Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
50
Countries
1
Sites
14
Primary adrenal insufficiency (PAI)
Differences in health-related quality of life (HRQoL) scores in patients receiving Plenadren and conventional Cortisone at time of diagnosis and 1, 6, and 12 months.
Key facts
- Sponsor
- Helse Bergen HF
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hormonal diseases [C19]
- Trial duration
- 3 Aug 2023 → ongoing
- Decision date (initial)
- 2024-08-07
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-512888-31-00
- EudraCT number
- 2021-006487-24
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Therapy
Differences in health-related quality of life (HRQoL) scores in patients receiving Plenadren and conventional Cortisone at time of diagnosis and 1, 6, and 12 months.
Conditions and MedDRA coding
Primary adrenal insufficiency (PAI)
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Age 16-80 years
- Established PAI according to the diagnostic criteria as specified above.
- Participants must be recently diagnosed, specifically treated with glucocorticoid replacement therapy for less than 31 days prior to inclusion to secure treatment naivety.
- Women of childbearing potential (WOCBP) must have a negative pregnancy test performed at the time of screening.
- Participants must be capable of giving signed informed consent
Exclusion criteria 8
- High dose glucocorticoid therapy for other disease during last three months prior to screening.
- Ongoing treatment for active malignant disease.
- Severe hepatic or renal disease.
- Sever psychiatric disease.
- Chronic abuse of alcohol or drug abuse.
- Current pregnancy, and if the participant plan to become pregnant during the 12 months of study participation.
- Known hypersensitivity to the active substance or any of the excipients.
- Participation in another blinded clinical study involving an investigational medicinal product within 1 month prior to study inclusion.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- HRQoL score.
Secondary endpoints 6
- Blood pressure, body weight, waist circumference, body mass index, cholesterols, glucose, insulin, HOMA index.
- Hair cortisol level, Salivary cortisol day curves, 24 h urine cortisol and metabolites.
- Sleep diary, actigraphy, sleep radar.
- Cognitive testing and biomarker for brain plasticity (BDNF) in serum.
- Bone mineral density, body composition and bone markers
- Adverse events, Serious adverse events, Adrenal crisis symptoms and treatment.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Plenadren 20 mg modified-release tablets
PRD3796058 · Product
- Active substance
- Hydrocortisone
- Substance synonyms
- CORTISOL
- Pharmaceutical form
- MODIFIED-RELEASE TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 21900 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- H02AB09 — HYDROCORTISONE
- Marketing authorisation
- EU/1/11/715/006
- MA holder
- TAKEDA PHARMACEUTICALS INTERNATIONAL AG IRELAND BRANCH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
PRD9486167 · Product
- Active substance
- Cortisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- H02AB10 — CORTISONE
- Marketing authorisation
- 2827
- MA holder
- ORIFARM GENERICS A/S
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Helse Bergen HF
- Sponsor organisation
- Helse Bergen HF
- Address
- Haukelandsveien 22
- City
- Bergen
- Postcode
- 5021
- Country
- Norway
Scientific contact point
- Organisation
- Helse Bergen HF
- Contact name
- Eystein Husebye
Public contact point
- Organisation
- Helse Bergen HF
- Contact name
- Eystein Husebye
Locations
1 EU/EEA country · 14 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Ongoing, recruiting | 50 | 14 |
| Rest of world | — | 0 | — |
Investigational sites
Helse Nord-Trondelag HF
Department of Medicine, Kirkegata 2, 7600, Levanger
Helse Moere Og Romsdal HF
Department of Medicine, Aasehaugen 1, 6017, Aalesund
Sorlandet Sykehus HF
Department of Medicine, Egsveien 100, 4615, Kristiansand S
Sykehuset Oestfold HF Kalnes
Department of Medicine, Kalnesveien 300, 1714, Graalum
Helse Bergen HF
Department of Medicine, Haukelandsveien 22, 5021, Bergen
Sykehuset I Vestfold HF
Department of Medicine, Halfdan Wilhelmsens Alle 17, 3116, Toensberg
Helse Fonna HF
Department of Medicine, Karmsundgata 120, 5528, Haugesund
Stavanger University Hospital HF
Department of Medicine, Helse Stavanger HF, Postboks 8100, Stavanger
Sykehuset Innlandet HF
Department of Medicine, Kyrre Grepps Gate 11, 2819, Gjoevik
Universitetssykehuset Nord-Norge HF
Department of Medicin, Sykehusvegen 38, 9019, Tromsoe
Oslo University Hospital HF
Department of Medicine, Sognsvannsveien 20, 0372, Oslo
Vestre Viken HF
Department of Medicine, Dronninggata 28, 3004, Drammen
St. Olavs Hospital HF
Department of Medicine, Ragnhilds Gate 15, 7030, Trondheim
Akershus University Hospital
Department of Medicine, Sykehusveien 27, 1478, Lorenskog
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Norway | 2023-08-03 | 2023-08-03 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-136234
- Sponsor became aware
- 2026-05-22
- Date of breach
- 2026-05-22
- Submission date
- 2026-05-28
- Member states concerned
- Norway
- Categories
- Regulation
- Areas impacted
- Data reliability or robustness
- Benefit-risk balance changed
- No
- Description
- There has been an inadequate follow-up of responses to the distributed quality-of-life questionnaires. The sponsor is responsible for both the distribution of the electronic questionnaires and the collection of responses, and has become aware of missing responses. Although patients received several reminders to complete the questionnaires, there was initially no system in place to track and follow up on responses. After the inclusion of the planned amount of participants, a review showed that 43 participants had completed the questionnaire at the first visit. The five patients who were excluded from the study, were were among those who did not respond.
- Sponsor actions
- Patients have a relatively short time frame to complete the quality-of-life questionnaire. We have now established a procedure to follow up on responses and to contact patients with reminders. We will also implement a protocol amendment to increase the target number of inclusions from 50 to 65 patients. An SM will be submitted in CTIS to request approval for an increased number of inclusions in order to secure sufficient statistical power to detect any differences between the study arms.
| Organisation | City | Country | Type |
|---|---|---|---|
| Helse Bergen HF | Bergen | Norway | Sponsor (non commercial) |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol EU CT number 2024-512888-31-00_Redacted | 7.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 2.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF all participants | 5.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_ SmPC Plenadren | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis NO 2024-512888-31-00 | 1.0 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-05 | Norway | Acceptable 2024-08-06
|
2024-08-07 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-10-13 | Norway | Acceptable 2025-11-11
|
2025-11-12 |