A Subcutaneous Octreotide Hydrogel Implant for the Treatment of Acromegaly |
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| Affiliation: | 1. Division of Endocrinology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;2. Endo Pharmaceuticals Inc., Clinical Research and Development, Chadds Ford, Pennsylvania;3. Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, Illinois.;1. Department of Chemistry, University of Missouri-Kansas City, Kansas City, Missouri 64110;2. Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Science, University of Missouri-Kansas City, Kansas City, Missouri 64108;1. Princess Margaret Cancer Centre, Toronto, Ontario, Canada;2. University of Saskatchewan, Saskatoon, Saskatchewan, Canada;3. University of Alberta, Edmonton, Alberta, Canada;4. CHU de Québec–Université Laval, Québec, Québec, Canada;5. Dalhousie University, Halifax, Nova Scotia, Canada;6. St Paul''s Hospital, Vancouver, British Columbia, Canada;7. The University of Ottawa, Ottawa Hospital, Ottawa, Ontario, Canada;8. University of Manitoba, Winnipeg, Manitoba, Canada;9. McMaster University, Hamilton, Ontario, Canada;10. Toronto Western Hospital, Toronto, Ontario, Canada;11. McGill University Health Centre, Montreal, Québec, Canada;12. Western University, London, Ontario, Canada. |
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| Abstract: | ObjectiveTo evaluate the pharmacokinetics, efficacy, and safety of a subcutaneous octreotide hydrogel implant in patients with acromegaly.MethodsIn 2 phase II open-label randomized studies, patients aged ≥ 18 years with confirmed acromegaly and octreotide responsiveness received one or two 52 mg hydrated implants (52 mg study) or a hydrated or nonhy drated 84 mg implant (84 mg study) inserted subcutane ously in the upper arm. Implants were removed after 6 months. The 84 mg study assessed pharmacokinetics in patients with undetectable baseline octreotide concentra tions. Both studies assessed efficacy (serum growth hor mone [GH], insulin-like growth factor 1 [IGF-1]) and safety (adverse events, physical examination, clinical chemistry).ResultsEleven patients received 1 (n = 5) or 2 (n = 6) 52 mg implants; 34 received a hydrated (n = 17 [safety]; n = 16 [efficacy analysis]) or nonhydrated (n = 17) 84 mg implant. With the nonhydrated versus hydrated 84 mg implant, mean maximum serum concen tration (Cmax) and mean area under the drug concentration versus time curve from time 0 to 6 months were decreased (P = 0.002 and P = 0.03, respectively) and mean time to Cmax was increased (P = 0.002). In both studies, IGF-1 and GH declined in month 1 and were significantly suppressed during the 6-month treatment versus baseline (P < 0.001). With the 52 mg and 84 mg implants, respectively, 3 of 11 patients (27%) and 17 of 33 patients (52%) achieved IGF-1 normalization and 8 of 11 patients (73%) and 13 of 33 patients (39%) exhibited GH < 2.5 ng/mL; 9 of 11 patients (82%) and 11 of 34 patients (32%) experienced treatment related adverse events, which were mainly gastrointestinal.ConclusionOctreotide hydrogel implants were well tolerated and maintained stable octreotide release and sup pression of IGF-1 and GH over 6 months. (Endocr Pract. 2012;18:870-881) |
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