Cushing's syndrome is a rare, severe condition. Glucocorticoid hypersecretion can cause vital organ damage and metabolic impairment, and limited surgical and medical therapies are available. The proposed pivotal clinical trial will be the first ever prospective international evaluation of the efficacy and safety of a symptomatic treatment in this rare condition. HRA Pharma is developing the antiglucocorticoid agent HRA052015 (mifepristone) for therapeutic use in oncology-related endocrine disorders. Prior research and clinical experience indicates that HRA052015 is a promising agent for use in patients with Cushing's Syndrome secondary to ectopic ACTH secretion. HRA Pharma will carry out a single pivotal Phase 2/3 clinical trial intended to evaluate the compound's safety and efficacy in patients with this disorder. It is hypothesized that chronic daily administration of mifepristone up to a maximum of 20 mg/kg/day in subjects with ectopic ACTH secretion will normalize glucocorticoid-dependent parameters within a few weeks through its cortisol-blocking action. The efficacy of treatment will be assessed by comparing quantitative glucocorticoid-sensitive parameters before and during treatment. Specifically, the primary objective of this study is to demonstrate that daily administration of mifepristone in subjects with Cushing's syndrome caused by ectopic ACTH secretion will improve the glucocorticoid-dependent parameters of blood pressure and/or glucose tolerance. Secondary objectives include assessment of the impact of long-term administration of mifepristone on other glucocorticoid-dependent parameters (including clinical features, depression, quality of life, and hormonal and biochemical parameters), and the safety of the agent.
