Efficacy and Safety of the Combined Oral Contraceptive (COC) NOMAC-E2 Compared to a COC Containing DRSP/EE (292001)(COMPLETED)(P05724)

Phase 3

Completed

• Conditions: Contraception
• Interventions: Drug: DRSP-EE; Drug: NOMAC-E2

• Registration Number: NCT00511199
• Lead Sponsor: Organon and Co

Brief Summary

The primary purpose of this study is to assess contraceptive efficacy, vaginal bleeding patterns (cycle control), general safety and acceptability of the nomegestrol acetate-estradiol (NOMAC-E2) combined oral contraceptive (COC) in a large group of women aged 18-50 years.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-01
• Study First Submitted: 2007-08-02
• Study First Submitted QC: 2007-08-02
• Study First Posted: 2007-08-03
• Primary Completion: 2008-04-01
• Study Completion: 2008-04-01
• Disposition First Submitted: 2009-05-01
• Disposition First Submitted QC: 2009-10-02
• Disposition First Posted: 2009-10-06
• Results First Submitted: 2011-07-28
• Results First Submitted QC: 2011-07-28
• Results First Posted: 2011-08-29
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-07
• Last Update Posted: 2022-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 2152

Inclusion Criteria

• Sexually active women, at risk for pregnancy and not planning to use condoms.
• Women in need for contraception and willing to use an oral contraceptive (OC) for 12 months (13 cycles).
• At least 18 but not older than 50 years of age at the time of screening.
• Body mass index (BMI) of >/= 17 and </= 35.
• Good physical and mental health.
• Willing to give informed consent in writing.

Exclusion Criteria

• Contraindications for contraceptive steroids.
• In accordance with the Summary of Product Characteristics (SmPC)/Package Insert of DRSP-EE, additional

contraindications related to the antimineralocorticoid activity of drospirenone

(conditions that predispose to hyperkalemia):

• Renal insufficiency
• Hepatic dysfunction
• Adrenal insufficiency
• An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia [CIN],

Squamous Intraepithelial Lesion [SIL], carcinoma in situ, invasive carcinoma) at screening.

• Clinically relevant abnormal laboratory result at screening as judged by the investigator.
• Use of an injectable hormonal method of contraception; within 6 months of an injection with a 3-month duration, within 4 months of an injection with a 2-month duration, within 2 months of an injection with a 1-month duration.
• Before spontaneous menstruation has occurred following a delivery or abortion.
• Breastfeeding or within 2 months after stopping breastfeeding prior to the start of trial medication.
• Present use or use within 2 months prior to the 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 posttreatment contraceptive method) and herbal remedies containing Hypericum perforatum (St John's Wort).
• Administration of 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DRSP-EE	DRSP-EE	Drospirenone (DRSP) and Ethinyl Estradiol (EE), 3 mg DRSP and 30 mcg EE monophasic combined oral contraceptive
NOMAC-E2	NOMAC-E2	Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive

Primary Outcome Measures

Name	Time	Method
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)	1 year (13 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 women years) that the women were under risk of becoming pregnant.
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)	1 year (13 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 period of 14 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 women years) that the women were under risk of becoming pregnant.

Secondary Outcome Measures

Name	Time	Method
Average Number of Withdrawal Bleeding/Spotting Days	Every 28-day cycle for 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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.
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting	Every 28-day cycle for 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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	Every 28-day cycle for 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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	Every 28-day cycle for 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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: LNG-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 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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	Every 28-day cycle for 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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 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 Continued Withdrawal Bleeding	Every 28-day cycle for 12 cycles	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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	Every 28-day cycle for 13 cycles (one year total)	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. 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.