Clinical Trial: Vaginal Prednisone Administration for Prevention of Adrenal Crisis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Vaginal Prednisone Administration for Prevention of Adrenal Crisis - a Bioequivalence Study

Brief Summary: Patients with chronic adrenal insufficiency need to adapt their glucocorticoid replacement dose in conditions of physical or psychological stress to prevent life threatening adrenal crisis. In cases of more severe impairment or unsecure gastrointestinal absorption (e.g. gastroenteritis, severe infectious disease), rapid and highly dosed administration of glucocorticoids is crucial. The study is conducted to offer female patients the possibility to perform efficient prednisone self-administration in emergency situations in a way of administration, which is easy to perform and accepted by the patients. Therefore, pharmacokinetics and safety of vaginal prednisone administration will be studied and compared to rectal administration.

Detailed Summary:

As patients with adrenal insufficiency still die from adrenal crisis, improvement of both prevention and also emergency management is needed. It is clear that perfect equipment and education of patients is key for further crisis prevention and management. Vaginal administration of prednisone-suppositories is easy to perform and independent of the gastro-intestinal system. Thus, this study aims at the efficacy, feasibility and safety of vaginal administration of prednisone-suppositories.

Recruitment:

Patients with primary adrenal insufficiency will be recruited. The adrenal insufficiency registry of Würzburg comprises more than 150 patients with primary adrenal insufficiency. Several patients have already indicated their interest to participate in the study. According to the European Medicines Agency (EMA) notes for guidance on the investigation of bioavailability and bioequivalence the number of 12 participants is regarded as the minimum required number.

Trial flow:

Pharmacokinetic studies will be performed at two different study visits. Patients will receive a 100mg prednisone suppository (Rectodelt® 100 mg) vaginal and rectal on two different study visits (interval longer then one week). Blood samples for determination of prednisone and adrenocorticotropic Hormone (ACTH) levels will be collected over a time period of 6 hours. Patients receive a diary to document eventual local or systemic adverse events during the following 7 days.

Stopping rules:

Participation of patients is fully voluntarily. Patients are able to stop participation in the study at any point in time. In addition, patients might claim the eliminati
Sponsor: Wuerzburg University Hospital

Current Primary Outcome: Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood) [ Time Frame: up to 12 months ]

The hypothesis is that the same prednisolone levels can be achieved within the same time frame after vaginale administration compared to rectal application.


Original Primary Outcome: Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood) over a time frame of six hours [ Time Frame: up to 16 months ]

The hypothesis is that the same prednisolone levels can be achieved within the same time frame after vaginale administration compared to rectal application.


Current Secondary Outcome:

  • Safety of the vaginal administration of prednisone compared to rectal application, assessed by the number of participants with treatment-related adverse events (using the NCI-CTC, version 4.0). [ Time Frame: up to 12 months ]
  • Suppressive effects on ACTH levels after vaginal administration of prednisone compared to rectal application, assessed by repeated determination of ACTH-levels [ Time Frame: up to 1 week ]
    ACTH-levels are measured in plasma
  • Tolerability by the patients assessed by a questionnaire [ Time Frame: up to 1 month ]
    Questions record the preference of the patients between vaginal and rectal application.


Original Secondary Outcome:

  • Safety of the vaginal administration of prednisone compared to rectal application, assessed by the number of participants with treatment-related adverse events (using the NCI-CTC, version 4.0). [ Time Frame: up to 16 months ]
  • Suppressive effects on ACTH levels after vaginal administration of prednisone compared to rectal application, assessed by repeated determination of ACTH-levels over a time frame of six hours [ Time Frame: up to 16 months ]
    ACTH-levels are measured in plasma
  • Tolerability by the patients assessed by a questionnaire [ Time Frame: up to 16 months ]
    Questions record the preference of the patients between vaginal and rectal application.


Information By: Wuerzburg University Hospital

Dates:
Date Received: February 8, 2016
Date Started: April 2016
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017