E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In stages 1+2 of the study healthy volunteers will be used to determine the bioequivalence of nasal synacthen with 1 microgram of intravenous synacthen. Stage 3 will use healthy children to establish normal ranges for the adrenal response to a low-dose synacthen test. In stage 4 adrenal function in asthmatic individuals on inhaled corticosteroids will be studied. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001367 |
E.1.2 | Term | Adrenal Insufficiency |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006482 |
E.1.2 | Term | Bronchospasm |
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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 establish whether nasally administered synacthen, combined with salivary cortisol sampling, can be used effectively to investigate potential adrenal suppression and therefore be a valid non-invasive alternative to the current, intravenous low-dose Short Synacthen Test. |
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E.2.2 | Secondary objectives of the trial |
Stage 1a: To establish the bioequivalence of nasal synacthen with 1 microgram of intravenous synacthen in adult volunteers. To determine the bioavailability and pharmacokinetics of nasally administered synacthen and the subsequent peak cortisol response. To determine the inter-individual variability of nasally administered synacthen.
Stage 1b: To determine the intra-individual variability of nasally administered synacthen
Stage 2: To establish whether the peak cortisol response, bioavailability and pharmacokinetics are similar in the paediatric population to that of adult males.
Stage 3: To establish the first normative data for the Short Synacthen Test in healthy children.
Stage 4: To establish which children on inhaled corticosteroids are at greatest risk of adrenal suppression. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Stage 1(a+b): Healthy, male volunteers aged 18-64, with no exclusion criteria listed below.
Stage 2: Healthy children of either sex, aged between 2 years and 15 years, with no exclusion criteria listed below.
Stage 3: Healthy children of both sexes, aged between 6 months and 15 years, without exclusion criteria 1,2,3,5,6,7,8,9,10,11,12 and 14 listed below.
Phase 4: Children of both sexes, aged between 6 months and 15 years, prescribed varying doses of regular inhaled corticosteroids and without exclusion criteria 1,5,9,10,11,12 and 14 as listed below.
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E.4 | Principal exclusion criteria |
1. Past or present history of an endocrinopathy. 2. Past or present history of asthma. 3. Past or present history of allergic rhinitis 4. Past or present history of peptic ulcer disease/GI bleed/significant dyspepsia. 5. Past history of intra-cranial, renal or adrenal pathology. 6. Presently on any prescribed medication. 7. Presently, or within the last 3 months, been prescribed any type of corticosteroid (oral, inhaled, nasal, rectal, intravenous, intramuscular, intra-articular, intra-ocular, topical). 8. Ever been prescribed a prolonged course (more than 1 month) of oral steroids. 9. Previous serious allergic reaction or an episode of anaphylaxis. 10. Previous adverse reaction (including mild hypersensitivity)to ACTH or synacthen. 11. Coryzal symptoms within the last week. 12. Current smoker. 13. Body Mass Index more than 30. 14. Currently pregnant 15. Currently anaemic |
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E.5 End points |
E.5.1 | Primary end point(s) |
A validated non-invasive test of adrenal function (stages 1+2).
Normative data for the low-dose short synacthen test in children (stage 3).
The dose of inhaled corticosteroids that causes adrenal suppression in children (stage 4). |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | Yes |
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) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Yes |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |