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Primary Adrenal InsufficiencyPhase 2CHAMPAINNCT05222152

Chronocort Versus Plenadren Replacement Therapy in Adults With Adrenal Insufficiency

A Phase 2 study testing Chronocort and Plenadren in people with Primary Adrenal Insufficiency, run by Neurocrine UK Limited at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Primary Adrenal Insufficiency
What is being tested?
Chronocort and Plenadren
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
8 sitesin 2 countries
Study dates
23 Nov 2021to 18 Oct 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female participants must be aged 18 years or older at the time of signing the informed consent.
  • Participants with known (documented) primary AI, defined as early morning pre-dose cortisol <50 nmol/L and currently treated with glucocorticoid as replacement therapy. Primary AI includes any cause of acquired or congenital primary adrenal failure including autoimmune Addison's disease and bilateral adrenalectomy (except when performed for Cushing's syndrome).
  • Participants on stable glucocorticoid treatment for ≥3 months prior to the Screening Visit.
  • Participants on a stable dose of fludrocortisone (if applicable) for ≥3 months prior to the Screening Visit.
  • Male participants must agree to use contraception as detailed in Appendix 4 of the protocol, during the Screening, Treatment, and Follow-up Periods and refrain from donating sperm during these periods and for 7 days after the last dose of study treatment.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and for whom at least one of the following conditions applies: not a woman of childbearing potential (WOCBP), or a WOCBP with a negative urine pregnancy test at entry into the study who agrees to follow the contraceptive guidance during the Screening, Treatment and Follow-up Periods and for 7 days after the last dose of study treatment. Note: Females presenting with oligomenorrhea or amenorrhea who are ≤55 years should be considered potentially fertile (unless permanently sterile) and therefore, as well as undergoing pregnancy testing like all other female participants, will be expected to use an acceptable method of contraception as described in Appendix 4 during the Screening, Treatment and Follow-up Periods and for 7 days after the last dose of study treatment.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

Who cannot join

  • Participants with Congenital adrenal hyperplasia (CAH).
  • Participants with secondary and tertiary AI.
  • Past or current history of Cushing's syndrome.
  • Adrenal suppression and/or AI induced by exogenous steroids.
  • Drug-induced AI.
  • Clinical or biochemical evidence of hepatic disease: elevated liver function tests (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3 times the upper limit of normal [ULN]).
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  • Clinical or biochemical evidence of renal disease: serum creatinine level of >221 μmol/L (2.5 mg/dL) or calculated creatinine clearance of <25 mL/min.
  • History of malignant brain tumours or traumatic brain injury.
  • History of malignancy within the last 5 years or treated basal cell carcinoma within the past year.
  • Participants who have type 1 diabetes or type 2 diabetes receiving regular insulin.
  • Participants with type 2 diabetes whose screening HbA1c exceeds 9%.
  • Participants who have elective surgical procedures scheduled during the study.
  • Participants with significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
  • Participants who have had bariatric surgery within the past 6 months and participants who plan to undertake a major weight loss and/or exercise program during the same time period as anticipated study involvement.
  • Restless legs syndrome/Willis-Ekbom disease.
  • Participants who have increased gastrointestinal motility e.g., chronic diarrhoea, that may be at risk of impaired cortisol exposure. There are no data in patients with confirmed slow gastric emptying or decreased motility disease/disorder so the clinical response should be monitored in patients with these conditions.
  • Participants anticipating regular prophylactic use of additional steroids e.g., for strenuous exercise.
  • Participants with co-morbidities requiring daily administration of a medication (or consumption of any material) that interferes with the metabolism of glucocorticoids.
  • Participants on regular daily inhaled, topical, nasal, or oral steroids for any indication other than AI.
  • Participants who have received intra-articular steroid injections within 1 year prior to the Screening Visit or for whom such injections are planned during the study.
  • Participants who are receiving <10 mg hydrocortisone dose at the Screening Visit or the hydrocortisone dose equivalent.
  • Participants taking sleeping medication.
  • Participants treated at screening with either Chronocort or Plenadren.
  • Participation in another clinical study of an investigational or licensed drug or device within 12 weeks or 5 half-lives prior to the Screening Visit or at any time during study participation.
  • Active alcohol or drug abuse within 1 year prior to the Screening Visit.
  • Participants who routinely work night shifts and do not sleep during the usual night-time hours.
  • Participants who intend to travel and cross a time zone of greater than ±3 hours within 1 week of the scheduled visit dates.
  • Participants unable to comply with the requirements of the protocol in the opinion of the Investigator.
  • Participants with a known hypersensitivity to any of the components of the Chronocort capsules, the Plenadren tablets, the Chronocort placebo, or the Plenadren placebo.

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

Germany4 sites
  • Diurnal Investigational Site in Hamburg

    Hamburg, 20095

  • Diurnal Investigational Site in Munich

    Munich, 80336

  • Diurnal Investigational Site in Munich

    Munich, 81667

  • Diurnal Investigational Site in Würzburg

    Würzburg, 97080

Other trials in Germany

United Kingdom4 sites
  • Diurnal Investigational Site in Birmingham

    Birmingham, B15 2TT

  • Diurnal Investigational Site in Cardiff

    Cardiff, CF14 4XW

  • Diurnal Investigational Site in Newcastle

    Newcastle, NE1 4LP

  • Diurnal Investigational Site in Sheffield

    Sheffield, S10 2JF

Other trials in United Kingdom

About this study

Official title: A Double-Blind, Double-Dummy, Two-Way Cross-Over, Randomised, Phase II Study of Efficacy, Safety and Tolerability of Modified-Release Hydrocortisones: Chronocort® Versus Plenadren®, in Adrenal Insufficiency

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).

Read the detailed description

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.

Being tested
Chronocort, Plenadren
Medical subject headings
Addison Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChronocortDrug

    Also called Hydrocortisone modified-release hard capsule

    Hydrocortisone modified-release hard gelatin capsules for oral administration - 5mg and 10mg

  • PlenadrenDrug

    Also called hydrocortisone modified-release tablet

    Hydrocortisone modified-release tablets for oral administration - 5mg and 20mg

Study groups in NCT05222152
Study groupRoleWhat they receive
ChronocortExperimentalChronocort (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).
Receives: Drug: Chronocort
PlenadrenActive comparatorPlenadren (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).
Receives: Drug: Plenadren

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and end of each 4 week treatment period.

Secondary outcomes (9)
  1. 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.

    Measured: Baseline and end of each 4 week treatment period.

  2. 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].

    Measured: Baseline and end of each 4 week treatment period.

  3. 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.

    Measured: Baseline and end of each 4 week treatment period.

  4. 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.

    Measured: Baseline and end of each 4 week treatment period.

  5. 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.

    Measured: Baseline and end of each 4 week treatment period.

  6. 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.

    Measured: Baseline and end of each 4 week treatment period.

  7. 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.

    Measured: Baseline and end of each 4 week treatment period.

  8. 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.

    Measured: Baseline and end of each 4 week treatment period.

  9. 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.

    Measured: Baseline and end of each 4 week treatment period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2022
  2. Study start23 Nov 2021
  3. Primary completion18 Oct 2023
  4. Study completion18 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05222152
Sponsor's protocol ID
DIUR-016-AI
Acronym
CHAMPAIN
Status last verified
Sep 2026
First submitted
29 Nov 2021
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Prete A, Theiler-Schwetz V, Arlt W, Hazeldine J, Chifu IO, Harbeck B, Napier C, Newell-Price JDC, Rees DA, Reisch N, Stalla GK, Coope H, Maltby K, Porter J, Quirke J, Ross RJ. Effects of modified release hydrocortisone on restoration of early morning cortisol, quality of life, and fatigue in adrenal insufficiency (The CHAMPAIN study): a randomised, double-blind, double-dummy, cross-over study comparing Chronocort and Plenadren. EClinicalMedicine. 2026 Jan 2;91:103714. doi: 10.1016/j.eclinm.2025.103714. eCollection 2026 Jan.

    PubMed 41552007

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Chronocort and Plenadren in people with Primary Adrenal Insufficiency, run by Neurocrine UK Limited at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). (time frame: Baseline and end of each 4 week treatment period.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05222152, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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