Clinical Trial: Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase III Study of Efficacy, Safety and Tolerability of Chronocort® Compared With Standard Glucocorticoid Replacement Therapy in the Treatment of Congenital Adrenal Hyperp

Brief Summary: This study is a parallel arm, randomised, open-label study, including dose titration and admissions for four overnight stays for 24-hour endocrine profiles. It will compare the efficacy, safety and tolerability of Chronocort® with standard glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia (CAH) over a treatment period of 6 months. Dose titration decisions in both treatment groups will be made by a central independent physician, blinded to the treatment arm, using information generated from the 24-hour endocrine profiles. Each treatment arm will be subject to the same titration rules throughout the study, ensuring that opportunities for optimisation and control of androgens are the same in both groups.

Detailed Summary:

At baseline, subjects will be admitted overnight for a 24-hour endocrine profile whilst on their standard therapy. Subjects will attend the study site in the morning and have 17-hydroxyprogesterone (17-OHP) and androstenedione (A4) levels assessed at 15:00, 17:00, 19:00, 21:00, 23:00, 01:00, 03:00, 05:00, 07:00, 09:00, 11:00, 13:00 and 15:00. Safety laboratory tests, a DEXA scan for body composition, and height, weight and waist circumference will be recorded. Subjects will then be randomised to Chronocort® or to continue on their standard care. Randomisation will be stratified by baseline treatment:

  1. hydrocortisone only or
  2. prednisone or prednisolone, alone or in combination with hydrocortisone
  3. dexamethasone only or in combination with any other glucorticoid

The initial dose setting at the start of the Chronocort® treatment will be based on hydrocortisone dose equivalent of baseline therapy in accordance with standard clinical practice. Further dose refinement/titration will be conducted in both treatment groups as necessary after 4 weeks and 12 weeks using a standardised titration algorithm after the subject has been re-admitted for further 24-hour endocrine profiles. Safety endpoints will also be measured at the 07:00 morning sample of each 24-hour profile assessment day. The decision to change doses in both treatment groups will be made by a central independent blinded physician, with the actual change in dose then being made by the local investigator looking after the subject. At 6 months, all the baseline tests will be repeated (including the 24-hour profile). All subjects may then continue on Chronocort®, whatever their randomised treatment, as part of an open-label extension study (to be conduct
Sponsor: Diurnal Limited

Current Primary Outcome: Change from baseline in 17-OHP [ Time Frame: 24 weeks ]

Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for 17-OHP.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change from baseline in A4 [ Time Frame: 24 weeks ]
    Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for A4.
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 weeks ]
    AEs will be collected for all subjects from the time of consent up to 30 days ± 3 days following the last visit or, if applicable, the Early Withdrawal visit. Any ongoing AEs post study will be followed to resolution or stabilisation if resolution is not expected. Only treatment emergent AEs will be included in the main safety analysis: other AEs will be listed.
  • Use and reasons for use of rescue medication [ Time Frame: 24 weeks ]
    The number of times the patients needed rescue medication (supplied as a 'sick day safety pack' plus instructions for use that are called the 'sick days rules') during the study wil be recorded. The reason for the use of the rescue medication will also be recorded.


Original Secondary Outcome: Same as current

Information By: Diurnal Limited

Dates:
Date Received: February 26, 2016
Date Started: February 2016
Date Completion: June 2017
Last Updated: March 17, 2016
Last Verified: March 2016