Contraception
Conditions
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.
Interventions
DRUGNOMAC-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 13 consecutive 28-day menstrual cycles (1 year).
DRUGDRSP-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 13 consecutive 28-day menstrual cycles (1 year).
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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 \>=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. * Subjects with a diagnosis of the endometrial biopsy such as hyperplasia, atypical hyperplasia, carcinoma or any other abnormality judged clinically relevant by the investigator (This is applicable only for the subjects participating in the endometrial biopsy substudy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 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 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. |
| 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. |
| 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 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. |
| 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. |
Participant flow
Recruitment details
This study recruited participants from North America and South America
Pre-assignment details
In total, 2281 participants were randomized (NOMAC-E2 n=1710; DRSP-EE n=571) but 2220 participants were treated (NOMAC-E2 n=1666; DRSP-EE n=554).
Participants by arm
| Arm | Count |
|---|---|
| NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year). | 1,666 |
| DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year). | 554 |
| Total | 2,220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event/serious adverse event | 289 | 56 |
| Overall Study | Lost to Follow-up | 175 | 73 |
| Overall Study | Other reason | 70 | 34 |
| Overall Study | Pregnancy | 15 | 5 |
| Overall Study | Pregnancy wish | 17 | 6 |
| Overall Study | Pre-treatment (serious) adverse event | 1 | 0 |
| Overall Study | Withdrawal of informed consent | 111 | 36 |
Baseline characteristics
| Characteristic | NOMAC-E2 | DRSP-EE | Total |
|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 7.2 | 27.8 years STANDARD_DEVIATION 7 | 27.7 years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 1666 Participants | 554 Participants | 2220 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 720 / 1,666 | 162 / 554 |
| serious Total, serious adverse events | 32 / 1,666 | 6 / 554 |
Outcome results
Primary
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
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.
Time frame: 1 year (13 cycles)
Population: The restricted ITT set included all participants treated except for 27 nonpregnant participants whose exposure was excluded due to limited credibility of diary data, \& also excluded nonpregnant participants without \>= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse, based on e-diary data).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | Overall group | 2.192 Pregnancies per 100 woman years |
| NOMAC-E2 | Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | =<35 years old (n=1158; n=378) | 2.498 Pregnancies per 100 woman years |
| NOMAC-E2 | Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | >35 years old (n=212; n=66) | 0.807 Pregnancies per 100 woman years |
| DRSP-EE | Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | Overall group | 4.293 Pregnancies per 100 woman years |
| DRSP-EE | Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | =<35 years old (n=1158; n=378) | 4.638 Pregnancies per 100 woman years |
| DRSP-EE | Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | >35 years old (n=212; n=66) | 2.572 Pregnancies per 100 woman years |
Primary
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
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.
Time frame: 1 year (13 cycles)
Population: The restricted ITT set included all participants treated except for 27 nonpregnant participants whose exposure was excluded due to limited credibility of diary data, \& also excluded nonpregnant participants without \>= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse, based on e-diary data).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | Overall group | 1.754 Pregnancies per 100 woman years |
| NOMAC-E2 | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | =<35 years old (n=1158; n=378) | 1.963 Pregnancies per 100 woman years |
| NOMAC-E2 | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | >35 years old (n=212; n=66) | 0.807 Pregnancies per 100 woman years |
| DRSP-EE | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | Overall group | 3.005 Pregnancies per 100 woman years |
| DRSP-EE | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | =<35 years old (n=1158; n=378) | 3.092 Pregnancies per 100 woman years |
| DRSP-EE | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) | >35 years old (n=212; n=66) | 2.572 Pregnancies per 100 woman years |
Secondary
Average Number of Breakthrough Bleeding/Spotting Days
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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants who had breakthrough bleeding/spotting for the respective cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 3 (n=196 NOMAC-E2; n=40 DRSP-EE) | 3.2 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 7 (n=104 NOMAC-E2; n=25 DRSP-EE) | 3.9 days | Standard Deviation 2.9 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 1 (n=370 NOMAC-E2; n=84 DRSP-EE) | 4.5 days | Standard Deviation 3.6 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 9 (n=85 NOMAC-E2; n=30 DRSP-EE) | 3.5 days | Standard Deviation 3.2 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 4 (n=152 NOMAC-E2; n=34 DRSP-EE) | 3.5 days | Standard Deviation 2.7 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 10 (n=93 NOMAC-E2; n=29 DRSP-EE) | 2.6 days | Standard Deviation 2.1 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 2 (n=243 NOMAC-E2; n=55 DRSP-EE) | 3.5 days | Standard Deviation 2.7 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 11 (n=83 NOMAC-E2; n=27 DRSP-EE) | 3.6 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 5 (n=139 NOMAC-E2; n=29 DRSP-EE) | 3.6 days | Standard Deviation 3 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 12 (n=70 NOMAC-E2; n=15 DRSP-EE) | 2.9 days | Standard Deviation 2.4 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 8 (n=97 NOMAC-E2; n=23 DRSP-EE) | 3.4 days | Standard Deviation 2.4 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 13 (n=62 NOMAC-E2; n=20 DRSP-EE) | 2.8 days | Standard Deviation 2.2 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 6 (n=125 NOMAC-E2; n=18 DRSP-EE) | 3.2 days | Standard Deviation 2.7 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 13 (n=62 NOMAC-E2; n=20 DRSP-EE) | 3.0 days | Standard Deviation 1.9 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 1 (n=370 NOMAC-E2; n=84 DRSP-EE) | 4.0 days | Standard Deviation 2.9 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 2 (n=243 NOMAC-E2; n=55 DRSP-EE) | 2.7 days | Standard Deviation 2.3 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 3 (n=196 NOMAC-E2; n=40 DRSP-EE) | 2.6 days | Standard Deviation 2 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 4 (n=152 NOMAC-E2; n=34 DRSP-EE) | 3.2 days | Standard Deviation 2.5 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 5 (n=139 NOMAC-E2; n=29 DRSP-EE) | 2.6 days | Standard Deviation 2.1 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 6 (n=125 NOMAC-E2; n=18 DRSP-EE) | 3.0 days | Standard Deviation 1.7 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 8 (n=97 NOMAC-E2; n=23 DRSP-EE) | 2.6 days | Standard Deviation 2.4 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 9 (n=85 NOMAC-E2; n=30 DRSP-EE) | 3.2 days | Standard Deviation 2.2 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 10 (n=93 NOMAC-E2; n=29 DRSP-EE) | 3.2 days | Standard Deviation 2.1 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 11 (n=83 NOMAC-E2; n=27 DRSP-EE) | 2.9 days | Standard Deviation 2 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 12 (n=70 NOMAC-E2; n=15 DRSP-EE) | 3.1 days | Standard Deviation 2.9 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 7 (n=104 NOMAC-E2; n=25 DRSP-EE) | 2.9 days | Standard Deviation 2 |
Secondary
Average Number of Withdrawal Bleeding/Spotting Days
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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants who had withdrawal bleeding/spotting for the respective cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 3 (n=634 NOMAC-E2; n=241 DRSP-EE) | 4.8 days | Standard Deviation 4.4 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 8 (n=391 NOMAC-E2; n=173 DRSP-EE) | 4.1 days | Standard Deviation 2.4 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 5 (n=502 NOMAC-E2; n=216 DRSP-EE) | 4.5 days | Standard Deviation 3.5 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 9 (n=356 NOMAC-E2; n=165 DRSP-EE) | 3.9 days | Standard Deviation 2.2 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 2 (n=783 NOMAC-E2; n=293 DRSP-EE) | 5.0 days | Standard Deviation 4.6 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 10 (n=344 NOMAC-E2; n=162 DRSP-EE) | 4.2 days | Standard Deviation 2.8 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 6 (n=462 NOMAC-E2; n=198 DRSP-EE) | 4.1 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 11 (n=300 NOMAC-E2; n=154 DRSP-EE) | 3.8 days | Standard Deviation 1.9 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 4 (n=555 NOMAC-E2; n=220 DRSP-EE) | 4.5 days | Standard Deviation 2.9 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 12 (n=287 NOMAC-E2; n=142 DRSP-EE) | 3.8 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 7 (n=426 NOMAC-E2; n=183 DRSP-EE) | 4.2 days | Standard Deviation 3.4 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 13 (n=196 NOMAC-E2; n=126 DRSP-EE) | 2.8 days | Standard Deviation 2.3 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 1 (n=986 NOMAC-E2; n=375 DRSP-EE) | 5.7 days | Standard Deviation 5 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 13 (n=196 NOMAC-E2; n=126 DRSP-EE) | 4.3 days | Standard Deviation 1.6 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 1 (n=986 NOMAC-E2; n=375 DRSP-EE) | 6.0 days | Standard Deviation 3.5 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 2 (n=783 NOMAC-E2; n=293 DRSP-EE) | 6.2 days | Standard Deviation 17.1 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 3 (n=634 NOMAC-E2; n=241 DRSP-EE) | 6.6 days | Standard Deviation 18.9 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 4 (n=555 NOMAC-E2; n=220 DRSP-EE) | 6.5 days | Standard Deviation 19.8 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 5 (n=502 NOMAC-E2; n=216 DRSP-EE) | 6.6 days | Standard Deviation 19.9 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 6 (n=462 NOMAC-E2; n=198 DRSP-EE) | 6.6 days | Standard Deviation 20.8 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 7 (n=426 NOMAC-E2; n=183 DRSP-EE) | 6.5 days | Standard Deviation 21.6 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 8 (n=391 NOMAC-E2; n=173 DRSP-EE) | 6.8 days | Standard Deviation 22.3 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 9 (n=356 NOMAC-E2; n=165 DRSP-EE) | 6.9 days | Standard Deviation 22.8 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 10 (n=344 NOMAC-E2; n=162 DRSP-EE) | 6.8 days | Standard Deviation 23 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 11 (n=300 NOMAC-E2; n=154 DRSP-EE) | 6.8 days | Standard Deviation 23.6 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 12 (n=287 NOMAC-E2; n=142 DRSP-EE) | 6.9 days | Standard Deviation 24.6 |
Secondary
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants with evaluable cycles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 178 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 152 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 169 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 151 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 167 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 147 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 166 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 156 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 184 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 141 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 139 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 187 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 216 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 7 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 23 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 15 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 15 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 16 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 13 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 9 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 13 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 16 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 8 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 8 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 6 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 10 participants |
Secondary
Number of Participants With an Occurrence of Breakthrough Bleeding
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: 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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants with evaluable cycles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 43 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 25 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 30 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 24 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 47 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 27 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 29 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 19 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 39 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 16 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 31 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 16 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 100 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 2 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 19 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 5 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 5 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 7 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 4 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 4 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 5 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 5 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 7 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 9 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 5 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 3 participants |
Secondary
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants with evaluable cycles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 196 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 97 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 139 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 85 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 243 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 93 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 125 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 83 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 152 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 70 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 104 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 62 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 370 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 20 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 84 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 55 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 40 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 34 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 29 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 18 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 25 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 23 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 30 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 29 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 27 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 15 participants |
Secondary
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants with evaluable cycles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 168 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 78 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 114 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 64 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 211 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 71 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 102 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 67 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 126 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 59 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 85 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 46 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 306 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 18 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 72 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 50 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 36 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 30 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 25 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 16 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 20 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 18 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 23 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 21 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 22 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 12 participants |
Secondary
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
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.
Time frame: Every 28-day cycle for 12 cycles
Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 1 (n=1179 NOMAC-E2; n=393 DRSP-EE) | 367 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 2 (n=939 NOMAC-E2; n=304 DRSP-EE) | 309 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 3 (n=794 NOMAC-E2; n=254 DRSP-EE) | 225 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 4 (n=730 NOMAC-E2; n=235 DRSP-EE) | 192 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 5 (n=659 NOMAC-E2; n=227 DRSP-EE) | 171 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 6 (n=617 NOMAC-E2; n=207 DRSP-EE) | 149 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 7 (n=555 NOMAC-E2; n=194 DRSP-EE) | 142 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 8 (n=540 NOMAC-E2; n=188 DRSP-EE) | 128 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 9 (n=503 NOMAC-E2; n=171 DRSP-EE) | 116 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 10 (n=486 NOMAC-E2; n=169 DRSP-EE) | 121 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 11 (n=455 NOMAC-E2; n=159 DRSP-EE) | 90 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 12 (n=421 NOMAC-E2; n=149 DRSP-EE) | 95 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 11 (n=455 NOMAC-E2; n=159 DRSP-EE) | 94 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 1 (n=1179 NOMAC-E2; n=393 DRSP-EE) | 216 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 7 (n=555 NOMAC-E2; n=194 DRSP-EE) | 111 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 2 (n=939 NOMAC-E2; n=304 DRSP-EE) | 174 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 10 (n=486 NOMAC-E2; n=169 DRSP-EE) | 95 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 3 (n=794 NOMAC-E2; n=254 DRSP-EE) | 149 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 8 (n=540 NOMAC-E2; n=188 DRSP-EE) | 107 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 4 (n=730 NOMAC-E2; n=235 DRSP-EE) | 145 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 12 (n=421 NOMAC-E2; n=149 DRSP-EE) | 78 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 5 (n=659 NOMAC-E2; n=227 DRSP-EE) | 135 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 9 (n=503 NOMAC-E2; n=171 DRSP-EE) | 106 participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 6 (n=617 NOMAC-E2; n=207 DRSP-EE) | 122 participants |
Secondary
Number of Participants With an Occurrence of Early Withdrawal Bleeding
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.
Time frame: Every 28-day cycle for 13 cycles (one year total)
Population: The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.~n= number of participants with evaluable cycles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 66 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 29 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 36 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 17 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 68 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 27 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 28 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 17 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 48 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 10 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 22 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 9 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 175 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE) | 6 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE) | 46 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE) | 14 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE) | 24 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE) | 9 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE) | 11 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE) | 11 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE) | 11 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE) | 13 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE) | 9 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE) | 13 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE) | 7 participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE) | 6 participants |