Shlomo Melmed1, 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 Kleinberg, Sam Teichman, Irit Gliko-Kabir, Roni Mamluk, Asi Haviv, Christian Strasburger. 1. Cedars-Sinai Medical Center (S.M.), Los Angeles, California 90048; Clinical Center of Serbia (V.P.), Belgrade 11080, Serbia; Medizinische Klinik IV (M.Bi., J.S.), LMU, Munich 80336, Germany; ABC Medical Center (M.M.), Mexico City 00-16, Mexico; Erasmus Medical Center (A.J.V.D.L.), Rotterdam 3000, The Netherlands; Leiden University Medical Center (N.B.), Leiden 2333 ZA, The Netherlands; Wroclaw Medical University (M.Bo.), Wroclaw 50-345, Poland; National Institute of Endocrinology (M.C.), Bucharest 11420, Romania; Semmelweis University (K.R.), Budapest 1085, Hungary; Hadassah-Hebrew University Medical Center (B.G.), Jerusalem 9112001, Israel; Health Center (M.G.), Hungarian Defense Forces, Budapest 1134, Hungary; Sourasky Medical Center (Y.G.), Tel Aviv 64239, Israel; The Christie Hospital (P.T.), Manchester M20 4BX, United Kingdom; University of Pecs (E.M.), Pecs 7600, Hungary; Rabin Medical Center (I.S.), Petah-Tikva 4941492, Israel; University of Brescia (A.G.), Brescia 25100, Italy; Queen Mary University of London (M.K.), London E1 4NS, United Kingdom; Sao Paulo University (M.D.B.), Sao Paulo 03071-000, Brazil; New York University Langone Medical Center (D.K.), New York, New York 10016; Chiasma (S.T., I.G.-K., R.M., A.H.), Newton, Massachusetts 02459; and Charite Universitätsmedizin (C.S.), Berlin 10098, Germany.
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) receivinginjectable 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.
RCT Entities:
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.
Authors: Tomáš Česák; Pavel Poczos; Jaroslav Adamkov; Jiří Náhlovský; Petra Kašparová; Filip Gabalec; Petr Čelakovský; Ondrej Choutka Journal: Pituitary Date: 2018-12 Impact factor: 4.107
Authors: Peng Li; Leigh Ford; Shadabul Haque; Mitchell P McInerney; Hywel D Williams; Peter J Scammells; Philip E Thompson; Vincent Jannin; Christopher J H Porter; Hassan Benameur; Colin W Pouton Journal: Pharm Res Date: 2021-06-07 Impact factor: 4.200