Active Ulcerative Colitis MedDRA version: 8.0 Level: LLT Classification code 10058816
Conditions
Interventions
Product Name: OPC-6535
Product Code: OPC-6535
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Not applicable
CAS Number: N/A
Current Sponsor code: OPC-6535
Other descriptive name: OPC-6535
Con
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 established diagnosis of active ulcerative colitis, who have relapsed within 12 weeks before screening. All subjects must have had the diagnosis of ulcerative colitis established by colonoscopy prior to randomization. (Newly diagnosed subjects are also eligible.) Colonoscopy may be substituted for flexible sigmoidoscopy during Screening in order to meet this criteria. 3. Colonic involvement with ulcerative colitis beyond 15 cm of the anal verge. 4. Subjects with a score ³ 2 for rectal bleeding and a score ³ 2 on flexible sigmoidoscopy at the Screening/Baseline Visit, based on the DAI criteria. 5. Subjects who have been on a stable dose of oral 5-ASA for at least 14 days prior to the Screening/Baseline, OR subjects who have not been receiving treatment with 5-ASA for at least 14 days. 6. 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/Baseline Visit through 30 (females) and 90 (males) days, respectively, from the last dose of study medication. Females who are more than 12 months post-menopausal (documented by FSH) are also eligible to participate in the study. [See Section 5.4 of the protocol 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 severe disease, defined as a DAI of 12 at the Screening/Baseline Visit, and/or subjects whom the Investigator deems likely to require immunosuppressant therapy including corticosteroids and/or hospitalization during the period of study 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 corticosteroids (including oral budesonide) within 30 days, or topical intrarectal agents (corticosteroid or 5-ASA enemas, suppositories, foams) within 7 days of Screening/Baseline [Topical dermatological corticosteroids are not excluded] 5. Subjects who have used immunosuppressants within 28 days or IL-10, IL-11, FK-506 [tacrolimus], mycophenolate, cyclosporin, anti-TNF-a or monoclonal antibody medications within 60 days of Screening/Baseline 6. Subjects who have a history of active malignancies within 5 years (surgically-treated basal cell, squamous cell, non-melanoma 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 a known history of, or suspected, clinically relevant cardiac disease 9. Subjects with a positive stool culture for any enteric pathogens, pathogenic ova or parasites, or a positive assay for C. difficile toxin (a positive EIA that is subsequently confirmed by a positive cytoxin assay) 10. Subjects with partial bowel obstruction, as documented by proximal small bowel dilatation at Screening/Baseline 11. Female subjects who are pregnant or lactating 12. Female subjects who are likely to undergo an in vitro fertilization (IVF ) procedure from the Screening/Baseline Visit through 30 days after the last dose of study medication, OR male subjects likely to participate in an IVF procedure from the Screening/Baseline Visit through 90 days after the last dose of study medication 13. 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 14. Subjects with compromised renal function, characterized by serum creatinine levels 1.5 times the upper normal limit 15. Subjects with a platelet count 750,000/mm3 based on clinical laboratory results 16. Subjects with severe anemia, defined as hemoglobin of 1.2 based on clinical laboratory results 19. Subjects with a neutrophil count of <2000/mm3 based on clinical laboratory results 20. Subjects taking ³ 325 mg aspirin/day or chronic (³ 7 consecutive days) NSAID use within 7 days of Screening/Baseline 21. Subjects who have used antibiotics, other than topical antibiotics for dermatological use, within 14 days of Screening/Baseline 22. Subjects taking warfarin within 7 days of the Screening/Baseline Visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm the efficacy and safety profile seen in the phase II study of 25 mg and 50 mg once daily OPC-6535 oral tablets in the treatment of active ulcerative colitis.;Secondary Objective: ;Primary end point(s): Clinical improvement at week 8 based on the ITT population (denoted as clinical improvement (ITT)), with the restriction that subjects who drop out before completing the week 8 visit will be considered as not exhibiting clinical improvement, regardless of their Disease Activity Index (DAI) scores. Subjects who complete the Week 8 visit on or after day 52 from the date of randomisation (irrespective of whether or not they were still taking medication) and show clinical improvement (as defined below) will be counted as demonstrating clinical improvement (ITT). Clinical improvement is defined as a reduction from baseline in rectal bleading (RB) score of 2 or greater to a score of 0 or 1 plus an improvement of at least 1 point in one other subscale of the DAI: flexible sigmoidoscopy (FS), physician' global assessment (PGA), or stool frequency (SF). The primary efficacy comparisons are 25 mg OPC-6535 vs. placebo and 50 mg OPC-6535 vs. placebo stratified by 5-ASA (5-ASA users or non-users). | — |
Countries
Czech Republic, Hungary
Outcome results
None listed