Safety, tolerability, and pharmacokinetics of a single dose of pasireotide long-acting release in healthy volunteers: A single-center Phase I study

European Journal of Endocrinology

Volumn 166, Issue 5, 2012, Pages 821-828

  Dietrich, Hartmut ^a   Hu, Ke ^b   Ruffin, Matthieu ^b   Song, Dongweon ^a   Bouillaud, Emmanuel ^b   Wang, Yanfeng ^a   Hasskarl, Jens ^b  

^a ClinPharmCologne   (Germany)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCAGON; GLUCOSE; HEMOGLOBIN A1C; INSULIN; PASIREOTIDE;

ABDOMINAL DISCOMFORT; ABDOMINAL DISTENSION; ABDOMINAL PAIN; ABNORMAL FECES; ADULT; ANTIDIABETIC ACTIVITY; ARTICLE; BRADYCARDIA; CONTROLLED DRUG RELEASE; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; FLATULENCE; GALLBLADDER DISEASE; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN EXPERIMENT; INJECTION SITE PAIN; INJECTION SITE REACTION; INTESTINE MOTILITY; INTESTINE SOUND; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ABDOMINAL PAIN; ADOLESCENT; ADULT; DELAYED-ACTION PREPARATIONS; DIARRHEA; HUMANS; MALE; SOMATOSTATIN; YOUNG ADULT;

EID: 84862091799     PISSN: 08044643     EISSN: 1479683X     Source Type: Journal    
DOI: 10.1530/EJE-11-0773     Document Type: Article

References (17)

1. Schmid HA. Pasireotide (SOM230): development, mechanism of action and potential applications. Molecular and Cellular Endocrinology 2008 286 69-74. (doi:10.1016/j.mce.2007.09.006)
2. Bruns C, Lewis I, Briner U, Meno-Tetang G & Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. European Journal of Endocrinology 2002 146 707-716. (doi:10.1530/eje.0.1460707)
3. Van Der Hoek J, Waaijers M, van Koetsveld PM, Sprij-Mooij D, Feelders RA, Schmid HA, Schoeffter P, Hoyer D, Cervia D, Taylor JE, Culler MD, Lamberts SW& Hofland LJ. Distinct functional properties of native somatostatin receptor subtype 5 compared with subtype 2 in the regulation of ACTH release by corticotroph tumour cells. American Journal of Physiology. Endocrinology and Metabolism 2005 289 E278-E287. (doi:10.1152/ajpendo.00004.2005)
4. Batista DL, Zhang X, Gejman R, Ansell PJ, Zhou Y, Johnson SA, Swearingen B, Hedley-Whyte ET, Stratakis CA & Klibanski A. The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 2006 91 4482-4488. (doi:10.1210/jc.2006-1245)
5. Hofland LJ, Van Der Hoek J, Feelders R, van Aken MO, van Koetsveld PM, Waaijers M, Sprij-Mooij D, Bruns C, Weckbecker G, de Herder WW, Beckers A & Lamberts SW. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. European Journal of Endocrinology 2005 152 645-654. (doi:10.1530/eje.1. 01876)
6. Murray RD, Kim K, Ren SG, Lewis I, Weckbecker G, Bruns C & Melmed S. The novel somatostatin ligand (SOM230) regulates human and rat anterior pituitary hormone secretion. Journal of Clinical Endocrinology and Metabolism 2004 89 3027-3032. (doi:10.1210/jc.2003-031319)
7. Ma P, Wang Y, Van Der Hoek J, Nedelman J, Schran H, Tran L-L & Lamberts SW. Pharmacokinetic-pharmacodynamic comparison of a novel multiligand somatostatin analog, SOM230, with octreotide in patients with acromegaly. Clinical Pharmacology and Therapeutics 2005 78 69-80. (doi:10.1016/j.clpt.2005. 04.003)
8. Petersenn S, Unger N, Hu K, Weisshaar B, Zhang Y, Bouillaud E, Hermosillo Resendiz K, Wang Y & Mann K. Pasireotide (SOM230), a novel multi-receptor-targeted somatostatin analogue, is well tolerated when administered as a continuous 7-day subcutaneous infusion in healthy male volunteers. Journal of Clinical Pharmacology 2012 (doi:10.1177/0091270011408727)
9. Petersenn S, Hu K, Maldonado M, Zhang Y, Lasher J, Bouillaud E, Wang Y, Mann K & Unger N. Tolerability and dose-proportional pharmacokinetics of pasireotide administered as a single dose or two divided doses in healthy male volunteers: a single-center, open-label, ascending-dose study. Clinical Therapeutics 2012 [Epub ahead of print]. (doi:110.1016/j.clinthera.2012.01.015).
10. Golor G, Hu K, Ruffin M, Buchelt A, Bouillaud E, Wang Y & Maldonado M. A first-in-man study to evaluate the safety, tolerability, and pharmacokinetics of pasireotide (SOM230), a multireceptor-targeted somatostatin analog, in healthy volunteers. Drug Design, Development and Therapy 2012 6 in press.
11. Shenouda M, Maldonado M, Wang Y, Bouillaud E, Hudson M, Nesheiwat D & Hu K. An open-label dose-escalation study of once-daily and twice-daily pasireotide in healthy volunteers: safety, tolerability, and effects on glucose, insulin, and glucagon levels. American Journal of Therapeutics 2012 19 in press.
12. Farrall A, Ruffin M, Wetli-Hermosillo K & Petersenn S. Long-term treatment of acromegaly with pasireotide (SOM230): results from a phase II extension study. Endocrine Reviews 2010 31 (3 Suppl 1) S856 (abst OR16-5).
13. Petersenn S, Schopohl J, Barkan A, Mohideen P, Colao A, Abs R, Buchelt A, Ho Y-Y, Hu K, Farrall AJ, Melmed S & Biller BM. Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. Journal of Clinical Endocrinology and Metabolism 2010 95 2781-2789. (doi:10.1210/jc.2009-2272)
14. Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA & Bertherat J. Treatment of pituitary dependent Cushing's disease with the multi-receptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. Journal of Clinical Endocrinology and Metabolism 2009 94 115-122. (doi:10.1210/jc.2008-1008)
15. Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR & Biller BM. A 12-month Phase 3 study of Pasireotide in Cushing's disease. New England Journal of Medicine 2012 366 914-924.
16. Anthony L&FredaPU. Fromsomatostatin to octreotide LAR: evolution of a somatostatin analogue. CurrentMedical Research and Opinion 2009 25 2989-2999. (doi:10.1185/03007990903328959)
17. Freda PU. Somatostatin analogs in acromegaly. Journal of Clinical Endocrinology and Metabolism 2002 87 3013-3018. (doi:10.1210/jc.87.7.3013)