| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Familial Adenomatous Polyposis (FAP) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10056981 |
| E.1.2 | Term | Adenomatous polyposis coli |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Primary Objective To compare the time from randomization to treatment failure for subjects treated with celecoxib versus subjects treated with placebo, where treatment failure is defined as the earliest occurrence of one or more of the following: A. Appearance of >/= 20 polyps at any colonoscopy during the study, or B. Diagnosis of colorectal malignancy |
|
| E.2.2 | Secondary objectives of the trial |
| To compare in the intent-to-treat population the time from randomization to treatment failure for subjects treated with celecoxib versus subjects treated with placebo, where treatment failure is defined as the earliest occurrence of one or more of the following: A. Appearance of >/= 20 polyps at any colonoscopy during the study, or B. Diagnosis of colorectal malignancy, or C. Treatment related dropout Colorectal polyp number: Total number of colorectal polyps To compare polyp burden over 5 years for subjects treated with celecoxib versus subjects treated with placebo To compare the time to appearance of >/= 5 colorectal adenomas for subjects treated with celecoxib versus subjects treated with placebo |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1. Confirmed diagnosis of FAP based on genetic predisposition testing 2. Male or female subjects aged 10 to 17 years inclusive at the time of enrollment 3. Subject's parent or legal guardian has provided written informed consent prior to enrollment in this study 4. Subject has assented to participate prior to enrollment in this study 5. Subject and parent/legal guardian, agree to comply with study requirements and are able to be at the clinic for all required study visits 6. Willingness to abstain from the chronic use of NSAIDs (including aspirin, selective COX-2 inhibitors), oral adrenocorticosteroids, and other nonsteroidal OTC products for the duration of the study. Chronic use of NSAIDs is defined as a frequency of 1 week (7 consecutive days) for more than 3 weeks per year 7. If subject is female and of childbearing potential, she must meet all of the following conditions: Have been using adequate contraception (e.g. abstinence, condom, IUD, birth control pill, diaphragm and spermicide gel combination) since her last menses AND Be willing to use adequate contraception (as above) during the study AND Not be breastfeeding AND Have a negative urine or serum pregnancy test within 14 days prior to study drug administration 8. The subject will be allowed to proceed to baseline colonoscopy so long as all of the following laboratory criteria are met on Baseline evaluation: Hemoglobin > 10.0 gm/dl Platelet count > 100,000/ul WBC > 3,000/ul ALT < 1.5 x upper limit of normal; AST < 1.5 x upper limit of normal Alkaline Phosphatase < 1.5 x upper limit of normal Total Bilirubin < 1.5 x upper limit of normal unless the subject has Gilbert's disease for which Total Bilirubin must be </=2.0xULN Creatinine < 1.5 x upper limit of normal Cholesterol < 1.5 x upper limit of normal For tests not mentioned specifically, there must be no clinically significant abnormalities that in the opinion of the PI would preclude a subject's safe participation. 9.Intact colon 10. Colonoscopy will be performed at baseline according to the description provided in Section 9. To proceed to randomization, the subject must have all of the following: An assessable colon endoscopically evaluated following an adequate preparative procedure (described in Section 9.1) AND If < 20 polyps (> 2mm, visible without dye-enhancement), all must be removed so as to render the colon polyp-free and thus amenable to serial endoscopic surveillance 11. A normal electrocardiogram (ECG) at baseline οΎ– Subjects who have an abnormal tracing that is considered not clinically significant by the site investigator may be entered with sponsor approval |
|
| E.4 | Principal exclusion criteria |
| 1. Diagnosis of attenuated FAP 2. History of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs or salicylates 3. Use of any dose of NSAIDs or oral adrenocorticosteroids, at any frequency of 3 or more times per week during the three months prior to study entry will require a three-month washout period beginning with the time of last dose. Use of any dose of NSAIDs or oral adrenocorticosteroids, at any frequency of less than 3 times per week during the three months prior to study entry will require a one month washout period beginning with the time of last dose. If chronic inhaled steroid use is required, the subject agrees to use mometasone. Use of mometasone is not restricted. In countries were mometasone is not available, only fluticasone will be permitted 4. Anticipated need for concurrent use of fluconazole or lithium 5. Active peptic ulcer disease documented by endoscopy. Significant renal, hepatic or hematologic dysfunction (to be determined by investigator). History of H. pylori related peptic ulcer disease that has been successfully treated with antibiotics will not be exclusionary 6. >/=20 polyps (> 2 mm without dye enhancement) at baseline colonoscopy 7. < 20polyps(> 2 mm without dye enhancement) that have not all been removed at baseline colonoscopy 8. Known inability to participate in the scheduled follow-up tests 9. Significant medical or psychiatric problems, which, in the opinion of the site investigator, would make the subject a poor protocol candidate 10. Subject has undergone a colectomy or planned to have colectomy within the next 6 months 11. Subject has undergone chemotherapy within the past 6 months 12. Subject has received pelvic radiation 13. History of invasive carcinoma in the past five years 14. Familial hypercholesterolemia 15. Familial Hypertriglyceridemia 16. Diabetes 17. Coagulopathy 18. Use of any investigational agent within the last 3 months |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint for this study is time to treatment failure defined as the time from randomization to the earliest occurrence of the following events: a. Appearance of >/=20 polyps (>2mm, visible without dye enhancement) at any colonoscopy during the study, or b. Diagnosis of colorectal malignancy |
|
| 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 | 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 | Information not present in EudraCT |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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