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Pharmacokinetics, pharmacodynamics, and safety of pasireotide LAR in patients with acromegaly: A randomized, multicenter, open‐label, phase I study
Author(s) -
Petersenn Stephan,
Bollerslev Jens,
Arafat Ayman M.,
Schopohl Jochen,
Serri Omar,
Katznelson Laurence,
Lasher Janet,
Hughes Gareth,
Hu Ke,
Shen George,
Reséndiz Karina Hermosillo,
Gian Vanessa,
Beckers Albert
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.326
Subject(s) - pasireotide , acromegaly , medicine , tolerability , pharmacokinetics , adverse effect , pharmacodynamics , octreotide , gastroenterology , somatostatin , randomized controlled trial , pharmacology , growth hormone , hormone
Pasireotide (SOM230), a multireceptor‐targeted somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long‐acting‐release (LAR) formulation of pasireotide may offer advantages over the subcutaneous formulation. This randomized, open‐label, Phase I study evaluated the safety, PK, and PD of pasireotide LAR 20, 40, or 60 mg/month in patients with acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty‐five patients were randomized and completed the study. Steady‐state pasireotide concentrations were achieved following three monthly injections. Trough pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels ≤2.5 μg/L and IGF‐1 levels below ULN, respectively. Compared with baseline, fasting blood glucose and HbA 1c levels increased, whereas fasting blood insulin levels decreased. Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate. Pasireotide LAR was generally well tolerated. Steady‐state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH, IGF‐1, and symptoms improved, suggesting that pasireotide LAR may be an effective treatment for acromegaly.