Once-daily Oral Modified Release Hydrocortisone in Patients With Adrenal Insufficiency

Shire

Status and phase: Completed; Phase 3; Phase 2

Conditions: Adrenal Insufficiency

Treatments: Drug: Hydrocortisone, oral tablet, 10 mg; Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00915343

2006-007084-89 (EudraCT Number)

DC 06/02

104-07

Details and patient eligibility

About

This is a randomised, controlled, open, two-armed, two-period cross-over, multi-centre phase II/III study to assess the safety, tolerability and pharmacokinetics of once-daily oral modified-release hydrocortisone in comparison to conventional thrice-daily oral hydrocortisone tablets in patients with adrenal insufficiency

Full description

Adrenal insufficiency is a disease with more than 80% 1-year mortality before the availability of synthetic glucocorticoids. Current replacement therapy has improved this dramatically, but recent data suggest that outcome is still compromised. Patient receiving replacement therapy with hydrocortisone or cortisone acetate have compromised quality of life, reduced bone mass, increased risk factors for cardiovascular disease and premature mortality that is more than twice the mortality rate in the background population.

Circulating cortisol levels follow a distinct diurnal pattern with high levels in the early morning and low trough values around midnight. Using available formulations for replacement therapy this circadian rhythm is had to mimic and also during the active time of the day high peaks and low troughs occur.

In this trial a newly developed novel dual-, controlled release formulation of hydrocortisone that has in healthy volunteers been able to mimic the circadian pattern of circulating cortisol was studied in patients with primary adrenal insufficiency (Addison's disease).

Enrollment: 64 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Previously diagnosed (e.g. more than 6 months ago) primary adrenal insufficiency with a stable daily glucocorticoid substitution dose for at least 3 months prior to study entry
• Signed informed consent to participate in the study.

Exclusion criteria

• Clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, Hepatobiliary, pancreatic disease
• Clinically significant renal dysfunction
• Clinical or laboratory signs of significant gastrointestinal emptying or motility disease
• Any medication with agents which could interfere with hydrocortisone kinetics
• Pregnant or lactating women
• Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
• Oral oestrogen medication for the past 4 weeks
• Deranged mineralocorticoid status

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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64 participants in 2 patient groups

Novel once daily modified release

Experimental group

Description:

Test drug: hydrocortisone (modified release), oral tablet, available as 20 mg and 5 mg. The modified release hydrocortisone tablet was administered orally o.d. at 8 AM in the fasting state

Treatment:

Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg

Conventional TID hydrocortisone

Active Comparator group

Description:

Reference drug: hydrocortisone, oral tablet, 10 mg. The reference drug was administered orally thrice daily (at 8 AM, 12 AM and 4 PM)in the same total daily dose as the experimental drug. The morning dose was administered in the fasting state.

Treatment:

Drug: Hydrocortisone, oral tablet, 10 mg