title: Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial.
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 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: 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.
authors: Shlomo
authors: S
authors: Melmed
authors: Vera
authors: V
authors: Popovic
authors: Martin
authors: M
authors: Bidlingmaier
authors: Moises
authors: M
authors: Mercado
authors: Aart Jan
authors: AJ
authors: van der Lely
authors: Nienke
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authors: Biermasz
authors: Marek
authors: M
authors: Bolanowski
authors: Mihail
authors: M
authors: Coculescu
authors: Jochen
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authors: Schopohl
authors: Karoly
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authors: Racz
authors: Benjamin
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authors: Glaser
authors: Miklos
authors: M
authors: Goth
authors: Yona
authors: Y
authors: Greenman
authors: Peter
authors: P
authors: Trainer
authors: Emese
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authors: Mezosi
authors: Ilan
authors: I
authors: Shimon
authors: Andrea
authors: A
authors: Giustina
authors: Márta
authors: M
authors: Korbonits
authors: Marcello D
authors: MD
authors: Bronstein
authors: David
authors: D
authors: Kleinberg
authors: Sam
authors: S
authors: Teichman
authors: Irit
authors: I
authors: Gliko-Kabir
authors: Roni
authors: R
authors: Mamluk
authors: Asi
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authors: Haviv
authors: Christian
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authors: Strasburger
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007334:Insulin-Like Growth Factor I; D015282:Octreotide