|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Body processes [G] - Metabolic Phenomena [G03]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10014698 - Endocrine disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess whether IM Hydrocortisone Injection site using deltoid muscle is equally effective to thigh muscle during the state of hypocortisolaemia in patients with cortisol deficiency assessed by serum cortisol profiles
|Secondary objectives of the trial
|To investigate any differences in pain perception using differences sizes of needles, muscle groups (deltoid versus thigh) and hydrocortisone preparations (Solu-Cortef vesus Hydrocortisone 100mg/ml)
To understand if circumference of injections site and patient's BMI affect hydrocortisone absorption
To assess following nurse education on hydrocortisone self-injection whether the patient is able to self-inject during their state of hypocortisolaemia
To assess if the number of taught self-injections has an impact of patient's quality of life.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Age 18-70 inclusive
2. Written informed consent obtained prior to any study related assessments/procedure being conducted.
3. Men & Women with a BMI between 18-30kg/m2
4. Addison’s disease or Bilateral Adrenalectomised patients with pre hydrocortisone cortisol level below 100nmol/L and ACTH greater than 50ng/L on screening visit
5. All patients must be stabilised on hydrocortisone with no change in dosage for 6 months, other than transient increases for concurrent illness.
6. Able to self-inject into deltoid and thigh muscles following teaching at recruitment.
7. Female patients of child-bearing potential must be willing to use an acceptable method of birth control/abstinence from the time consent is signed until 6 weeks after treatment is discontinued. Acceptable methods include: physical barrier (male or female condom, contraceptive sponges, diaphragms and cervical caps), contraceptive pill or patch, spermicidal method alongside a physical barrier or an intrauterine device (IUD). Abstinence is also acceptable if it falls in line with the patients’ usual lifestyle however it must be complete abstinence and not either; periodic, ovulation timed, symptothermal or withdrawal based. Those patients that utilise hormonal contraceptives must have used the same method for at least three months before additional barrier contraception (as described above). Patients of non-child-bearing potential are defined as having 12 month amenorrhoea or are surgically sterile.
|Principal exclusion criteria
|1. Patient on oestrogen based or mixed oral contraceptives unless willing to use alternate effective method of contraception
2. Patient on any forms of oral steroids other than hydrocortisone.
3. Any patient with secondary adrenal failure
4. Patients with a diagnosis of any disease or condition listed in Hydrocortisone 100mg/ml and Solu-Cortef®’s as being contraindicated or precautionary for use
5. Patient with concurrent illness in the week preceding screening/study visit.
6. Patients must not have had an adrenal crisis in the week before screening
7. Patient with Nelson’s syndrome.
8. Participating in another IMP investigation
9. Patient taking any medications/substances that are known to interact with hydrocortisone e.g. CYP3A4 inhibitors
10. Patient is unable or unwilling to comply with the protocol.
11. Pregnant or breastfeeding patients
12. Patient has any other disease or condition that, in the opinion of the investigator, might compromise patient safety or interfere with the results of the trial
|E.5 End points
|Primary end point(s)
|Peak serum cortisol, mean cortisol, time to peak and serum cortisol area under curve following deltoid and thigh muscle injections of hydrocortisone (Hydrocortisone 100mg/ml versus Solu-Cortef®).
|Timepoint(s) of evaluation of this end point
|0.5hour, 1 hour, 2 hours, 6 hours and 8 hours
|Secondary end point(s)
|Injection site circumference to cortisol area under curve and time to peak
BMI to cortisol area under curve and time to peak
Leftover of hydorcortisone in ampoultes to serum cortisol area under curve and time to peak
Overall pain scores for both preparations and each of those
Size of needles to pain scores
Injection sites circumference to pain scores
Hypocortisolaemia symptoms and ability to self-inject
Hydrocortisone preparations and ability to self-inject
AddiQoL scores and ability to self-inject
|Timepoint(s) of evaluation of this end point
|Injection site measurement will be taken immediately after the injection
BMI will be collected on screening visit.
Leftover of hydrocortisone in ampoules will be measured after patient has administered the injection.
Pain score will be collected immediately after the injection then at 1 hour, 8 hours and 72 hours post injection.
Symptoms for hypocortisolaemia will be collected before hydrocortisone injection then at 6 hours
The name of the hydrocortisone will be recorded after each injection.
AddiQoL score will complete AddiQoL at baseline visit and at the end of the study or when they decided to terminate from the study
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Comparing effectiveness of two marketed drugs
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days