A Study to Examine the Safety and Efficacy of Drospirenone and Ethinyl Estradiol (YAZ) Versus Placebo In HS

Hidradenitis Suppurativa Clinical Trial

Official title:

A Single-Center, Randomized Double-Blind, Parallel-Group Study to Examine the Safety and Efficacy of YAZ Compared With Placebo In The Treatment Of Hidradenitis Suppurativa

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00722800
• Other study ID #: 20080p-000843
• Status: Terminated
• Phase: Phase 2
• First received: July 24, 2008
• Last updated: January 16, 2014
• Start date: October 2008
• Est. completion date: December 2011

Study information

• Verified date: January 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out if taking a birth control pill, YAZ, is safe and effective for treating hidradenitis suppurativa. Hidradenitis suppurativa (HS) is a chronic (long lasting) skin disorder that mostly affects the armpits and groin area. It appears as blackheads and one or more red, tender bumps that may enlarge, break open, and drain pus. Scarring may result after several attacks of the disease.

The exact cause of HS isn't known. However, it is believed that the plugging of hair follicles and bacterial infection that occur in acne also occur in HS. Many of the medications used for treating acne are also used for HS. However, none of the medications are consistently effective.

YAZ is a combination birth control pill. Nearly all birth control pills are made up of a combination of estrogen and progestin hormones. YAZ contains ethinyl estradiol (an estrogen) and drospirenone (a progestin). People who develop acne have sebaceous glands that are over-stimulated by male sex hormones (androgens). Sebaceous glands secrete an oily substance into a hair follicle to lubricate hair or skin. The progestin in YAZ actually blocks the male sex hormones (androgens) that cause acne. Hormones seem to play a role in HS as the condition occurs after puberty. It affects more women than men and HS often gets worse around the time a women has her menstrual period.

YAZ has been approved by the U.S. Food and Drug Administration (FDA) to treat moderate acne in women who desire an oral contraceptive for birth control.

This study uses a placebo. A placebo looks like the study drug but contains no active drug. We use placebos in research studies to learn if the effects seen in research subjects are truly from the study drug or from other reasons.

Description:

Hidradenitis suppurativa is a chronic suppurative and scarring disease primarily affecting the axillae and inguinal and perineal areas. The apocrine glands are the primary targets. It is characterized by firm, tender red nodules that soon become fluctuant and painful. Rupture of the lesion, suppuration, formation of sinus tracts and scarring may occur.

The exact etiology of HS remains obscure. Proposed etiologic factors include follicular occlusion and bacterial infection, genetics, host defense defects, hormones, cigarette smoking, and irritants. Hormones seem to play a role, as the condition occurs after puberty, affects more women than men, and often flares in the perimenstrual period.

Treating hidradenitis remains a challenge. Although many patients benefit from long-term treatment with systemic antibiotics (eg, tetracycline, minocycline, clindamycin, erythromycin in combination with metronidazole), no published evidence suggests that the long-term use of antibiotics alters the natural course of HS. Oral isotretinoin has been used, but is effective only in some cases. Some patients have had a beneficial response to biological agents, especially anti-TNF alpha biologicals such as infliximab. Oral contraceptives containing norgestrel or cyproterone acetate, alone or in combination with supplemental cyproterone acetate, spironolactone or dexamethasone (to block adrenal androgen production), have been shown to reduce the frequency and severity of attacks in women.

YAZ is an oral contraceptive that is FDA approved for acne vulgaris. Unlike other progestins, drospirenone has unique antimineralocorticoid (mild diuretic effect) and antiandrogenic properties. The antiandrogenic property of drospirenone means that it blocks the male sex hormones that can cause acne. It is hoped that that YAZ will offer patients with hidradenitis suppurativa a safe and effective therapeutic option.

Subjects will be assigned to a treatment group upon randomization. Bayer HealthCare Pharmaceuticals personnel, investigators, subjects and study nurse/coordinators will be blinded to the study product treatment assignment. The study duration will be 24 weeks with visits at screening, baseline (week 0), week 6, week 12, week 18, and week 24. Lesion counts (total, inflammatory, non-inflammatory) and an ISGA, and photography will be performed on every visit. A physical examination will be done at baseline and Week 24. Safety will be assessed from reported adverse events (AEs).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 45 Years

Eligibility

INCLUSION CRITERIA

1. Female Subjects 14-45 years of age who have achieved spontaneous menarche.

2. Clinical diagnosis of hidradenitis suppurativa of stage II or greater on the Hurley scale.

3. Willing and able to understand and sign informed consent.

4. Able to complete study and comply with study procedures.

EXCLUSION CRITERIA

1. Change is use of oral or topical antibiotics in past 90 days.

2. Use of intralesional steroids within 30 days.

3. Use of isotretinoin in past six months.

4. Use of biologics such as Infliximab (Remicade®) or Etanercept (Enbrel®) within the past 3 months or 5 half lives (whichever is shorter).

5. History of renal insufficiency

6. History of hepatic dysfunction

7. History of adrenal Insufficiency

8. History of vascular or metabolic disease including existing or previous arterial thromboembolic diseases (myocardial infarction, stroke), existing or previous venous thromboembolic diseases (deep vein thrombosis, pulmonary embolism), and any condition which could increase the risk to suffer any of the above mentioned disorders

9. History of hypertension

10. History of Diabetes mellitus with vascular involvement

11. Migraine headaches with focal neurological symptoms

12. Major surgery with prolonged immobilization

13. Known or suspected carcinoma of the breast

14. History of Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia

15. Undiagnosed abnormal genital bleeding

16. Cholestatic jaundice of pregnancy or jaundice with prior pill use

17. History of Liver tumor (benign or malignant) or active liver disease

18. Smokers

19. Regular intake of medications that may increase potassium levels such as NSAIDS, potassium sparing diuretics, potassium supplementation, ACE inhibitors, Angiotensin-II receptor antagonists, heparin and aldosterone antagonists.

20. Hypersensitivity to any component of the study drug

21. Clinically significant abnormal findings or conditions (other than acne), which might, in the opinion of the Principal Investigator, interfere with study evaluations or pose a risk to subject safety during the study.

22. Subjects who are known to be pregnant or planning a pregnancy.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hidradenitis
• Hidradenitis Suppurativa

Intervention

Drug:
• drospirenone and ethinyl estradiol (YAZ)
1 tablet daily for 24 weeks
• Placebo
1 tablet daily for 24 weeks

Locations

Country	Name	City	State
United States	Clinical Unit for Research Trials in Skin	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Improvement in the Sartorius Severity Score at Month 6.	The Sartorius Severity score reflects changes in hidradenitis suppurative symptoms, namely the number of lesions (abscesses, nodules, and fistulas) and the longest distance between lesions. A total score is derived based on assessments at up to 8 distinct anatomical regions and ranges from 5 to indefinite. Smaller numbers are better scores and indicate less lesion involvement, thus decreases (negative changes) from baseline indicate improvement in severity of disease.	6 months	No
Secondary	Change From Baseline in VAS Pain Scale at Month 6.	For this pain assessment, the participant indicated the level of average pain experienced over the past 24 hours on a horizontal line, 10 cm in length. A score of 0 indicated "no pain" and a score of 10 indicated "worst pain". The value indicates the change from the baseline participant assessment on the 0 to 10 scale. A negative value indicates a reduction in pain intensity.	6 months from Baseline	No
Secondary	Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Month 6.	Dermatology Life Quality Index (DLQI) Score is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which the participant's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. The DLQI score ranges from 0 (best) to 30 (worst).	6 months	No

External Links

•   Study sponsor's website