Can you drill down to the specific parameters—inclusion criteria, glucocorticoid dosing, set points for androstenedione control, overall 2-part trial design—for the pediatric CAHtalyst trial?
So, so in the pediatric trial, we wanted people who were on higher than a physiologic dose of glucocorticoids but still had an elevated Andros diet. So this was kind of like I've got nothing to offer you at this point. Um And, and I will say that it wound up being that, you know, the endocrine society clinical Practice guidelines are uh no more than 17 mg per meter squared per day of hydrocortisone. And most of these Children were right up against that limit, yet still had elevated adrenal androgens. And again, Andros Dione being the main biomarker we're looking for there. Um So how do we define super physiologic? What did we define as physiologic? Well, physiologic was defined as 11 mg per meter squared per day. That was based on studies where people looked at the daily cortisol production rate and because hydrocortisone is about 97% bioavailable when given orally uh that that was considered to be the replace physiologic dose. So in those studies, about 8 mg per meter squared was average and the 95th percentile plus two standard deviations was about 11 mg per meter squared per day. So that should be considered the upper limit of the normal range of daily cortisol production rate in the general population. That's how that was chosen. Um So the dose used was 2550 or 100 mg uh twice a day, which was uh in the adult trial, it was 100 twice a day. So it was dosed based on body size, depending on their uh uh body mass. They about 2550 or 100 and some kids that were growing during the course of the trial might need a dose increase. There was also a liquid form that was prepared for this trial for the younger Children and the youngest child that was enrolled was four. So, but most of them were teenagers. Um and because everybody had an elevated Andros Dion, that was the primary endpoint in the study is the Andros Dion at week four before the Glucocorticoid reduction period. But we also tracked glucocorticoid reduction and how many people could maintain that Andrine Dion control as was defined in the adult study. Uh yet get to less than 11 mg per meter squared per day of hydrocortisone wound up being that 30% of the people in the Ceron group could achieve both of those very strict end points in the placebo group. It was zero. And I think this is one of the differences between Children and adults is that in, in Children, the pediatric endocrinologists are most concerned about the androgen control and willing to let the glucocorticoids be a little bit higher uh in order to maintain Andros Dion control. So I there was a stricter adherence to Anders ion control which limited the number of people who got down to less than 11 in that study. But still uh the data speak for themselves about the improvements in Anders Dion that was uh achieved by adding kneer fun alone to these Children who were in very poor control.
