A Phase 3 interventional study of Chronocort® and standard glucocorticoid therapy in Congenital Adrenal Hyperplasia, sponsored by Neurocrine UK Limited. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-02.
Sponsored by Neurocrine UK Limited (formerly part of Neurocrine Biosciences) · Phase 3, Interventional, and Treatment
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.
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:
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 conducted under a separate protocol). Stress doses of hydrocortisone will be given throughout the study for intercurrent illnesses as medically indicated according to "sick day rules".
101 studies on the registry are indexed under Adrenal Hyperplasia, Congenital; 28 are open to participants now.
This study's enrollment of 122 is above the median of 37 across 50 interventional studies indexed under Adrenal Hyperplasia, Congenital.
Browse Adrenal Hyperplasia, Congenital studies →Neurocrine UK Limited is the lead sponsor of 18 studies on the registry; none are open to participants now.
First submitted before Neurocrine UK Limited left Neurocrine Biosciences.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Chronocort® will be provided as 5mg, 10mg and 20mg capsules for oral administration. The starting dose for each subject will be based on the subjects previous glucocorticoid therapy dose and then dose titrated to effect.
Drug: Chronocort®
Subjects in this arm will continue previous oral glucocorticoid therapy titrated to effect.
Drug: standard glucocorticoid therapy
Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.
Also known as: Hydrocortisone
Subjects in this arm will continue on their standard hydrocortisone therapy
Also known as: hydrocortisone, prednisone, prednisolone, dexamethasone
Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for 17-OHP
Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for 17-OHP (17-Hydroxyprogesterone). The primary efficacy variable was the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of 17-OHP. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed 17-OHP values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of 17-OHP when compared to baseline (0).
Time frame: 24 weeks
Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for A4
Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for A4 (androstenedione). This secondary efficacy variable was calculated as follows: the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of A4. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed A4 values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of A4 when compared to baseline (0).
Time frame: 24 weeks
17-OHP and A4 by Individual Baseline Treatment Strata.
17-OHP and A4 by individual baseline treatment strata presented in the same manner as the primary endpoint (using 24-hour SDS profile at 24 weeks). Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for 17-OHP and A4. This secondary efficacy variable was calculated as follows: the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of 17-OHP and A4. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed 17-OHP and A4 values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of 17-OHP and A4 when compared to baseline (0).
Time frame: 24 weeks
Number of Participants With 17-OHP and A4 Levels in the Optimal Range at 9:00 at Week 24 Visit
17-OHP and A4 levels at 09:00 at the week 24 visit, as a responder analysis (i.e. the number of participants achieving results in the optimal range). Optimal range for 17-OHP (male) = 1.2\* - 6.7 nmol/L (female) = 1.2\* - 8.6 Optimal range for A4 (male) = 1.4 - 5.2 nmol/L (female) = 1.0 - 7.0 nmol/L \* = There is no lower reference range available for 17-OHP, hence the lower limit of the optimal range was used in the derivation of the average Standard Deviation Score. This enabled calculation of an 'unsigned' SDS score which was used to assess potential over-treatment as well as under-treatment.
Time frame: 24 weeks
Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Fat Mass and Lean Mass)
Changes relative to Standard glucocorticoid therapy in body composition (DEXA) (fat mass and lean mass) - measured at all sites except Germany.
Time frame: Baseline and 24 weeks
Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Bone Mineral Density) - Measured at All Sites Except Germany.
Changes relative to Standard glucocorticoid therapy in body composition (DEXA - bone mineral density only) - measured at all sites except Germany.
Time frame: Baseline and 24 weeks
This study was conducted at 11 study sites in 7 countries: Denmark 1, France 2, Germany 1,Netherlands 1, Sweden 1, UK 4, and USA 1.
| Milestone | Chronocort® | Standard Glucocorticoid Therapy |
|---|---|---|
| Started | 61 | 61 |
| Completed | 58 | 59 |
| Not completed | 3 | 2 |
Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for 17-OHP (17-Hydroxyprogesterone). The primary efficacy variable was the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of 17-OHP. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed 17-OHP values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of 17-OHP when compared to baseline (0).
| Z-score | Chronocort® | Standard Glucocorticoid Therapy |
|---|---|---|
| Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for 17-OHP | -0.403 ± 0.8499 | -0.172 ± 0.7776 |
Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for A4 (androstenedione). This secondary efficacy variable was calculated as follows: the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of A4. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed A4 values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of A4 when compared to baseline (0).
| Z-score | Chronocort® | Standard Glucocorticoid Therapy |
|---|---|---|
| Change From Baseline to 24 Weeks of the Mean of the 24-hour Standard Deviation Score (SDS) Profile for A4 | 0.113 ± 0.9221 | -0.041 ± 0.7731 |
17-OHP and A4 by individual baseline treatment strata presented in the same manner as the primary endpoint (using 24-hour SDS profile at 24 weeks). Change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) - also referred to as a z-score - profile for 17-OHP and A4. This secondary efficacy variable was calculated as follows: the natural logarithm of the mean of the 24-hour SDS for the natural logarithm of 17-OHP and A4. The mean of the 24-hour SDS profile for each visit was the arithmetic mean of all the SDSs with the first and last (13th) weighted one half relative to the intermediate SDSs. For each of the 13 log-transformed 17-OHP and A4 values at each visit, an SDS was calculated by counting the number of SDs that were above or below the mean of the log-transformed range. A negative z-score indicated greater control of 17-OHP and A4 when compared to baseline (0).
| Z-score | Pre-Baseline - Hydrocortisone - 17-OHP | Pre-Baseline - Prednisone/Prednisolone - 17-OHP | Pre-Baseline - Dexamethasone - 17-OHP | Pre-Baseline - Chronocort vs. Hydrocortisone - 17-OHP | Pre-Baseline - Chronocort vs. Prednisone/Prednisolone - 17-OHP | Pre-Baseline - Chronocort vs. Dexamethasone - 17-OHP | Pre-Baseline - Hydrocortisone - A4 | Pre-Baseline - Prednisone/Prednisolone - A4 | Pre-Baseline - Dexamethasone - A4 | Pre-Baseline - Chronocort vs. Hydrocortisone - A4 | Pre-Baseline - Chronocort vs. Prednisone/Prednisolone - A4 | Pre-Baseline - Chronocort vs. Dexamethasone - A4 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 17-OHP and A4 by Individual Baseline Treatment Strata. | -0.248 ± 0.7661 | -0.061 ± 0.8051 | -0.245 ± 0.8522 | -0.431 ± 0.8727 | -0.320 ± 0.7627 | -0.565 ± 1.2343 | -0.211 ± 0.7426 | 0.100 ± 0.8339 | 0.368 ± 0.3521 | 0.015 ± 1.0128 | 0.328 ± 0.7256 | -0.092 ± 1.0310 |
17-OHP and A4 levels at 09:00 at the week 24 visit, as a responder analysis (i.e. the number of participants achieving results in the optimal range). Optimal range for 17-OHP (male) = 1.2\* - 6.7 nmol/L (female) = 1.2\* - 8.6 Optimal range for A4 (male) = 1.4 - 5.2 nmol/L (female) = 1.0 - 7.0 nmol/L \* = There is no lower reference range available for 17-OHP, hence the lower limit of the optimal range was used in the derivation of the average Standard Deviation Score. This enabled calculation of an 'unsigned' SDS score which was used to assess potential over-treatment as well as under-treatment.
| Participants | Chronocort - 09:00h Response - 17-OHP | Chronocort - 09:00h Response - A4 | Standard Glucocorticoid Therapy - 09:00h Response - 17-OHP | Standard Glucocorticoid Therapy - 09:00h Response - A4 |
|---|---|---|---|---|
| Number of Participants With 17-OHP and A4 Levels in the Optimal Range at 9:00 at Week 24 Visit | 30 | 25 | 30 | 30 |
Changes relative to Standard glucocorticoid therapy in body composition (DEXA) (fat mass and lean mass) - measured at all sites except Germany.
| kilograms | Chronocort - DEXA - Fat Mass | Standard Glucocorticoid Therapy - DEXA - Fat Mass | Chronocort - DEXA - Lean Mass | Standard Glucocorticoid Therapy - DEXA - Lean Mass |
|---|---|---|---|---|
| Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Fat Mass and Lean Mass) | -0.575 ± 3.2744 | 0.445 ± 2.4660 | 0.640 ± 2.3304 | 0.234 ± 1.3689 |
Changes relative to Standard glucocorticoid therapy in body composition (DEXA - bone mineral density only) - measured at all sites except Germany.
| g/cm^2 | Chronocort - DEXA - Bone Mineral Density | Standard Glucocorticoid Therapy - DEXA - Bone Mineral Density |
|---|---|---|
| Changes Relative to Standard Glucocorticoid Therapy in Body Composition (DEXA - Bone Mineral Density) - Measured at All Sites Except Germany. | -0.001 ± 0.0250 | -0.008 ± 0.0399 |
Collected over Adverse event information was collected from the point of enrolment to completion of the study (6 months).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Chronocort® | 0/61 (0%) | 7/61 (11.5%) | 59/61 (96.7%) |
| Standard Glucocorticoid Therapy | 0/61 (0%) | 5/61 (8.2%) | 48/61 (78.7%) |
| Event | Chronocort® | Standard Glucocorticoid Therapy |
|---|---|---|
| Adrenocortical Insufficiency (acute)Endocrine disorders | 0/61 | 3/61 |
| GastroenteritisInfections and infestations | 2/61 | 1/61 |
| Gastroenteritis ViralInfections and infestations | 0/61 | 1/61 |
| AppendicitisInfections and infestations | 1/61 | 0/61 |
| SalpingitisInfections and infestations | 1/61 | 0/61 |
| TonsilitisInfections and infestations | 1/61 | 0/61 |
| DiverticulitisInfections and infestations | 0/61 | 1/61 |
| Herpes ZosterInfections and infestations | 0/61 | 1/61 |
| Adrenal InsufficiencyEndocrine disorders | 1/61 | 0/61 |
| Oedema PeripheralGeneral disorders | 0/61 | 1/61 |
| Event | Chronocort® | Standard Glucocorticoid Therapy |
|---|---|---|
| HeadacheNervous system disorders | 15/61 | 15/61 |
| Viral Upper Respiratory Tract InfectionInfections and infestations | 12/61 | 13/61 |
| FatigueGeneral disorders | 9/61 | 10/61 |
| Therapeutic Response UnexpectedGeneral disorders | 10/61 | 1/61 |
| PyrexiaGeneral disorders | 9/61 | 4/61 |
| NauseaGastrointestinal disorders | 8/61 | 4/61 |
| DizzinessNervous system disorders | 7/61 | 4/61 |
| Renin IncreasedInvestigations | 3/61 | 7/61 |
| Increased AppetiteMetabolism and nutrition disorders | 5/61 | 2/61 |
| InsomniaPsychiatric disorders | 5/61 | 4/61 |
| Age, Categorical(Participants) | Chronocort® | Standard Glucocorticoid Therapy | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 61 | 59 | 120 |
| >=65 years | 0 | 2 | 2 |
| Age, Continuous(years) | Chronocort® | Standard Glucocorticoid Therapy | Total |
|---|---|---|---|
| Mean | 35.2 (19 to 61) | 37.5 (19 to 68) | 36.3 (19 to 68) |
| Sex: Female, Male(Participants) | Chronocort® | Standard Glucocorticoid Therapy | Total |
|---|---|---|---|
| Female | 42 | 36 | 78 |
| Male | 19 | 25 | 44 |
| Race/Ethnicity, Customized(Participants) | Chronocort® | Standard Glucocorticoid Therapy | Total |
|---|---|---|---|
| White | 60 | 60 | 120 |
| Asian | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| American Indian or Alaska Native | 0 | 0 | 0 |
| Native Hawaiian or other Pacific Islander | 0 | 0 | 0 |
| Other | 1 | 1 | 2 |
| Region of Enrollment(participants) | Chronocort® | Standard Glucocorticoid Therapy | Total |
|---|---|---|---|
| United States | 4 | 4 | 8 |
| Europe | 57 | 57 | 114 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Undecided — To be decided at a later date
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Hydrocortisone
Adrenal Hyperplasia, Congenital →