Browsing by Author "Farber, Robert H."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia
    (Endocrine Society, 2022) Auchus, Richard J.; Sarafoglou, Kyriakie; Fechner, Patricia Y.; Vogiatzi, Maria G.; Imel, Erik A.; Davis, Shanlee M.; Giri, Nagdeep; Sturgeon, Julia; Roberts, Eiry; Chan, Jean L.; Farber, Robert H.; Medicine, School of Medicine
    Context: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess androgen production. Corticotropin-releasing factor type 1 receptor (CRF1R) antagonism may decrease adrenal androgen production. Objective: This work aimed to evaluate the safety, tolerability, and efficacy of crinecerfont (NBI-74788), a selective CRF1R antagonist, in 21OHD. Methods: This open-label, phase 2 study, with sequential cohort design (NCT03525886), took place in 6 centers in the United States. Participants included men and women, aged 18 to 50 years, with 21OHD. Interventions included 4 crinecerfont regimens, each administered orally for 14 consecutive days: 50 or 100 mg once daily at bedtime (cohorts 1 and 2, respectively); 100 mg once daily in the evening (cohort 3); and 100 mg twice daily (cohort 4). Participants could enroll in more than 1 cohort. Main outcomes included changes from baseline to day 14 in adrenocorticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. Results: Eighteen participants (11 women, 7 men) were enrolled: cohort 1 (n = 8), cohort 2 (n = 7), cohort 3 (n = 8), cohort 4 (n = 8). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (-66%), 17OHP (-64%), and androstenedione (-64%) with crinecerfont 100 mg twice a day. In female participants, 73% (8/11) had a 50% or greater reduction in testosterone levels; male participants had median 26% to 65% decreases in androstenedione/testosterone ratios. Conclusion: Crinecerfont treatment for 14 days lowered ACTH and afforded clinically meaningful reductions of elevated 17OHP, androstenedione, testosterone (women), or androstenedione/testosterone ratio (men) in adults with 21OHD. Longer-term studies are required to evaluate the effects of crinecerfont on clinical end points of disordered steroidogenesis and glucocorticoid exposure in patients with 21OHD.
  • Thumbnail Image
    Item
    Pharmacokinetics of Budesonide Oral Suspension in Children and Adolescents with Eosinophilic Esophagitis
    (Wolters Kluwer, 2022-06) Gupta, Sandeep K.; Hill, Malcolm; Vitanza, Joanne M.; Farber, Robert H.; Desai, Nirav K.; Williams, James; Song, Ivy H.; Pediatrics, School of Medicine
    The pharmacokinetic (PK) profile of budesonide oral suspension (BOS) was evaluated during a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study in pediatric patients with eosinophilic esophagitis (EoE)(MPI 101-01/NCT00762073). Non-compartmental methods were used to calculate PK parameters in 37 patients after receiving morning doses of BOS, with volume and dose adjusted for age (low dose: 0.35 or 0.5 mg; high dose: 1.4 or 2.0 mg [2–9 or 10–18 years old, respectively]). Relationships between apparent oral clearance and volume of distribution versus bodyweight and body mass index were also evaluated. Budesonide systemic exposure increased with BOS dose. After oral administration, time to maximum plasma budesonide concentration occurred ~1 hour post-dose and the half-life of budesonide was 3.3–3.5 hours. PK parameters were similar between age groups for low- and high-dose BOS, indicating that volume and dose adjustments for age were appropriate for pediatric patients with EoE. BOS was well tolerated.