Session: OR17-From Genetics to Clinical Trials in Pituitary Disease
W192 (McCormick Place West Building)
Methods:After screening, 155 subjects shown to be controlled (defined as IGF-I levels <1.3 ULN, and 2hr integrated GH <2.5 ng/mL, measured centrally), while on 3 months of injectable somatostatin receptor ligand (SRL), were enrolled. Following OOA pre-treatment baseline establishment and after 4 weeks from last SRL injection, subjects were switched to OOA. All entered a dose escalation phase, initially receiving OOA 40 mg/day, titrated as required to 60 mg/day, and up to 80 mg/day (divided into two separate daily doses), to normalize IGF-I levels. This was followed by a fixed dose phase for up to a total duration of 7 months of OOA treatment (core treatment period). Controlled patients were then offered an additional 6-month extension phase.
Results:Of 151 evaluable subjects that initiated OOA treatment and had at least one evaluation following first dose, 98 (65%) achieved the primary endpoint of hormonal control at their last assessment during the core treatment period, with IGF-I levels <1.3 ULN and mean 2 hr GH concentrations of <2.5 ng/mL. Following individual dose titration based on IGF-I levels, 61, 33, and 57 patients reached doses of 40, 60, and 80 mg, respectively. Of the 91 subjects who were controlled (IGF-I <1.3 ULN) at the end of dose escalation, 83 (91%) maintained this response at the end of the core treatment period. A total of 102 subjects completed the core treatment period, of whom 88 (86%) elected to continue treatment in the 6 month extension phase. Twenty-four subjects (15%) were considered treatment failures due to IGF-I level >1.3 ULN and terminated prior to the end of the core period. Seventeen subjects (11%) terminated for possible drug-related adverse events (AEs), consistent with known octreotide or disease-related AEs. Ten of the early terminations were due to GI symptoms (mostly mild to moderate nausea, diarrhea, or abdominal pain). Two deaths were reported: one of myocardial infarction in a patient with pancreatic carcinoma and obstructive jaundice, and another of suspected biliary obstruction and sepsis.
Conclusions: Oral octreotide acetate exhibits efficacy in controlling IGF-I and GH levels in acromegaly patients treated for at least 7 months, following a switch from injectable SRLs with a safety profile consistent with approved SRLs. OOA is a viable option for administration as oral acromegaly monotherapy.
Disclosure: SM: Principal Investigator, Pfizer, Inc., Ad Hoc Consultant, Genentech, Inc., Ad Hoc Consultant, Novartis Pharmaceuticals, Ad Hoc Consultant, Ipsen. VP: Coinvestigator, Roche Pharmaceuticals. MM: Speaker, Sanofi/Ipsen, Consultant, Sanofi/Ipsen, Speaker, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals. JS: Study Investigator, Chiasma, Study Investigator, Novartis Pharmaceuticals. PJT: Advisory Group Member, Roche Pharmaceuticals, Investigator, Chiasma, Advisory Group Member, unrelated to this study/product - unpaid ad hoc advisory board member. IS: Ad Hoc Consultant, Novartis Pharmaceuticals, Ad Hoc Consultant, Pfizer, Inc., Ad Hoc Consultant, Novo Nordisk, Ad Hoc Consultant, Neopharm. DLK: Advisory Group Member, Genentech, Inc.. SLT: Employee, chiasma. RM: Employee, Chiasma. AH: Employee, Chiasma Pharma. CJS: Advisory Group Member, Chiasma. Nothing to Disclose: MB, AV, NRB, MB, MC, KR, BG, MIG, YG, EM, AG
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