Date: 2013-06-14
Type of information:
phase: 3
Announcement: FDA' agreement on study design
Company: Cosmo Pharmaceuticals (Italy)
Product: Methylene Blue MMX®
Action
mechanism: Methylene Blue MMX® (CB-17-01) tablet, is an oral colon-release formulation, in the form of coated tablets, containing Methylene Blue as manufactured by Prove-pharm. The tablets are formulated using a patented multimatrix technology MMX® that allows the delivery of the active ingredient directly inside the colon. With this technology, the selected local availability of the active ingredient and, consequently, the staining and contrasting effect are optimized and there is no absorption in the upper gastrointestinal tract.
Methylene blue has the interesting property to stain the specialized columnar epithelium of the intestine with high accuracy. Methylene blue has been used to screen for colonic neoplasia, to diagnose villous atrophy and to screen for areas of dysplasia and carcinoma. In the gastrointestinal epithelium the dysplastic epithelium areas and cancers absorb methylene blue in a different way than the normal mucosa. Thus, after staining with methylene blue these abnorma-lities appear as areas of absent or light staining or as a heterogeneous staining pattern against a background of uniformly blue-stained mucosa.
Proveblue®, the substance that is used in CB-17-01, is also used in an injectable medicinal product developed by the Provepharm Company and approved by EMA for use as antidote to treat symptoms of acquired methaemoglobineamia in the EU. Cosmo and Provepharm have entered into an exclusive licensing agreement for Proveblue® that is manufactured under cGMP conditions and is compliant with European and US Pharmacopeias.
Disease: polyp and adenoma detection rate in patients undergoing full colonoscopy
colon cancer diagnosis
Therapeutic area: Cancer - Oncology
Country:
Trial
details:
Latest
news: * On June 14, 2013, Cosmo Pharmaceuticals has announced that the FDA agrees that the design and planned analysis of the study proposed by Cosmo adequately address the objectives necessary to support a regulatory submission for Marketing authorization of the product. The FDA based its review on the clinical documentation including the protocol titled “The Safety and Efficacy of Methylene Blue MMX® modified release tablets administered to subjects undergoing screening or surveillance colonoscopy” submitted by Cosmo in a request for a Special Protocol Assessment (SPA).Cosmo is now completing the preparations for the phase III clinical trial. EMA has previously approved the access to the centralized procedure for the future Marketing Authorization. The trial will be conducted in major North American and European hospitals.* On October 22, 2012, Cosmo Pharmaceuticals has announced that its phase II clinical trials program for the evaluation of the polyp and adenoma detection rate in patients undergoing full colonoscopy after colonic staining with Methylene Blue MMX® tablets attained all the objectives and has generated the information required to complete the design of the phase III clinical trials.
In the tested patient population (n=96) the polyp detection rate in the whole colon was on average 1.8 polyps per patient and the adenoma detection rate was 0.9 detected adenomas per patient. Polyps were detected in 63.5% of patients, adenomas in 46.9% and serrated lesions in 27.1% of patients. According to literature, polyps are normally detected in 35% or less of patients, and according to an abstract published in 2012 by the Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic in Ohio USA, based on 18’003 colonoscopies, the adenoma detection was 31.5% and the serrated lesions detection rate was 20.6%
Patients took Methylene Blue MMX® tablets together with a bowel cleansing preparation. There were no drug related adverse events.
Cosmo is completing the preparations for the phase III trials. In the EU EMA has approved the access to the centralized procedure for the future Marketing Authorization; in the US, a Special Protocol Assessment (SPA) was requested from the FDA and an IND will follow. Barring unforeseen events, the phase III trials should end no later than H2 2013. Approximately 1500 patients will be screened, the majority of these are classical colon cancer screening patients but the clinical trials program will also include patients diagnosed with active ulcerative colitis for more than 8 years. Longstanding ulcerative colitis patients, have a higher risk of contracting colorectal cancer. The trials will be conducted in major North American and European hospitals.
