DIUR-006
Research type
Research Study
Full title
A Phase III extension study of efficacy, safety and tolerability of Chronocort® in the treatment of congenital adrenal hyperplasia (CAH)
IRAS ID
208188
Contact name
Richard Ross
Contact email
Sponsor organisation
Diurnal Ltd
Eudract number
2015-005448-32
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 1 months, 30 days
Research summary
The glucocorticoid medications currently used to treat CAH are like cortisol, but they cannot simulate natural cortisol in terms of how it is released by the body. This is because cortisol is normally released in different amounts throughout the day with a pulse, or burst, during the early morning hours and very low amounts in the body in the evening.
Chronocort® has been designed so that the amounts of cortisol in the body more closely mimic the human body’s normal release pattern of cortisol.
The purpose of this research study is to follow on from a study that is comparing the safety and effectiveness of Chronocort® with current glucocorticoid treatment regimens in the treatment of CAH over a 6 month period. This extension study will last approximately 28 months, dependent on when patients enter, and will look at the safety and tolerability of Chronocort® over a longer period than the feed-in study.
Patients will be invited if they have successfully completed the previous feed-in study.
Summary
Lay summary of study results: THANK YOU!
Diurnal thanks all the participants involved in this study. Everyone who took part has helped us to learn more about how Chronocort® works to treat Congenital Adrenal Hyperplasia (CAH). This means that people with CAH will have better treatment options in the future.This summary provides information on the results of the study. If you took part in the study and have questions about the results, please speak with staff at the study site, who will be happy to help you.
Please note that researchers look at the results of many studies to understand which drugs work and how they work. It takes lots of people in many studies all around the world to advance medical science. This summary only shows the results from one study. Other studies may find different results.
BRIEF SUMMARY
The DIUR-006 study was a Phase 3 extension study for participants who completed studies DIUR-003 or DIUR-005 so that they could either continue Chronocort therapy or switch to Chronocort from their current therapy. 91 participants with CAH received treatment in the trial across 5 countries.
The primary aim of the DIUR-006 extension study was to assess the safety of Chronocort over time. The data from this study confirm that Chronocort’s safety profile does not differ substantially from the known published safety profile of other established hydrocortisone preparations. Chronocort also demonstrated a potential for disease control, based on androgen results, on a lower dose of steroid and using a more convenient twice daily (or 'toothbrush') dosing regimen than conventional replacement therapy.
ABOUT THE STUDY
Where was the study done?
The study was conducted in the following countries:• United Kingdom
• Germany
• France
• Sweden
• United StatesWhen was the study done?
The study started in August 2016 and ended in July 2022.Why was the study done?
The purpose of this study was to assess the long-term safety of Chronocort and assess how effective it is as a treatment.This study was “open-label". This means that both the participants and doctors knew that all participants in the study were receiving Chronocort and knew how much they were receiving.
What participants were included in this study?
This study included participants who were adult men and women with CAH who had successfully completed the DIUR-003 or DIUR-005 clinical studies.The results of this study only apply to this population under these specific conditions, and not to any other population. More information may be available later and details of other studies investigating Chronocort can be found on https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5Bc4SHnPEg2Xk-2FiljbDyDonNNpQF_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLRe74ldzM05VzuFDvmROS89pracFcuRsxV-2BwyGKDNqRnh6w30a0SL3MmxRMvl1SbYaaQdjlhNTfhf2Gh3TLMJ8p1cYCuQIeLIMUNtUihEbJ94KNIGzZDjG22-2FHUSTIqlmpq3KYrfzpiquMet8-2BD38GYBh-2FgqgA3x9EkMy8VxmYfg-3D-3D&data=05%7C01%7Cleicestercentral.rec%40hra.nhs.uk%7Cfc45b378fe0f4bb6437208db83bbae24%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638248614322664674%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=V%2FDU%2F3w8DFYQiyVO3dYr4YgPC1A6qco9s2VyKA1nrgg%3D&reserved=0
ABOUT THE MEDICINE
Which medicines were studied?
The name of the drug being tested was Chronocort. The same drug was given to all participants, but the dose level given was specific to the participant and based on laboratory test results of androgens (hormones produced naturally in the body) and on clinical symptoms.Chronocort is a preparation of hydrocortisone, which is a steroid medicine. Hydrocortisone is given to patients with CAH as replacement therapy because their bodies do not naturally produce enough of the hormone cortisol. This study was only one of a number of studies in an overall drug development process.
What were the side effects?
Side effects are unwanted medical events (such as a headache) that happen during the study, and are reported to assess whether the side effects might be related to the treatments in the study or not.Severe side effects are those that make normal daily activities difficult and require treatment. 24 out of 91 participants [26.4%] had severe side effects. Most severe side effects were also considered serious. 6 out of 91 participants [6.6%] left the study because of their side effects.
Serious side effects are those that are life threatening or where the individual needs to go to hospital and may or may not be caused by the study drug being tested. 28 out of 91 participants [30.8%] had serious side effects, with 2 being considered by the study doctor to be related to Chronocort (low blood potassium in both participants). 1 out of 91 participants [1.1%] died as a result of their side effects. This side effect was myocardial infarction (heart attack) and the study doctor did not believe it was caused by Chronocort.
ABOUT THE RESULTS
What were the overall results of the study?
The DIUR-006 study was completed as planned. The results are available at: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMMOSqCZyT9bwj4gGjuIDsDA-3D-3DJMWM_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLRe74ldzM05VzuFDvmROS8ru9SIysJ283Xp04O08r-2BxH0-2FaWiTSTYvQkWgALHfVrKi2ABUfbe9GVLN1ej9r4h3Yi3Z0y6TpF4sS3auKOP5qutumsNojEPVStiPJ-2Bzp1qoK2k3aDS-2F19PGDwQkDEOYXJCeZoVA1GENimPaeVRChXQ-3D-3D&data=05%7C01%7Cleicestercentral.rec%40hra.nhs.uk%7Cfc45b378fe0f4bb6437208db83bbae24%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638248614322664674%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=ZBtiM9yDwRzhyuSGKdtgRTd%2BXMJXHrw48ip4H2mILsE%3D&reserved=0The primary purpose of this study was to assess the safety of Chronocort over time. Although most participants experienced at least 1 side effect during the study, most were of mild or moderate intensity. A total of 28 participants (30.8%) had a serious side effect, with only 2 considered related to Chronocort (both were low blood potassium levels). Only 7 participants reported side effects indicative of adrenal crisis (medical emergency due to insufficient cortisol), none of which were considered related to Chronocort therapy. A total of 33 side effects considered to be of unexpected therapeutic benefit were reported for 21 participants (23.1%). The most common unexpected therapeutic benefits were feeling more alert/less tired/better sleep, improved menstrual cycle, and increased bone density (a measure of the amount of minerals in the bone).
The results of the study show a reduction of 10 mg in the median total daily dose of Chronocort (the middle daily dose level taken by all participants when they are arranged from smallest to largest) over the course of the study and also an increase in the amount of participants achieving CAH disease control (particularly in the early morning) as demonstrated by blood-test results in the optimal/normal range for androgens.
How has the study helped participants and researchers?
This research helps future patients and families by helping us understand more about Chronocort today. The results from this study show that Chronocort demonstrates a potential for CAH disease control (based on androgen results) at a lower dose of steroid and using a more convenient twice daily (or 'toothbrush') dosing regimen than conventional replacement therapy.Are there any plans for further studies?
Other clinical studies with Chronocort are ongoing and further studies are planned.Where can I find out more about this study?
You can find more detailed information about the study on this website: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMMOSqCZyT9bwj4gGjuIDsDA-3D-3DtlhN_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLRe74ldzM05VzuFDvmROS8Y3iEJR-2FqB4J5ZxG9tm0RujbDAbVDCrouoYfBtVYHZQ-2BlmyJQGNyCPi-2FtA2NxT5JhcXTGLjDFm-2F-2FJrxiVCkL-2FwUsevjPkOeW7nHGgS8nRgacf1cpNltM6s5jd275W-2BcjX0Gd6SELSAdv-2F7srCHIZSIQ-3D-3D&data=05%7C01%7Cleicestercentral.rec%40hra.nhs.uk%7Cfc45b378fe0f4bb6437208db83bbae24%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638248614322664674%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=hzkq3HiJkbx01rhj7nBPMpL5sIuaER6uxK%2BUnwHs7n8%3D&reserved=0REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
16/EM/0278
Date of REC Opinion
20 Jul 2016
REC opinion
Further Information Favourable Opinion