• DOI:10.1210/jc.2014-4113
• Corpus ID: 21296256

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

@article{Melmed2015SafetyAE,
  title={Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial.},
  author={Shlomo Melmed and V. P. Popovi{\'c} and Martin Bidlingmaier and Mois{\'e}s Mercado and Aart J van der Lely and Nienke R. Biermasz and Marek Bolanowski and Mihail Coculescu and Jochen Schopohl and K{\'a}roly R{\'a}cz and Benjamin Glaser and Mikl{\'o}s I. G{\'o}th and Yona Greenman and Peter J. Trainer and Emese Mezosi and Ilan Shimon and Andrea Giustina and M{\'a}rta Korbonits and Marcello Delano Bronstein and David L. Kleinberg and Sam L. Teichman and Irit Gliko-Kabir and Roni Mamluk and Asi Haviv and Christian J Strasburger},
  journal={The Journal of clinical endocrinology and metabolism},
  year={2015},
  volume={100 4},
  pages={
          1699-708
        }
}

• S. Melmed, V. Popović, +22 authors C. Strasburger
• Published 9 January 2015
• Medicine, Biology
• The Journal of clinical endocrinology and metabolism

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 151 evaluable 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 × ULN) terminated early, and 23 withdrew 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.