This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by diffuse, continuous inflammation of the colon. Recent estimates suggest that approximately 17,000children between 5 and 17 years of age in the U.S. are diagnosed with UC. Estimates of the average age at onset in children vary, although 80-90% of patients are 9 years of age or older when symptoms. Evidence from the medical literature suggests that the clinical course and manifestations of UC are similar in children and adults. The most consistent symptoms of UC (diarrhea, abdominal pain, rectal bleeding, fever, and weight loss) are found in comparable proportions in both children and adults with the disease, and are more dependent on the disease activity than age . In addition, in children and adults, extent of disease, which is sometimes used as an indicator of severity, does not necessarily predict disease activity or likelihood of surge, and there is little evidence that childhood onset of UC carries a worse prognosis than adult onset disease. 5-ASA products like Asacol used off-label as first-line therapy to treat children with UC. In children, Asacol 400 mg delayed-release mesalamine tablets are used in the United States (US) for the treatment of mildly-to- moderately active UC and for the maintenance of remission of UC. The currently indicated dosage for adults in the US for active UC is two 400 mg tablets taken 3 times a day (for a total daily dose of 2.4 grams) for 6 weeks. The purpose of this study is to assess the safety and efficacy of high dose and low dose Asacol administered as 400 mg delayed-release tablets given every 12 hours for 6 weeks to children and adolescents with mildly-to-moderately active ulcerative colitis. This is Phase III randomized, double-blind, parallel-group, 6-week study of 2 dose levels of Asacol consisting of a high dose and a low dose in pediatric patients ages 5?17 years. Randomization will be stratified by weight (17 ?33 kg, 33 ?54 kg, and 54 ?90 kg) and by disease severity (mild and moderate). High dose and low dose will be defined as follows for the 3 different weight groups. in the context of what is considered to be the current standard of care for pediatric UC patients (120 mg/kg/day). The high doses in each weight category (17 ? 33 kg, 33 ?54 kg, and 54 ?90 kg) are approximately 1.67, 1.8 and 2 times the low dose, respectively. Patients will take study medication twice daily every 12 hours, at approximately the same time each day without regard to meals.Doses were selected based on the following considerations;clinical standard of care (not exceeding the maximum dose utilized in clinical practice of120 mg/kg/day);estimated local colonic/topical exposures;(see Appendix 7.6 for details).About 100 patients will be enrolled with the expectation that about 80 (40 combined high dose and 40 combined low dose) will complete. Patients must have a history of biopsy and endoscopy confirmed UC (either newly diagnosed or that has recently relapsed) with ongoing symptoms of mild to moderate UC to include both rectal bleeding and stool frequency. Patients will be treated with Asacol for 6 weeks with clinic visits for evaluation of safety, compliance, and efficacy at Baseline, Week 3, and Week 6. Sparse population PK samples will be obtained at Weeks 3 and 6. Disease activity in this study will be assessed using the following clinical symptom assessments: the validated PUCAI and a """"""""Truncated Mayo"""""""" (TM-Mayo) assessment including the stool frequency and rectal bleeding domains of the Mayo scoring system. While endoscopies are not mandated by this protocol, data from any endoscopy that is performed for medical cause at the Investigator's discretion during the course of the study will be collected and entered into the study data base. Study Procedures: Medical history;medication history;personal/demographic data;physical examination;body weight/height;vital signs (heart rate, blood pressure, body temperature);blood sample for hematology and serum chemistry tests (If a sample has been collected within 7 days of Screening at a local laboratory, these results may be used to determine patient eligibility; blood sample for serum biomarkers (lactoferrin and calprotectin). This will be done when core laboratory blood samples are drawn (either Screening or Baseline).The total volume of blood collected will be approximately 70 mL. Urine pregnancy test (post-menarchal females only); Note: The urine pregnancy test will be done using a pregnancy test kit provided by the central laboratory. urinalysis;stool sample for bacterial pathogens, ova and parasites, and C. difficile will also be collected.
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