Gastroenterology

Gastroenterology

Volume 143, Issue 5, November 2012, Pages 1218-1226.e2
Gastroenterology

Original Research
Clinical—Alimentary Tract
Once-Daily Budesonide MMX® Extended-Release Tablets Induce Remission in Patients With Mild to Moderate Ulcerative Colitis: Results From the CORE I Study

https://doi.org/10.1053/j.gastro.2012.08.003Get rights and content

Background & Aims

Budesonide is a corticosteroid with minimal systemic corticosteroid activity due to first-pass hepatic metabolism. Budesonide MMX® is a once-daily oral formulation of budesonide that extends budesonide release throughout the colon using multi-matrix system (MMX) technology.

Methods

We performed a randomized, double-blind, double-dummy, placebo-controlled trial to evaluate the efficacy of budesonide MMX for induction of remission in 509 patients with active, mild to moderate ulcerative colitis (UC). Patients were randomly assigned to groups that were given budesonide MMX (9 mg or 6 mg), mesalamine (2.4 g, as reference), or placebo for 8 weeks. The primary end point was remission at week 8.

Results

The rates of remission at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 17.9%, 13.2%, and 12.1%, respectively, compared with 7.4% for placebo (P = .0143, P = .1393, and P = .2200). The rates of clinical improvement at week 8 among patients given 9 mg or 6 mg budesonide MMX or mesalamine were 33.3%, 30.6%, and 33.9%, respectively, compared with 24.8% for placebo (P = .1420, P = .3146, and P = .1189). The rates of endoscopic improvement at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 41.5%, 35.5%, and 33.1%, respectively, compared with 33.1% for placebo. The rates of symptom resolution at week 8 among subjects given 9 mg or 6 mg budesonide MMX or mesalamine were 28.5%, 28.9%, and 25.0%, respectively, compared with 16.5% for placebo (P = .0258, P = .0214, and P = .1025). Adverse events occurred at similar frequencies among groups.

Conclusions

Budesonide MMX (9 mg) was safe and more effective than placebo in inducing remission in patients with active, mild to moderate UC. ClinicalTrials.gov, Number: NCT00679432.

Section snippets

Materials and Methods

All authors had access to the study data and reviewed and approved the final manuscript.

Patients

Supplementary Figure 1 shows the disposition of patients. A total of 489 patients were included in the modified ITT population. Twenty randomized patients were excluded from the modified ITT analysis because of normal histology at baseline (17 patients) or major entry criteria violations (3 patients with confirmed infectious colitis at study entry). The baseline characteristics were similar across the treatment groups, except that the percentage of male patients in the budesonide MMX 9 mg group

Discussion

Treatment with budesonide MMX 9 mg showed a significant benefit over placebo in the rate of combined clinical and endoscopic remission at week 8 among patients with active, mild to moderate UC. Exploratory analyses suggested a possible benefit for symptom resolution, and there were trends toward greater rates of clinical improvement and endoscopic improvement. Incidence rates of treatment-emergent adverse events were similar across treatment groups, and no clinically important safety trends

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  • Cited by (0)

    Conflicts of interest The authors disclose the following: Dr Sandborn has received consulting fees from Abbott Laboratories, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys Inc, Atlantic Healthcare Ltd, Aptalis, BioBalance Corp, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corp, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine PharmaSciences Inc, Eagle Pharmaceuticals, enGene Inc, Eli Lilly and Company, EnteroMedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexion Therapeutics Inc, Funxional Therapeutics Ltd, Genzyme Corp, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, KaloBios Pharmaceuticals Inc, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL BioPharma, Pfizer Inc, Procter & Gamble, Prometheus Laboratories, ProtAb Ltd, PurGenesis Technologies Inc, Relypsa Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus Inc, Schering-Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Sirtris Pharmaceuticals, SLA Pharma UK Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Ltd, Warner Chilcott UK Ltd, and Wyeth; has received research grants from Abbott Laboratories, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium Pharmaceuticals, Novartis, Pfizer, Procter & Gamble, Shire Pharmaceuticals, 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. Dr Travis has received consulting fees from Abbott Laboratories, Asahi, Aspreva, Cosmo Technologies, Elan, Ferring Pharmaceuticals, Genzyme Corp, Genentech, Glenmark, GlaxoSmithKline, Lexicon Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millennium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, PDL BioPharma, Pfizer Inc, Procter & Gamble, Santarus Inc, Schering-Plough, Shire Pharmaceuticals, Sigmoid Pharma Ltd, Tillotts Pharma AG, TxCell SA, UCB Pharma, Vertex, Vifor, Warner Chilcott UK Ltd, and Wyeth; has received research grants from Abbott, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Procter & Gamble, Shire Pharmaceuticals, and UCB Pharma; has received payments for lectures/speakers bureau from Abbott Laboratories, Ferring Pharmaceuticals, Merck, Shire Pharmaceuticals, Tillotts, Warner Chilcott, and Vertex; and holds no stock/stock options. Dr Moro and Dr Jones are employees of and own stock in Cosmo Pharmaceuticals SpA. Drs Ballard, Bagin, Huang, and Yeung and Ms Gautille are employees of and own stock in Santarus, Inc.

    Funding Supported by Santarus, Inc, and Cosmo Pharmaceuticals SpA.

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