Once-Daily Oral Modified-Release Hydrocortisone in Patients With Adrenal Insufficiency (DC 06/02)
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
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Adrenal Insufficiency |
Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg Drug: Hydrocortisone, oral tablet, 10 mg |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- To compare bioavailability between a once-daily modified release hydrocortisone oral tablet and a conventional thrice-daily replacement therapy in patients with chronic primary adrenal insufficiency. [ Time Frame: At randomisation, 1 week and 12 weeks ] [ Designated as safety issue: Yes ]
- To compare safety, tolerability and efficacy of the novel modified release formulation to the conventional thrice-daily replacement therapy. [ Time Frame: At randomisation, 4, 8 and 12 weeks ] [ Designated as safety issue: Yes ]
- To assess the safety of using the novel modified release formulation as "rescue therapy" during minor intercurrent illnesses in patients with primary adrenal insufficiency. [ Time Frame: At randomisation, 1, 4, 8 and 12 weeks ] [ Designated as safety issue: Yes ]
- To assess long-term safety, tolerability and efficacy of the novel modified release formulation during glucocorticoid replacement therapy. [ Time Frame: At randomisation and 12 weeks ] [ Designated as safety issue: Yes ]
| Enrollment: | 64 |
| Study Start Date: | August 2007 |
| Study Completion Date: | January 2009 |
| Primary Completion Date: | July 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
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Experimental: Novel once daily modified release
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 |
Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg
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
Other Name: DuoCort
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Active Comparator: Conventional TID hydrocortisone
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.
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Drug: Hydrocortisone, oral tablet, 10 mg
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.
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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).
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations More Information
Publications:
| Responsible Party: | Maria Forss, DuoCort AB |
| ClinicalTrials.gov Identifier: | NCT00915343 History of Changes |
| Other Study ID Numbers: | EudraCT: 2006-0007084-89, 104-07 |
| Study First Received: | June 5, 2009 |
| Last Updated: | June 5, 2009 |
| Health Authority: | Europe: European Medicines Agency (EMEA) |
Keywords provided by DuoCort AB:
|
Adrenal insufficiency Primary adrenal insufficiency Addison's disease Hydrocortisone Modified release |
Additional relevant MeSH terms:
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Addison Disease Adrenal Insufficiency Adrenal Gland Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Cortisol succinate Hydrocortisone acetate |
Hydrocortisone 17-butyrate 21-propionate Hydrocortisone Hydrocortisone-17-butyrate Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Dermatologic Agents |
ClinicalTrials.gov processed this record on June 17, 2013