information: Completion of patient enrollment
Announcement: completion of patient enrollment
Company: Diurnal Limited (UK)
Product: Chronocort® (hydrocortisone modified release capsules)
- hormone/corticosteroid. Chronocort® is a modified-release hydrocortisone preparation specifically designed to provide cortisol replacement throughout the day in a manner that mimics, as closely as possible, the natural circadian rhythm (the body’s natural 24 hour hormone cycle) of cortisol. Congenital adrenal hyperplasia is usually caused by deficiency of 21-hydroxylase. This enzyme is required to produce the adrenal steroid hormone, cortisol. The block in the cortisol production pathway causes the over-production of male steroid hormones, which are precursors to cortisol. The cortisol deficiency and over-production of male sex hormones has been associated with increased mortality, infertility, reduced quality of life and cardiovascular morbidity. Sufferers, even if treated, remain at risk of death through an adrenal crisis.
- Current therapy uses a variety of generic steroids (hydrocortisone, dexamethasone and prednisolone) which, at best, adequately treat approximately one-third of CAH patients.
- Chronocort® has been granted Orphan Drug Designations in Europe and the US in the treatment of CAH.
Disease: congenital adrenal hyperplasia (CAH)
area: Rare diseases - Endocrine diseases - Hormonal diseases
- The Phase III trial is an open label study in which adult patients with congenital adrenal hyperplasia, currently treated with a single or combination of generic steroids (standard-of-care), are randomised to either receive Chronocort® on a twice daily "toothbrush" regimen or continue on their standard-of-care regimen.
- The primary endpoint of the trial is the control of androgens at six months on equivalent or lower total daily dose of steroid when treated with Chronocort® compared to standard-of-care treatment. This primary endpoint is similar to an endpoint previously reported in the Phase II clinical trial, where the data showed a significant reduction in the morning levels of 17-hydroxyprogesterone (the main androgen) in patients after six months on Chronocort® (median 70nmol/l vs 5.65nmol/l p= 0.014), with 94% of values in the normal or optimal range compared to 31% before Chronocort® therapy.
- Secondary endpoints include an assessment of fatigue levels and the relative effect of Chronocort® on body mass index and bone turnover, all of which are indicative of clinical benefits.
- • On February 12, 2018, Diurnal, a specialty pharmaceutical company targeting patient needs in chronic endocrine diseases, announced that it has successfully completed patient enrolment for its European pivotal Phase III clinical trial of Chronocort® (modified release hydrocortisone) for the treatment of Congenital Adrenal Hyperplasia (CAH) in adults. Headline data from this trial is expected in Q3 2018 and, if positive, could lead to potential market authorisation in Europe in 2020.
- Data from the Chronocort® Phase II trial demonstrated that the trial met its primary endpoint of fully characterising the pharmacokinetic profile of Chronocort® in 16 male and female adult subjects with CAH. The results showed Chronocort® provides circadian levels of the stress hormone, cortisol, similar to the healthy population mimicking the overnight rise in cortisol levels, such that patients wake with a normal cortisol level.
- In addition, the secondary objective of examining the effect of Chronocort® on the morning biochemical efficacy markers of the disease showed a significant reduction in the morning levels of 17-hydroxyprogesterone (the main androgen) in patients after six months on Chronocort (median 70nmol/l vs 5.65nmol/l p= 0.014) with 94% of values in the normal or optimal range compared to 31% before Chronocort therapyi. Chronocort® was well-tolerated during the six-month trial. The trial was reported in the Journal of Clinical Endocrinology and Metabolism (Mallappa et al JCEM 2014).