E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To investigate the effects of hydrocortisone replacement in participants with previous PMR and GCA, who are in GC-free remission and exhibit biochemical evidence of mild to moderate adrenal insufficiency. |
Forsøgets formål er at undersøge binyrebarkfunktionen hos patienter der planmæssigt afslutter prednisonbehandling for PMR eller GCA. Dernæst ønsker vi at undersøge, hvilken effekt en behandling med hydrokortison har hos patienter med let til moderat binyrebarkinsufficiens bedømt på testresultatet. |
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E.1.1.1 | Medical condition in easily understood language |
Hydrocortisone replacement in participants with previous polymyalgia rheumatica and giant cell arteritis , who are in GC-free remission and exhibit biochemical evidence of adrenal insufficiency. |
Binyrebarkfunktionen hos patienter der afslutter prednisolon behandling for muskelgigt eller kæmpecelle karbetændelse. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001369 |
E.1.2 | Term | Adrenal insufficiency NOS |
E.1.2 | System Organ Class | 100000004860 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effects of hydrocortisone replacement in participants with previous PMR and GCA, who are in GC-free remission and exhibit biochemical evidence of mild to moderate adrenal insufficiency. |
Forsøgets formål er at undersøge binyrebarkfunktionen hos patienter der planmæssigt afslutter prednisonbehandling for PMR eller GCA. Dernæst ønsker vi at undersøge, hvilken effekt en behandling med hydrokortison har hos patienter med let til moderat binyrebarkinsufficiens bedømt på testresultatet. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria Age ≥ 50 years A diagnosis of PMR or GCA in GC free remission for >2 week and <12 weeks after treatment with prednisolone (any dosage) for ≥12 weeks.
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Inklusionskriterier: Personer over 50 år der som led i sygdommene GCA og PMR planmæssigt afslutter behandling med prednison, der har varet mere end 12 uger.
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E.4 | Principal exclusion criteria |
Exclusion criteria Known primary or secondary adrenal insufficiency Known Cushing´s syndrome Severe comorbidity: Heart failure (New York Heart Association class IV) Kidney failure with an estimated glomerular filtration rate <30 mL/min (chronic kidney disease stage 4-5) Liver disease in the form of cirrhosis Active cancer Known severe immune deficiency A history of psychiatric disease requiring treatment by a psychiatric department (for affective disorders only if within the last year before study entry) Alcohol consumption >21 units per week Planned major surgery during the study period at study entry. Use of drugs that interfere with cortisol metabolism/measurements: Estrogen treatment (discontinued < 1 month before inclusion) Strong CYP3A4 inhibitors or inducers Use of other GC formulations: Inhaled corticosteroids, intra-articular or intramuscular injections, steroid creams European steroid group IV-V used in the genital area Permitted GC formulations: Eye-drops, nasal spray, GC creams European steroid group I-III, and European steroid group IV-V used in the non-genital area only. Inability to provide written informed consent.
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Eksklusionskriterier: Kendt binyre insufficiens eller Cushing´s syndrom, Svær co-morbiditet (herunder hjertesvigt, nyresvigt, skrumpelever, aktiv kræftsygdom, svær immundefekt, svær psykisk sygdom) Alkoholforbrug >21 genstande per uge, Planlagt kirurgi I studieperioden, Brug af medicin der påvirker omsætning eller måling af kortisol. Pågående behandling med glukokortikoid som inhalationer eller indsprøjtninger i muskel eller led. Ikke i stand til at give informeret samtykke
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome • Adrenal insufficiency symptoms (AddiQoL-30)
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Primary outcome • Adrenal insufficiency symptoms (AddiQoL-30) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 and 12 months |
6 og 12 mdr |
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E.5.2 | Secondary end point(s) |
Key secondary outcomes • Participant-reported symptoms of fatigue assessed with EMA-MFI and PRO-CTCAE • Questionnaire-based HRQoL (other than AddiQoL-30) • Incidence of adrenal crises, hospitalizations, sick days, diagnoses and therapy • Cardiovascular health (blood pressure, arterial stiffness, and coagulation markers) • Body composition and muscle function • Normalization of adrenal function evaluated by ACTH test Other secondary endpoints • Glucose homeostasis • Bone and calcium metabolism • Circulating and tissue biomarkers of GC sensitivity and action
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Key secondary outcomes • Participant-reported symptoms of fatigue assessed with EMA-MFI and PRO-CTCAE • Questionnaire-based HRQoL (other than AddiQoL-30) • Incidence of adrenal crises, hospitalizations, sick days, diagnoses and therapy • Cardiovascular health (blood pressure, arterial stiffness, and coagulation markers) • Body composition and muscle function • Normalization of adrenal function evaluated by ACTH test Other secondary endpoints • Glucose homeostasis • Bone and calcium metabolism • Circulating and tissue biomarkers of GC sensitivity and action
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 an 12 months |
6 og 12 mdr |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |