Prospective controlled cohort study on the safety of a monophasic oral contraceptive containing nomegestrol acetate (2.5mg) and 17ß-estradiol (1.5mg) (PRO-E2)

Study identification

• EU PAS number:
  EUPAS2196
• Study ID:
  41500
• Official title and acronym:
  Prospective controlled cohort study on the safety of a monophasic oral contraceptive containing nomegestrol acetate (2.5mg) and 17ß-estradiol (1.5mg) (PRO-E2)
• DARWIN EU® study:
  No
• Study countries:
  Australia

  Austria

  Colombia

  France

  Germany

  Hungary

  Italy

  Mexico

  Poland

  Russian Federation

  Spain

  Sweden
• Study description:
  NOMAC-E2 (‘Zoely®’) is a monophasic oral contraceptive containing a fixed dose of nomegestrol acetate (2.5mg) and 17β-estradiol (1.5mg) which is taken for 24 days followed by 4 days of placebo. The most relevant adverse clinical outcome that has been linked to the use of COCs is venous thromboembolism (VTE). Data from randomized clinical trials did not show any serious health concerns for NOMAC-E2. However, the statistical power to detect rare adverse events is limited in these studies. PRO-E2 is a large, prospective, controlled, long-term active surveillance study to investigate the safety of NOMAC-E2 with regard to venous thromboembolism, arterial thromboembolism, depressive disorders, cholelithiasis, inflammatory bowel disease, effects on short- and long-term fertility and pregnancy outcomes. This study follows the EURAS design methodology with some modifications due to country and product-specific characteristics. The outcomes of interest will be validated via the attending physicians. A multi-faceted follow-up procedure will ensure a low loss to follow-up rate. This study will involve women from Europe, Australia and Latin America who will be followed for up to 2 years. Data analysis will include multivariable techniques such as Cox regression.
• Study status:
  Finalised

Research institutions and networks

Institutions

Berlin Center for Epidemiology & Health Research, ZEG Berlin

Germany

Study timelines

Date when funding contract was signed

Planned: 04/04/2011

Actual: 04/04/2011

Study start date

Planned: 01/02/2012

Actual: 18/07/2012

Date of final study report

Planned: 30/04/2021

Actual: 22/04/2021

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Merck Sharp & Dohme Corp. (60%) / Theramex (40%)

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 1 (imposed as condition of marketing authorisation)