Vaginal Prednisone Administration for Prevention of Adrenal Crisis

NCT02689960 | Completed Phase 2 DMC

• 1 other identifier: Vapreda
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Adrenal Insufficiency

Keywords

addison disease; adrenal crisis; prednisone

Outcome Measures

Primary Outcomes (1)

• Bioequivalence of vaginal prednisone administration compared to rectal application, assessed by repeated determination of prednisolon levels (in blood)

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

  up to 12 months

Secondary Outcomes (3)

• 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).

  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

  up to 1 week

• Tolerability by the patients assessed by a questionnaire

  up to 1 month

Study Arms (2)

vaginal administration first

OTHER

Intervention first visit: vaginal administration of 100mg prednisone suppository, Intervention second visit: rectal administration of 100mg prednisone suppository

Drug: 100mg prednisone suppository

rectal administration first

OTHER

Intervention first visit: rectal administration of 100mg prednisone suppository, Intervention second visit: vaginal administration 100mg prednisone suppository

Drug: 100mg prednisone suppository

Interventions

100mg prednisone suppository DRUG

vaginal administration of 100mg prednisone suppository (Rectodelt)

Also known as: Rectodelt (approval number 6329964.00.00)

rectal administration first; vaginal administration first

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients with chronic primary adrenal insufficiency due to autoimmune adrenalitis or bilateral adrenalectomy (disease duration at least 6 months)
• Age ≥ 18 years
• Patient´s written informed consent
• Ability to comply with the protocol procedures
• Established stable replacement therapy, no anticipated change in medication
• Negative pregnancy test and contraception (besides oral contraceptive pill) in pre-menopausal females

You may not qualify if:

• Diabetes mellitus
• Infectious disease with fever at time of investigation
• Known intolerance to the study drug or constituents
• Oral contraception
• Pregnancy or breast feeding
• Renal failure (creatinine \>2.5 ULN)
• Disposition to vaginal mycosis (requiring treatment in the last 6 months or of necessity \>2 antimycotic therapies/year)
• Recurrent urinary tract infections (of necessity \>2 antibiosis therapies/year)

Sponsors & Collaborators

• Wuerzburg University Hospital: lead

Related Publications (7)

• Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.

  PMID: 25419882 BACKGROUND

• Hahner S, Hemmelmann N, Quinkler M, Beuschlein F, Spinnler C, Allolio B. Timelines in the management of adrenal crisis - targets, limits and reality. Clin Endocrinol (Oxf). 2015 Apr;82(4):497-502. doi: 10.1111/cen.12609. Epub 2014 Nov 6.

  PMID: 25200922 BACKGROUND

• Hahner S, Loeffler M, Bleicken B, Drechsler C, Milovanovic D, Fassnacht M, Ventz M, Quinkler M, Allolio B. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010 Mar;162(3):597-602. doi: 10.1530/EJE-09-0884. Epub 2009 Dec 2.

  PMID: 19955259 BACKGROUND

• Hahner S, Burger-Stritt S, Allolio B. Subcutaneous hydrocortisone administration for emergency use in adrenal insufficiency. Eur J Endocrinol. 2013 Jun 29;169(2):147-54. doi: 10.1530/EJE-12-1057. Print 2013 Aug.

  PMID: 23672956 BACKGROUND

• Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015 Mar;172(3):R115-24. doi: 10.1530/EJE-14-0824. Epub 2014 Oct 6.

  PMID: 25288693 BACKGROUND

• Smans LC, Van der Valk ES, Hermus AR, Zelissen PM. Incidence of adrenal crisis in patients with adrenal insufficiency. Clin Endocrinol (Oxf). 2016 Jan;84(1):17-22. doi: 10.1111/cen.12865. Epub 2015 Aug 27.

  PMID: 26208266 BACKGROUND

• Anderson M, Kutzner S, Kaufman RH. Treatment of vulvovaginal lichen planus with vaginal hydrocortisone suppositories. Obstet Gynecol. 2002 Aug;100(2):359-62. doi: 10.1016/s0029-7844(02)02117-8.

  PMID: 12151163 BACKGROUND

MeSH Terms

Conditions

Adrenal Insufficiency; Addison Disease

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Stefanie Hahner, MD, Prof.

  University Hospital Wuerzburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2016
• First Posted: February 24, 2016
• Study Start: January 1, 2017
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 20, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share