The primary purpose of this study is to assess contraceptive efficacy, vaginal bleeding
patterns (cycle control), general safety and acceptability of the NOMAC-E2 COC in a large
group of women aged 18-50 years.
This trial - in conjunction with trial 292001 (multi-center trial on safety and efficacy in
Europe, Asia and Australia) - is designed to obtain a sufficient number of evaluable cycles
of exposure to the NOMAC- E2 COC in the subset of women of 35 years or younger to fulfill the
CHMP criterion on the precision of the two-sided 95% CI for the Pearl Index estimate with a
power of at least 80%. In addition, 400 subjects aged 18-35 years should complete 13 cycles
of treatment. Assuming that the Pearl Index is in the range of 0 to 2. 0 (for sample size
purposes), an exposure of 16675 evaluable cycles to NOMAC-E2 will be required in women of 35
years and younger. With this sample size, also the FDA requirement of at least 10000 cycles
(for women aged ≤ 35 years) will be fulfilled. This trial is designed to contribute half of
the required exposure.
Assuming 45% discontinuations and up to 30% non-evaluable cycles (contributing an average of
3 cycles of exposure), approximately 1410 subjects will be randomized to the NOMAC- E2 COC in
this trial and age subset (18-35 years) and 470 subjects to the DRSP-EE comparator group. To
these numbers, a fixed number of subjects above 35 years of age has been added (NOMAC-E2:
330, DRSP-EE: 110) giving the maximum sample size of 1740 in the NOMAC- E2 group and 580 in
the DRSP-EE comparator group.
The trial will be conducted in an open-label fashion, as the differences in regimen between
the NOMAC-E2 COC (24 active plus 4 placebo tablets per cycle) and comparator drug (21 active
plus 7 placebo tablets per cycle) will lead to obvious differences in the timing of
withdrawal bleeding, which will reveal the treatment. To exclude enrollment bias, the
randomization process will be done by making use of an Interactive Voice Response System
(IVRS).
Bleeding pattern, adherence to the treatment will be assessed by means of an electronic
diary, to be completed by the subject on a daily basis. In addition, condom use and vaginal
intercourse will be recorded by the subject at the end of each cycle on the electronic diary.
Satisfaction and quality of life, libido and menstrual symptoms will be assessed by Patient
Reported Outcome Questionnaires. Subjects will also complete these questionnaires on the
electronic diary. Acne will be assessed by skin examination. In addition, several safety
assessments (vital signs, physical and gynecological examinations, cervical smear, routine
laboratory parameters and adverse events) will be performed.
An endometrial biopsy sub-study will take place in a subset of the study subjects.
Inclusion Criteria:
- Sexually active women, at risk for pregnancy and not planning to use condoms;
- Women in need for contraception and willing to use an OC for 12 months (13 cycles);
- At least 18 but not older than 50 years of age at the time of screening;
- Body mass index ≥17 and ≤35;
- Good physical and mental health;
- Willing to give informed consent in writing.
Exclusion Criteria:
- Contraindications for contraceptive steroids
- In accordance with the SmPC/Package Insert of DRSP-EE, additional contraindications
related to the antimineralocorticoid activity of drospirenone (conditions that
predispose to hyperkalemia):
- Renal insufficiency;
- Hepatic dysfunction;
- Adrenal insufficiency.
- An abnormal cervical smear (i. e.: dysplasia, cervical intraepithelial neoplasia [CIN],
SIL, carcinoma in situ, invasive carcinoma) at screening;
- Clinically relevant abnormal laboratory result at screening as judged by the
investigator;
- Use of an injectable hormonal method of contraception; within 6 months of an injection
with a 3-month duration, within 4 months of an injection with a 2-month duration,
within 2 months of an injection with a 1-month duration;
- Before spontaneous menstruation has occurred following a delivery or abortion;
- Breastfeeding or within 2 months after stopping breastfeeding prior to the start of
trial medication;
- Present use or use within 2 months prior to the start of the trial medication of the
following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine,
topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole,
sex steroids (other than pre- and posttreatment contraceptive method) and herbal
remedies containing Hypericum perforatum (St John's Wort);
- Administration of investigational drugs and/or participation in another clinical trial
within 2 months prior to the start of the trial medication or during the trial
period.
Organon Investigational Sites, Buenos Aires, Argentina
Organon Investigational Site, Campinas, Brazil
Organon Investigational Site, Ribeirão Preto, Brazil
Organon Investigational Site, São Paulo, Brazil
Organon Investigational Sites, Porto Alegre, Brazil
Organon Investigational Site, Regina, Canada
Organon Investigational Site, Montreal, Canada
Organon Investigational Sites, Ottawa, Canada
Ottawa, Quebec City, Canada
Organon Investigational Site, Ste-Foy, Canada
Organon Investigational Site, Toronto, Canada
Organon Investigational Site, Calgary, Canada
Organon Investigational Site, Pointe-Claire, Canada
Organon Investigational Site, Langley, Canada
Organon Investigational Sites, Markham, Canada
Organon Investigational Site, Winnipeg, Canada
Organon Investigational Site, Coquitlam, Canada
Organon Investigational Site, London, Canada
Organon Investigational Sites, Santiago, Chile
Organon Investigational Site, Temuco, Chile
Organon Investigational Sites, Mexico DF, Mexico
Organon Investigational Site, Guadalajara, Mexico
Organon Investigational Site, Monterrey, Mexico
Organon Investigational Site, Phoenix, Arizona, United States
Organon Investigational Sites, Scottsdale, Arizona, United States
Organon Investigational Site, Little Rock, Arkansas, United States
Organon Investigational Site, San Francisco, California, United States
Organon Investigational Site, San Diego, California, United States
Organon Investigational Site, Los Angeles, California, United States
Organon Investigational Site, Aurora, Colorado, United States
Organon Investigational Site, Waterbury, Connecticut, United States
Organon Investigational Site, Avon, Connecticut, United States
Organon Investigational Site, Boynton Beach, Florida, United States
Organon Investigational Site, Melbourne, Florida, United States
Organon Investigational Site, Miami, Florida, United States
Organon Investigational Site, Gainesville, Florida, United States
Organon Investigational Site, Jacksonville, Florida, United States
Organon Investigational Site, St. Petersburg, Florida, United States
Organon Investigational Sites, Atlanta, Georgia, United States
Organon Investigational Site, Tucker, Georgia, United States
Organon Investigational Site, Boise, Idaho, United States
Organon Investigational Sites, Chicago, Illinois, United States
Organon Investigational Site, South Bend, Indiana, United States
Organon Investigational Site, Louisville, Kentucky, United States
Organon Investigational Site, North Dartmouth, Massachusetts, United States
Organon Investigational Site, West Yarmouth, Massachusetts, United States
Organon Investigational Site, Detroit, Michigan, United States
Organon Investigational Site, Lincoln, Nebraska, United States
Organon Investigational Site, Lawrenceville, New Jersey, United States
Organon Investigational Site, Moorestown, New Jersey, United States
Organon Investigational Site, Albuquerque, New Mexico, United States
Organon Investigational Site, Port Jefferson, New York, United States
Organon Investigational Site, New York, New York, United States
Organon Investigational Site, Hickory, North Carolina, United States
Organon Investigational Site, Wilmington, North Carolina, United States
Organon Investigational Sites, Raleigh, North Carolina, United States
Organon Investigational Sites, Winston-Salem, North Carolina, United States
Organon Investigational Sites, Cincinnati, Ohio, United States
Organon Investigational Site, Beaverton, Oregon, United States
Organon Investigational Sites, Medford, Oregon, United States
Organon Investigational Site, Philadelphia, Pennsylvania, United States
Organon Investigational Site, Pittsburgh, Pennsylvania, United States
Organon Investigational Site, Pottstown, Pennsylvania, United States
Organon Investigational Site`, Waco, Texas, United States
Organon Investigational Site, San Antonio, Texas, United States
Organon Investigational Site, Burlington, Vermont, United States
Organon Investigational Site, Norfolk, Virginia, United States
Organon Investigational Site, Richmond, Virginia, United States
Organon Investigational Site, Seattle, Washington, United States
Organon Investigational Site, Lakewood, Washington, United States
Organon Investigational Site, Wenatchee, Washington, United States
