Clinical trial NCT01656434: Study of the Contraceptive Efficacy and Safety of a NOMAC-E2 Combined Oral Contraceptive (COC)(P06448)
Official title: A Phase III, Randomized, Open-label, Active-controlled, Multicenter Trial to Study the Contraceptive Efficacy and Safety of the Commercial Batch of Oral Tablets of MK-8175A (Nomegestrol Acetate - 17ß-estradiol) in Healthy, Sexually-active Women Aged 18-50 Years
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Contraception
Keywords: Combined Oral Contraceptives
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2012-08-03
Enrollment: 3173
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study was to assess the contraceptive efficacy of a nomegestrol acetate + 17ß-estradiol (NOMAC-E2) combined oral contraceptive (COC) in healthy, sexually-active American women at risk for pregnancy. Vaginal bleeding patterns of women taking NOMAC-E2 were assessed and compared to those of women taking a norethisterone acetate + ethinyl estradiol (NETA-EE) COC. The safety of NOMAC-E2 was also assessed.

Participants were randomized to receive either NOMAC-E2 or NETA-EE in a 3:1 ratio. As of Amendment 1 (which increased the sample size of the NOMAC-E2 group), the randomization ratio was adapted accordingly for participants randomized after the sample size increase.

Detailed description: This study was terminated early. The decision to terminate the study was based upon difficulties encountered with data collection (related to incomplete e-Diary entries) in concert with business considerations. The decision was not related to any new or unexpected safety or efficacy findings with NOMAC-E2. As a result of this early termination, none of the pre-specified efficacy endpoints were analyzed.

Eligibility criteria: Inclusion Criteria:

* Sexually active woman, at risk for pregnancy and in need of contraception
* Not planning to use other contraceptive methods (including barrier methods \[e.g., condoms\]) than the study drug, during the study
* Willing to use a COC for 12 months (13 cycles)
* Body mass index (BMI) of ≥18 and \<38 kg/m\^2
* Good physical and mental health
* Willing to complete an electronic diary on a daily basis for the duration of the study

Exclusion Criteria:

* Current smoker and age of \>35 years
* Presence or history of either venous thromboembolic diseases (deep vein thrombosis \[DVT\], pulmonary embolism) or arterial thromboembolic diseases (myocardial infarction, stroke)
* History of migraine with focal neurological symptoms
* Diabetes mellitus with vascular involvement
* Less than two weeks of full remobilization from prolonged immobilization, major surgery, any surgery to the legs, or major trauma
* Severe hypertension
* Severe abnormal lipoproteins in the blood
* Pancreatic dysfunction
* Presence of history of severe liver disease or liver tumors
* Known or suspected sex steroid-influenced malignancies (e.g., of the genital organs or the breasts)
* Undiagnosed vaginal bleeding
* Known or suspected pregnancy
* Current or history of abuse of alcohol or drugs (e.g., laxatives)
* Abnormal cervical smear at screening
* Prior to start of treatment, spontaneous menstruation has not occurred following a delivery or abortion
* Breastfeeding or has been breastfeeding within 2 months prior to start of treatment
* Use of any investigational drugs and/or participation in any other clinical trial within 2 months prior to start of treatment
* Use of any of the following medications prior to or during the study may prohibit inclusion: sex hormones (other than pre- and post-treatment non-injectable contraceptives), injectable hormonal contraception, phenytoin, barbiturates, primidone, bosentan, carbamazepine, topiramate, felbamate, rifampicin, ritonavir, nevirapine, efavirenz, griseofulvin, herbal remedies containing Hypericum perforatum (e.g., St. John's wort)

Primary outcomes:
measure: Number of In-Treatment Pregnancies Per 100 Woman Years of Exposure (Pearl Index)
timeFrame: Up to 1 year (13 cycles)
Secondary outcomes:
measure: Percentage of Participants With an Occurrence of Breakthrough Bleeding/Spotting
timeFrame: Up to 1 year (13 cycles)
measure: Percentage of Participants With an Absence of Withdrawal Bleeding
timeFrame: Up to 1 year (13 cycles)
measure: Percentage of Participants Who Experienced At Least One Adverse Event
timeFrame: Up to 54 weeks
measure: Number of Participants Who Experience at Least One Venous or Arterial Thrombotic/Thromboembolic Event
timeFrame: Up to 54 weeks
measure: Change From Baseline in Body Weight
timeFrame: Baseline and Week 52
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Rolla E. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res. 2019 Apr 23;8:F1000 Faculty Rev-529. doi: 10.12688/f1000research.14817.1. eCollection 2019.