OR07-08 A Double-blind Study of Modified-release Hydrocortisones, Chronocort versus Plenadren, in Adrenal Insufficiency (CHAMPAIN)

Disclosure: A. Prete: None. V. Theiler-Schwetz: None. W. Arlt: None. I.O. Chifu: None. B. Harbeck: None. C. Napier: None. J.D. Newell-Price: None. A. Rees: None. N. Reisch: None. G.K. Stalla: None. H. Coope: Neurocrine Biosciences. K. Maltby: Neurocrine Biosciences. J. Porter: Neurocrine Biosciences. J. Quirke: Neurocrine Biosciences. R.J. Ross: Neurocrine Biosciences.

Background: Patients with adrenal insufficiency (AI) have impaired quality of life (QoL), low energy and increased mortality. Immediate-release hydrocortisone is first-line replacement therapy, however, fails to restore the physiologic diurnal cortisol rhythm. There are two modified-release hydrocortisone formulations: 1) Plenadren®, taken in a single morning dose, and 2) Chronocort® delayed release, taken twice daily in a toothbrush regimen (last thing at night, first thing in the morning). Chronocort but not Plenadren mimics the physiologic rise in early morning cortisol. We compared Plenadren to Chronocort to test the hypothesis that waking with physiological cortisol levels will reduce fatigue and improve QoL.

Methods: double-blind, double-dummy, two-way cross-over, randomised, study comparing Chronocort vs Plenadren, one month on each treatment at 25mg/24 hours. Inclusion criteria were primary AI with morning pre-dose cortisol <50 nmol/L (1.8 µg/dl). The primary endpoint was the difference in 07:00h cortisol after 4 weeks of treatment. The key secondary outcome was the Multidimensional Assessment of Fatigue (MAF) score after 4 weeks. Other secondary outcomes included the disease specific questionnaire AddiQol, the fatigue questionnaire PROMIS 7b, and QoL as measured by SF36 and EQ-5D-5L. 

Results: Of 49 evaluable participants, 45 achieved a physiological morning cortisol (>140 nmol/l, 5ug/dl) with Chronocort compared with 2 on Plenadren (median serum cortisol 417.0 (15) vs 6.04 (0.2) nmol/L (µg/dl), P<0.0001). The MAF score was not significantly different between the two treatments; however, a sensitivity analysis showed that in the first treatment period Chronocort reduced MAF Score (P=0.008) suggesting a carry-over effect from period 1 to 2. The majority of the other QoL measures in the secondary efficacy analysis showed significant benefit for Chronocort including: The disease specific questionnaire AddiQol (P=0.03), the fatigue questionnaire PROMIS 7b (P=0.02), SF36 physical functioning (P=0.03) and EQ-5D-5L (P=0.02). The sensitivity analysis for all these measures showed greater benefit for Chronocort and patients showed a preference for the Chronocort treatment period. The safety profiles were similar, as expected for patients with AI, with no new safety signals identified. 

Conclusion: In adrenal insufficiency Chronocort provides physiological waking cortisol levels and is associated with reduced fatigue and improved QoL as compared to Plenadren.

Presentation: Saturday, July 12, 2025