A Phase 2 interventional study of Chronocort and Plenadren in Primary Adrenal Insufficiency, sponsored by Neurocrine UK Limited. Completed at 8 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.
Sponsored by Neurocrine UK Limited (formerly part of Neurocrine Biosciences) · Phase 2, Interventional, and Treatment
This study is a double-blind, double-dummy, two-way cross-over, randomised, Phase II study to be conducted at approximately 6 investigational sites in 2 countries. The study will compare the efficacy, safety and tolerability of twice daily Chronocort, a modified-release hydrocortisone, with once daily Plenadren, a modified-release hydrocortisone, over a treatment period of up to 2 months in participants aged 18 years and over, diagnosed with primary Adrenal Insufficiency (AI).
The 4-month study period will comprise a Screening Period of up to 4 weeks (during which participants will receive usual standard of care [SoC] treatment), two 4-week cross-over periods (Treatment Periods 1 and 2), and a 4-week Follow-up Period. Participants will be randomly assigned on a 1:1 basis to either Chronocort in Treatment Period 1 and Plenadren in Treatment Period 2 (Treatment Sequence I), or Plenadren in Treatment Period 1 and Chronocort in Treatment Period 2 (Treatment Sequence II). The total daily dose of Chronocort or Plenadren will be 25 mg according to international guidelines and the Plenadren Summary of Product Characteristics (SmPC). Plenadren 25 mg will be taken once daily in the morning on waking (typically between 06:00 and 08:00 hours). Chronocort 10 mg will be taken in the morning on waking (typically between 06:00 and 08:00 hours) and Chronocort 15 mg will be taken at night just prior to going to bed (typically between 22:00 hours and midnight). Placebo capsules and tablets will be provided to each participant to mask the treatment being received and maintain the study blinding. The first dose of study drug will be taken in the evening of Day 1 and the morning dose on Day 29 will be the last study drug dose in Treatment Period 1. The first dose of study drug in Treatment Period 2 will be taken in the evening of Day 29 and the morning dose on Day 57 will be the last study drug dose in Treatment Period 2 and the end of the dosing periods. The dose will not be changed during the study, but participants will receive stress dosing rules and an emergency treatment pack. Use of stress doses and reasons for use will be collected in an electronic participant diary. If a stress dose is taken within 48 hours before any clinic visit, then the visit should be delayed until the participant has had a 48-hour period without use of any stress doses.
36 studies on the registry are indexed under Addison Disease; 9 are open to participants now.
This study's enrollment of 58 is above the median of 24 across 25 interventional studies indexed under Addison Disease.
Browse Addison Disease 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.
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.
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.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
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.
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.
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.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
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 blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
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.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
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.
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.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
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.
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.
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.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
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.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
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.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Chronocort (hydrocortisone modified-release hard capsule) supplied as 5 mg and 10 mg strengths will be administered orally. Chronocort 10 mg will be taken on waking (typically between 06:00 and 08:00 hours) and Chronocort 15 mg will be taken just prior to going to bed (typically between 22:00 hours and midnight).
Drug: Chronocort
Plenadren (hydrocortisone modified-release tablet) supplied as 5 mg and 20 mg strengths and administered orally. Plenadren 25 mg will be taken on waking (typically between 06:00 and 08:00 hours).
Drug: Plenadren
Hydrocortisone modified-release hard gelatin capsules for oral administration - 5mg and 10mg
Also known as: Hydrocortisone modified-release hard capsule
Hydrocortisone modified-release tablets for oral administration - 5mg and 20mg
Also known as: hydrocortisone modified-release tablet
To measure the change in morning serum cortisol levels from baseline, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
The primary efficacy outcome variable is the 07:00 hour serum cortisol level after 4 weeks of treatment. The treatment effect (Chronocort minus Plenadren, after logarithmic transformation) will be estimated in the efficacy evaluable analysis set (EEAS) (defined as participants with morning serum cortisol assessed at baseline and after each treatment period, with no major protocol violations) using a linear mixed model.
Time frame: Baseline and end of each 4 week treatment period.
To measure change in morning fatigue from baseline, using the Multidimensional Assessment of Fatigue (MAF) questionnaire within 1 hr of waking, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
MAF morning fatigue score after 4 weeks of treatment. MAF is a 16 item scale that measures fatigue according to 4 dimensions; degree and severity, distress that it causes, timing of fatigue, and it's impact of various activities of daily living to give a Global Fatigue Score of up to 50, where a higher value equates to more fatigue.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline, in terms of achieving physiological morning cortisol levels after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
Whether or not a participant has achieved a physiological morning cortisol level (defined as the 07:00 hour serum cortisol before the morning dose of \>140 nmol/L after 4 weeks of treatment) will be summarised and compared between treatment periods. Note: a morning cortisol level below 140 nmol/L is considered to reflect relative AI in international guidelines \[Bornstein, 2016\].
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in terms of closeness of overall salivary cortisone levels during the day to a normal physiological profile, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
A salivary cortisone profile score will be derived at the end of 4 weeks of treatment. The profile score is calculated by comparing the on-study salivary cortisol profile with a profile obtained from healthy volunteers. Five timepoints are compared, where a more similar profile to the normal healthy volunteer profile is preferred.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in ACTH control in the morning, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
The 07:00 hour plasma ACTH level after 4 weeks of treatment will be summarised and compared between treatment periods.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline to the bone marker of osteocalcin, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
Osteocalcin levels after 4 weeks of treatment will be summarised and compared between treatment periods.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in morning fatigue using the PROMIS® 7b questionnaire within 1 hour of waking, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
Morning fatigue, using the Patient-Reported Outcomes Measurement Information System (PROMIS® 7b) questionnaire, within 1 hour of waking after 4 weeks of treatment will be summarized and compared between treatment periods. PROMIS 7b is a 7-item scale that measures self-reported fatigue that may impact daily activities and normal functioning. A higher PROMIS 7b score indicates greater fatigue and therefore a less favorable outcome.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in QoL using the EuroQol 5-level Standardized Health Questionnaire (EQ-5D-5L™), after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
QoL, using the EQ-5D-5L after 4 weeks of treatment, will be summarized and compared between treatment periods. The scale measures on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Where the minimum score is 0 and maximum score is 100, a high score indicates a more favorable outcome.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in QoL using the Health-related Quality of Life in Addison's disease (AddiQoL) questionnaire, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
QoL, using the AddiQoL questionnaire after 4 weeks of treatment, will be summarized and compared between treatment periods. AddiQoL is a 30 item scale measuring health-related quality of life in Addison's disease. A higher score indicates a higher quality of life and therefore a more favorable outcome.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in terms of QoL using the 36-Item Short Form Health Survey (SF-36®) questionnaire, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
QoL, using SF-36 questionnaire after 4 weeks of treatment, will be summarized and compared between treatment periods. Analyses of SF-36 at other timepoints are exploratory analyses. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). All components contribute in different proportions to the overall measures. Where the minimum score is 0 and maximum score is 100 and a high score is a more favorable score.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change in terms of activity, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
Mean daily steps, mean steps between 07:00-15:00 hours, and mean steps between 15:00-23:00 hours, as assessed by a wearable device, will be summarized and compared between treatment periods, where more steps, i.e. more activity is considered preferable.
Time frame: After the end of each 4 week treatment period.
To measure the change in terms of sleep, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
Mean sleep hours, mean rapid eye movement (REM) sleep, mean light sleep, and mean deep sleep, as assessed by a wearable device, will be summarized and compared between treatment periods, where greater length of sleep is considered preferable.
Time frame: After the end of each 4 week treatment period.
To measure the change from baseline in terms of QoL using the Diurnal Alertness visual analogue scale (VAS), after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
QoL, using the Diurnal Alertness VAS, after 4 weeks of treatment and at other timepoints will be summarized and compared between treatment periods. QoL will be assessed using a Visual Analog Scale (VAS), which is a 10cm scale ranging from 'Brain Fog: unable to perform normal daily tasks' to 'Fully Alert: able to perform normal daily tasks easily'. A higher score indicates a better outcome.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in terms of QoL using the General Anxiety Disorder-7 (GAD-7) scale, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
The GAD-7 scale is a screening tool and symptom severity measure for the seven most common anxiety disorders. QOL measured using the GAD-7 scale after 4 weeks of treatment and at other timepoints will be summarized and compared between treatment periods. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions, where a lower score indicates a better outcome.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in terms of QoL using the Patient Health Questionnaire-9 (PHQ-9) scale, after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
The PHQ-9 is a self-administered assessment scale for the evaluation of depression symptoms. QoL, using the PHQ-9 scale, after 4 weeks of treatment and at other timepoints will be summarized and compared between treatment periods. The PHQ-9 scale consists of 9 questions, each with a score of 0-3, with 0 meaning Not at All, 1 meaning Several Days, 2 meaning More than half of the days and 3 Nearly every day. As the score increases then this is indicative of a more serious depressive disorder. There is a 10th question which is only answered if one of the scores for questions 1 to 9 are 1 or more.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change from baseline in terms of QoL using the Gissen Complaints Questionnaire-24 (GBB-24) scale (German participants only), after 4 weeks treatment with Chronocort compared with 4 weeks treatment with Plenadren (crossover study).
The GBB-24 scale measures self reported physical complaints in terms of whether the issue is fully or partially psychosomatically induced. QoL, using the GBB-24 scale, after 4 weeks of treatment and at other timepoints will be summarized and compared between treatment periods. The GBB-24 consists of 24 different health complaints, the severity of each is rated according to a five point scale; 0 (not at all), 1 (slightly), 2 (somewhat), 3 (considerably) and 4 (very much) \[23\]. The complaints are grouped and summarized into four subscales with six complaints in each of the following groups: Cardiovascular complaints, gastrointestinal complaints, musculoskeletal complaints and exhaustion, where a lower score indicates a more favorable outcome.
Time frame: Baseline and end of each 4 week treatment period.
To assess the participant's preference to treatment, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
Participant preference for assigned treatment during Treatment Period 1 relative to pre-study treatment, and for assigned treatment during Treatment Period 2 relative to that during Treatment Period 1, will be summarised and compared between treatments.
Time frame: After the end of each 4 week treatment period.
To assess treatment compliance, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
The percentage treatment compliance between visits and overall will be summarised.
Time frame: After the end of each 4 week treatment period.
To measure change in terms of safety and tolerability, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
The incidence, nature, severity, relatedness, duration, outcome, seriousness, and expectedness of treatment-emergent adverse events (TEAEs) will be tabulated by treatment period.
Time frame: After the end of each 4 week treatment period.
To measure change from baseline in terms of blood pressure, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
Blood pressure after 4 weeks of treatment will be summarised and compared between treatment periods.
Time frame: Baseline and end of each 4 week treatment period.
To measure change from baseline in terms of glycated haemoglobin (HbA1c), after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
HbA1c levels after 4 weeks of treatment will be summarised and compared between treatment periods.
Time frame: Baseline and end of each 4 week treatment period.
To measure the change in terms of stress dosing (use of participant administered emergency treatment pack), after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
The number of extra doses per period will be summarised and compared between treatment periods.
Time frame: After the end of each 4 week treatment period.
To measure the change from baseline in terms of lipid profile, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).
Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides, apolipoprotein (Apo) A-I, Apo B, and lipoprotein(a) (Lp(a)) will be summarized and compared between treatment periods.
Time frame: Baseline and end of each 4 week treatment period.
This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Hydrocortisone