| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active mild-to-moderate distal ulcerative colitis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| 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 |
| To evaluate the safety and tolerability of PUR 0110 rectal enema 250 mg, 500 mg and 1000 mg OD versus placebo (vehicle) OD in patients with active mild-to-moderate distal ulcerative colitis |
|
| E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
To explore the effectiveness of PUR 0110 rectal enema, 250 mg, 500 mg and 1000 mg OD versus placebo OD in patients with active mild-to-moderate distal ulcerative colitis.
To evaluate through an exploratory analysis the effect of PUR 0110 rectal enema on:
(a) serum lutein levels; and
(b) the concentrations of biomarkers of inflammation, in vivo oxidative stress, apoptosis and antioxidant defence mechanisms in the plasma, serum, feces, urine and biopsy tissue of patients with active mild-to-moderate distal ulcerative colitis. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
i. Outpatient males and females between 18 and 75 years.
ii. Females of child bearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin) at screening and must be sexually inactive (abstinent) for 3 months prior to dosing and throughout the study or be using one of the following acceptable methods of contraception:
- barrier methods (condom, diaphragm with spermicide);
- IUD in place for at least 3 months;
- surgical sterilization of the partner (vasectomy for at least 6 months); or
- hormonal contraceptives for at least 3 months prior to dosing.
[Female subjects of childbearing potential must be advised to remain sexually inactive or maintain the same method of contraception for ≥7 days following the end of dosing of study treatment]
iii. Patients newly diagnosed or with ongoing active distal ulcerative colitis of > or equal 3 months duration, confirmed by flexible sigmoidoscopy during screening, and extending 10 to 50 cm from the anal margin. Sigmoidoscopy must be conducted within not more than 3 +/- 1 days before the Baseline (Day 0) Visit.
iv. Patients with ongoing active distal ulcerative colitis of ≥3 months duration must be on a stable dose of oral mesalamine (5-ASA) for ≥2 months before the Baseline (Day 0) Visit, EXCEPT the high strength oral MMX mesalamine, Mezavant®, which is not allowed within 2 weeks of the Baseline Visit to the Day 21 Visit. Patients newly diagnosed will be treated with ONLY the randomized study medication, concurrent oral mesalamine treatment is not allowed for newly diagnosed patients.
v. Modified Mayo Score (Disease Activity Index) of ≥5 to ≤10 at Baseline, including a sigmoidoscopic inflammation grade score of ≥2 and a rectal bleeding score ≥2.
vi. Negative stool test at screening to rule out parasites, bacterial pathogens and Clostridium difficile.
vii. Able and willing to fill in (maintain) daily diary cards from Day -7 to Day 21 of the study.
viii. Able to provide voluntary written informed consent prior to initiation of screening, must be capable of following the verbal and written study instructions, and be able to commit to the return visits during the entire period of the study.
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|
| E.4 | Principal exclusion criteria |
i. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, or psychiatric disease, that could compromise patient’s ability to participate in the study, and/or interfere with absorption of the study drug or the interpretation of the study data.
ii. Patients with a diagnosis of Crohn’s disease.
iii. Patients with a modified Mayo score of ≥11 at the Screening (Day -7 & Day -3) Visits.
iv. Patients at immediate or significant risk of toxic megacolon; those with bowel stricture, colonic dysplasia, adenoma or carcinoma.
v. Use of botanical treatments and supplements for ulcerative colitis within 14 days prior to the Baseline Visit.
vi. Patients with any enteric pathogens, ova or parasites, or Clostridium difficile toxin in stool.
vii. Female patients with a positive pregnancy test or lactating at the Screening/Baseline Visits.
viii. History of allergic reaction or hypersensitivity to spinach, spinach tablet, spinach powder or spinach extract; and to latex, molds and mushrooms.
ix. History of gout, pseudogout or hyperuricemia, or kidney stones.
x. History of pseudoallergic hypersensitivity to the food color additives, tartrazine (E102), sunset yellow (E110) and FD & C Blue No.1 (Brilliant blue FCF; E133), allergic asthma, aspirin intolerance, and severe or multiple allergies.
xi. Past medical history of significant gastrointestinal surgery including but not limited to colostomy, ileostomy, or previous colonic surgery other than appendectomy.
xii. Patients with anatomical abnormalities of the colon, e.g., short bowel or other abnormalities.
xiii. Patients with any current infectious, ischemic, or immunologic disease with gastrointestinal involvement.
xiv. Patients with a history of failure to retain enemas.
xv. Use of antibiotics for reasons related to the primary diagnosis or for other gastrointestinal-related conditions within 14 days of Baseline Visit.
xvi. Patients who used non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors, within 14 days prior to Baseline Visit. Except aspirin ≤325 mg/day for cardiovascular prophylaxis.
xvii. Patients who used the following medications used for treating ulcerative colitis from the times indicated below to the end of Week 3 (Visit 6):
a. Topical intrarectal corticosteroids or topical intrarectal mesalamine within 14 days of Baseline Visit;
b. Oral MMX mesalamine, Mezavant, within 14 days of the Baseline Visit.
c. Systemic corticosteroids (oral or injectable, including ACTH) within 30 days of Baseline Visit;
d. Immunosuppresant therapy (methotrexate, azathioprine, 6-mercatopurine or cyclosporine) within 60 days of Baseline Visit; and
e. Biologic therapy (tumor necrosis factor-α inhibitors, monoclonal antibodies, etc.) within 90 days of Baseline Visit.
xviii. Patients with a history of active malignancy within the past 5 years except for squamous cell or basal cell cancers of the skin.
xix. History of any clinical laboratory abnormality deemed significant by the Principal Investigator.
xx. History of significant alcohol or drug abuse within one year prior to the Screening Visit.
xxi. Patients who tested positive at Screening for HIV, HbsAg or HCV.
xxii. Exposure to any investigational or non-registered drug within 30 days prior to administration of study drug.
xxiii. Patients with proctitis: with the extent of inflammation confined to ≤10 cm from the anus.
xxiv. Patients who use loperamide or other antidiarrhoeal agents or mucilages within 7 days of the Baseline Visit.
xxv. Moderate-to-severe abnormal renal, hepatic or blood count test results as follows: plasma creatinine value >1.5 X ULN; AST/ALT > 3 X ULN; GGT/alkaline phosphatase > 3 X ULN; WBC <3,500/mm3 or >15,000/mm3; and platelets <100,000/mm3 or >800,000/mm3.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety will be assessed as per the following:
• Incidence, nature and severity of adverse events
• Incidence, nature and severity of clinical laboratory test abnormalities
|
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| 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 | No |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
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