LUIZ ROBERTO SALGADO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
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- Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study(2014) PIVONELLO, Rosario; PETERSENN, Stephan; NEWELL-PRICE, John; FINDLING, James W.; GU, Feng; MALDONADO, Mario; TROVATO, Andrew; HUGHES, Gareth; SALGADO, Luiz R.; LACROIX, Andre; SCHOPOHL, Jochen; BILLER, Beverly M. K.Objective Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Design Phase III study with double-blind randomization of two pasireotide doses. Methods Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels >= 1.5 x upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 mu g bid). At month 3, patients with UFC <= 2 x ULN and not exceeding the baseline value continued their randomized dose; all others received 300 mu g bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 mu g bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Results Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72.8% of patients. Conclusions In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased.
- A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease(2012) COLAO, Annamaria; PETERSENN, Stephan; NEWELL-PRICE, John; FINDLING, James W.; GU, Feng; MALDONADO, Mario; SCHOENHERR, Ulrike; MILLS, David; SALGADO, Luiz Roberto; BILLER, Beverly M. K.BACKGROUND Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 mu g (82 patients) or 900 mu g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 mu g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS Twelve of the 82 patients in the 600-mu g group and 21 of the 80 patients in the 900-mu g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose- lowering medication was initiated in 74 of 162 patients. CONCLUSIONS The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropinsecreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.)