The Effects of Two Brands of Hydrocortisone Injected Intramuscularly Into Deltoid and Thigh Muscles

An Open Label Pilot Study to Investigate the Effects of Two Preparations of Hydrocortisone (Hydrocortisone 100mg/ml and Solu-Cortef) Injected Intramuscularly Into the Deltoid and Upper Thigh Muscle During the State of Hypocortisolaemia

The study will be looking at the cortisol profiles of hypocortisolaemic patients following 100mg injections of two hydrocortisone preparations (Solu-Cortef® & Hydrocortisone 100mg/ml). The investigators plan to use two methods of intramuscular injection to administer the preparations, one using a 1inch orange needle into the deltoid muscle and the other using a 1.25inch blue needle into the thigh muscle.

Study Overview

• Status: Recruiting
• Conditions: Addison's Disease
• Intervention / Treatment: Drug: Solu-Cortef 100 MG Injection; Drug: Hydrocortisone 100mg/ml

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Christine Topham; Phone Number: 0203 219 3570; Email: clinicalresearch@thelondonclinic.co.uk
• Study Contact Backup: Name: Phillip Yeoh; Phone Number: 0207 953 4444

Study Locations

• United Kingdom
  • London, United Kingdom, W1G 6HL
    • Recruiting
    • The London Clinic
    • Contact: Phillip Yeoh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 inclusive
2. Written informed consent provided, 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 patient's 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.

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 SmPC as being contraindicated or precautionary for use
5. Patient with concurrent illness in the week preceding screening/study visit.
6. Patient 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 who is unable or unwilling to comply with the protocol.
10. Patient taking any medications/substances that are known to interact with hydrocortisone e.g. CYP3A4 inhibitors
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Solu-Cortef® in deltoid muscle	Drug: Solu-Cortef 100 MG Injection; Licensed medicine used in clinical practice. Preparations will be used unmodified in this trial withinmarketing authorisations.
Experimental: Solu-Cortef® in thigh muscle	Drug: Solu-Cortef 100 MG Injection; Licensed medicine used in clinical practice. Preparations will be used unmodified in this trial withinmarketing authorisations.
Experimental: Hydrocortisone 100mg/ml in deltoid muscle	Drug: Hydrocortisone 100mg/ml; Licensed medicine used in clinical practice. Preparations will be used unmodified in this trial within marketing authorisations.
Experimental: Hydrocortisone 100mg/ml in thigh muscle	Drug: Hydrocortisone 100mg/ml; Licensed medicine used in clinical practice. Preparations will be used unmodified in this trial within marketing authorisations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
State of Hypocortisolaemia when injected into deltoid muscle or thigh muscle	Measure of Peak Serum Cortisol	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain perception following use of difference sizes of needles (1inch orange needle versus 1.25inch blue needle), muscle groups (deltoid versus thigh) and hydrocortisone preparations (Solu-Cortef® versus Hydrocortisone 100mg/ml)	Verbal Numerical Rating Scale for Pain from 0 (no pain) to 10 (worst pain) Size of needle Injection site used Hydrocortisone preparation	4 Weeks
Hydrocortisone absorption	Measured by Injection site circumference measured in Centimeters and BMI (weight in kilograms, height in meters) BMI combined to view Area under curve and Time to peak concentration	4 Weeks
Ability to Self-Inject	Measure by assessment of the following: Hypocortisolaemia symptoms Leftover IMP in ampoules (Quanitity of IMP measure in ml to calculate remaining mg of IMP) Time taken to inject	4 Weeks
Subjective health status/impact on quality of life	AddiQol score (AddiQol Health-related quality of life in Addison's disease) total score 30 Ability to self-inject	5 Weeks

Collaborators and Investigators

• Sponsor: The London Clinic
• Investigators: Principal Investigator: Pierre Bouloux, Endocrinology Consultant

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency; Addison Disease; Anti-Inflammatory Agents; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: ATC 017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No