Conditions: Adrenal Insufficiency
Keywords: Adrenal insufficiency Primary adrenal insufficiency Addison's disease Hydrocortisone Modified release
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 64
Healthy volunteers: no

Brief summary:
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

Detailed 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).

Arms:
arm 1: 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 arm 2: 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.

Interventions: intervention 1: hydrocortisone (modified release), oral tablet 20 and 5 mg intervention 2: Hydrocortisone, oral tablet, 10 mg
Intervention descriptions: intervention 1: The modified release hydrocortisone tablet was administered orally o.d. at 8 AM in the fasting state. The dose was the same as patients have had before entering the trial intervention 2: The reference drug was administered orally thrice daily (at 8 AM, 12 AM and 4 PM). The morning dose was administered in the fasting state. The total daily dose was the same as in the experimental treatment arm.

Protocol document: