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Once-daily Oral Modified Release Hydrocortisone in Patients With Adrenal Insufficiency (DC 06/02)

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT00915343
First received: June 5, 2009
Last updated: March 19, 2014
Last verified: March 2014

June 5, 2009
March 19, 2014
August 2007
July 2008   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00915343 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Once-daily Oral Modified Release Hydrocortisone in Patients With Adrenal Insufficiency
A, Randomised, Controlled, Two-armed, Two-period Cross-over, Multi-centre Phase II/III Study to Assess the Safety and Pharmacokinetics of Once-daily Oral Modified-release Hydrocortisone in Patients With Adrenal Insufficiency

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

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).

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Adrenal Insufficiency
  • 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
  • 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.
  • 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

    Intervention: Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg
  • 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.
    Intervention: Drug: Hydrocortisone, oral tablet, 10 mg

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
64
January 2009
July 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00915343
EudraCT: 2006-0007084-89, 104-07
No
Maria Forss, DuoCort AB
Shire
Not Provided
Study Director: Maria Forss, MSc BA DuoCort AB
Principal Investigator: Anna G Nilsson, MD, PhD Sahlgrenska Academy, Gothenburg University
Shire
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP