Adrenal Insufficiency (AI) MedDRA version: 20.0 Level: PT Classification code 10052381 Term: Primary adrenal insufficiency System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Trade Name: Chronocort® (Efmody) 5 mg modified-release hard capsules
Product Name: Chronocort®
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: Hydrocortisone
CAS Number: 50-23
Sponsors
Diurnal Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants aged =18 years. 2. Participants with known (documented) primary AI, defined as early morning pre-dose cortisol =65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Participants with CAH. 2. Participants with secondary and tertiary AI. 3. Past or current history of Cushing’s syndrome. 4. Adrenal suppression and/or AI induced by exogenous steroids. 5. Drug-induced AI. 6. 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]). 7. 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. 8. History of malignant brain tumours or traumatic brain injury. 9. History of malignancy within the last 5 years or treated basal cell carcinoma within the past year. 10. Participants who have type 1 diabetes or type 2 diabetes receiving regular insulin. 11. Participants with type 2 diabetes whose screening HbA1c exceeds 9%. 12. Participants who have elective surgical procedures scheduled during the study. 13. Participants with significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study. 14. 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. 15. Restless legs syndrome/Willis-Ekbom disease. 16. 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. 17. Participants anticipating regular prophylactic use of additional steroids e.g., for strenuous exercise. 18. Participants with co-morbidities requiring daily administration of a medication (or consumption of any material) that interferes with the metabolism of glucocorticoids. 19. Participants on regular daily inhaled, topical, nasal, or oral steroids for any indication other than AI. 20. 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. 21. Participants who are receiving <10 mg hydrocortisone dose at the Screening Visit or the hydrocortisone dose equivalent. 22. Participants taking sleeping medication. 23. Participants treated at screening with either Chronocort or Plenadren. 24. 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. 25. Active alcohol or drug abuse within 1 year prior to the Screening Visit. 26. Participants who routinely work night shifts and do not sleep during the usual night-time hours. 27. Participants who intend to travel and cross a time zone of greater than ±3 hours within 1 week of the scheduled visit dates. 28. Participants unable to comply with the requirements of the protocol in the opinion of the Investigator. 29. Participants with a known hypersensitivity to any of the components of the Chronocort capsules, the Plenadren tablets, the Chronocort placebo, or the Plenadren placebo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Efficacy - To compare Chronocort to Plenadren in terms of morning serum cortisol levels. Safety - To compare Chronocort to Plenadren in terms of safety and tolerability; in terms of blood pressure; in terms of glycated haemoglobin (HbA1c) levels; in terms of stress dosing (use of participant administered emergency treatment pack); in terms of lipid profile. ;Secondary Objective: Efficacy - To compare Chronocort to Plenadren in terms of: - morning fatigue using the Multidimensional Assessment of Fatigue (MAF) questionnaire within 1 hour of waking - achieving physiological morning cortisol levels. - closeness of overall salivary cortisone levels during the day to a normal physiological profile - adrenocorticotropic hormone (ACTH) control in the morning - the impact on the bone marker of osteocalcin. - morning fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS® 7b) questionnaire within 1 hour of waking - QoL using the EuroQol 5-level Standardised Health Questionnaire (EQ-5D-5L™) - QoL using the Health-related Quality of Life in Addison’s disease (AddiQoL) questionnaire - QoL using the 36-Item Short Form Health Survey (SF-36®) questionnaire. Exploratory Efficacy - activity; Sleep; preference for treatment; QoL using the Diurnal Alertness visual analogue scale (VAS); QoL using the General Anxiety Disorder-7 (GAD-7) ;Primary end point(s): 1. To compare Chronocort to Plenadren in terms of morning serum cortisol levels. 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 significant" protocol deviations) using a linear mixed model. Superiority of Chronocort to Plenadren will be declared if the 95% confidence interval (CI) for the treatment effect is wholly above zero 2. To compare Chronocort | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcomes are focused on whether this reduces fatigue and improves QoL in patients with AI. Therefore, the same total daily dose of Plenadren and Chronocort will be used. 1. To compare Chronocort to Plenadren in terms of achieving physiological morning cortisol levels. 2. To compare Chronocort to Plenadren in terms of closeness of overall salivary cortisone levels during the day to a normal physiological profile. 3. To compare Chronocort to Plenadren in terms of ACTH control in the morning. 4. To compare Chronocort to Plenadren in terms of the impact on the bone marker of osteocalcin. 5. To compare Chronocort to Plenadren in terms of morning fatigue using the Patient-Reported Outcomes Measurement Information System (PROMIS® 7b) questionnaire within 1 hour of waking. 6. To compare Chronocort to Plenadren in terms of QoL using the EuroQol 5-level Standardised Health Questionnaire (EQ-5D-5L™). 7. To compare Chronocort to Plenadren in terms of QoL using the Health-related Quality of Life in Addison’s disease (AddiQoL) questionnaire 8. To compare Chronocort to Plenadren in terms of QoL using the 36-Item Short Form Health Survey (SF-36®) questionnaire ;Timepoint(s) of evaluation of this end point: 1. 07:00 hour serum cortisol before the morning dose of >140 nmol/L after 4 weeks of treatment 2. A salivary cortisone profile score will be derived at the end of 4 weeks of treatment. 3. The 07:00 hour plasma ACTH level after 4 weeks of treatment 4. Osteocalcin levels after 4 weeks of treatment 5. Morning fatigue, using the PROMIS 7b questionnaire, within 1 hour of waking after 4 weeks of treatment 6. QoL, using the EQ-5D-5L after 4 weeks of treatment 7. QoL, using the AddiQoL questionnaire after 4 weeks of treatment 8. QoL, using SF-36 questionnaire after 4 weeks of treatment | — |
Countries
Germany, United Kingdom
Contacts
Public ContactRegulatory Department
Diurnal Limited
Outcome results
None listed