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

Melmed, Shlomo; Popović, Vera; Bidlingmaier, Martin; Mercado, Moisés; Lely, Aart Jan van der; Biermasz, Nienke R.; Bolanowski, Marek; Coculescu, Mihail; Schopohl, Jochen; Rácz, Kàroly; Gläser, Benjamin; Góth, Miklós; Greenman, Yona; Trainer, Peter J; Mezősi, Emese; Shimon, Ilan; Giustina, Andrea; Korbonits, Márta; Bronstein, Marcello D.; Kleinberg, David L.; Teichman, Sam L.; Gliko-Kabir, Irit; Mamluk, Roni; Haviv, Asi; Strasburger, Christian J.

doi:10.1210/jc.2014-4113

Cited by 155 publications

(119 citation statements)

References 42 publications

(47 reference statements)

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“…Also, the two available LAN preparations (LAR and ATG) induce similar results (Murray & Melmed 2008). Recently the results of a phase III multicenter trial on the efficacy of an oral OCT formulation showed that switching from injectable SSA to the oral formulation effectively maintains disease control in the majority of cases (Melmed et al 2015).…”

Section: Medical Treatmentmentioning

confidence: 89%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.

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Section: Medical Treatmentmentioning

confidence: 89%

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly

Căpățînă¹,

Wass²

2015

Journal of Endocrinology

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“…TPEÒ has successfully completed pharmacokinetic and pharmacological studies in rats and monkeys and subsequently a multicentre 13 month Phase III trial in 155 acromegaly patients with the somatostatin analog, oral octreotide (Mycappsa TM ). 18,19 It consists of octreotide solubilized with C 8 and other common excipients in the hydrophilic component. As with other MCFAs, C 8 in the OS temporarily rearranged zonula occludens-1 (ZO-1) in the tight junction.…”

Section: Fatty Acidsmentioning

confidence: 99%

Safety concerns over the use of intestinal permeation enhancers: A mini-review

2016

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Intestinal permeation enhancers (PEs) are key components in »12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo-and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.

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“…Results of a pivotal phase III study of oral octreotide in acromegaly were presented at ICE/ENDO 2014 meeting (52). The investigators concluded that oral octreotide acetate is a viable option as an oral acromegaly monotherapy.…”

Section: Oral Octreotidementioning

confidence: 99%