E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active colonic Crohn's disease |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011402 |
E.1.2 | Term | Crohn's disease (colon) |
|
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 determine whether the Sildenafil-induced improvement in forearm blood flow demonstrated in patients with moderate to severe colonic Crohn’s disease translates into clinical benefits in patients with active disease. |
|
E.2.2 | Secondary objectives of the trial |
To determine whether orally administered Sildenafil citrate induces remission (absolute CDAI </=150) and reduces the endoscopic index of inflammation (Rutgeerts’ score) and histopathological grading of severity in patients with moderate to severe colonic Crohn's disease.
To determine the effects of orally administered sildenafil citrate on colonic mucosal blood blow level, plasma neutrophil and white cell count, platelet count, erythrocyte sedimentation rate, serum C-reactive protein level and faecal calprotectin levels after a six week treatment period compared with baseline.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Able to give informed consent 2) Definite diagnosis of colonic Crohn's disease based on radiological, endoscopic and/or histological criteria 3) Moderate-to-severe disease activity, defined as a Crohn's Disease Activity Index (CDAI) score of 220475 4) Patients on no medication, or having received stable doses of antibiotics, aminosalicylates or nutritional supplements for at least 4 weeks 5) Patients on immunosuppressants (except steroids) must have received a stable dose for at least three months 6) 18 years of age or older 7) Able to comply with trial requirements (drug taking and visits) 8) Negative serum pregnancy test in females of child-bearing potential, who must agree to use an adequate method of contraception for the duration of trial 9) Stool sample negative for pathogenic bacteria, ova and/or parasites, and C. difficile toxin
|
|
E.4 | Principal exclusion criteria |
1) Use of steroids within four weeks or infliximab within eight weeks of start of trial medication; use of any trial medication within the preceding 3 months 2) Existing colostomy or ileostomy; current symptoms of bowel obstruction; any other severe concurrent morbidity including bleeding disorders or active upper gastrointestinal peptic ulceration; likely need for hospitalisation during the period of the study 3) Recent stroke or myocardial infarction (within the preceding 6 months), unstable angina pectoris, moderate or severe cardiac failure, uncontrolled arrhythmias, uncontrolled hypertension, QT3 prolongation on ECG, any patient with hypotension or in whom vasodilation is clinically inadvisable 4) Significant hepatic or renal dysfunction (ALT > twice ULN; creatinine > 149 micromol/L) 5) Current use of any phosphodiesterase-5 inhibitor 6) Current use of CYP 3A4 inhibitors (e.g. erythromycin, saquanavir, ketoconazole, itraconazole) 7) Current use of organic nitrates or organic nitrites in any form (e.g. glyceryl trinitrate, isosorbide salts, sodium nitroprusside, amyl nitrite, nicorandil) 8) Alpha-blocker therapy, unless stable dose for at least 1 month 9) Prior episode non-arteritic anterior ischaemic optic neuropathy 10) Previous adverse reaction to any phosphodiesterase-5 inhibitor 11) Women who are currently or attempting to become pregnant, or those who are breast-feeding 12) Male patients with anatomical deformation of the penis or predisposition to prolonged erection
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the proportion of patients experiencing a 100 point fall in the Crohn's disease activity index (CDAI score) at Week 6 (end of treatment) compared to baseline. |
|
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
The trial will end at the time of the final patient's last visit (week 8; 2 weeks post end of treatment) unless unexpected adverse events occur or new data become available during the course of the trial, which would mandate early cessation. |
|
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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |