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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EA Phase 3 trial showed that pasireotide, a multireceptor-targeted somatostatin analog, led to rapid and sustained decreases in cortisol levels and provided clinical benefit in patients with Cushing disease. Surgery is the first-line treatment for this disease, and most current medical options block adrenal cortisol production but do not treat the underlying disease. Pasireotide may provide the first reliable pituitary-directed medical therapy that targets the underlying cause of Cushing disease.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EAdrenal Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EA Phase 3 trial showed that pasireotide, a multireceptortargeted somatostatin analog, led to rapid and sustained decreases in cortisol levels and provided clinical benefit in patients with Cushing disease. Surgery is the first-line treatment for this disease, and most current medical options block adrenal cortisol production but do not treat the underlying disease. Pasireotide may provide the first reliable pituitary-directed medical therapy that targets the underlying cause of Cushing disease.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EBeverly M.K. Biller, MD, Neuroendocrine Clinical Center, Massachusetts General Hospital, Boston, Massachusetts, USA, explained that pasireotide has high affinity for sst\u003Csub\u003E5\u003C\/sub\u003E, the most prevalent somatostatin receptor on adrenocorticotropic hormone-secreting pituitary adenomas. The drug was found to inhibit production of adrenocorticotropic hormone in corticotroph adenomas \u003Cem\u003Ein vitro\u003C\/em\u003E and was promising in a 15-day Phase 2 study.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe multicenter Phase 3 trial included 162 patients with persistent\/recurrent Cushing disease (n=135) or patients with \u003Cem\u003Ede novo\u003C\/em\u003E disease who were poor surgical candidates, refused surgery, or had surgically unapproachable tumors (n=27). The patients were randomly assigned in a double-blind manner to receive pasireotide at a dose of 600 \u03bcg (n=82) or 900 \u03bcg (n=80) subcutaneously twice a day. At 3 months, a urinary free cortisol (UFC) level was determined. If the level was \u22642 times the upper limit of normal (ULN; defined as 145 nmol\/24 hr) and was less than the baseline level, the randomly assigned dose was continued (double-blinded) until Month 6. The study was unblinded for all other patients, and the dose was increased by 300 \u03bcg twice daily, with treatment continuing until Month 6. These latter patients were considered to be nonresponders for the primary efficacy analysis. Months 6 to 12 were open-label, with the dose titrated as needed. The primary endpoint was a UFC level less than the ULN at 6 months without the need for an increase from the randomized dose.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EAt 6 months, the primary endpoint was met in 14.6% of the patients in the 600-\u03bcg group and in 26.3% in the 900-\u03bcg group; the results at 12 months were similar (13.4% and 25.0%, respectively), confirming the durability of the effect. The predetermined criterion for the primary endpoint (a lower bound of the 95% CI\u0026gt;15%) was met for the 900-\u03bcg group (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). The median decrease in UFC from baseline to Month 6 was approximately 48% for both groups. Higher rates of UFC normalization were associated with lower baseline levels of UFC. Patients who had an inadequate biochemical response could be identified on the basis of UFC levels within 1 to 2 months with 90% accuracy.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12279\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12279\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12279\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EResults of Primary Endpoint at Six Months.\u003Csup\u003E*\u003C\/sup\u003E\n            \u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EPasireotide was associated with significant improvement in signs and symptoms of hypercortisolism, regardless of whether a normal UFC level was achieved. At Month 12, there were substantial decreases in blood pressure, low-density lipoprotein-cholesterol level, and body weight, as well as an increase in the health-related quality of life. Dr. Biller noted that the safety profile of the drug was generally similar to that of other somatostatin analogs, with the important exception of an increased frequency of hyperglycemia. At least 1 hyperglycemia-related adverse event occurred in 73% of patients overall. There were no cases of diabetic ketoacidosis or hyperosmolar coma, and the fasting glucose levels returned to baseline once pasireotide was discontinued. Gastrointestinal events occurred frequently, with 58% of patients overall reporting diarrhea and 52% reporting vomiting. As expected with an effective treatment for Cushing disease, hypocortisolism occurred in some patients (8%); this complication responded to dose reduction and\/or temporary corticosteroid substitution.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/5\/12.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn20d\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzn20d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}