P402 A novel high-dose mesalazine tablet is as effective as conventional low-dose mesalazine tablets in inducing remission in patients with mildly to moderately active ulcerative colitis (UC): A double-blind, double-dummy, multicentre, randomised
A. Dignaß*1, R. Schnabel2, J. Romatowski3, V. Pavlenko4, A. Dorofeyev5, J. Derova6, L. Jonaitis7, T. Nacak8, R. Greinwald8
1Agaplesion Markus Krankenhaus, Dept. of Medicine I, Frankfurt a.M., Germany, 2Pannónia Magánorvosi Centrum Kft, Budapest, Hungary, 3Gastromed sc, Bialystok, Poland, 4Stavropol State Medical University, Stavropol, Russian Federation, 5Regional Bowel Diseases Centre of Donetsk State Medical University, Donetsk, Ukraine, 6Latvian Maritime Medical Centre, Riga, Latvia, 7Lithuanian University of Health Sciences, Dept. of Gastroenterology, Kaunas, Lithuania, 8Dr. Falk Pharma GmbH, Clinical Research, Freiburg, Germany
A novel high-dose mesalazine tablet has been developed to reduce the pill burden for UC patients, which is known to have a negative impact on adherence to regular drug intake.
This pivotal study aimed to compare the efficacy, tolerability and safety of a novel high-dose 1000 mg mesalazine tablet vs the registered Eudragit-coated 500 mg mesalazine tablet Salofalk® in patients with mildly to moderately active UC. Patients with a clinical activity index (CAI) > 4 and ≤ 12 and Endoscopic Index (EI) ≥ 4 were eligible for this phase III study, which used a group-sequential adaptive design. Patients received either 1000 mg mesalazine TID (M1000 group) or 2x500 mg mesalazine TID (M2x500 group) per day for 8 weeks. Primary endpoint was the percentage of patients being in clinical remission, defined as CAI ≤ 4 with stool frequency and rectal bleeding sub-scores of 0 at week 8 (LOCF) (per-protocol [PP] analysis). Endoscopic remission was measured at week 8 (LOCF) and was defined as EI score < 4.
In total, 306 patients were randomised and considered for the safety (SAF) and full analysis set (FAS), 278 patients for the PP population for final analysis (217 PP patients for a pre-planned interim analysis I). The primary endpoint results for clinical remission are summarised in Table 1. High endoscopic remission rates were obtained for both treatment regimens: 68.9% in the M1000 group and 68.4% in the M2x500 group (FAS). Both treatment regimens were safe and no serious adverse event was observed. Importantly, the majority of patients preferred the intake of one high-dose mesalazine tablet (47.7%) over 2 low-dose mesalazine tablets (10.5%).
Table 1. Clinical Remission
A novel high-dose 1 000 mg mesalazine tablet was non-inferior to the registered Salofalk® 500 mg mesalazine tablet for induction of clinical remission in mildly to moderately active UC. The high endoscopic remission rates obtained in this clinical trial confirm that oral mesalazine is a powerful and safe first-line treatment modality in patients with mild to moderate UC.