Effects on Ovarian Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing DRSP/EE (292003)(COMPLETED)(P05723)

• ClinicalTrials.gov Identifier: NCT00511433
• Recruitment Status: Completed
• First Posted: August 3, 2007
• Results First Posted: August 29, 2011
• Last Update Posted: February 9, 2022
• Sponsor: Organon and Co
• Information provided by (Responsible Party): Organon and Co

Tracking Information

• First Submitted Date: August 2, 2007
• First Posted Date: August 3, 2007
• Results First Submitted Date: July 28, 2011
• Results First Posted Date: August 29, 2011
• Last Update Posted Date: February 9, 2022
• Study Start Date: October 2006
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2011)

• Effect on Ovarian Function as Determined by the Number of Participants With an Occurrence of Ovulation [ Time Frame: Cycle 1, Cycle 2, and Cycle 6 ]
  During treatment, ovulation was assessed for each participant by the investigator on the basis of ultrasound scanning (USS). The final analysis was based on assessor-blind adjudication.
• Effect on Ovarian Function as Determined by the Maximum Follicle Diameter [ Time Frame: Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ]
  The maximum follicular diameter was defined as the largest follicular diameter during a treatment cycle.
• Effect on Ovarian Function as Determined by the Maximum Progesterone Value [ Time Frame: Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ]
  The maximum progesterone value was defined as the largest value during a cycle.
• Effect on Ovarian Function as Determined by 17 Beta-estradiol (E2) [ Time Frame: Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ]
  The parameter was measured at pre-defined study days.
• Effect on Ovarian Function as Determined by Follicle Stimulating Hormone (FSH) [ Time Frame: Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ]
  The parameter was measured at pre-defined study days.
• Effect on Ovarian Function as Determined by Luteinizing Hormone (LH) [ Time Frame: Cycle 1, Cycle 2, Cycle 3, and Cycle 6 ]
  The parameter was measured at pre-defined study days.

• Original Primary Outcome Measures (submitted: August 2, 2007): Ovarian function as determined by blood sampling (P, FSH, LH and E2), and vaginal USS of the ovaries to assess follicular growth. [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: July 28, 2011)

• Effect on Cervical Mucus as Determined by Insler Score [ Time Frame: Screening Cycle, Cycle 1, Cycle 2, and Cycle 7 (post-treatment cycle) ]
  The Insler Score was assessed on Day 6 after ovulation during the Screening Cycle, on Day 21 of Cycle 1, and when the maximum follicle diameter was greater than or equal to 15 mm. The Insler Score consisted of four categories each scaled from 0 (none) to 3 (complete). The higher the score, the greater the cervical reaction.
• Effect on Maximum Endometrial Thickness [ Time Frame: Screening Cycle, Cycle 1, Cycle 2, and Cycle 6 ]
  Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle.
• Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: 6 cycles ]
  In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a maximum of two days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 woman years) that the women were under risk of becoming pregnant.
• Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
• Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
• Number of Participants With an Occurrence of Breakthrough Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle.
• Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle.
• Number of Participants With an Occurrence of Early Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period". Expected bleeding period: DRSP-EE: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
• Number of Participants With an Occurrence of Continued Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 5 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
• Average Number of Breakthrough Bleeding/Spotting Days [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
• Average Number of Withdrawal Bleeding Days [ Time Frame: Every 28-day cycle for 6 cycles ]
  Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding was defined as bleeding/spotting episode that started during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.

Original Secondary Outcome Measures (submitted: August 2, 2007)

• Return of ovulation as determined by blood sampling (P levels) and vaginal USS of the ovaries to assess follicular growth. [ Time Frame: 6 months ]
• Effects on cervical mucus as determined by Insler score. [ Time Frame: 6 months ]
• Effects on endometrial thickness as determined by vaginal USS of the endometrium. [ Time Frame: 6 months ]
• Effects on androgen, SHBG and folic acid levels as determined by blood sampling. [ Time Frame: 6 months ]
• Contraceptive efficacy as determined by serum HCG pregnancy test (or home pregnancy test). [ Time Frame: 6 months ]
• Drug safety as determined by [S]AE monitoring, cervical cytology, physical & gynecological exams, and monitoring vital signs. [ Time Frame: 6 months ]
• Cycle control as determined by patient diary records. [ Time Frame: 6 months ]

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

Descriptive Information

• Brief Title: Effects on Ovarian Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing DRSP/EE (292003)(COMPLETED)(P05723)
• Official Title: A Randomized, Open-Label, Comparative Trial to Evaluate the Effects on Ovarian Function of a Monophasic Combined Oral Contraceptive (COC) Containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2), Compared to a Monophasic COC Containing 3 mg Drospirenone (DRSP) and 30 ug Ethinyl Estradiol (EE)
• Brief Summary: The primary purpose of this study is to evaluate the effects of the nomegestrol acetate-estradiol (NOMAC-E2) combined oral contraceptive (COC) on ovarian function.
• Detailed Description: Not Provided
• 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

  Nomegestrol Acetate and Estradiol Tablets, 2.5 mg NOMAC and 1.5 mg E2 taken once daily from Day 1 of menstrual period up to and including Day 28

  for 6 consecutive 28-day menstrual cycles.

• Drug: DRSP-EE
  Drospirenone and Ethinyl Estradiol Tablets, 3 mg DRSP and 30 mcg EE taken once daily from Day 1 of menstrual period up to and including Day 28 for 6 consecutive 28-day menstrual cycles.

Study Arms

• Experimental: NOMAC-E2
  Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive
  Intervention: Drug: NOMAC-E2
• Active Comparator: DRSP-EE
  Drospirenone (DRSP) and Ethinyl Estradiol (EE), 3 mg DRSP and 30 mcg EE monophasic combined oral contraceptive
  Intervention: Drug: DRSP-EE

• Publications *: Duijkers IJ, Klipping C, Grob P, Korver T. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 beta-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol. Eur J Contracept Reprod Health Care. 2010 Oct;15(5):314-25. doi: 10.3109/13625187.2010.504313.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 2, 2007): 48
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2008
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Willing to use COC for at least 6 cycles.
• 18 - 35 years of age at screening.
• Body Mass Index (BMI) of >/= 17 and </= 35.
• Good physical and mental health.
• Willing to use condoms as the sole contraceptive method during screening cycle and 1 post-treatment cycle.
• Willing to give informed consent.

Exclusion Criteria:

• Contraindications for contraceptive steroids (general).
• Additional contraindications (renal, hepatic or adrenal insufficiency).
• Breastfeeding.
• Present use (or use within 2 months prior to 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 post treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St. John's Wort).

• Administration of any other 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.
• Abnormal cervical smear at screening, or documentation of an abnormal smear performed within 6 months before screening.
• Clinically relevant abnormal laboratory result at screening as judged by the investigator.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 35 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: Netherlands

Administrative Information

• NCT Number: NCT00511433
• Other Study ID Numbers: P05723; Organon protocol 292003
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Organon and Co
• Original Responsible Party: Not Provided
• Current Study Sponsor: Organon and Co
• Original Study Sponsor: Organon
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Organon and Co
• Verification Date: February 2022