primary Outcome Variable: Efficacy: The primary efficacy measure is time to treatment failure, defined as (1) relapse of ulcerative colitis or (2) discontinuation from the study for any other reason. Relapse is defined as either (RB = 1 and FS = 1) or the need for other medication for treatment of an acute flare, as judged by the principal investigator. OPC-6535 25 mg QD and OPC-6535 50 mg QD will be compared t | — |
Countries
Hungary, Ireland
Outcome results
None listed