ECE2022 Poster Presentations Pituitary and Neuroendocrinology (127 abstracts)
Safety comparison of 40- vs 60- mg/day doses of oral octreotide capsules for treatment of acromegaly in the chiasma optimal trial
Susan L. Samson 1 , Lisa B. Nachtigall 2 , Maria Fleseriu 3 , Mark E. Molitch 4 , Andrea Giustina 5 , Asi Haviv 6 , Nienke Biermasz 7 , Laurence Kennedy 8 , Mojca Jensterle 9 , Patrick Manning 10 , Atanaska Elenkova 11 , Shlomo Melmed 12 & Christian J. Strasburger 13
1Mayo Clinic, Department of Medicine and Neurological Surgery, Jacksonville, United States; 2Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Neuroendocrine Unit, Boston, United States; 3Oregon Health & Science University, Pituitary Center, Portland, United States; 4Northwestern University Feinberg School of Medicine, Chicago, United States; 5San Raffaele Vita-Salute University, Institute of Endocrine and Metabolic Sciences, Milan, Italy; 6Amryt Pharmaceuticals DAC, Dublin, Ireland; 7Leiden University Medical Center (LUMC), Leiden, Netherlands; 8Cleveland Clinic Foundation, Cleveland, United States; 9University Medical Center Ljubljana, Department of Endocrinology, Diabetes and Metabolic Diseases, Slovenia; 10Dunedin Hospital, Dunedin, New Zealand; 11Medical University Sofia, USHATE “Acad. Ivan Penchev”, Department of Endocrinology, Sofia, Bulgaria; 12Cedars-Sinai Medical Center, Los Angeles, United States; 13Charite-Universitätsmedizin, Campus Mitte, Department of Clinical Endocrinology, Berlin, Germany
Background: Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States who have previously responded to injectable somatostatin receptor ligands (iSRLs, octreotide or lanreotide). In previous phase 3 studies, the safety of OOC was shown to be consistent with iSRLs, without dose-dependent adverse reactions. In the double-blind, placebo-controlled period (DPC) of the CHIASMA OPTIMAL trial (NCT03252353), patients were randomized to twice-daily OOC at 40- mg/day, with the option for up-titration to 80- mg/day. In contrast, patients entered the open-label extension (OLE) at a 60- mg/day dose.
Objective: Examine the safety of 40- mg/day vs 60- mg/day OOC doses.
Methods: Eligible patients had the option to enroll in the OLE following the core trial. All patients received OOC 60- mg/day upon entering the OLE regardless of prior treatment in the DPC, including patients who received placebo in the DPC. OOC doses were up- or down-titrated based on insulin-like growth factor I (IGF-I) level and/or acromegaly signs or symptoms. The current analysis compared the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAE-related study drug discontinuation, and acromegaly-related TEAEs (defined as new or worsening signs or symptoms of acromegaly).
Results: Twenty-eight patients randomized to OOC in the DPC (40- mg/day dose) and 19 who were originally randomized to placebo and continued into the OLE (60- mg/day dose) were included in the analysis. Biochemical control was similar in both groups as demonstrated by mean IGF-I levels over the respective periods. Ninety-six percent of patients on 40- mg/day and 57.9% on 60- mg/day experienced ≥1 TEAEs. Two patients on 60- mg/day reported a total of 2 SAEs, both deemed unrelated to study drug. Two patients on 40- mg/day experienced TEAEs leading to study drug discontinuation (headache and gastrointestinal symptoms). The incidence of acromegaly-related TEAEs was generally lower in those on 60- mg/day vs 40- mg/day.
Conclsions: This is the first analysis exploring differences in OOC doses. The nature and incidence of TEAEs occurring with a starting OOC dose of 60- mg/day vs 40- mg/day were similar, though this analysis was limited by differences in TEAE reporting across sequential phases of a lengthy trial. A trend was observed for decreased incidence of acromegaly-related TEAEs with the 60- mg/day dose. This finding is in line with previous analyses showing no dose-related TEAEs with OOC.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more