WO 2016/015055 Al 28 January 2016 (28.01.2016) P O P C T
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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/015055 Al 28 January 2016 (28.01.2016) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 38/10 (2006.01) A61P 1/00 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 38/04 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/US20 15/042298 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 27 July 2015 (27.07.2015) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/028,963 25 July 2014 (25.07.2014) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: IRONWOOD PHARMACEUTICALS, INC. DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, [US/US]; 301 Binney Street, Cambridge, MA 02142 (US). LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, (72) Inventors: CURRIE, Mark, G.; 18 Hall Avenue, Sterling, GW, KM, ML, MR, NE, SN, TD, TG). MA 01564 (US). KURTZ, Caroline; 40 Stone Road, Sud bury, MA 01776 (US). JOHNSTON, Jeffrey; 26 Hanson Published: Street, Unit #2, Boston, MA 02 118 (US). LI, Xiaobing; 56 — with international search report (Art. 21(3)) John C. Porter Way, North Attleboro, MA 02760 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, © o (54) Title: COLON CLEANSING COMPOSITIONS (57) Abstract: The present invention relates to compositions comprising guanylate cyclase C agonist peptides, and dosage forms, methods, and kits thereof. The compositions, dosage forms, methods and kits may be used for colon cleansing prior to colonoscopy, or in preparation for other medical, radiologic and/or surgical procedures. COLON CLEANSING COMPOSITIONS Field The present invention relates t o compositions, dosage forms, methods, and kits for colon cleansing prior t o colonoscopy, or in preparation for other medical, radiologic and/or surgical procedures. Claim of Priority This application also claims priority t o U.S. Provisional Patent Application Serial No. 62/028,963 filed July 25, 2014. The entire contents of the aforementioned applications are incorporated herein by reference. Background In 2006, an estimated 55,170 people in the United States died from colorectal cancer and 148,650 new cases were diagnosed. According t o the National Cancer Institute, colon cancer is the second most deadly cancer in the United States. Of great importance in each case is early and accurate diagnosis, in which case colonoscopy is the standard tool for examination. Colonoscopy screening has been shown t o reduce the expected morbidity and mortality of colorectal carcinoma by 76% t o 90%. Colon cleansing is a required prerequisite for successful colonoscopy as well as most other medical or surgical colorectal procedures. Given the requirement t o identify flat or recessed lesions (nonpolypoid colorectal neoplasms), which are more likely t o be cancerous than polyps, there is now an even greater need for proper colon preparation. Flat or recessed lesions are much more difficult t o spot than raised polyps with traditional colonoscopy, because their appearance is similar t o normal tissue. Colonoscopy preparation is commonly achieved by orally administering purgative solutions that lavage the colon t o rid it of fecal matter. Many of these solutions comprise various phosphate or sulfate salts often in combination with polyethylene glycol (PEG). A major disadvantage of this method is that patients are required t o ingest large volume of liquid within a short period of time for purgation. For instance, patients may have t o ingest four liters of solution within a period of two t o three hours. A large number of patients experience significant volume-related discomfort and adverse side effects such as nausea, abdominal discomfort, cramping, and vomiting. Some preparations can also cause fluid and electrolyte disturbances in subjects with certain medical conditions, including diabetes or renal insufficiency. Another drawback of many of these preparations is their salty and unpleasant taste, which may also lead t o patient noncompliance. Poor bowel preparation, due to lack of patient compliance or insufficient cleansing, decreases the diagnostic efficacy and increases the cost of these procedures, especially if a procedure must be repeated. Further, patients may elect t o forego routine colon cancer screening because it is uncomfortable and unpleasant. Thus, there is need for compositions, methods and kits to be used for colon cleansing that are safe, easy to use, and well tolerated by the patient, while also providing quality preparation of the colon. Summary The compositions, methods, dosage forms and kits disclosed herein address the need for safe, well tolerated and effective colon cleansing. In some embodiments, a GCCA peptide or a pharmaceutically acceptable salt thereof is provided in a composition suitable for administration t o a subject in need of colon cleansing. In some embodiments, the composition comprising the GCCA peptide or salt thereof further comprises one or more purgative agents. In some embodiments, the composition comprising the GCCA peptide or salt thereof, and optionally one or more purgative agents, further comprises an electrolyte solution. In some embodiments, dosage forms are provided comprising a composition comprising a GCCA peptide or pharmaceutically acceptable salt thereof in an amount effective to cleanse the colon in a single dose, either alone or in conjunction with one or more purgative agents. In some embodiments, the dosage form comprises a GCCA peptide or salt thereof in an amount effective t o cleanse the colon in two doses, either alone or in conjunction with one or more purgative agents. In some embodiments, the dosage form comprises a GCCA peptide or salt thereof in an amount effective t o cleanse the colon in three, four, five or six doses, either alone or in conjunction with one or more purgative agents. In some embodiments, the dosage form comprises one or more purgative agents. In some embodiments, the dosage form comprising the GCCA peptide or salt thereof, and optionally one or more purgative agents, further comprises a ready to drink electrolyte solution, or a dry, powdered, or concentrated dosage form of electrolytes that can be reconstituted t o form an electrolyte solution. In some embodiments, methods are provided for cleansing the colon of a patient in need thereof by administering a GCCA peptide or a pharmaceutically acceptable salt thereof. In some embodiments, the GCCA peptide or a pharmaceutically acceptable salt thereof is administered without a purgative agent t o a patient in need of colon cleansing. In some embodiments, the GCCA peptide is administered in conjunction with effective amounts of one or more purgative agents to a patient in need of colon cleansing. In some embodiments, the GCCA peptide is administered to a patient at the same time as one or more purgative agents. When the GCCA peptide is administered to a patient at the same time as one or more purgative agents, the purgative agents may be administered as a separate dosage form or as part of a single composition. In some embodiments, the GCCA peptide is administered to a patient before administration of one or more purgative agents. In some embodiments, the GCCA peptide is administered to a patient after administration of one or more purgative agents. In some embodiments, methods are provided for cleansing the colon of a patient in need thereof comprising administering a GCCA peptide or salt thereof, and optionally one or more purgative agents, and further administering an electrolyte solution. In some embodiments, the GCCA peptide, and optionally one or more purgative agents, is administered to a patient at the same time as the electrolyte solution. When the GCCA peptide is administered to a patient at the same time as the electrolyte solution, the electrolyte solution may be administered as a separate dosage form or as part of a single composition. In some embodiments, the GCCA peptide, and optionally one or more purgative agents, is administered to a patient before administration of the electrolyte solution. In some embodiments, the GCCA peptide, and optionally one or more purgative agents, is administered to a patient after administration of the electrolyte solution. In some embodiments, the GCCA peptide or pharmaceutically acceptable salt thereof is administered t o a patient in need of colon cleansing once before a diagnostic or therapeutic procedure requiring a cleansed colon. In some embodiments the GCCA peptide is administered to a patient in need of colon cleansing twice before the diagnostic or therapeutic procedure. In some embodiments, the GCCA peptide is administered to a patient in need of colon cleansing three or four times before the diagnostic or therapeutic procedure. In some embodiments, an effective amount of the GCCA peptide is administered to a patient in need of colon cleansing five, six, seven o r eight times before the diagnostic or therapeutic procedure.