An open-label, cross-over, multi-site, prospective, phase IIb study of effects on circadian rhythms and quality of life of modifieddual-release hydrocortisone Efmody™ versus immediate-release hydrocortisone in patients with Addison’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Royal College Of Surgeons In Ireland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

22 Dec 2023 → 9 Sep 2024

Decision date (initial)

2023-07-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The study primary objectives can be summarised as follows:
• To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on quality QoL
• To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on sleep efficiency
• To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on patient interdaily stability
• To assess the effect changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on dim-light melatonin onset (DLMO).

Secondary objectives 14

1. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on quality of sleep.
2. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on total sleep time.
3. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on sleep onset
4. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on wake after sleep
5. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on total sleep time variability
6. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on sleep onset variability
7. To evaluate the effect of changing from immediate release hydrocortisone to modified release hydrocortisone Efmody™ therapy on wake after sleep onset variability
8. To evaluate the effect of changing from immediate release Hydrocortisone to modified release hydrocortisone Efmody™ therapy on intradaily variability
9. To assess the effect of changing to modified release hydrocortisone on 24 hours salivary cortisol profiles in patients with AD.
10. To assess the effect of changing to modified release hydrocortisone on 24 hours salivary melatonin profiles in patients with AD.
11. To assess the effect of changing to modified release hydrocortisone on systolic and diastolic blood pressure in patients with AD.
12. To measure change in terms of safety and tolerability of Efmody™ vs immediate release hydrocortisone
13. To assess participant's preference to Efmody™ vs immediate release hydrocortisone
14. To assess the use and reasons for use of rescue medication

Conditions and MedDRA coding

Addison’s Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Male or female participants must be aged 18 years or older
2. 2. Ability to comprehend the Patient Information Leaflet and to provide signed and dated informed consent.
3. 3. Participants with an established diagnosis of Addison’s disease currently treated with immediate-release hydrocortisone as replacement therapy .
4. 4. Participants on stable immediate-release hydrocortisone treatment for ≥ 4 weeks prior to enrolment.
5. 5. Participants on a stable dose of fludrocortisone for ≥ 4 weeks prior to enrolment
6. 6. Evidence of effective contraception for WOCBP* (see Appendix 11) *Women of childbearing potential (WOCBP) are eligible to participate if they are not pregnant, not breastfeeding and agree to adhere to the contraceptive guidance during the screening and treatment periods. Effective contraception should be maintained until treatment discontinuation. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. The effective methods of contraception are described in Appendix 11
7. 7. In the Investigator’s opinion, able and willing to comply with all trial requirements.

Exclusion criteria 24

1. Participants aged < 18 years
2. 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]).
3. 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.
4. Participants who have type 1 diabetes or type 2 diabetes receiving regular insulin.
5. Participants who have elective surgical procedures scheduled during the study.
6. Current diagnosis of moderate to severe depression, bipolar disorder, eating disorders, schizophrenia or other psychosis. A past history of psychiatric disorder is not an exclusion criterion, provided the patient is currently well (not on psychoactive treatment) in the investigator’s judgement. Participants with psychiatric conditions that in the opinion of the Investigator would preclude participation in the study: such as severe depression, schizophrenia, eating disorders.
7. Participants with an acute medical or surgical illness.
8. History of significant medical co-morbidities which disrupt sleep (for example, obstructive sleep apnoea, congestive cardiac failure or restless leg syndrome)
9. History of cataracts or other ophthalmologic conditions which could affect retina light perception.
10. Conditions that would place the individual at increased risk or preclude the individual’s full compliance with or completion of the study – such as intellectual disability or cognitive impairment
11. Patients who have difficulty understanding the required protocol and follow up instructions (e.g. language barriers)
12. Participants with life expectancy of less than 6 months.
13. Participants with a history of malabsorption and/or motility disorders due to risk of impaired cortisol exposure.
14. Participants treated with agents that interfere with corticosteroid metabolism.
15. Participants who have received intra-articular steroid injections within 2 months prior to the Screening Visit or for whom such injections are planned during the study.
16. Participants who are prescribed inhaled or topical steroid preparations
17. Participants with ongoing use of drugs which affect sleep - such as sedatives or antidepressants.
18. Patients who have participated in another research trial involving an investigational product in the past 12 weeks.
19. Ongoing habitual alcohol intake in excess of 20 units per week.
20. History of night-shift work in the previous two years
21. Participants who intend to travel and cross a time zone of greater than ±3 hours within 1 week of the scheduled actigraphy and DLMO measurements.
22. Participants with a known hypersensitivity to any of the components of the Efmody™ capsules.
23. Pregnancy
24. Breastfeeding Mothers

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. To measure the change from baseline in QoL using the Health-related Quality of Life in Addison's disease (AddiQoL) questionnaire, after 11 weeks treatment with Efmody™ compared with immediate-release hydrocortisone [ Time Frame: Baseline and end of each 11 week treatment period. (see protocol section 10.3.1 for further details)

Secondary endpoints 1

1. 1. To measure the change from baseline in terms of QoL using the 36-Item Short Form Health Survey (SF-36®) questionnaire, after 11 weeks treatment with Efmody™ compared with immediate-release Hydrocortisone. [ Time Frame: Baseline and end of each 11 week treatment period]. See protocol section 10.3.2 for further details

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Royal College Of Surgeons In Ireland

Sponsor organisation

Royal College Of Surgeons In Ireland

Address

123 Saint Stephen's Green

City

Dublin 2

Postcode

D02 YN77

Country

Ireland

Scientific contact point

Organisation

Royal College Of Surgeons In Ireland

Contact name

Mandy Jackson

Public contact point

Organisation

Royal College Of Surgeons In Ireland

Contact name

Mandy Jackson

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications