| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Ulcerative colitis is characterized by acute and chronic inflammatory changes to the mucosa and submucosa of the colon and rectum. Clinical presentations include increased stool frequency, bloody diarrhea, and abdominal or rectal pain.
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the efficacy and safety of adding 200 mg or 600 mg daily oral RDP58 to 2.4 g/day of oral mesalazine background therapy vs. 4.8 g/day oral mesalazine for induction of complete remission of moderately active ulcerative colitis (UC) at Day 56.
Moderately active UC is defined as a Mayo Score of 7-11 plus a Modified Baron’s Sigmoidoscopy Score ≥ 2 (based on the Investigator’s assessment). Complete remission is defined as:
• A Modified Baron’s Sigmoidoscopy Score of 0 or 1, based on the investigator’s assessment, and
• Complete resolution of rectal bleeding (RB = 0), and
• Complete resolution of stool frequency (SF = 0).
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess the impact of adding 200 mg or 600 mg daily oral RDP58 to 2.4 g/day of oral mesalazine background therapy vs. 4.8 g/day oral mesalazine in patients with moderately active UC for achieving the following at Day 56:
• Complete remission (as defined above) in patients who entered the study with rectal bleeding and increased stool frequency.
• Complete remission or partial response in those patients who entered the study with rectal bleeding and increased stool frequency. Partial response is defined as improvement from Baseline in the PGA, accompanied by improvement in at least 1 other category of symptoms or findings (stool frequency, rectal bleeding, or Modified Baron’s Sigmoidoscopy Score) and no worsening in any of the remaining categories.
• Improvement in histology from rectal biopsy at Day 56.
• Complete remission (as defined above) based on the central facility assessment of the sigmoidoscopy at Baseline and Day 56.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Patients meeting all of the following criteria will be considered for admission to the study:
a) Are willing and able to provide written informed consent;
b) Are male or female between 18 and 75 years of age, inclusive, at Screening.
c) If female, must be (as documented in patient notes):
• postmenopausal (at least 1 year without spontaneous menses), or
• surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrollment), or
• using acceptable contraception (e.g., oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrollment, or
• have a sexual partner with non-reversed vasectomy (with confirmed azoospermia), or
• be using 2 barrier methods (e.g., condom, diaphragm, spermicide, or intra-uterine device).
Women who are using contraception will be required to undergo pregnancy testing at Screening, Baseline, Day 28, Day 56, and Day 84.
d) Have a confirmed diagnosis of moderately active ulcerative colitis, extending proximally beyond 15 cm from the anal verge, as confirmed by flexible sigmoidoscopy performed within 7 days prior to Baseline (Day 1). Moderately active disease is defined as a Mayo Score of 7-11 (see Appendix 1) and a Modified Baron's Sigmoidoscopy Score of 2 or 3 on the flexible sigmoidoscopy (see Appendix 1). The sigmoidoscopy score will be supported by photograph (video is preferred, but still photographs are also acceptable).
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| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study:
a) Isolated proctitis;
b) A history or presence of any condition causing malabsorption or an effect on gastrointestinal motility or history of extensive small bowel resection (> ½ the length of the small intestine);
c) Documented diagnosis of a current renal or hepatic disease;
d) History of a positive test for HIV;
e) Current abuse of alcohol or use of illicit drugs;
f) Change in use of nicotine products within 7 days prior to Screening;
g) Use of anti-spasmodic or anti-diarrheal agents within 7 days prior to Baseline;
h) Multiple food/drug allergies, or a known hypersensitivity to 5-ASA or salicylates;
i) Laboratory values outside the local laboratory reference range as follows:
• blood urea nitrogen (BUN) or serum creatinine level > 1.5 times the upper limit of normal,
• liver enzyme test (alkaline phosphatase, aspartate transaminase [AST/SGOT], alanine transaminase [ALT/SGPT], total bilirubin, or gamma glutamyl transferase [GGT] level > 2 times the upper limit of normal,
• positive stool examination for ova and parasites, positive culture for bacterial pathogens, or presence of Clostridium difficile toxin;
• any other laboratory abnormality that the Investigator considers clinically significant to the patient’s participation in the trial;
j) If female, a positive pregnancy test, or actively breast-feeding;
k) Participation in a previous study of RDP58;
l) A significant co-existing illness or other medical or psychological condition that, in the judgment of the Investigator, contraindicate(s) administration of the study drug and/or any study procedure(s);
m) Dependence on steroids (delivered by any route);
n) Patients who have received the following will be excluded from study entry:
• Intravenous or intramuscularly administered corticosteroids within 1 month prior to the Baseline visit (including Budesonide);
• Oral steroids in excess of prednisone 15 mg/day or its equivalent (in patients not considered to be steroid-dependent). Patients entering the study on an oral steroid at a dose of ≤ 15 mg/day oral prednisone or its equivalent must have been maintained on their current dose for at least 14 days. At the investigator’s discretion, corticosteroids can be decreased if the subject has achieved a complete remission. In this instance, flexible sigmoidoscopy, without rectal biopsy, must be performed to define the patient’s Modified Baron’s Sigmoidoscopy Score prior to a planned decrease in the dose of the oral steroid.
• Any other topical rectal therapy during the 7 days prior to the Screening visit;
• Received immunomodulator therapy including, but not limited to, 6-mercaptopurine, azathioprine or methotrexate within 3 months prior to the Baseline visit;
• Exposure to cyclosporine at any time;
• Drugs that possibly affect expression of tumor necrosis factor (e.g., pentoxifyline and infliximab);
• Any mesalazine-containing compound by any route from which more than 2.4 g/day of mesalazine was available within 7 days prior to the Screening visit (NOTE: 6 g/day of sulfasalazine and 6.75 g/day of balsalazide are equivalent to 2.4 g/day of mesalazine);
• Antibiotics (other than topical antibiotics) and metronidazole, within 7 days prior to the Screening visit.
• Any experimental or investigational drug, device or procedure during the 1-month period prior to the Baseline visit;
o) Any of the following coexisting conditions:
• A history of malignancy other than non-melanoma skin cancer or cervical intra-epithelial neoplasia;
• Toxic megacolon;
• Physical or radiologic evidence of an abdominal abscess;
• Conditions requiring imminent surgical intervention;
• Dependence on total parenteral nutrition;
• Inability to tolerate fluids by mouth;
• Presence of colostomy or ileostomy or a history of colectomy. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint to be measured is the proportion of patients in each treatment group who achieve complete remission of moderately active UC at Day 56. Moderately active UC is defined as a Mayo score of 7-11 and a Modified Baron’s Sigmoidoscopy Score ≥ 2. Complete remission is defined as follows:
• Modified Baron’s Sigmoidoscopy Score of 0 or 1, and
• Complete resolution of rectal bleeding (RB = 0), and
• Complete resolution of stool frequency (SF = 0).
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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