E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary adrenal insufficiency |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052381 |
E.1.2 | Term | Primary adrenal insufficiency |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare bioavailability between a once-daily modified-release hydrocortisone tablet and a conventional thrice-daily replacement therapy in patients with chronic primary adrenal insufficiency. |
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E.2.2 | Secondary objectives of the trial |
To compare safety, tolerability and efficacy of the novel modified release formulation to the conventional thrice-daily replacement therapy.
To assess the safety of using the novel modified release formulation as “rescue therapy“ during minor intercurrent illnesses in patients with primary adrenal insufficiency.
To assess long-term safety, tolerability and efficacy of the novel modified release formulation during glucocorticoid replacement therapy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Males and females; age 18 years and above - Previously diagnosed (e.g. more than 6 months ago) primary adrenal insufficiency with a stable daily glucocorticoid substitution dose of at least 3 months prior to study entry. - An oral hydrocortisone substation therapy dose of 30 mg total daily dose - Signed informed consent to participate in the study
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E.4 | Principal exclusion criteria |
- Clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, hepaticobiliary, pancreatic disease, which in the investigators judgment may interfere with the study assessment or completion of the study - Clinically significant renal dysfunction with a serum creatinine above 150 mmol/L. - Clinical or laboratory signs of significant GI emptying or motility disease or disorder including pharmacological therapies affecting GI emptying or motility, which in the investigators judgment may interfere with the ADME of hydrocortisone - Any medication with agents which may interfere with hydrocortisone kinetics within 14 days prior to study start - Any additional underlying disease that may need regular or periodic pharmacological treatment with glucocorticoids. - Administration of other investigational drugs within eight weeks preceding the pre-entry examination - Alcohol/drug abuse or any condition associated with poor patient compliance, including expected non-cooperation, as judged by the investigator - Pregnant or lactating women - Regular DHEA medication for the past 4 weeks. - Oral oestrogen medication for the past 4 weeks (transdermal oestrogen medication is allowed) - Deranged mineralcorticoid status as determined by clinical (hypotension, ortostatic hypotension) and biochemical status (PRA outside the normal range and abnormal serum sodium and potassium levels).
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety and efficacy of dosing the novel combined modified release formulation in comparison to conventional therapy as assessing bioavailability and pharmacokinetics by difference in total S-cortisol AUC0-24h of od compared to tid therapy for all subjects (study arm I+II) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
two-armed, two-period 12-week cross-over, with an o |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Information not present in EudraCT |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |