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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
  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
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, 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
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
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.
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.

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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00915343

Sponsors and Collaborators
Shire
Investigators
Study Director: Maria Forss, MSc BA DuoCort AB
Principal Investigator: Anna G Nilsson, MD, PhD Sahlgrenska Academy, Gothenburg University
  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: March 19, 2014
Health Authority: Europe: European Medicines Agency (EMEA)

Keywords provided by Shire:
Adrenal insufficiency
Primary adrenal insufficiency
Addison's disease
Hydrocortisone
Modified release

Additional relevant MeSH terms:
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on October 19, 2014