Chronocort Versus Plenadren Replacement Therapy in Adults With Adrenal Insufficiency

NCT05222152 | Completed Phase 2

• 1 other identifier: DIUR-016-AI
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 8

Brief 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 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).

Conditions

Primary Adrenal Insufficiency

Outcome Measures

Primary Outcomes (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.

  Baseline and end of each 4 week treatment period.

Secondary Outcomes (9)

• 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).

  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).

  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).

  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).

  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).

  Baseline and end of each 4 week treatment period.

Other Outcomes (13)

• To measure the change in terms of activity, after 4 weeks treatment with Chronocort compared to 4 weeks treatment with Plenadren (crossover study).

  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).

  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).

  Baseline and end of each 4 week treatment period.

Study Arms (2)

Chronocort

EXPERIMENTAL

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

ACTIVE COMPARATOR

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

Interventions

Chronocort DRUG

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

Also known as: Hydrocortisone modified-release hard capsule

Chronocort

Plenadren DRUG

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

Also known as: hydrocortisone modified-release tablet

Plenadren

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[ULN\]).
• 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.

Sponsors & Collaborators

• Neurocrine UK Limited: lead

Study Sites (8)

Diurnal Investigational Site in Hamburg

Hamburg, 20095, Germany

Location

Diurnal Investigational Site in Munich

Munich, 80336, Germany

Location

Diurnal Investigational Site in Munich

Munich, 81667, Germany

Location

Diurnal Investigational Site in Würzburg

Würzburg, 97080, Germany

Location

Diurnal Investigational Site in Birmingham

Birmingham, B15 2TT, United Kingdom

Location

Diurnal Investigational Site in Cardiff

Cardiff, CF14 4XW, United Kingdom

Location

Diurnal Investigational Site in Newcastle

Newcastle, NE1 4LP, United Kingdom

Location

Diurnal Investigational Site in Sheffield

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41552007 DERIVED

MeSH Terms

Conditions

Addison Disease

Condition Hierarchy (Ancestors)

Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• R Ross

  Neurocrine UK Limited

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: February 3, 2022
• Study Start: November 23, 2021
• Primary Completion: October 18, 2023
• Study Completion: October 18, 2023
• Last Updated: May 14, 2024

Record last verified: 2024-05

Locations

DE (4); GB (4)