Original ResearchFull Report: Clinical—Alimentary TractThe Role of Centralized Reading of Endoscopy in a Randomized Controlled Trial of Mesalamine for Ulcerative Colitis
Section snippets
Patients
This randomized, double-blind, placebo-controlled, multicenter, phase 3 study was conducted in patients with mildly to moderately active UC at 26 centers in Belarus, India, Turkey, and Ukraine (Appendix 1). The study was approved by the independent ethics committee at each center, and all patients provided written informed consent.
Adult patients (18 years or older) with a documented diagnosis of UC were eligible to participate if they met the following criteria: (1) disease extending at least
Patient Disposition and Characteristics
A total of 343 patients were screened for eligibility; 281 met the eligibility criteria and were randomized and received at least one dose of study medication (ITT and safety populations) (Supplementary Figure 1). The first patient enrolled in the study provided informed consent on November 5, 2009, and the last patient completed the last clinic visit on May 19, 2011. Of the 281 patients randomized, 140 received mesalamine and 141 received placebo. There was a single relevant protocol
Discussion
These results provide consistent evidence that treatment with mesalamine 800-mg tablets at a dosage of 4.8 g/day is more effective than placebo for the treatment of patients with mildly to moderately active UC. Although the observed difference between the treatment groups for the primary end point, clinical remission at week 6 in the ITT population, was marginally significant (30.0% vs 20.6%, P =.069), analyses of the prespecified secondary outcome measures consistently favored mesalamine.
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Conflicts of interest The authors disclose the following: B. Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, Abbott Laboratories, Novartis Pharmaceuticals, Centocor, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGeniX, and Wyeth; has received consulting fees from Millennium Pharmaceuticals, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, Abbott Laboratories, AstraZeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novo Nordisk, GlaxoSmithKline, ActoGeniX, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, gIcare Pharma, and Sigmoid Pharma; and is a member of the speakers bureau for UCB, Abbott Laboratories, and J&J/Janssen. W. J. Sandborn has received consulting fees from Abbott Laboratories, ActoGeniX, AGI Therapeutics, Alba Therapeutics, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Atlantic Healthcare, Aptalis, BioBalance, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine PharmaSciences, Eagle Pharmaceuticals, EnGene, Eli Lilly, EnteroMedics, Exagen Diagnostics, Ferring Pharmaceuticals, Flexion Therapeutics, Funxional Therapeutics, Genzyme, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, PDL BioPharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb, PurGenesis Technologies, Relypsa, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering-Plough, Shire, Sigmoid Pharma, Sirtris Pharmaceuticals, SLA Pharma UK, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics, Warner Chilcott UK, and Wyeth; has received research grants from Abbott Laboratories, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire, and UCB Pharma; has received payments for lectures/speakers bureau from Abbott Laboratories, Bristol-Myers Squibb, and Janssen; and holds stock/stock options in EnteroMedics. G. D'Haens has received grant/research support from Merck, Abbott Laboratories, Centocor, Given Imaging, UCB Pharma, and ActoGeniX and has received consulting fees from Boehringer Ingelheim, Cosmo Technologies, EnGene, Ferring Pharmaceuticals, Millennium Pharmaceuticals, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, UCB Pharma, Abbott Laboratories, AstraZeneca, Shire, Tillotts Pharma AG, Novo Nordisk, GlaxoSmithKline, ActoGeniX, Pfizer, and Sigmoid Pharma. J. W. D. McDonald, D. King, C. Wong, G. Zou, A. Donner, L. Shackelton, S. Nelson, and M. Vandervoort are employees of Robarts Clinical Trials, which was the research organization that conducted this study. P. Rutgeerts has received consulting fees from Centocor, Merck, UCB, Abbott Laboratories, Millennium/Takeda, Genentech/Hoffmann-La Roche, Neovacs, Merck/Serono, Bristol-Myers Squibb, Robarts Clinical Trials, Tillotts Pharma AG, Pfizer, and Falk Pharma; has received lecture fees from Centocor, Merck, and Abbott Laboratories; and has received research support (university) from Centocor, Merck, UCB, and Abbott Laboratories. P. Munkholm and U. Mittmann have received consulting fees from Tillotts Pharma AG. D. Gilgen is an employee of Tillotts Pharma AG. E.V. Loftus Jr has received consulting fees from Abbott Laboratories, UCB Pharma, Janssen Biotech, Given Imaging, Elan, Hospira, and Eisai and has received research/grant support from Abbott Laboratories, UCB Pharma, Janssen Biotech, Amgen, GlaxoSmithKline, Millennium-Takeda, Braintree Labs, Bristol-Myers Squibb, Pfizer, Genentech, Santarus, and Shire. R. Panaccione has received consulting and/or lecture fees from Abbott Laboratories, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research, Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Millennium Pharmaceuticals (now Takeda), Ocera Therapeutics, Otsuka America Pharmaceutical, Pfizer, Shire, Prometheus Laboratories, Schering-Plough, Synta Pharmaceuticals, Teva, UCB Pharma, and Warner Chilcott. S. Travis is a board member for Abbott Laboratories, Centocor, Schering-Plough, Cosmo Technologies, Elan Pharma, Genentech, Guiliani, GlaxoSmithKline, Merck, Takeda, PDL BioPharma, Pfizer, Shire, UCB Pharma, Asahi, Aspreva, Ferring Pharmaceuticals, Vertex, Warner Chilcott, Vifor, Novartis, Novo Nordisk, Santarus, Genzyme, and Procter & Gamble; has received consulting fees from Abbott Laboratories, Centocor, Schering-Plough, Bristol-Myers Squibb, ChemoCentryx, Cosmo Technologies, Elan Pharma, Genentech, Guiliani, Merck, Takeda, Otsuka Pharmaceuticals, PDL BioPharma, Pfizer, Shire, and Glenmark Pharma; has received grant funding from Ferring, Abbott Laboratories, Schering-Plough, Merck Sharpe & Dohme, Procter & Gamble, Warner Chilcott, and the International Organization of IBD; and has received payment for lectures including service on speakers bureaus for Abbott Laboratories, Schering-Plough, Centocor, Merck, Given Imaging, UCB Pharma, Ferring Pharmaceuticals, Tillotts Pharma AG, Shire, Sanofi Aventis, and Vifor. G. Van Assche has received research support from Merck, Abbott, and Janssen and has received honoraria from Merck, Janssen, Ferring Pharmaceuticals, Elan/Biogen, Bristol-Myers Squibb, Novartis, UCB Pharma, Abbott Laboratories, Shire, Novo Nordisk, and Zealand Pharma. S. Vermeire has received research grants from Abbott Laboratories, MSD, and UCB and lecture fees and advisory board fees from MSD, Abbott Laboratories, UCB, Ferring, Chiesi, Pfizer, and Shire. B. G. Levesque has received consulting fees from Prometheus Laboratories and Santarus; has served on the speakers bureau for Salix; and is an employee of Robarts Clinical Trials, which was the research organization that conducted this study. Robarts Clinical Trials provides central endoscopy reading services for compensation and served as the clinical research organization for this trial. The remaining authors disclose no conflicts.
Funding Supported by Tillotts Pharma AG.