Ulcerative colitis MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis
Conditions
Interventions
Product Name: CyCol
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: ciclosporin
CAS Number: 59865-13-3
Current Sponsor code: ciclosporin
Other descriptive name: cyclosporine (
Sponsors
Sigmoid Pharma Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged >18 years. 2. Subjects with a mild to moderate diagnosis of UC involving at least the rectum and sigmoid colon determined by colonoscopy with biopsies along with appropriate stool assays to evaluate the extent and histologic severity of colitis and to exclude Clostridium difficile, Hemorrhagic E. Coli 0157:H7, Salmonella, Shigella, Crohn's colitis, ischemic colitis, NSAID-induced colitis, or radiation colitis. 3. Subjects clinical severity must be restricted to either mild or moderate clinical disease defined as: - Mild clinical disease — Subjects with mild clinical disease often present insidiously with intermittent rectal bleeding associated with the passage of mucus, and mild diarrhoea with fewer than 4 small loose stools per day. Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease. - Moderate clinical disease — Subjects with moderate clinical disease have frequent loose, bloody stools (up to 8 per day), mild anaemia not requiring blood transfusions, abdominal pain that is not severe, and low grade fever. Adequate nutrition is usually maintained. 4. Subjects must have disease extent (UC involving at least the rectum and sigmoid colon, i.e. ulcerative proctosigmoiditis, left-sided ulcerative colitis or pancolitis) and severity assessed by use of the Disease Activity Index (DAI [or Mayo UC scores] of 3 to 6, inclusive, as defined in the protocol) documented and confirmed by diagnostic endoscopy (see protocol Appendix A) within 1 week of Day 0. 5. Subjects must have a disease duration of at least 3 months prior to commencing study treatment (i.e. Day 0). 6. Subjects must agree not to change the dosing regimen of any current inflammatory bowel disease medications (e.g. low dose steroids, 5-ASA compounds, or immunomodulatory agents) throughout the 4-week treatment period of the study. 7. Subjects must agree to refrain from intake of St. Johns Wort or any other prescription, over-the-counter, or herbal preparation that is known to affect cytochrome P450 throughout the 4-week treatment period of the study. 8. Subjects must agree to refrain from intake of grapefruit or grapefruit juice or any other food or drink that is known to affect cytochrome P450 throughout the 4-week treatment period of the study. 9. Subjects must sign a written informed consent. 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 ;Inclusion criteria: 1. Male and female subjects aged >18 years. 2. Subjects with a mild to moderate diagnosis of UC involving at least the rectum and sigmoid colon determined by colonoscopy with biopsies along with appropriate stool assays to evaluate the extent and histologic severity of colitis and to exclude Clostridium difficile, Hemorrhagic E. Coli 0157:H7, Salmonella, Shigella, Crohn's colitis, ischemic colitis, NSAID-induced colitis, or radiation colitis. 3. Subjects clinical severity must be restricted to either mild or moderate clinical disease defined as: - Mild clinical disease — Subjects with mild clinical disease often present insidiously with intermittent rectal bleeding associated with the passage of mucus, and mild diarrhoea with fewer than 4 small loose stools per day. Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease. - Moderate clinical disease — Subjects with moderate clinical disease have frequent loose, bloody stools (up to 8 per day), mild anaemia not requiring blood transfusions, abdominal pain that is not severe, and low grade fever. Adequate nutrition is usually maintained. 4. Subjects must have disease extent (UC involving at least the rectum and sigmoid colon, i.e. ulcerative proctosigmoiditis, left-sided ulcerative colitis or pancolitis) and severity assessed by use of the Disease Activity Index (DAI [or Mayo UC scores] of 3 to 6, inclusive, as defined in the protocol) documented and confirmed by diagnostic endoscopy (see protocol Appendix A) within 1 week of Day 0. 5. Subjects must have a disease duration of at least 3 months prior to commencing study treatment (i.e. Day 0). 6. Subjects must agree not to change the dosing regimen of any current inflammatory bowel disease medications (e.g. low dose steroids, 5-ASA compounds, or immunomodulatory agents) throughout the 4-week treatment period of the study. 7. Subjects must agree to refrain from intake of St. Johns Wort or any other prescription, over-the-counter, or herbal preparation that is known to affect cytochrome P450 throughout the 4-week treatment period of the study. 8. Subjects must agree to refrain from intake of grapefruit or grapefruit juice or any other food or drink that is known to affect cytochrome P450 throughout the 4-week treatment period of the study. 9. Subjects must sign a written informed consent. 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 with severe or fulminant UC. 2. Subjects with UC limited to rectum only. 3. Subjects who have had any previous colonic surgery. 4. Subjects who have any histological evidence of dysplasia on colonoscopic biopsy. 5. Women of childbearing potential who are unable or unwilling to use an acceptable method of birth control to avoid pregnancy. 6. Subjects who have failed on previous ciclosporin therapy. 7. Subjects who have had any biologic therapy within the past 2 months prior to Day 0. 8. Subjects who have had steroid treatment dose of greater than 10 mg/day prednisolone (or equivalent) in previous 2 months. 9. Subjects with renal impairment, hepatic impairment, uncontrolled hypertension, premalignant skin lesions or current malignancies or any other severe co-morbid condition. 10. Subjects with any known hypersensitivity to ciclosporin or any of its excipients. ;Exclusion criteria: 1. Subjects with severe or fulminant UC. 2. Subjects with UC limited to rectum only. 3. Subjects who have had any previous colonic surgery. 4. Subjects who have any histological evidence of dysplasia on colonoscopic biopsy. 5. Women of childbearing potential who are unable or unwilling to use an acceptable method of birth control to avoid pregnancy. 6. Subjects who have failed on previous ciclosporin therapy. 7. Subjects who have had any biologic therapy within the past 2 months prior to Day 0. 8. Subjects who have had steroid treatment dose of greater than 10 mg/day prednisolone (or equivalent) in previous 2 months. 9. Subjects with renal impairment, hepatic impairment, uncontrolled hypertension, premalignant skin lesions or current malignancies or any other severe co-morbid condition. 10. Subjects with any known hypersensitivity to ciclosporin or any of its excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of CyCol (a controlled release minicapsule formaultion of ciclosporin) in inducing clinical remission, defined as a Disease Activity Index (DAI) score less than or equal to 2 after 4 weeks of treatment, in patients with mild to moderate ulcerative colitis (UC) involving at least the rectum and sigmoid colon.;Secondary Objective: To evaluate further the efficacy of CyCol in this subject population based on the following: - mucosal healing - histological healing - reduction in DAI score of greater than or equal to 2 To evaluate safety and tolerability of CyCol in this subject population.;Primary end point(s): Efficacy: clinical remission at Week 4 as defined in the protocol.;Main Objective: To evaluate the efficacy of CyCol (a controlled release minicapsule formaultion of ciclosporin) in inducing clinical remission, defined as a Disease Activity Index (DAI) score less than or equal to 2 after 4 weeks of treatment, in patients with mild to moderate ulcerative colitis (UC) involving at least the rectum and sigmoid colon.;Secondary Objective: To evaluate further the efficacy of CyCol in this subject population based on the following: - mucosal healing - histological healing - reduction in DAI score of greater than or equal to 2 To evaluate safety and tolerability of CyCol in this subject population.;Primary end point(s): Efficacy: clinical remission at Week 4 as defined in the protocol. | — |
Countries
Ireland, United Kingdom
Contacts
Public Contact; ;
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Outcome results
None listed