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NEW YORK (Reuters Health) - A new once-daily formulation of mesalamine is effective in treating ulcerative colitis, and may improve compliance, according to phase III trial results reported in the January issue of Gastroenterology.
The new formulation uses Multi Matrix System (MMX) technology, designed to deliver the active drug throughout the colon. MMX mesalamine (marketed as Lialda in the US and as Mezavant in Europe) has been approved for use in the US by the Food and Drug Administration for treatment of active, mild-to-moderate ulcerative colitis, representatives of Shire Pharmaceuticals, Inc. recently announced.
Lead investigator Dr. Michael A. Kamm, from St. Mark's Hospital in London, UK, and associates explain that MMX technology combines a pH-dependent, gastro-resistant coating with a tablet core containing mesalamine with hydrophilic and lipophilic excipients.
Once the capsule reaches an area with a basic pH -- normally in the terminal ileum -- it dissolves, and the hydrophilic matrix swells to form an outer viscous gel mass, designed to slow diffusion of the active drug into the colonic lumen. The lipophilic matrix is added to slow the penetration of aqueous fluids into the tablet core, thereby reducing the rate of drug dissolution.
Dr. Kamm and his associates enrolled 341 patients with active, mild-to-moderate ulcerative colitis who were randomly assigned to one of four treatment groups: MMX mesalamine 2.4 g (2 tablets) qd; MMX mesalamine 4.8 g qd; ASACOL, a delayed-release mesalamine (Procter & Gamble) 0.8 g tid; or placebo. Because of the double-dummy design of the trial, patients were required to take four tablets and two capsules in the morning, two capsules at lunchtime, and two capsules in the evening.
The primary end-point was clinical and endoscopic remission at the end of 8 weeks, defined as "a modified ulcerative colitis disease activity index score of no higher than 1, with a score of 0 for rectal bleeding and stool frequency and at least a 1-point reduction from baseline in sigmoidoscopy score." The authors note that, to increase stringency, mucosal friability was given a sigmoidoscopy score of at least 2.
In the intent-to-treat analysis, the primary end point was achieved by significantly more patients receiving MMX mesalamine 2.4 g/day (40.5%, p = 0.01) or 4.8 g/day (41.2%, p = 0.007), compared with placebo (22.1%).
In contrast, the remission rate in the ASACOL group was not significantly greater than placebo (32.6%, p = 0.124).
The two mesalamine regimens were also significantly more effective than placebo in several secondary end points, including clinical remission (no blood in feces and normal stool frequency). All three active treatment groups were more likely than placebo to achieve endoscopic remission -- sigmoidoscopy score no greater than 1 with no mucosal friability -- and clinical improvement.
"All treatments were well tolerated," Dr. Kamm and his team report. The most frequently reported adverse events were headache, flatulence, and abdominal pain.
The investigators add: "The majority of adverse events were mild or moderate in intensity; treatment-related adverse events were infrequent; and none of the eight serious adverse events or the five adverse events that led to withdrawal from the study was considered to be related to study medication."
MMX mesalamine "offers the prospect of effective treatment for acute episodes of mild or moderate, left-sided, or extensive ulcerative colitis," Dr. Kamm and colleagues write, "bringing a substantial proportion of patients into complete clinical and endoscopic remission."
They add, "Treatment with either 2 or 4 tablets given once per day ... should ensure effective patient acceptance and compliance."
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