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

Volumn 21, Issue 3, 2014, Pages 164-173

  Shenouda, Magdy ^a   Maldonado, Mario ^b   Wang, Yanfeng ^b   Bouillaud, Emmanuel ^b   Hudson, Michelle ^b   Nesheiwat, Dalal ^b   Hu, Ke ^b  

^a Iberica Clinical Research Center   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

hyperglycemia; insulin; pasireotide; safety; SOM230

Indexed keywords

GLUCAGON; GLUCOSE; INSULIN; PASIREOTIDE; GLUCOSE BLOOD LEVEL; SOMATOSTATIN;

ADULT; ARTICLE; CONTROLLED STUDY; DIARRHEA; DIET RESTRICTION; DOSAGE SCHEDULE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; GLUCAGON RELEASE; GLUCOSE BLOOD LEVEL; HEADACHE; HUMAN; HUMAN EXPERIMENT; HYPERGLYCEMIA; INJECTION SITE BURNING; INJECTION SITE CONTUSION; INJECTION SITE ERYTHEMA; INJECTION SITE PRURITUS; INSULIN BLOOD LEVEL; INSULIN RELEASE; MALE; MORNING DOSAGE; MULTIPLE CYCLE TREATMENT; NAUSEA AND VOMITING; NORMAL HUMAN; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; UPPER ABDOMINAL PAIN; ADOLESCENT; ANALOGS AND DERIVATIVES; CHEMICALLY INDUCED; CLINICAL TRIAL; COMPARATIVE STUDY; DOSE RESPONSE; DRUG ADMINISTRATION; DRUG EFFECTS; SECRETION (PROCESS); YOUNG ADULT;

ADOLESCENT; ADULT; BLOOD GLUCOSE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; GLUCAGON; HUMANS; HYPERGLYCEMIA; INSULIN; MALE; SOMATOSTATIN; YOUNG ADULT;

EID: 84900827014     PISSN: 10752765     EISSN: 15363686     Source Type: Journal    
DOI: 10.1097/MJT.0b013e31824c3eb4     Document Type: Article

References (15)

1. Ambrosi B, Bochicchio D, Fadin C, et al. Failure of somatostatin and octreotide to acutely affect the hypothalamic-pituitary-Adrenal function in patients with corticotropin hypersecretion. J Endocrinol Invest. 1990;13: 257-261.
2. Lamberts SW, Uitterlinden P, Klijn JM. The effect of the long-Acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelsons syndrome and Cushings disease. Acta Endocrinol (Copenh). 1989;120:760-766.
3. Bruns C, Lewis I, Briner U, et al. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002;146: 707-716.
4. Schmid HA. Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol. 2008;286:69-74.
5. Batista DL, Zhang X, Gejman R, et al. The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab. 2006;91:4482-4488.
6. Hofland LJ, Van Der Hoek J, Feelders R, et al. The multiligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol. 2005;152: 645-654.
7. Van Der Hoek J, Waaijers M, van Koetsveld PM, et al. Distinct functional properties of native somatostatin receptor subtype 5 compared with subtype 2 in the regulation of ACTH release by corticotroph tumour cells. Am J Physiol Endocrinol Metab. 2005;289:E278-E287.
8. Colao A, Petersenn S, Newell-Price J, et al. Pasireotide (SOM230) demonstrates efficacy in patients with Cushing disease: results from a large, randomized-dose, doubleblind, Phase III Study. Endocr Rev. 2011;32. Abstract OR09-6.
9. Lamberts SW, Uitterlinden P, del Pozo E. SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years. J Clin Endocrinol Metab. 1987;65:703-710.
10. Van Der Hoek J, de Herder WW, Feelders RA, et al. A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients. J Clin Endocrinol Metab. 2004;89: 638-645.
11. Boscaro M, Ludlam WH, Atkinson B, et al. Treatment of pituitary dependent Cushings disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): A multicenter, phase II trial. J Clin Endocrinol Metab. 2009; 94:115-122.
12. Petersenn S, Schopohl J, Barkan A, et al. Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, Phase II trial. J Clin Endocrinol Metab. 2010;95:2781-2789.
13. Croxtall JD, Scott LJ. Lanreotide autogel: a review of its use in the management of acromegaly. Drugs. 2008;68: 711-723.
14. Cook D. Octreotide long-Acting repeatable in acromegaly: achieving optimal control. The Endocrinologist. 2009;19: 142-147.
15. Henry RR, Mudaliar S, Wetli-Hermosillo K, et al. Mechanism and management of hyperglycemia associated with pasireotide: results from studies in healthy volunteers. Endocrine Abstracts. 2011;26. Abstract P260.