Orion Corporation applied for a patent on darolutamide in October 2010, and this patent was published in May 2011. Darolutamide entered phase I clinical trials in April 2011, with the results of the first clinical study of darolutamide initially published in 2012. The U.S. Food and Drug Administration (FDA) approved darolutamide in July 2019, under the agencys priority review designation.Approval was based on ARAMIS, a multicenter, double-blind, placebo-controlled clinical trial in 1,509 patients with non-metastatic castration resistant prostate cancer. Patients were randomized (2:1) to receive either 600 mg darolutamide orally twice daily (n=955) or matching placebo (n=554). All patients received a gonadotropin-releasing hormone (GnRH) analog concurrently or had a previous bilateral orchiectomy. Twelve patients with previous seizure histories were treated on the darolutamide arm.The primary endpoint was metastasis free survival (MFS), defined as the time from randomization to first evidence of distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first. The median MFS was 40.4 months (95% CI: 34.3, not reached) for patients treated with darolutamide compared with 18.4 months (95% CI: 15.5, 22.3) for those receiving placebo (hazard ratio 0.41; 95% CI: 0.34, 0.50; p<0.0001).
Piedraia hortae survives in the scalp is due to the slow rate of the keratin degradation near the cortex and the compact formation of the nodules and the hyphae are tightly packed in black piedra cases. The initial invasion of human hair by P. hortae is achieved by using an eroding hyphae, which force their way beneath or between the cuticular layer. The force applied between or beneath the hair cuticle arises from the growth of the fungus itself. The breakdown of keratin is mainly due to enzymatic processes and corresponds to the abundance of localized mitochondria. The breakdown of keratin begins with the cementing material and progresses to the cortex of the hair shaft. In the cortex two types of degradative patterns are produced which are either parallel or vertical to the axis hair shaft. The parallel pattern arises from hyphal separation of the external cortical layers. The vertical pattern is produced by direct hyphal penetration which creates channels that increase in size as the cortex degrades. Treatment
The infection cannot easily be removed mechanically, although further proliferation of infection can be achieved by avoidance of moisture. Removal generally involves cutting or shaving of the hair, but chemical treatments may be similarly useful. For women some individuals use a fine comb to remove as much of the infection as possible and then they cut or shave their hair. This is then followed by the application of a sublimate solution in 60% alcohol solution to the scalp.