Safety and efficacy of oral octreotide in acromegaly: Results of a multicenter phase III trial

Shlomo Melmed, Vera Popovic, Martin Bidlingmaier, Moises Mercado, Aart Jan Van Der Lely, Nienke Biermasz, Marek Bolanowski, Mihail Coculescu, Jochen Schopohl, Karoly Racz, Benjamin Glaser, Miklos Goth, Yona Greenman, Peter Trainer, Emese Mezosi, Ilan Shimon, Andrea Giustina, Márta Korbonits, Marcello D. Bronstein, David KleinbergSam Teichman, Irit Gliko-Kabir, Roni Mamluk, Asi Haviv, Christian Strasburger

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68 Citations (Scopus)

Abstract

Background: A novel oral octreotide formulation was tested for efficacy and safety in a phase III, multicenter, open-label, dose-titration, baseline-controlled study in patients with acromegaly. Methods: We enrolled 155 complete or partially controlled patients (IGF-1 <1.3 × upper limit of normal [ULN], and 2-h integrated GH <2.5 ng/mL) receiving injectable somatostatin receptor ligand (SRL) for ≥3 months. Subjects were switched to 40 mg/d oral octreotide capsules (OOCs), and the dose escalated to 60 and then up to 80 mg/d to control IGF-1. Subsequent fixed doses were maintained for a 7-month core treatment, followed by a voluntary 6-month extension. Results: Of 15 1evaluable subjects initiating OOCs, 65% maintained response and achieved the primary endpoint of IGF-1<1.3×ULN and mean integrated GH <2.5 ng/mL at the end of the core treatment period and 62% at the end of treatment (up to 13 mo). The effect was durable, and 85%of subjects initially controlled on OOCs maintained this response up to 13 months. When controlled on OOCs, GH levels were reduced compared to baseline, and acromegaly-related symptoms improved. Of 102 subjects completing the core treatment, 86% elected to enroll in the 6-month extension. Twenty-six subjects who were considered treatment failures (IGF-1≥1.3×sULN)terminatedearly, and 23 with drew for adverse events, consistent with those known for octreotide or disease related. Conclusions: OOC, an oral therapeutic peptide, achieves efficacy in controlling IGF-1 and GH after switching from injectable SRLs for up to 13 months, with a safety profile consistent with approved SRLs. OOC appears to be effective and safe as an acromegaly monotherapy.

Original languageEnglish
Pages (from-to)1699-1708
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Melmed, S., Popovic, V., Bidlingmaier, M., Mercado, M., Van Der Lely, A. J., Biermasz, N., Bolanowski, M., Coculescu, M., Schopohl, J., Racz, K., Glaser, B., Goth, M., Greenman, Y., Trainer, P., Mezosi, E., Shimon, I., Giustina, A., Korbonits, M., Bronstein, M. D., ... Strasburger, C. (2015). Safety and efficacy of oral octreotide in acromegaly: Results of a multicenter phase III trial. Journal of Clinical Endocrinology and Metabolism, 100(4), 1699-1708. https://doi.org/10.1210/jc.2014-4113