Safety and Efficacy of Oral Octreotide in Acromegaly: Results of a Multicenter Phase III Trial

Author:

Melmed Shlomo1,Popovic Vera2,Bidlingmaier Martin3,Mercado Moises4,van der Lely Aart Jan5,Biermasz Nienke6,Bolanowski Marek7,Coculescu Mihail8,Schopohl Jochen3,Racz Karoly9,Glaser Benjamin10,Goth Miklos11,Greenman Yona12,Trainer Peter13,Mezosi Emese14,Shimon Ilan15,Giustina Andrea16,Korbonits Márta17,Bronstein Marcello D.18,Kleinberg David19,Teichman Sam20,Gliko-Kabir Irit20,Mamluk Roni20,Haviv Asi20,Strasburger Christian21

Affiliation:

1. Cedars-Sinai Medical Center (S.M.), Los Angeles, California 90048

2. Clinical Center of Serbia (V.P.), Belgrade 11080, Serbia

3. Medizinische Klinik IV (M.Bi., J.S.), LMU, Munich 80336, Germany

4. ABC Medical Center (M.M.), Mexico City 00-16, Mexico

5. Erasmus Medical Center (A.J.V.D.L.), Rotterdam 3000, The Netherland;s

6. Leiden University Medical Center (N.B.), Leiden 2333 ZA, The Netherlands

7. Wroclaw Medical University (M.Bo.), Wroclaw 50-345, Poland

8. National Institute of Endocrinology (M.C.), Bucharest 11420, Romania

9. Semmelweis University (K.R.), Budapest 1085, Hungary

10. Hadassah-Hebrew University Medical Center (B.G.), Jerusalem 9112001, Israel;

11. Health Center (M.G.), Hungarian Defense Forces, Budapest 1134, Hungary

12. Sourasky Medical Center (Y.G.), Tel Aviv 64239, Israel

13. The Christie Hospital (P.T.), Manchester M20 4BX, United Kingdom

14. University of Pecs (E.M.), Pecs 7600, Hungary

15. Rabin Medical Center (I.S.), Petah-Tikva 4941492, Israel

16. University of Brescia (A.G.), Brescia 25100, Italy

17. Queen Mary University of London (M.K.), London E1 4NS, United Kingdom

18. Sao Paulo University (M.D.B.), Sao Paulo 03071-000, Brazil

19. New York University Langone Medical Center (D.K.), New York, New York 10016

20. Chiasma (S.T., I.G.-K., R.M., A.H.), Newton, Massachusetts 02459;

21. 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) 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.

Publisher

The Endocrine Society

Subject

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

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