Study of the Contraceptive Efficacy and Safety of a NOMAC-E2 Combined Oral Contraceptive (COC)(P06448)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Contraception

Intervention / Treatment
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* Drug: NOMAC-E2
* Drug: NETA-EE
* Other: Placebo
* Drug: ethinylestradiol (EE)
* Drug: ferrous fumarate


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NOMAC-E2<br>Participants received a NOMAC-E2 tablet (2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NOMAC-E2 tablets on Days 1 to 24 and placebo tablets on Days 25 to 28. | Drug: NOMAC-E2<br>* NOMAC-E2 film-coated oral tablets containing 2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol.<br>* Other names: Org 2317 (E2);Other: Placebo<br>* tablet<br>|
| Active Comparator: NETA-EE<br>Participants received a NETA-EE tablet (1 mg norethisterone acetate and 10 μg ethinylestradiol), taken orally once daily for 13 cycles. Each cycle was 28 days. For each cycle, participants received NETA-EE tablets on Days 1 to 24; EE 10 μg tablets on Days 25 and 26; and ferrous fumarate 75 mg tablets on Days 27 and 28. | Drug: NETA-EE<br>* NETA-EE film-coated oral tablets containing 1 mg norethisterone acetate and 10 μg ethinylestradiol.<br>* Other names: Lo Loestrin® Fe;Drug: ethinylestradiol (EE)<br>* EE 10 μg tablet<br>Drug: ferrous fumarate<br>* ferrous fumarate 75 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of In-Treatment Pregnancies Per 100 Woman Years of Exposure (Pearl Index) | Primary Efficacy Outcome measure for this study was contraceptive efficacy, or the prevention of in-treatment pregnancy. The total incidence of in-treatment pregnancies was expressed as the Pearl Index, which is defined as the number of in-treatment pregnancies per 100 woman-years of exposure. | Up to 1 year (13 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Participants kept e-diaries to record their vaginal bleeding events. They were asked to record, on a daily basis, whether they experienced vaginal bleeding, which included BLEEDING or SPOTTING, at any time during a cycle other than normal menstruation while in the study. (This is also known as breakthough bleeding.) Vaginal bleeding that required >=1 pad/tampon per day was classified as BLEEDING. Vaginal bleeding that did not require a pad/tampon per day was classified as SPOTTING. | Up to 1 year (13 cycles) | 
| Percentage of Participants With an Absence of Withdrawal Bleeding | Participants kept e-diaries to record vaginal bleeding events. They were asked to record, on a daily basis, whether vaginal bleeding was present. Absence of withdrawal bleeding was defined as no bleeding/spotting during the expected bleeding period. | Up to 1 year (13 cycles) | 
| Percentage of Participants Who Experienced At Least One Adverse Event | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. | Up to 54 weeks | 
| Number of Participants Who Experience at Least One Venous or Arterial Thrombotic/Thromboembolic Event |  | Up to 54 weeks | 
| Change From Baseline in Body Weight | Participants' body weights were measured in a consistent manner throughout the trial, using standardized equirpment. Last In-Treatment Measurement refers to a participant's end of trial visit, the timing of which differed among participants. | Baseline and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined Oral Contraceptives