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

Phase 3
Completed
Conditions
Contraception
Interventions
Drug: DRSP-EE
Registration Number
NCT00511433
Lead Sponsor
Organon and Co
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
48
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DRSP-EEDRSP-EEDrospirenone (DRSP) and Ethinyl Estradiol (EE), 3 mg DRSP and 30 mcg EE monophasic combined oral contraceptive
NOMAC-E2NOMAC-E2Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive
Primary Outcome Measures
NameTimeMethod
Effect on Ovarian Function as Determined by the Number of Participants With an Occurrence of OvulationCycle 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 Progesterone ValueScreening 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 Luteinizing Hormone (LH)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 the Maximum Follicle DiameterScreening 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 17 Beta-estradiol (E2)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)Cycle 1, Cycle 2, Cycle 3, and Cycle 6

The parameter was measured at pre-defined study days.

Secondary Outcome Measures
NameTimeMethod
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)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 BleedingEvery 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 Early Withdrawal BleedingEvery 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.

Effect on Maximum Endometrial ThicknessScreening Cycle, Cycle 1, Cycle 2, and Cycle 6

Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle.

Number of Participants With an Occurrence of Breakthrough Bleeding/SpottingEvery 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 Breakthrough Spotting (Spotting Only)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.

Effect on Cervical Mucus as Determined by Insler ScoreScreening 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.

Number of Participants With an Occurrence of Absence of Withdrawal BleedingEvery 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.

Average Number of Withdrawal Bleeding DaysEvery 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.

Average Number of Breakthrough Bleeding/Spotting DaysEvery 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 Continued Withdrawal BleedingEvery 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.

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