Effects on Ovarian Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing DRSP/EE (292003)(COMPLETED)(P05723)
Study Details
Study Description
Brief Summary
The primary purpose of this study is to evaluate the effects of the nomegestrol acetate-estradiol (NOMAC-E2) combined oral contraceptive (COC) on ovarian function.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: NOMAC-E2 Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive |
Drug: NOMAC-E2
Nomegestrol Acetate and Estradiol Tablets, 2.5 mg NOMAC and 1.5 mg E2 taken once daily from Day 1 of menstrual period up to and including Day 28
for 6 consecutive 28-day menstrual cycles.
|
Active Comparator: DRSP-EE Drospirenone (DRSP) and Ethinyl Estradiol (EE), 3 mg DRSP and 30 mcg EE monophasic combined oral contraceptive |
Drug: DRSP-EE
Drospirenone and Ethinyl Estradiol Tablets, 3 mg DRSP and 30 mcg EE taken once daily from Day 1 of menstrual period up to and including Day 28 for 6 consecutive 28-day menstrual cycles.
|
Outcome Measures
Primary Outcome Measures
- Effect on Ovarian Function as Determined by the Number of Participants With an Occurrence of Ovulation [Cycle 1, Cycle 2, and Cycle 6]
During treatment, ovulation was assessed for each participant by the investigator on the basis of ultrasound scanning (USS). The final analysis was based on assessor-blind adjudication.
- Effect on Ovarian Function as Determined by the Maximum Follicle Diameter [Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6]
The maximum follicular diameter was defined as the largest follicular diameter during a treatment cycle.
- Effect on Ovarian Function as Determined by the Maximum Progesterone Value [Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6]
The maximum progesterone value was defined as the largest value during a cycle.
- Effect on Ovarian Function as Determined by 17 Beta-estradiol (E2) [Cycle 1, Cycle 2, Cycle 3, and Cycle 6]
The parameter was measured at pre-defined study days.
- Effect on Ovarian Function as Determined by Follicle Stimulating Hormone (FSH) [Cycle 1, Cycle 2, Cycle 3, and Cycle 6]
The parameter was measured at pre-defined study days.
- Effect on Ovarian Function as Determined by Luteinizing Hormone (LH) [Cycle 1, Cycle 2, Cycle 3, and Cycle 6]
The parameter was measured at pre-defined study days.
Secondary Outcome Measures
- Effect on Cervical Mucus as Determined by Insler Score [Screening Cycle, Cycle 1, Cycle 2, and Cycle 7 (post-treatment cycle)]
The Insler Score was assessed on Day 6 after ovulation during the Screening Cycle, on Day 21 of Cycle 1, and when the maximum follicle diameter was greater than or equal to 15 mm. The Insler Score consisted of four categories each scaled from 0 (none) to 3 (complete). The higher the score, the greater the cervical reaction.
- Effect on Maximum Endometrial Thickness [Screening Cycle, Cycle 1, Cycle 2, and Cycle 6]
Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle.
- Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [6 cycles]
In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a maximum of two days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 woman years) that the women were under risk of becoming pregnant.
- Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
- Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
- Number of Participants With an Occurrence of Breakthrough Bleeding [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle.
- Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle.
- Number of Participants With an Occurrence of Early Withdrawal Bleeding [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period". Expected bleeding period: DRSP-EE: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
- Number of Participants With an Occurrence of Continued Withdrawal Bleeding [Every 28-day cycle for 5 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
- Average Number of Breakthrough Bleeding/Spotting Days [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
- Average Number of Withdrawal Bleeding Days [Every 28-day cycle for 6 cycles]
Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding was defined as bleeding/spotting episode that started during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing to use COC for at least 6 cycles.
-
18 - 35 years of age at screening.
-
Body Mass Index (BMI) of >/= 17 and </= 35.
-
Good physical and mental health.
-
Willing to use condoms as the sole contraceptive method during screening cycle and 1 post-treatment cycle.
-
Willing to give informed consent.
Exclusion Criteria:
-
Contraindications for contraceptive steroids (general).
-
Additional contraindications (renal, hepatic or adrenal insufficiency).
-
Breastfeeding.
-
Present use (or use within 2 months prior to start of the trial medication) of the following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex
steroids (other than pre- and post treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St. John's Wort).
-
Administration of any other investigational drugs and/or participation in another clinical trial within 2 months prior to the start of the trial medication or during the trial period.
-
Abnormal cervical smear at screening, or documentation of an abnormal smear performed within 6 months before screening.
-
Clinically relevant abnormal laboratory result at screening as judged by the investigator.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P05723
- Organon protocol 292003
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Period Title: Overall Study | ||
STARTED | 32 | 16 |
COMPLETED | 26 | 15 |
NOT COMPLETED | 6 | 1 |
Baseline Characteristics
Arm/Group Title | NOMAC-E2 | DRSP-EE | Total |
---|---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. | Total of all reporting groups |
Overall Participants | 32 | 16 | 48 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
22.8
(3.3)
|
22.9
(4.3)
|
22.8
(3.6)
|
Sex: Female, Male (Count of Participants) | |||
Female |
32
100%
|
16
100%
|
48
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Effect on Cervical Mucus as Determined by Insler Score |
---|---|
Description | The Insler Score was assessed on Day 6 after ovulation during the Screening Cycle, on Day 21 of Cycle 1, and when the maximum follicle diameter was greater than or equal to 15 mm. The Insler Score consisted of four categories each scaled from 0 (none) to 3 (complete). The higher the score, the greater the cervical reaction. |
Time Frame | Screening Cycle, Cycle 1, Cycle 2, and Cycle 7 (post-treatment cycle) |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants with non-missing values at the respective time point. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Screening cycle (n=32 NOMAC-E2 / n=16 DRSP-EE) |
8.9
(2.55)
|
7.3
(3.61)
|
Cycle 1 (n=30 NOMAC-E2 / n=15 DRSP-EE) |
2.3
(1.93)
|
3.2
(2.43)
|
Cycle 2 (n=0 NOMAC-E2 / n=2 DRSP-EE) |
NA
(NA)
|
4.5
(0.71)
|
Cycle 7 (n=22 NOMAC-E2 / n=15 DRSP-EE) |
7.0
(2.94)
|
8.7
(1.53)
|
Title | Effect on Maximum Endometrial Thickness |
---|---|
Description | Maximum endometrial thickness was defined as the largest endometrial thickness during a cycle. |
Time Frame | Screening Cycle, Cycle 1, Cycle 2, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants completing the respective cycle. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Screening cycle (n=32 NOMAC-E2 / n=16 DRSP-EE) |
9.9
(1.91)
|
10.1
(2.50)
|
Cycle 1 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
5.9
(1.22)
|
6.1
(1.25)
|
Cycle 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
5.3
(0.71)
|
6.8
(1.73)
|
Cycle 6 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
4.9
(0.66)
|
5.5
(1.30)
|
Title | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) |
---|---|
Description | In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a maximum of two days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 woman years) that the women were under risk of becoming pregnant. |
Time Frame | 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
The "restricted ITT" set included all participants treated and excluded nonpregnant participants who didn't have >=1 cycle expected to be at risk for pregnancy (with recorded use of condoms or without sexual intercourse per diary card data). |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 24 | 12 |
Measure woman years (rounded to nearest integer) | 8 | 5 |
Number (95% Confidence Interval) [Pregnancies per 100 woman years] |
0
|
0
|
Title | Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
7
21.9%
|
1
6.3%
|
Cycle 2 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
6
18.8%
|
0
0%
|
Cycle 3 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
5
15.6%
|
0
0%
|
Cycle 4 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
5
15.6%
|
0
0%
|
Cycle 5 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
8
25%
|
0
0%
|
Cycle 6 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
5
15.6%
|
0
0%
|
Title | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
3
9.4%
|
0
0%
|
Cycle 2 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
2
6.3%
|
0
0%
|
Cycle 3 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
2
6.3%
|
0
0%
|
Cycle 4 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
2
6.3%
|
0
0%
|
Cycle 5 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
2
6.3%
|
0
0%
|
Cycle 6 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
4
12.5%
|
1
6.3%
|
Title | Number of Participants With an Occurrence of Breakthrough Bleeding |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
0
0%
|
0
0%
|
Cycle 2 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
0
0%
|
0
0%
|
Cycle 3 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
0
0%
|
0
0%
|
Cycle 4 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
1
3.1%
|
0
0%
|
Cycle 5 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
1
3.1%
|
0
0%
|
Cycle 6 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
0
0%
|
0
0%
|
Title | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2:21-day period starting on Day 4 of the cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
7
21.9%
|
1
6.3%
|
Cycle 2 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
6
18.8%
|
0
0%
|
Cycle 3 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
5
15.6%
|
0
0%
|
Cycle 4 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
4
12.5%
|
0
0%
|
Cycle 5 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
7
21.9%
|
0
0%
|
Cycle 6 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
5
15.6%
|
0
0%
|
Title | Number of Participants With an Occurrence of Early Withdrawal Bleeding |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period". Expected bleeding period: DRSP-EE: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
4
12.5%
|
2
12.5%
|
Cycle 2 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
4
12.5%
|
0
0%
|
Cycle 3 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
1
3.1%
|
0
0%
|
Cycle 4 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
2
6.3%
|
0
0%
|
Cycle 5 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
1
3.1%
|
0
0%
|
Cycle 6 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
2
6.3%
|
0
0%
|
Title | Number of Participants With an Occurrence of Continued Withdrawal Bleeding |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle. |
Time Frame | Every 28-day cycle for 5 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. n=number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined). | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. n=number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined). |
Measure Participants | 30 | 16 |
Cycle 1 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
11
34.4%
|
12
75%
|
Cycle 2 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
8
25%
|
10
62.5%
|
Cycle 3 (n=25 NOMAC-E2 / n=15 DRSP-EE) |
8
25%
|
11
68.8%
|
Cycle 4 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
12
37.5%
|
12
75%
|
Cycle 5 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
9
28.1%
|
10
62.5%
|
Title | Effect on Ovarian Function as Determined by the Number of Participants With an Occurrence of Ovulation |
---|---|
Description | During treatment, ovulation was assessed for each participant by the investigator on the basis of ultrasound scanning (USS). The final analysis was based on assessor-blind adjudication. |
Time Frame | Cycle 1, Cycle 2, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) group consisted of all participants who were treated. n=number of participants completing the respective cycle with non-missing values. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Cycle 1 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
0
0%
|
0
0%
|
Cycle 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
0
0%
|
0
0%
|
Cycle 6 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
0
0%
|
0
0%
|
Title | Effect on Ovarian Function as Determined by the Maximum Follicle Diameter |
---|---|
Description | The maximum follicular diameter was defined as the largest follicular diameter during a treatment cycle. |
Time Frame | Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants completing the respective cycle with non-missing values. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Screening cycle (n=32 NOMAC-E2 / n=16 DRSP-EE) |
19.3
(3.13)
|
19.6
(4.32)
|
Cycle 1 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
7.6
(1.51)
|
8.1
(1.98)
|
Cycle 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
8.2
(1.82)
|
10.8
(4.76)
|
Cycle 3 (n=27 NOMAC-E2 / n=14 DRSP-EE) |
7.8
(1.88)
|
8.4
(2.31)
|
Cycle 6 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
6.9
(2.07)
|
7.4
(2.06)
|
Title | Effect on Ovarian Function as Determined by the Maximum Progesterone Value |
---|---|
Description | The maximum progesterone value was defined as the largest value during a cycle. |
Time Frame | Screening cycle, Cycle 1, Cycle 2, Cycle 3, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants completing the respective cycle with non-missing values. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Screening cycle (n=32 NOMAC-E2 / n=16 DRSP-EE) |
38.7
(12.62)
|
38.7
(17.01)
|
Cycle 1 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
1.7
(0.46)
|
1.6
(0.28)
|
Cycle 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
1.5
(0.46)
|
1.5
(0.26)
|
Cycle 3 (n=27 NOMAC-E2 / n=14 DRSP-EE) |
1.26
(0.10)
|
1.34
(0.27)
|
Cycle 6 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
1.3
(0.29)
|
1.5
(0.26)
|
Title | Effect on Ovarian Function as Determined by 17 Beta-estradiol (E2) |
---|---|
Description | The parameter was measured at pre-defined study days. |
Time Frame | Cycle 1, Cycle 2, Cycle 3, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants with non-missing values at the respective time point. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Cycle 1, Day 2 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
168.75
(62.37)
|
79.82
(18.34)
|
Cycle 1, Day 5 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
194.57
(93.17)
|
66.66
(10.53)
|
Cycle 1, Day 8 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
172.35
(66.92)
|
61.15
(3.66)
|
Cycle 1, Day 11 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
184.63
(95.70)
|
60.51
(1.96)
|
Cycle 1, Day 14 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
197.57
(123.23)
|
60.26
(1.48)
|
Cycle 1, Day 18 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
182.72
(84.03)
|
60.58
(2.93)
|
Cycle 1, Day 21 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
191.08
(139.50)
|
59.82
(0)
|
Cycle 1, Day 24 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
232.80
(281.15)
|
69.84
(23.50)
|
Cycle 1, Day 27 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
99.65
(42.53)
|
150.79
(46.45)
|
Cycle 2, Day 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
176.43
(91.99)
|
135.86
(106.62)
|
Cycle 2, Day 5 (n=29 NOMAC-E2 / n=15 DRSP-EE) |
213.64
(104.85)
|
142.74
(186.99)
|
Cycle 2, Day 8 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
192.59
(68.83)
|
131.98
(196.51)
|
Cycle 2, Day 11 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
185.77
(63.97)
|
112.23
(152.19)
|
Cycle 2, Day 14 (n=29 NOMAC-E2 / n=15 DRSP-EE) |
183.66
(74.39)
|
78.44
(69.99)
|
Cycle 2, Day 18 (n=28 NOMAC-E2 / n=15 DRSP-EE) |
213.84
(123.35)
|
60.11
(0.95)
|
Cycle 2, Day 21 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
192.47
(66.43)
|
59.91
(0.37)
|
Cycle 2, Day 24 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
206.20
(147.27)
|
61.33
(3.95)
|
Cycle 2, Day 27 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
97.99
(40.88)
|
155.63
(63.65)
|
Cycle 3, Day 2 (n=27 NOMAC-E2 / n=14 DRSP-EE) |
148.16
(52.09)
|
141.11
(115.89)
|
Cycle 6, Day 14 (n=25 NOMAC-E2 / n=14 DRSP-EE) |
205.89
(104.45)
|
59.98
(0.59)
|
Cycle 6, Day 18 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
200.04
(90.28)
|
64.20
(12.99)
|
Cycle 6, Day 21 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
188.47
(90.12)
|
60.82
(3.02)
|
Cycle 6, Day 24 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
187.16
(106.60)
|
69.60
(33.97)
|
Cycle 6, Day 27 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
99.51
(35.60)
|
133.49
(61.28)
|
Title | Effect on Ovarian Function as Determined by Follicle Stimulating Hormone (FSH) |
---|---|
Description | The parameter was measured at pre-defined study days. |
Time Frame | Cycle 1, Cycle 2, Cycle 3, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants with non-missing values at the respective time point. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Cycle 1, Day 2 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
4.29
(1.45)
|
4.51
(1.14)
|
Cycle 1, Day 5 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
4.08
(1.59)
|
4.23
(1.33)
|
Cycle 1, Day 8 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
3.59
(1.59)
|
3.40
(1.57)
|
Cycle 1, Day 11 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
3.44
(2.07)
|
2.46
(1.40)
|
Cycle 1, Day 14 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
3.06
(1.90)
|
2.32
(1.71)
|
Cycle 1, Day 18 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
2.95
(1.76)
|
1.91
(1.69)
|
Cycle 1, Day 21 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
2.87
(1.96)
|
1.61
(1.53)
|
Cycle 1, Day 24 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
2.88
(1.99)
|
4.50
(4.05)
|
Cycle 1, Day 27 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
5.42
(2.51)
|
7.91
(3.95)
|
Cycle 2, Day 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
5.32
(2.05)
|
5.48
(1.82)
|
Cycle 2, Day 5 (n=29 NOMAC-E2 / n=15 DRSP-EE) |
4.59
(1.54)
|
4.08
(1.54)
|
Cycle 2, Day 8 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
3.99
(1.71)
|
2.77
(1.19)
|
Cycle 2, Day 11 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
3.47
(1.68)
|
1.96
(1.13)
|
Cycle 2, Day 14 (n=29 NOMAC-E2 / n=15 DRSP-EE) |
3.34
(2.18)
|
1.44
(1.00)
|
Cycle 2, Day 18 (n=28 NOMAC-E2 / n=15 DRSP-EE) |
3.18
(1.84)
|
1.22
(0.94)
|
Cycle 2, Day 21 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
3.02
(1.64)
|
1.04
(0.98)
|
Cycle 2, Day 24 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
3.05
(1.76)
|
3.52
(3.51)
|
Cycle 2, Day 27 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
5.92
(2.77)
|
6.99
(2.78)
|
Cycle 3, Day 2 (n=27 NOMAC-E2 / n=14 DRSP-EE) |
6.01
(2.08)
|
5.17
(1.44)
|
Cycle 6, Day 14 (n=25 NOMAC-E2 / n=14 DRSP-EE) |
3.08
(1.88)
|
1.43
(1.32)
|
Cycle 6, Day 18 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
2.82
(1.79)
|
1.29
(1.28)
|
Cycle 6, Day 21 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
3.30
(2.14)
|
0.92
(0.96)
|
Cycle 6, Day 24 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
2.86
(2.09)
|
3.18
(3.04)
|
Cycle 6, Day 27 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
5.65
(2.57)
|
6.22
(2.99)
|
Title | Average Number of Breakthrough Bleeding/Spotting Days |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=7 NOMAC-E2; n=1 DRSP-EE) |
3.0
(2.2)
|
2.0
(NA)
|
Cycle 2 (n=6 NOMAC-E2; n=0 DRSP-EE) |
2.7
(1.9)
|
NA
(NA)
|
Cycle 3 (n=5 NOMAC-E2; n=0 DRSP-EE) |
2.2
(1.1)
|
NA
(NA)
|
Cycle 4 (n=5 NOMAC-E2; n=0 DRSP-EE) |
4.0
(2.8)
|
NA
(NA)
|
Cycle 5 (n=8 NOMAC-E2; n=0 DRSP-EE) |
3.5
(2.3)
|
NA
(NA)
|
Cycle 6 (n=5 NOMAC-E2; n=0 DRSP-EE) |
3.6
(2.1)
|
NA
(NA)
|
Title | Average Number of Withdrawal Bleeding Days |
---|---|
Description | Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary card booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding was defined as bleeding/spotting episode that started during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle. |
Time Frame | Every 28-day cycle for 6 cycles |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 30 | 16 |
Cycle 1 (n=27 NOMAC-E2; n=16 DRSP-EE) |
7.2
(6.7)
|
7.0
(4.7)
|
Cycle 1 (n=25 NOMAC-E2; n=16 DRSP-EE) |
7.4
(7.5)
|
5.0
(1.7)
|
Cycle 3 (n=24 NOMAC-E2; n=15 DRSP-EE) |
4.3
(2.4)
|
5.4
(1.5)
|
Cycle 4 (n=24 NOMAC-E2; n=15 DRSP-EE) |
4.7
(1.9)
|
5.3
(1.0)
|
Cycle 5 (n=24 NOMAC-E2; n=15 DRSP-EE) |
5.5
(6.1)
|
4.9
(1.1)
|
Cycle 6 (n=22 NOMAC-E2; n=13 DRSP-EE) |
5.2
(6.3)
|
3.9
(0.9)
|
Title | Effect on Ovarian Function as Determined by Luteinizing Hormone (LH) |
---|---|
Description | The parameter was measured at pre-defined study days. |
Time Frame | Cycle 1, Cycle 2, Cycle 3, and Cycle 6 |
Outcome Measure Data
Analysis Population Description |
---|
ITT group consisted of all participants who were treated. n=number of participants with non-missing values at the respective time point. |
Arm/Group Title | NOMAC-E2 | DRSP-EE |
---|---|---|
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. |
Measure Participants | 32 | 16 |
Cycle 1, Day 2 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
3.73
(1.64)
|
3.69
(1.58)
|
Cycle 1, Day 5 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
2.98
(1.49)
|
4.34
(2.35)
|
Cycle 1, Day 8 (n=32 NOMAC-E2 / n=16 DRSP-EE) |
2.50
(1.68)
|
3.09
(2.36)
|
Cycle 1, Day 11 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
2.13
(1.50)
|
1.89
(1.45)
|
Cycle 1, Day 14 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
1.85
(1.77)
|
2.32
(2.05)
|
Cycle 1, Day 18 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
1.76
(1.41)
|
1.61
(1.29)
|
Cycle 1, Day 21 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
1.45
(1.33)
|
1.19
(0.86)
|
Cycle 1, Day 24 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
1.59
(1.44)
|
2.63
(2.07)
|
Cycle 1, Day 27 (n=30 NOMAC-E2 / n=16 DRSP-EE) |
3.04
(1.95)
|
4.34
(2.38)
|
Cycle 2, Day 2 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
3.47
(2.20)
|
4.81
(3.01)
|
Cycle 2, Day 5 (n=29 NOMAC-E2 / n=15 DRSP-EE) |
3.04
(1.94)
|
5.08
(3.21)
|
Cycle 2, Day 8 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
2.48
(1.85)
|
3.33
(1.97)
|
Cycle 2, Day 11 (n=29 NOMAC-E2 / n=16 DRSP-EE) |
2.54
(2.01)
|
2.70
(2.18)
|
Cycle 2, Day 14 (n=29 NOMAC-E2 / n=15 DRSP-EE) |
2.39
(2.17)
|
1.69
(1.42)
|
Cycle 2, Day 18 (n=28 NOMAC-E2 / n=15 DRSP-EE) |
2.05
(1.76)
|
1.60
(1.31)
|
Cycle 2, Day 21 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
1.68
(1.44)
|
0.97
(0.67)
|
Cycle 2, Day 24 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
1.81
(1.75)
|
2.38
(2.01)
|
Cycle 2, Day 27 (n=27 NOMAC-E2 / n=16 DRSP-EE) |
3.37
(2.90)
|
3.92
(2.17)
|
Cycle 3, Day 2 (n=27 NOMAC-E2 / n=14 DRSP-EE) |
3.71
(2.23)
|
4.79
(2.67)
|
Cycle 6, Day 14 (n=25 NOMAC-E2 / n=14 DRSP-EE) |
2.29
(1.86)
|
2.15
(2.83)
|
Cycle 6, Day 18 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
1.88
(2.05)
|
1.27
(1.02)
|
Cycle 6, Day 21 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
2.00
(1.68)
|
1.14
(0.89)
|
Cycle 6, Day 24 (n=26 NOMAC-E2 / n=14 DRSP-EE) |
1.85
(1.75)
|
2.56
(2.12)
|
Cycle 6, Day 27 (n=26 NOMAC-E2 / n=15 DRSP-EE) |
3.13
(2.21)
|
4.03
(2.57)
|
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | NOMAC-E2 | DRSP-EE | ||
Arm/Group Description | 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 6 consecutive 28-day menstrual cycles. | Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol 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 6 consecutive 28-day menstrual cycles. | ||
All Cause Mortality |
||||
NOMAC-E2 | DRSP-EE | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
NOMAC-E2 | DRSP-EE | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/32 (3.1%) | 0/16 (0%) | ||
Gastrointestinal disorders | ||||
Appendicitis perforated | 1/32 (3.1%) | 1 | 0/16 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
NOMAC-E2 | DRSP-EE | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 30/32 (93.8%) | 15/16 (93.8%) | ||
Cardiac disorders | ||||
Palpitations | 2/32 (6.3%) | 2 | 0/16 (0%) | 0 |
Eye disorders | ||||
Conjunctivitis | 0/32 (0%) | 0 | 2/16 (12.5%) | 2 |
Gastrointestinal disorders | ||||
Abdominal distension | 3/32 (9.4%) | 3 | 0/16 (0%) | 0 |
Abdominal pain | 3/32 (9.4%) | 3 | 0/16 (0%) | 0 |
Abdominal pain lower | 5/32 (15.6%) | 6 | 3/16 (18.8%) | 4 |
Constipation | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Diarrhoea | 11/32 (34.4%) | 13 | 0/16 (0%) | 0 |
Food poisoning | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Nausea | 8/32 (25%) | 11 | 3/16 (18.8%) | 5 |
Toothache | 3/32 (9.4%) | 4 | 1/16 (6.3%) | 1 |
Vomiting | 2/32 (6.3%) | 2 | 4/16 (25%) | 5 |
General disorders | ||||
Fatigue | 2/32 (6.3%) | 2 | 1/16 (6.3%) | 1 |
Hangover | 5/32 (15.6%) | 7 | 1/16 (6.3%) | 1 |
Malaise | 3/32 (9.4%) | 3 | 1/16 (6.3%) | 1 |
Immune system disorders | ||||
Hypersensitivity | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Infections and infestations | ||||
Cystitis | 4/32 (12.5%) | 8 | 3/16 (18.8%) | 4 |
Gastroenteritis | 3/32 (9.4%) | 3 | 0/16 (0%) | 0 |
Influenza | 5/32 (15.6%) | 7 | 7/16 (43.8%) | 7 |
Nasopharyngitis | 15/32 (46.9%) | 23 | 9/16 (56.3%) | 12 |
Pyelonephritis | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Vaginal candidiasis | 2/32 (6.3%) | 2 | 1/16 (6.3%) | 1 |
Injury, poisoning and procedural complications | ||||
Foreign body in eye | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Procedural pain | 3/32 (9.4%) | 3 | 0/16 (0%) | 0 |
Sunburn | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Investigations | ||||
Weight decreased | 2/32 (6.3%) | 2 | 0/16 (0%) | 0 |
Weight increased | 4/32 (12.5%) | 4 | 1/16 (6.3%) | 1 |
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 2/32 (6.3%) | 3 | 1/16 (6.3%) | 1 |
Back pain | 5/32 (15.6%) | 8 | 1/16 (6.3%) | 2 |
Nervous system disorders | ||||
Dizziness | 3/32 (9.4%) | 4 | 0/16 (0%) | 0 |
Headache | 8/32 (25%) | 17 | 4/16 (25%) | 7 |
Psychiatric disorders | ||||
Affect lability | 4/32 (12.5%) | 4 | 1/16 (6.3%) | 1 |
Depressed mood | 3/32 (9.4%) | 3 | 0/16 (0%) | 0 |
Renal and urinary disorders | ||||
Dysuria | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Micturition urgency | 1/32 (3.1%) | 1 | 1/16 (6.3%) | 1 |
Reproductive system and breast disorders | ||||
Breast enlargement | 1/32 (3.1%) | 1 | 3/16 (18.8%) | 3 |
Breast pain | 0/32 (0%) | 0 | 4/16 (25%) | 7 |
Breast tenderness | 2/32 (6.3%) | 2 | 0/16 (0%) | 0 |
Dysmenorrhoea | 2/32 (6.3%) | 2 | 1/16 (6.3%) | 1 |
Pelvic pain | 3/32 (9.4%) | 4 | 2/16 (12.5%) | 2 |
Vaginal discharge | 2/32 (6.3%) | 2 | 1/16 (6.3%) | 3 |
Vaginal odour | 0/32 (0%) | 0 | 2/16 (12.5%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||||
Pharyngolaryngeal pain | 4/32 (12.5%) | 5 | 1/16 (6.3%) | 1 |
Skin and subcutaneous tissue disorders | ||||
Acne | 6/32 (18.8%) | 6 | 1/16 (6.3%) | 1 |
Dry skin | 2/32 (6.3%) | 2 | 0/16 (0%) | 0 |
Eczema | 0/32 (0%) | 0 | 1/16 (6.3%) | 2 |
Hirsutism | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Pain of skin | 0/32 (0%) | 0 | 1/16 (6.3%) | 2 |
Skin odour abnormal | 0/32 (0%) | 0 | 1/16 (6.3%) | 1 |
Vascular disorders | ||||
Hot flush | 2/32 (6.3%) | 2 | 0/16 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor recognizes the right of the investigator(s) to publish, but all publications must be based on data validated and released by the Sponsor. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the Sponsor, at least six weeks ahead of estimated publication or presentation, for written consent, which shall not be withheld unreasonably.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | |
ClinicalTrialsDisclosure@merck.com |
- P05723
- Organon protocol 292003