Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial.
Melmed, S Popovic, V Bidlingmaier, M Mercado, M Van Der Lely, A Biermasz, N Bolanowski, M Coculescu, M Schopohl, J Racz, K
Melmed, S
Popovic, V
Bidlingmaier, M
Mercado, M
Van Der Lely, A
Biermasz, N
Bolanowski, M
Coculescu, M
Schopohl, J
Racz, K
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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 for 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.
Authors
Melmed, S
Popovic, V
Bidlingmaier, M
Mercado, M
Van Der Lely, A
Biermasz, N
Bolanowski, M
Coculescu, M
Schopohl, J
Racz, K
Glaser, B
Goth, M
Greenman, Y
Trainer, Peter J
Mezosi, E
Shimon, I
Giustina, A
Korbonits, M
Bronstein, M
Kleinberg, D
Teichman, S
Gliko-Kabir, I
Mamluk, R
Haviv, A
Strasburger, C
Popovic, V
Bidlingmaier, M
Mercado, M
Van Der Lely, A
Biermasz, N
Bolanowski, M
Coculescu, M
Schopohl, J
Racz, K
Glaser, B
Goth, M
Greenman, Y
Trainer, Peter J
Mezosi, E
Shimon, I
Giustina, A
Korbonits, M
Bronstein, M
Kleinberg, D
Teichman, S
Gliko-Kabir, I
Mamluk, R
Haviv, A
Strasburger, C
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Date
2015-02-09
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Article
Citation
Safety and Efficacy of Oral Octreotide in Acromegaly: Results of a Multicenter Phase III Trial. 2015:jc20144113 J Clin Endocrinol Metab