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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E.1.1.1 | Medical condition in easily understood language |
Inability to produce the stress hormone, cortisol, is known as adrenal insufficiency. It can cause serious illness and even death. Inhaled steroids taken for asthma can cause adrenal insufficiency. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064973 |
E.1.2 | Term | Allergic bronchospasm |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001367 |
E.1.2 | Term | Adrenal insufficiency |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
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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 (with chitosan), 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, 1mcg 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 chitosan) with 1mcg of intravenous Synacthen in adults. 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 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 1mcg SST in the healthy paediatric population. Stage 4: To establish which children on inhaled corticosteorids 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: Healthy, male volunteers aged between 18-64, with no exclusion criteria listed below. Stage 2: Healthy children of either sex, aged between 2 and 15 years (up to their 16th birthday), with none of the exclusion criteria listed below. Stage 3: Healthy children of both sexes, aged between 6 months and 15 years, with none of the exclusion criteria listed below. Stage 4: Children of both sexes, aged between 6 months and 15 years, with asthma taking varying doses of inhaled corticosteroids, with none of the exclusion criteria except numbers 2,4,5 and 6. |
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E.4 | Principal exclusion criteria |
1. Past or present history of an endocrinopathy (all stages) 2. Past or present history of asthma (stages 1,2,3) 3. Past or present history of allergic rhinitis (stages 1,2,3) 4. Past or present history of peptic ulcer disease/GI bleed/significant dyspepsia (stages 1+2) 5. Past history of intra-cranial or renal/adrenal pathology (all stages) 6. Presently on any medication (stages 1,2,3) 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) (stages 1,2,3) 8. Ever been prescribed a prolonged course of oral corticosteroids (more than 1 month) (stages 1,2,3) 9. Previous adverse reaction (including mild hypersensitivity) to ACTH or Synacthen (all stages) 10. Previous severe allergic reaction or anaphylaxis (all stages) 11. Coryzal symptoms within the last week (and will be asked to report any new symptoms occurring within 24 hours of the test) (all stages) 12. Current smoker (all stages) 13. Body Mass Index less than 18.5 or more than 30kg/m2 (stages 1+2) 14. Currently pregnant (stages 2,3,4) 15. Currently anaemic (stages 1+2) |
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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.5.1.1 | Timepoint(s) of evaluation of this end point |
Stages 1+2 are anticipated to take 18 months to complete. Stage 3 it is anticipated will take 8 months to complete. Stage 4 it is anticipated will take 10 months to complete |
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E.5.2 | Secondary end point(s) |
Stage 1a: To establish the bioequivalence of an i.n SST with the 1mcg i.v SST. To establish the first bioavailability and pharmacokinetic data of nasal Synacthen, enhanced by the addition of chitosan, in humans. To establish the inter-individual variability of nasal Synacthen in man. Stage 1b: To establish the intra-individual variability of the selected nasal Synacthen dose in humans. Stage 2: To establish that the chosen dose, peak cortisol response, bioavailability and pharmacokinetics are similar in the paediatric population compared with adult males tested in stage 1. Stage 3: To establish, by use of the validated non-invasive SST, the first normative data for the low-dose SST in the paediatric population. Stage 4: To establish, with a validated test and normative data, which asthmatic children on inhaled corticosteroids are at risk of adrenal suppression and whether dose, age, gender or pubertal stage impact on the risk. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Stages 1+2 are anticipated to take 18 months to complete. Stage 3 it is anticipated will take 8 months to complete. Stage 4 it is anticipated will take 10 months to complete |
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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 | Yes |
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 | Yes |
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 |
1 mcg intravenous Synacthen |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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.8.6 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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Each stage will be completed after the final visit of the last subject. The study will be completed at the end of the final visit of the final subject in stage 4. Interim analysis will be performed after each volunteer has completed three visits in stage 1a and after 10 subjects have completed stage 2, if the data is adequate for the pharmacokinetic modelling required stage 2 will be prematurely discontinued. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |