DUS on the Prescribing Indications for CPA/EE in 5 European Countries

• Sponsor: Center for Epidemiology and Health Research, Germany (Other)
• Overall Status: Completed
• CT.gov ID: NCT02494297
• Collaborator: Bayer (Industry)
• Enrollment: 1,597
• Location: 1
• Actual Duration (Months): 19.9
• Patients Per Site Per Month: 80.3

Study Details

Study Description

Brief Summary

This study was designed to compile the reasons and specific indications for the prescription of Cyproterone Acetate combined with Ethinyl Estradiol by Health Care Providers. The primary objective of the study was to characterize the prescribing behaviors for Cyproterone Acetate combined with Ethinyl Estradiol in 5 European countries (Austria, Czech Republic, France, the

Netherlands, and Spain), including:

• prescription indications for Cyproterone Acetate combined with Ethinyl Estradiol

• use of Cyproterone Acetate combined with Ethinyl Estradiol in accordance with the updated label

• concomitant use of Cyproterone Acetate combined with Ethinyl Estradiol and combined hormonal contraceptives

• second line treatment with Cyproterone Acetate combined with Ethinyl Estradiol for the indication acne

Condition or Disease	Intervention/Treatment	Phase
Hirsutism; Androgenetic Alopecia; Severe Anemia; Seborrhea; PCOS

Detailed Description

Cyproterone acetate (CPA) 2mg, in combination with ethinyl estradiol (EE) 35mcg, is a medicinal product currently indicated for the treatment of moderate to severe acne in women of reproductive age. Due to the combination with ethinyl estradiol and the dosing, the preparations also act as effective contraceptives.

In 2012, the French health authority conducted a national review of Cyproterone Acetate combined with Ethinyl Estradiol and highlighted serious thromboembolic events and extensive off-label use of these medicines as a contraceptive only. This triggered an Urgent Union Procedure at the beginning of 2013. The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) concluded that the benefits of Cyproterone Acetate combined with Ethinyl Estradiol (cyproterone acetate 2mg / ethinyl estradiol 35mcg) outweigh the risks, providing that several measures are taken to minimize the risk of thromboembolism. These medicines should be used solely for the treatment of moderate to severe acne related to androgen sensitivity and/or hirsutism in women of reproductive age. Since Cyproterone Acetate combined with Ethinyl Estradiol acts as a hormonal contraceptive, women should not take these medicines in combination with hormonal contraceptives. As one of the risk minimization measures, the Market Authorization Holders were required to conduct a number of studies including this drug utilization survey.

This study was a multi-national, cross sectional, prospective, non-interventional, drug utilization study conducted in 5 countries. Study participants were recruited by a network of health care professionals. Physicians collected information from study participants based on questionnaires. This was a one-time survey with no follow-up.

Bayer initiated this study and supported it by an unconditional grant to ZEG. Bayer was not actively involved in the study conduct.

Prolongation of recruitment:

At the beginning of May 2016 the recruitment was finished in 4 of the 5 European countries in which the study was conducted (Austria, Czech Republic, The Netherlands, and Spain). At that point in time, only few patients were enrolled in France because of a delayed recruitment start. Therefore, it was agreed to extend the recruitment phase in France until 31st October 2016, in order to ensure that information on the use of Cyproterone Acetate (combined with Ethinyl Estradiol) would be collected from all participating countries.

Study Design

• Study Type: Observational
• Actual Enrollment: 1597 participants
• Observational Model: Other
• Time Perspective: Cross-Sectional
• Official Title: Drug Utilization Study on the Prescribing Indications for Cyproterone Acetate and Ethinyl Estradiol in 5 European Countries
• Actual Study Start Date: Mar 6, 2015
• Actual Primary Completion Date: Oct 31, 2016
• Actual Study Completion Date: Oct 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Cyproterone Acetate and Ethinyl Estradiol Users of Diane 35 (EE/CPA, BAY86-5264)

Outcome Measures

Primary Outcome Measures

1. Drug Utilization Pattern of Cyproterone Acetate and Ethinyl Estradiol [within 18 months]

   Information was obtained from doctors prescribing CPA/EE. Categories in the Outcom Measure Data Table below are based on current disease status.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women who are prescribed Cyproterone Acetate combined with Ethinyl Estradiol during the study period

• Women who are willing to participate in the drug utilization study

Exclusion Criteria:

• Women who are not willing to sign the informed consent

• Women with a language barrier

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center of Epidemiology and Health Research	Berlin		Germany	10115

Sponsors and Collaborators

• Center for Epidemiology and Health Research, Germany
• Bayer

Investigators

• Principal Investigator: Klaas Heinemann, PhD, MD, MSc, MBA, Center for Epidemiology and Health Research Berlin

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Study Synopsis from Bayer AG

Publications

None provided.

• Responsible Party: Center for Epidemiology and Health Research, Germany
• ClinicalTrials.gov Identifier: NCT02494297
• Other Study ID Numbers: ZEG2014_04
• First Posted: Jul 10, 2015
• Last Update Posted: Aug 27, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Alopecia; Hirsutism

Study Results

Participant Flow

Recruitment Details	Recruitment from March-2015 to 11-May-2016 in Austria, Czech Republic, The Netherlands and Spain; recruitment in France from January-2016 to 31-October-2016, due to late start. Recruitment was conducted by gynecologists, dermatologists and general practitioners.

Arm/Group Title	Cyproterone Acetate and Ethinyl Estradiol
Arm/Group Description	Users of Diane 35 (EE/CPA, BAY86-5264), uncontrolled, single armed drug utilization study
Period Title: Overall Study
STARTED	1597
COMPLETED	1597
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cyproterone Acetate and Ethinyl Estradiol
Arm/Group Description	Users of Diane 35 (EE/CPA, BAY86-5264), uncontrolled, single armed drug utilization study
Overall Participants	1597
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.0 (7.92)
Age, Customized (Count of Participants)
<18 years	200 12.5%
18-24 years	647 40.5%
25-34 years	533 33.4%
35-49 years	203 12.7%
>=50 years	14 0.9%
Sex: Female, Male (Count of Participants)
Female	1597 100%
Male	0 0%
Region of Enrollment (participants) [Number]
Austria	282 17.7%
Czech Republic	563 35.3%
France	108 6.8%
Netherlands	32 2%
Spain	612 38.3%

Outcome Measures

1. Primary Outcome

Title	Drug Utilization Pattern of Cyproterone Acetate and Ethinyl Estradiol
Description	Information was obtained from doctors prescribing CPA/EE. Categories in the Outcom Measure Data Table below are based on current disease status.
Time Frame	within 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyproterone Acetate and Ethinyl Estradiol
Arm/Group Description	Users of Diane 35 (EE/CPA, BAY86-5264), uncontrolled, single armed drug utilization study
Measure Participants	1597
Moderate or severe acne (without hirsutism)	594 37.2%
Acne with hirsutism	128 8%
Hirsutism without acne	106 6.6%
Other androgenic diseases and contraception	769 48.2%

Adverse Events

Time Frame	Adverse events were not monitored in this study, which was a non-interventional observational cross sectional study on drug utilization patterns that exclusively obtained information at the time point of prescription. There were no questions that could generate adverse events (AEs) and no follow-up questionnaires.
Adverse Event Reporting Description	Since this was a drug utilization study, exclusively obtaining information at the time of prescription, no adverse events were reported.
Arm/Group Title	Cyproterone Acetate and Ethinyl Estradiol
Arm/Group Description	Users of Diane 35 (EE/CPA, BAY86-5264), uncontrolled, single armed drug utilization study
All Cause Mortality
	Cyproterone Acetate and Ethinyl Estradiol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cyproterone Acetate and Ethinyl Estradiol
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Cyproterone Acetate and Ethinyl Estradiol
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

The data cannot indicate a difference in prescribing habits between participating and non-participating physicians. The information about previous treatments of acne is likely to be incomplete because of recall bias.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.