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

• ClinicalTrials.gov Identifier: NCT01656434
• Recruitment Status: Terminated
• First Posted: August 3, 2012
• Results First Posted: March 17, 2015
• Last Update Posted: February 3, 2022
• Sponsor: Organon and Co
• Information provided by (Responsible Party): Organon and Co

Tracking Information

• First Submitted Date: July 31, 2012
• First Posted Date: August 3, 2012
• Results First Submitted Date: February 9, 2015
• Results First Posted Date: March 17, 2015
• Last Update Posted Date: February 3, 2022
• Actual Study Start Date: November 2, 2012
• Actual Primary Completion Date: February 12, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2015)

Number of In-Treatment Pregnancies Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: Up to 1 year (13 cycles) ]

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.

• Original Primary Outcome Measures (submitted: August 2, 2012): Number of In-Treatment Pregnancies Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: 1 year (13 cycles) ]

Current Secondary Outcome Measures (submitted: March 12, 2015)

• Percentage of Participants With an Occurrence of Breakthrough Bleeding/Spotting [ Time Frame: Up to 1 year (13 cycles) ]
  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.
• Percentage of Participants With an Absence of Withdrawal Bleeding [ Time Frame: Up to 1 year (13 cycles) ]
  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.
• Percentage of Participants Who Experienced At Least One Adverse Event [ Time Frame: Up to 54 weeks ]
  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.
• Number of Participants Who Experience at Least One Venous or Arterial Thrombotic/Thromboembolic Event [ Time Frame: Up to 54 weeks ]
• Change From Baseline in Body Weight [ Time Frame: Baseline and Week 52 ]
  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.

Original Secondary Outcome Measures (submitted: August 2, 2012)

• Percentage of Participants with an Occurrence of Breakthrough Bleeding/Spotting [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]
• Percentage of Participants with an Absence of Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]
• Percentage of Participants Who Experience At Least One Adverse Event [ Time Frame: Up to 54 weeks ]
• Percentage of Participants Who Experience at Least One Venous or Arterial Thrombotic/Thromboembolic Event [ Time Frame: Up to 54 weeks ]
• Change from Baseline in Body Weight [ Time Frame: Baseline and Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Contraception

Intervention

• Drug: NOMAC-E2
  NOMAC-E2 film-coated oral tablets containing 2.5 mg nomegestrol acetate and 1.5 mg 17ß-estradiol.
  Other Names:

  • MK-8175A
  • SCH 900121
  • Org 10486-0 (NOMAC)
  • Org 2317 (E2)
• Drug: NETA-EE
  NETA-EE film-coated oral tablets containing 1 mg norethisterone acetate and 10 μg ethinylestradiol.
  Other Name: Lo Loestrin® Fe
• Other: Placebo
  tablet
• Drug: ethinylestradiol (EE)
  EE 10 μg tablet
• Drug: ferrous fumarate
  ferrous fumarate 75 mg tablet

Study Arms

• Experimental: NOMAC-E2
  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.
  Interventions:

  • Drug: NOMAC-E2
  • Other: Placebo
• Active Comparator: NETA-EE
  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.
  Interventions:

  • Drug: NETA-EE
  • Drug: ethinylestradiol (EE)
  • Drug: ferrous fumarate

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 20, 2014): 3173
• Original Estimated Enrollment (submitted: August 2, 2012): 2480
• Actual Study Completion Date: February 12, 2014
• Actual Primary Completion Date: February 12, 2014 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT01656434
• Other Study ID Numbers: P06448; MK-8175A-022 ( Other Identifier: Merck Protocol Number ); SCH 900121 P06448 ( Other Identifier: Merck Protocol ID )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Organon and Co
• Original Responsible Party: Merck Sharp & Dohme LLC
• Current Study Sponsor: Organon and Co
• Original Study Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Organon and Co
• Verification Date: February 2022