8 research outputs found
Long-term efficacy and safety of osilodrostat in Cushing's disease: final results from a Phase II study with an optional extension phase (LINC 2)
Background Many patients with Cushing's disease (CD) require long-term medical therapy to control their hypercortisolism. In the core phase of a Phase II study (LINC 2; NCT01331239), osilodrostat normalized mean urinary free cortisol (mUFC) in 78.9% of patients with CD. Here, we report long-term efficacy and safety data for osilodrostat following completion of an optional extension to LINC 2.Methods Adult patients with CD were enrolled in a 22-week prospective Phase II study. Patients with mUFC <= upper limit of normal (ULN) or receiving clinical benefit at week 22 could enter the optional extension. The proportion of complete (mUFC <= ULN) or partial (mUFC > ULN but >= 50% decrease from baseline) mUFC responders was assessed over time.Results Sixteen of 19 enrolled patients entered the extension. Median (range) osilodrostat exposure from baseline to study end was 5.4 years (0.04-6.7); median (range) average dose was 10.6 mg/day (1.1-47.9). Overall response rate (complete and partial mUFC responders) was consistently >= 50%. Sustained control of most cardiovascular-related parameters was observed during the extension. The long-term safety profile was consistent with that reported during the core phase. Testosterone levels (females) decreased towards baseline levels during long-term follow-up, with no new or worsening cases of hirsutism during the extension.Conclusions In the longest prospective study of a steroidogenesis inhibitor to date, osilodrostat provided sustained reductions in mUFC for up to 6.7 years of treatment, with no new safety signals emerging during the extension. These findings support osilodrostat as an effective long-term treatment for patients with CD
results from an open-ended, open-label
Pasireotide can induce sustained decreases in urinary cortiso
The Paradoxical Increase in Cortisol Secretion Induced by Dexamethasone in Primary Pigmented Nodular Adrenocortical Disease Involves a Glucocorticoid Receptor-Mediated Effect of Dexamethasone on Protein Kinase A Catalytic Subunits
Identification of Potential Gene Markers and Insights into the Pathophysiology of Pheochromocytoma Malignancy
In Vivo and in Vitro Screening for Illegitimate Receptors in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Causing Cushingās Syndrome: Identification of Two Cases of Gonadotropin/Gastric Inhibitory Polypeptide-Dependent Hypercortisolism
Midnight Salivary Cortisol Determination for Assessing the Outcome of Transsphenoidal Surgery in Cushingās Disease
Mutations in Regulatory Subunit Type 1A of Cyclic Adenosine 5ā²-Monophosphate-Dependent Protein Kinase (PRKAR1A): Phenotype Analysis in 353 Patients and 80 Different Genotypes
Background: The ācomplex of myxomas, spotty skin pigmentation, and endocrine overactivity,ā or āCarney complexā (CNC), is caused by inactivating mutations of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A) gene and as yet unknown defect(s) in other gene(s). Delineation of a genotype-phenotype correlation for CNC patients is essential for understanding PRKAR1A function and providing counseling and preventive care