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 (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.
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: 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 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 Europe, Asia and Australia.
Pre-assignment details
In total, 2152 subjects were randomized, of which 1613 subjects to NOMAC-E2 and 539 subjects to DRSP-EE. A total of 2126 subjects were randomized and treated, of which 1591 subjects on NOMAC-E2 and 535 subjects on DRSP-EE.
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). | 1,591 |
| 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). | 535 |
| Total | 2,126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 40 | 17 |
| Overall Study | Other Adverse Event (AE)/ Serious AE | 227 | 52 |
| Overall Study | Other Reason | 78 | 37 |
| Overall Study | Pregnancy | 6 | 3 |
| Overall Study | Pregnancy Wish | 16 | 8 |
| Overall Study | Unacceptable Vaginal Bleeding | 63 | 4 |
| Overall Study | Withdrawal of Informed Consent | 19 | 4 |
Baseline characteristics
| Characteristic | NOMAC-E2 | DRSP-EE | Total |
|---|---|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 7 | 27.6 years STANDARD_DEVIATION 7 | 28.0 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 1591 Participants | 535 Participants | 2126 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 | 849 / 1,591 | 242 / 535 |
| serious Total, serious adverse events | 38 / 1,591 | 13 / 535 |
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: Restricted ITT set included all participants treated except for 2 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 confirmed 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 | 0.817 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=1193; n=402) | 0.999 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=249; n=84) | 0.000 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 | 1.356 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=1193; n=402) | 1.682 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=249; n=84) | 0.000 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: Restricted ITT set included all participants treated except for 2 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 confirmed 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 | 0.467 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= 1193; n=402) | 0.571 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= 249; n=84) | 0.000 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 | 1.017 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= 1193; n=402) | 1.261 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= 249; n=84) | 0.000 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 13 (n=94 NOMAC-E2; n=33 DRSP-EE) | 2.7 days | Standard Deviation 2 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 5 (n=221 NOMAC-E2; n=62 DRSP-EE) | 3.2 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 2 (n=289 NOMAC-E2; n=75 DRSP-EE) | 3.5 days | Standard Deviation 2.8 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 6 (n=182 NOMAC-E2; n=53 DRSP-EE) | 3.3 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 3 (n=297 NOMAC-E2; n=54 DRSP-EE) | 3.4 days | Standard Deviation 2.6 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 7 (n=165 NOMAC-E2; n=45 DRSP-EE) | 3.2 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 12 (n=110 NOMAC-E2; n=30 DRSP-EE) | 3.1 days | Standard Deviation 2.2 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 8 (n=127 NOMAC-E2; n=47 DRSP-EE) | 3.1 days | Standard Deviation 2.4 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 11 (n=125 NOMAC-E2; n=29 DRSP-EE) | 2.8 days | Standard Deviation 2.4 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 9 (n=129 NOMAC-E2; n=47 DRSP-EE) | 3.4 days | Standard Deviation 2.6 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 4 (n=231 NOMAC-E2; n=59 DRSP-EE) | 3.1 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 10 (n=121 NOMAC-E2; n=32 DRSP-EE) | 3.1 days | Standard Deviation 2.5 |
| NOMAC-E2 | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 1 (n=483 NOMAC-E2; n=130 DRSP-EE) | 4.6 days | Standard Deviation 3.6 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 10 (n=121 NOMAC-E2; n=32 DRSP-EE) | 3.1 days | Standard Deviation 2.6 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 1 (n=483 NOMAC-E2; n=130 DRSP-EE) | 4.2 days | Standard Deviation 3 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 11 (n=125 NOMAC-E2; n=29 DRSP-EE) | 2.6 days | Standard Deviation 2.5 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 12 (n=110 NOMAC-E2; n=30 DRSP-EE) | 2.6 days | Standard Deviation 2.3 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 2 (n=289 NOMAC-E2; n=75 DRSP-EE) | 3.2 days | Standard Deviation 2.5 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 3 (n=297 NOMAC-E2; n=54 DRSP-EE) | 3.6 days | Standard Deviation 2.8 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 13 (n=94 NOMAC-E2; n=33 DRSP-EE) | 3.2 days | Standard Deviation 2.6 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 4 (n=231 NOMAC-E2; n=59 DRSP-EE) | 2.9 days | Standard Deviation 2.5 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 5 (n=221 NOMAC-E2; n=62 DRSP-EE) | 2.9 days | Standard Deviation 2.8 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 6 (n=182 NOMAC-E2; n=53 DRSP-EE) | 2.4 days | Standard Deviation 2 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 7 (n=165 NOMAC-E2; n=45 DRSP-EE) | 3.0 days | Standard Deviation 2.8 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 8 (n=127 NOMAC-E2; n=47 DRSP-EE) | 2.7 days | Standard Deviation 1.9 |
| DRSP-EE | Average Number of Breakthrough Bleeding/Spotting Days | Cycle 9 (n=129 NOMAC-E2; n=47 DRSP-EE) | 2.6 days | Standard Deviation 2.2 |
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 7 (n=686 NOMAC-E2; n=309 DRSP-EE) | 5.8 days | Standard Deviation 22.4 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 4 (n=891 NOMAC-E2; n=369 DRSP-EE) | 6.0 days | Standard Deviation 19.9 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 8 (n=639 NOMAC-E2; n=289 DRSP-EE) | 5.6 days | Standard Deviation 22.3 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 1 (n=1182 NOMAC-E2; n=456 DRSP-EE) | 5.7 days | Standard Deviation 11.2 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 9 (n=616 NOMAC-E2; n=282 DRSP-EE) | 5.7 days | Standard Deviation 21.9 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 5 (n=819 NOMAC-E2; n=351 DRSP-EE) | 6.0 days | Standard Deviation 20.8 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 10 (n=564 NOMAC-E2; n=259 DRSP-EE) | 5.7 days | Standard Deviation 23.5 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 3 (n=975 NOMAC-E2; n=380 DRSP-EE) | 5.9 days | Standard Deviation 19 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 11 (n=538 NOMAC-E2; n=260 DRSP-EE) | 6.0 days | Standard Deviation 24.1 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 12 (n=516 NOMAC-E2; n=247 DRSP-EE) | 5.6 days | Standard Deviation 21.3 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 6 (n=733 NOMAC-E2; n=339 DRSP-EE) | 5.8 days | Standard Deviation 21.8 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 13 (n=387 NOMAC-E2; n=227 DRSP-EE) | 4.9 days | Standard Deviation 23.9 |
| NOMAC-E2 | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 2 (n=1102 NOMAC-E2; n=423 DRSP-EE) | 5.6 days | Standard Deviation 15.1 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 13 (n=387 NOMAC-E2; n=227 DRSP-EE) | 4.2 days | Standard Deviation 3.8 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 1 (n=1182 NOMAC-E2; n=456 DRSP-EE) | 6.0 days | Standard Deviation 3.3 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 2 (n=1102 NOMAC-E2; n=423 DRSP-EE) | 5.5 days | Standard Deviation 2.2 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 3 (n=975 NOMAC-E2; n=380 DRSP-EE) | 5.4 days | Standard Deviation 2.4 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 4 (n=891 NOMAC-E2; n=369 DRSP-EE) | 5.4 days | Standard Deviation 3.5 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 5 (n=819 NOMAC-E2; n=351 DRSP-EE) | 5.3 days | Standard Deviation 3.4 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 6 (n=733 NOMAC-E2; n=339 DRSP-EE) | 5.2 days | Standard Deviation 2.8 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 7 (n=686 NOMAC-E2; n=309 DRSP-EE) | 5.2 days | Standard Deviation 2.5 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 8 (n=639 NOMAC-E2; n=289 DRSP-EE) | 5.7 days | Standard Deviation 8.5 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 9 (n=616 NOMAC-E2; n=282 DRSP-EE) | 5.7 days | Standard Deviation 8.5 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 10 (n=564 NOMAC-E2; n=259 DRSP-EE) | 5.5 days | Standard Deviation 8.2 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 12 (n=516 NOMAC-E2; n=247 DRSP-EE) | 5.7 days | Standard Deviation 8.9 |
| DRSP-EE | Average Number of Withdrawal Bleeding/Spotting Days | Cycle 11 (n=538 NOMAC-E2; n=260 DRSP-EE) | 5.6 days | Standard Deviation 8.3 |
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 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 279 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 284 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE) | 258 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 244 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 245 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 249 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 245 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 235 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 245 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 245 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 232 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 227 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 237 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 17 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 14 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 11 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 14 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 17 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 12 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE) | 18 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 9 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 20 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 12 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 17 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 13 participants |
| DRSP-EE | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding | Cycle 6 (n=982 NOMAC-E2; n=349 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: 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.
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=1233 NOMAC-E2; n=398 DRSP-EE) | 61 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 28 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 52 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 32 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 63 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 23 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 43 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 27 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 54 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 30 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 41 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 21 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 129 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 12 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 24 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 20 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE) | 16 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 11 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 12 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 8 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 7 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 5 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 7 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 7 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 7 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 13 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=1233 NOMAC-E2; n=398 DRSP-EE) | 297 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 127 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 221 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 129 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 289 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 121 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 182 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 125 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 231 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 110 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 165 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 94 participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 483 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 33 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 130 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 75 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE) | 54 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 59 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 62 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 53 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 45 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 47 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 47 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 32 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 29 participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 30 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=1233 NOMAC-E2; n=398 DRSP-EE) | 257 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 104 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 180 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 106 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 244 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 105 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 148 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 100 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 186 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 87 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 135 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 76 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 408 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 22 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 118 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 58 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE) | 42 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 51 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 52 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 45 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 40 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 43 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 40 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 27 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 22 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 18 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=1455 NOMAC-E2; n=466 DRSP-EE) | 412 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 2 (n=1320 NOMAC-E2; n=437 DRSP-EE) | 406 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 3 (n=1201 NOMAC-E2; n=397 DRSP-EE) | 364 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 4 (n=1120 NOMAC-E2; n=387 DRSP-EE) | 321 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 5 (n=1051 NOMAC-E2; n=365 DRSP-EE) | 280 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 6 (n=965 NOMAC-E2; n=348 DRSP-EE) | 285 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 7 (n=920 NOMAC-E2; n=318 DRSP-EE) | 247 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 8 (n=868 NOMAC-E2; n=296 DRSP-EE) | 224 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 9 (n=854 NOMAC-E2; n=291 DRSP-EE) | 228 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 10 (n=806 NOMAC-E2; n=269 DRSP-EE) | 191 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 11 (n=766 NOMAC-E2; n=276 DRSP-EE) | 195 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 12 (n=725 NOMAC-E2; n=257 DRSP-EE) | 184 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 11 (n=766 NOMAC-E2; n=276 DRSP-EE) | 162 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 1 (n=1455 NOMAC-E2; n=466 DRSP-EE) | 283 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 7 (n=920 NOMAC-E2; n=318 DRSP-EE) | 190 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 2 (n=1320 NOMAC-E2; n=437 DRSP-EE) | 274 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 10 (n=806 NOMAC-E2; n=269 DRSP-EE) | 158 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 3 (n=1201 NOMAC-E2; n=397 DRSP-EE) | 243 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 8 (n=868 NOMAC-E2; n=296 DRSP-EE) | 170 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 4 (n=1120 NOMAC-E2; n=387 DRSP-EE) | 222 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 12 (n=725 NOMAC-E2; n=257 DRSP-EE) | 153 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 5 (n=1051 NOMAC-E2; n=365 DRSP-EE) | 203 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 9 (n=854 NOMAC-E2; n=291 DRSP-EE) | 176 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Continued Withdrawal Bleeding | Cycle 6 (n=965 NOMAC-E2; n=348 DRSP-EE) | 190 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=1233 NOMAC-E2; n=398 DRSP-EE) | 80 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 31 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 55 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 33 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 93 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 19 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 34 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 27 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 69 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 18 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 36 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 17 Participants |
| NOMAC-E2 | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 142 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE) | 8 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE) | 52 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE) | 29 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE) | 22 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE) | 20 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE) | 22 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE) | 16 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE) | 18 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE) | 12 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE) | 11 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE) | 9 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE) | 9 Participants |
| DRSP-EE | Number of Participants With an Occurrence of Early Withdrawal Bleeding | Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE) | 9 Participants |