Effects on Ovarian Function of the Combined Oral Contraceptive NOMACE2 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 acetateestradiol (NOMACE2) combined oral contraceptive (COC) on ovarian function.
Condition or Disease  Intervention/Treatment  Phase 

Phase 3 
Study Design
Arms and Interventions
Arm  Intervention/Treatment 

Experimental: NOMACE2 Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive 
Drug: NOMACE2
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 28day menstrual cycles.

Active Comparator: DRSPEE Drospirenone (DRSP) and Ethinyl Estradiol (EE), 3 mg DRSP and 30 mcg EE monophasic combined oral contraceptive 
Drug: DRSPEE
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 28day 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 assessorblind 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 Betaestradiol (E2) [Cycle 1, Cycle 2, Cycle 3, and Cycle 6]
The parameter was measured at predefined 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 predefined 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 predefined study days.
Secondary Outcome Measures
 Effect on Cervical Mucus as Determined by Insler Score [Screening Cycle, Cycle 1, Cycle 2, and Cycle 7 (posttreatment 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 Intreatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [6 cycles]
Intreatment 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 intreatment 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 28day 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 nonbleeding period" that was neither an early nor a continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2: 21day period starting on Day 4 of the cycle.
 Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [Every 28day 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: DRSPEE group: 7day period starting on Day 22 of the cycle; NOMACE2: 7day 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 28day 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 nonbleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2:21day period starting on Day 4 of the cycle.
 Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [Every 28day 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 nonbleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2:21day period starting on Day 4 of the cycle.
 Number of Participants With an Occurrence of Early Withdrawal Bleeding [Every 28day 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: DRSPEE: 7day period starting on Day 22 of the cycle; NOMACE2: 7day 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 28day 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 nonbleeding period" of the next cycle. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2: 21day period starting on Day 4 of the cycle.
 Average Number of Breakthrough Bleeding/Spotting Days [Every 28day 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 nonbleeding period" that was neither an early nor a continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2: 21day period starting on Day 4 of the cycle.
 Average Number of Withdrawal Bleeding Days [Every 28day 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: DRSPEE group: 7day period starting on Day 22 of the cycle; NOMACE2: 7day 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 posttreatment 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 (FullText)
None provided.More Information
Publications
None provided. P05723
 Organon protocol 292003
Study Results
Participant Flow
Recruitment Details  

Preassignment Detail 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Period Title: Overall Study  
STARTED  32  16 
COMPLETED  26  15 
NOT COMPLETED  6  1 
Baseline Characteristics
Arm/Group Title  NOMACE2  DRSPEE  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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day 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 (posttreatment cycle) 
Outcome Measure Data
Analysis Population Description 

ITT group consisted of all participants who were treated. n=number of participants with nonmissing values at the respective time point. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Screening cycle (n=32 NOMACE2 / n=16 DRSPEE) 
8.9
(2.55)

7.3
(3.61)

Cycle 1 (n=30 NOMACE2 / n=15 DRSPEE) 
2.3
(1.93)

3.2
(2.43)

Cycle 2 (n=0 NOMACE2 / n=2 DRSPEE) 
NA
(NA)

4.5
(0.71)

Cycle 7 (n=22 NOMACE2 / n=15 DRSPEE) 
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  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Screening cycle (n=32 NOMACE2 / n=16 DRSPEE) 
9.9
(1.91)

10.1
(2.50)

Cycle 1 (n=32 NOMACE2 / n=16 DRSPEE) 
5.9
(1.22)

6.1
(1.25)

Cycle 2 (n=29 NOMACE2 / n=16 DRSPEE) 
5.3
(0.71)

6.8
(1.73)

Cycle 6 (n=26 NOMACE2 / n=15 DRSPEE) 
4.9
(0.66)

5.5
(1.30)

Title  Number of Intreatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) 

Description  Intreatment 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 intreatment 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  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day 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 nonbleeding period" that was neither an early nor a continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2: 21day period starting on Day 4 of the cycle. 
Time Frame  Every 28day 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 nonevaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=30 NOMACE2 / n=16 DRSPEE) 
7
21.9%

1
6.3%

Cycle 2 (n=27 NOMACE2 / n=16 DRSPEE) 
6
18.8%

0
0%

Cycle 3 (n=26 NOMACE2 / n=15 DRSPEE) 
5
15.6%

0
0%

Cycle 4 (n=26 NOMACE2 / n=15 DRSPEE) 
5
15.6%

0
0%

Cycle 5 (n=26 NOMACE2 / n=15 DRSPEE) 
8
25%

0
0%

Cycle 6 (n=26 NOMACE2 / n=14 DRSPEE) 
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: DRSPEE group: 7day period starting on Day 22 of the cycle; NOMACE2: 7day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle. 
Time Frame  Every 28day 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 nonevaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=30 NOMACE2 / n=16 DRSPEE) 
3
9.4%

0
0%

Cycle 2 (n=27 NOMACE2 / n=16 DRSPEE) 
2
6.3%

0
0%

Cycle 3 (n=26 NOMACE2 / n=15 DRSPEE) 
2
6.3%

0
0%

Cycle 4 (n=26 NOMACE2 / n=15 DRSPEE) 
2
6.3%

0
0%

Cycle 5 (n=26 NOMACE2 / n=15 DRSPEE) 
2
6.3%

0
0%

Cycle 6 (n=26 NOMACE2 / n=14 DRSPEE) 
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 nonbleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2:21day period starting on Day 4 of the cycle. 
Time Frame  Every 28day 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 nonevaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=30 NOMACE2 / n=16 DRSPEE) 
0
0%

0
0%

Cycle 2 (n=27 NOMACE2 / n=16 DRSPEE) 
0
0%

0
0%

Cycle 3 (n=26 NOMACE2 / n=15 DRSPEE) 
0
0%

0
0%

Cycle 4 (n=26 NOMACE2 / n=15 DRSPEE) 
1
3.1%

0
0%

Cycle 5 (n=26 NOMACE2 / n=15 DRSPEE) 
1
3.1%

0
0%

Cycle 6 (n=26 NOMACE2 / n=14 DRSPEE) 
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 nonbleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2:21day period starting on Day 4 of the cycle. 
Time Frame  Every 28day 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 nonevaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=30 NOMACE2 / n=16 DRSPEE) 
7
21.9%

1
6.3%

Cycle 2 (n=27 NOMACE2 / n=16 DRSPEE) 
6
18.8%

0
0%

Cycle 3 (n=26 NOMACE2 / n=15 DRSPEE) 
5
15.6%

0
0%

Cycle 4 (n=26 NOMACE2 / n=15 DRSPEE) 
4
12.5%

0
0%

Cycle 5 (n=26 NOMACE2 / n=15 DRSPEE) 
7
21.9%

0
0%

Cycle 6 (n=26 NOMACE2 / n=14 DRSPEE) 
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: DRSPEE: 7day period starting on Day 22 of the cycle; NOMACE2: 7day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle. 
Time Frame  Every 28day 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 nonevaluable in case of insufficient bleeding data or improper cycle length. n= number of participants with evaluable cycles. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=30 NOMACE2 / n=16 DRSPEE) 
4
12.5%

2
12.5%

Cycle 2 (n=27 NOMACE2 / n=16 DRSPEE) 
4
12.5%

0
0%

Cycle 3 (n=26 NOMACE2 / n=15 DRSPEE) 
1
3.1%

0
0%

Cycle 4 (n=26 NOMACE2 / n=15 DRSPEE) 
2
6.3%

0
0%

Cycle 5 (n=26 NOMACE2 / n=15 DRSPEE) 
1
3.1%

0
0%

Cycle 6 (n=26 NOMACE2 / n=14 DRSPEE) 
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 nonbleeding period" of the next cycle. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2: 21day period starting on Day 4 of the cycle. 
Time Frame  Every 28day 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 nonevaluable in case of insufficient bleeding data or improper cycle length. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day 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 NOMACE2 / n=16 DRSPEE) 
11
34.4%

12
75%

Cycle 2 (n=27 NOMACE2 / n=16 DRSPEE) 
8
25%

10
62.5%

Cycle 3 (n=25 NOMACE2 / n=15 DRSPEE) 
8
25%

11
68.8%

Cycle 4 (n=26 NOMACE2 / n=15 DRSPEE) 
12
37.5%

12
75%

Cycle 5 (n=26 NOMACE2 / n=14 DRSPEE) 
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 assessorblind adjudication. 
Time Frame  Cycle 1, Cycle 2, and Cycle 6 
Outcome Measure Data
Analysis Population Description 

Intenttotreat (ITT) group consisted of all participants who were treated. n=number of participants completing the respective cycle with nonmissing values. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Cycle 1 (n=32 NOMACE2 / n=16 DRSPEE) 
0
0%

0
0%

Cycle 2 (n=29 NOMACE2 / n=16 DRSPEE) 
0
0%

0
0%

Cycle 6 (n=26 NOMACE2 / n=15 DRSPEE) 
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 nonmissing values. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Screening cycle (n=32 NOMACE2 / n=16 DRSPEE) 
19.3
(3.13)

19.6
(4.32)

Cycle 1 (n=32 NOMACE2 / n=16 DRSPEE) 
7.6
(1.51)

8.1
(1.98)

Cycle 2 (n=29 NOMACE2 / n=16 DRSPEE) 
8.2
(1.82)

10.8
(4.76)

Cycle 3 (n=27 NOMACE2 / n=14 DRSPEE) 
7.8
(1.88)

8.4
(2.31)

Cycle 6 (n=26 NOMACE2 / n=15 DRSPEE) 
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 nonmissing values. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Screening cycle (n=32 NOMACE2 / n=16 DRSPEE) 
38.7
(12.62)

38.7
(17.01)

Cycle 1 (n=32 NOMACE2 / n=16 DRSPEE) 
1.7
(0.46)

1.6
(0.28)

Cycle 2 (n=29 NOMACE2 / n=16 DRSPEE) 
1.5
(0.46)

1.5
(0.26)

Cycle 3 (n=27 NOMACE2 / n=14 DRSPEE) 
1.26
(0.10)

1.34
(0.27)

Cycle 6 (n=26 NOMACE2 / n=15 DRSPEE) 
1.3
(0.29)

1.5
(0.26)

Title  Effect on Ovarian Function as Determined by 17 Betaestradiol (E2) 

Description  The parameter was measured at predefined 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 nonmissing values at the respective time point. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Cycle 1, Day 2 (n=32 NOMACE2 / n=16 DRSPEE) 
168.75
(62.37)

79.82
(18.34)

Cycle 1, Day 5 (n=32 NOMACE2 / n=16 DRSPEE) 
194.57
(93.17)

66.66
(10.53)

Cycle 1, Day 8 (n=32 NOMACE2 / n=16 DRSPEE) 
172.35
(66.92)

61.15
(3.66)

Cycle 1, Day 11 (n=30 NOMACE2 / n=16 DRSPEE) 
184.63
(95.70)

60.51
(1.96)

Cycle 1, Day 14 (n=29 NOMACE2 / n=16 DRSPEE) 
197.57
(123.23)

60.26
(1.48)

Cycle 1, Day 18 (n=29 NOMACE2 / n=16 DRSPEE) 
182.72
(84.03)

60.58
(2.93)

Cycle 1, Day 21 (n=30 NOMACE2 / n=16 DRSPEE) 
191.08
(139.50)

59.82
(0)

Cycle 1, Day 24 (n=30 NOMACE2 / n=16 DRSPEE) 
232.80
(281.15)

69.84
(23.50)

Cycle 1, Day 27 (n=30 NOMACE2 / n=16 DRSPEE) 
99.65
(42.53)

150.79
(46.45)

Cycle 2, Day 2 (n=29 NOMACE2 / n=16 DRSPEE) 
176.43
(91.99)

135.86
(106.62)

Cycle 2, Day 5 (n=29 NOMACE2 / n=15 DRSPEE) 
213.64
(104.85)

142.74
(186.99)

Cycle 2, Day 8 (n=29 NOMACE2 / n=16 DRSPEE) 
192.59
(68.83)

131.98
(196.51)

Cycle 2, Day 11 (n=29 NOMACE2 / n=16 DRSPEE) 
185.77
(63.97)

112.23
(152.19)

Cycle 2, Day 14 (n=29 NOMACE2 / n=15 DRSPEE) 
183.66
(74.39)

78.44
(69.99)

Cycle 2, Day 18 (n=28 NOMACE2 / n=15 DRSPEE) 
213.84
(123.35)

60.11
(0.95)

Cycle 2, Day 21 (n=27 NOMACE2 / n=16 DRSPEE) 
192.47
(66.43)

59.91
(0.37)

Cycle 2, Day 24 (n=27 NOMACE2 / n=16 DRSPEE) 
206.20
(147.27)

61.33
(3.95)

Cycle 2, Day 27 (n=27 NOMACE2 / n=16 DRSPEE) 
97.99
(40.88)

155.63
(63.65)

Cycle 3, Day 2 (n=27 NOMACE2 / n=14 DRSPEE) 
148.16
(52.09)

141.11
(115.89)

Cycle 6, Day 14 (n=25 NOMACE2 / n=14 DRSPEE) 
205.89
(104.45)

59.98
(0.59)

Cycle 6, Day 18 (n=26 NOMACE2 / n=15 DRSPEE) 
200.04
(90.28)

64.20
(12.99)

Cycle 6, Day 21 (n=26 NOMACE2 / n=15 DRSPEE) 
188.47
(90.12)

60.82
(3.02)

Cycle 6, Day 24 (n=26 NOMACE2 / n=14 DRSPEE) 
187.16
(106.60)

69.60
(33.97)

Cycle 6, Day 27 (n=26 NOMACE2 / n=15 DRSPEE) 
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 predefined 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 nonmissing values at the respective time point. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Cycle 1, Day 2 (n=32 NOMACE2 / n=16 DRSPEE) 
4.29
(1.45)

4.51
(1.14)

Cycle 1, Day 5 (n=32 NOMACE2 / n=16 DRSPEE) 
4.08
(1.59)

4.23
(1.33)

Cycle 1, Day 8 (n=32 NOMACE2 / n=16 DRSPEE) 
3.59
(1.59)

3.40
(1.57)

Cycle 1, Day 11 (n=30 NOMACE2 / n=16 DRSPEE) 
3.44
(2.07)

2.46
(1.40)

Cycle 1, Day 14 (n=29 NOMACE2 / n=16 DRSPEE) 
3.06
(1.90)

2.32
(1.71)

Cycle 1, Day 18 (n=29 NOMACE2 / n=16 DRSPEE) 
2.95
(1.76)

1.91
(1.69)

Cycle 1, Day 21 (n=30 NOMACE2 / n=16 DRSPEE) 
2.87
(1.96)

1.61
(1.53)

Cycle 1, Day 24 (n=30 NOMACE2 / n=16 DRSPEE) 
2.88
(1.99)

4.50
(4.05)

Cycle 1, Day 27 (n=30 NOMACE2 / n=16 DRSPEE) 
5.42
(2.51)

7.91
(3.95)

Cycle 2, Day 2 (n=29 NOMACE2 / n=16 DRSPEE) 
5.32
(2.05)

5.48
(1.82)

Cycle 2, Day 5 (n=29 NOMACE2 / n=15 DRSPEE) 
4.59
(1.54)

4.08
(1.54)

Cycle 2, Day 8 (n=29 NOMACE2 / n=16 DRSPEE) 
3.99
(1.71)

2.77
(1.19)

Cycle 2, Day 11 (n=29 NOMACE2 / n=16 DRSPEE) 
3.47
(1.68)

1.96
(1.13)

Cycle 2, Day 14 (n=29 NOMACE2 / n=15 DRSPEE) 
3.34
(2.18)

1.44
(1.00)

Cycle 2, Day 18 (n=28 NOMACE2 / n=15 DRSPEE) 
3.18
(1.84)

1.22
(0.94)

Cycle 2, Day 21 (n=27 NOMACE2 / n=16 DRSPEE) 
3.02
(1.64)

1.04
(0.98)

Cycle 2, Day 24 (n=27 NOMACE2 / n=16 DRSPEE) 
3.05
(1.76)

3.52
(3.51)

Cycle 2, Day 27 (n=27 NOMACE2 / n=16 DRSPEE) 
5.92
(2.77)

6.99
(2.78)

Cycle 3, Day 2 (n=27 NOMACE2 / n=14 DRSPEE) 
6.01
(2.08)

5.17
(1.44)

Cycle 6, Day 14 (n=25 NOMACE2 / n=14 DRSPEE) 
3.08
(1.88)

1.43
(1.32)

Cycle 6, Day 18 (n=26 NOMACE2 / n=15 DRSPEE) 
2.82
(1.79)

1.29
(1.28)

Cycle 6, Day 21 (n=26 NOMACE2 / n=15 DRSPEE) 
3.30
(2.14)

0.92
(0.96)

Cycle 6, Day 24 (n=26 NOMACE2 / n=14 DRSPEE) 
2.86
(2.09)

3.18
(3.04)

Cycle 6, Day 27 (n=26 NOMACE2 / n=15 DRSPEE) 
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 nonbleeding period" that was neither an early nor a continued withdrawal bleeding. Expected nonbleeding period: DRSPEE group: 21day period starting on Day 1 of the cycle; NOMACE2: 21day period starting on Day 4 of the cycle. 
Time Frame  Every 28day 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 nonevaluable 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  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=7 NOMACE2; n=1 DRSPEE) 
3.0
(2.2)

2.0
(NA)

Cycle 2 (n=6 NOMACE2; n=0 DRSPEE) 
2.7
(1.9)

NA
(NA)

Cycle 3 (n=5 NOMACE2; n=0 DRSPEE) 
2.2
(1.1)

NA
(NA)

Cycle 4 (n=5 NOMACE2; n=0 DRSPEE) 
4.0
(2.8)

NA
(NA)

Cycle 5 (n=8 NOMACE2; n=0 DRSPEE) 
3.5
(2.3)

NA
(NA)

Cycle 6 (n=5 NOMACE2; n=0 DRSPEE) 
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: DRSPEE group: 7day period starting on Day 22 of the cycle; NOMACE2: 7day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle. 
Time Frame  Every 28day 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 nonevaluable 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  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  30  16 
Cycle 1 (n=27 NOMACE2; n=16 DRSPEE) 
7.2
(6.7)

7.0
(4.7)

Cycle 1 (n=25 NOMACE2; n=16 DRSPEE) 
7.4
(7.5)

5.0
(1.7)

Cycle 3 (n=24 NOMACE2; n=15 DRSPEE) 
4.3
(2.4)

5.4
(1.5)

Cycle 4 (n=24 NOMACE2; n=15 DRSPEE) 
4.7
(1.9)

5.3
(1.0)

Cycle 5 (n=24 NOMACE2; n=15 DRSPEE) 
5.5
(6.1)

4.9
(1.1)

Cycle 6 (n=22 NOMACE2; n=13 DRSPEE) 
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 predefined 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 nonmissing values at the respective time point. 
Arm/Group Title  NOMACE2  DRSPEE 

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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles. 
Measure Participants  32  16 
Cycle 1, Day 2 (n=32 NOMACE2 / n=16 DRSPEE) 
3.73
(1.64)

3.69
(1.58)

Cycle 1, Day 5 (n=32 NOMACE2 / n=16 DRSPEE) 
2.98
(1.49)

4.34
(2.35)

Cycle 1, Day 8 (n=32 NOMACE2 / n=16 DRSPEE) 
2.50
(1.68)

3.09
(2.36)

Cycle 1, Day 11 (n=30 NOMACE2 / n=16 DRSPEE) 
2.13
(1.50)

1.89
(1.45)

Cycle 1, Day 14 (n=29 NOMACE2 / n=16 DRSPEE) 
1.85
(1.77)

2.32
(2.05)

Cycle 1, Day 18 (n=29 NOMACE2 / n=16 DRSPEE) 
1.76
(1.41)

1.61
(1.29)

Cycle 1, Day 21 (n=30 NOMACE2 / n=16 DRSPEE) 
1.45
(1.33)

1.19
(0.86)

Cycle 1, Day 24 (n=30 NOMACE2 / n=16 DRSPEE) 
1.59
(1.44)

2.63
(2.07)

Cycle 1, Day 27 (n=30 NOMACE2 / n=16 DRSPEE) 
3.04
(1.95)

4.34
(2.38)

Cycle 2, Day 2 (n=29 NOMACE2 / n=16 DRSPEE) 
3.47
(2.20)

4.81
(3.01)

Cycle 2, Day 5 (n=29 NOMACE2 / n=15 DRSPEE) 
3.04
(1.94)

5.08
(3.21)

Cycle 2, Day 8 (n=29 NOMACE2 / n=16 DRSPEE) 
2.48
(1.85)

3.33
(1.97)

Cycle 2, Day 11 (n=29 NOMACE2 / n=16 DRSPEE) 
2.54
(2.01)

2.70
(2.18)

Cycle 2, Day 14 (n=29 NOMACE2 / n=15 DRSPEE) 
2.39
(2.17)

1.69
(1.42)

Cycle 2, Day 18 (n=28 NOMACE2 / n=15 DRSPEE) 
2.05
(1.76)

1.60
(1.31)

Cycle 2, Day 21 (n=27 NOMACE2 / n=16 DRSPEE) 
1.68
(1.44)

0.97
(0.67)

Cycle 2, Day 24 (n=27 NOMACE2 / n=16 DRSPEE) 
1.81
(1.75)

2.38
(2.01)

Cycle 2, Day 27 (n=27 NOMACE2 / n=16 DRSPEE) 
3.37
(2.90)

3.92
(2.17)

Cycle 3, Day 2 (n=27 NOMACE2 / n=14 DRSPEE) 
3.71
(2.23)

4.79
(2.67)

Cycle 6, Day 14 (n=25 NOMACE2 / n=14 DRSPEE) 
2.29
(1.86)

2.15
(2.83)

Cycle 6, Day 18 (n=26 NOMACE2 / n=15 DRSPEE) 
1.88
(2.05)

1.27
(1.02)

Cycle 6, Day 21 (n=26 NOMACE2 / n=15 DRSPEE) 
2.00
(1.68)

1.14
(0.89)

Cycle 6, Day 24 (n=26 NOMACE2 / n=14 DRSPEE) 
1.85
(1.75)

2.56
(2.12)

Cycle 6, Day 27 (n=26 NOMACE2 / n=15 DRSPEE) 
3.13
(2.21)

4.03
(2.57)

Adverse Events
Time Frame  

Adverse Event Reporting Description  
Arm/Group Title  NOMACE2  DRSPEE  
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 124, active tablets; Days 2528, placebo tablets) for 6 consecutive 28day 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 121, active tablets; Days 2228, placebo tablets) for 6 consecutive 28day menstrual cycles.  
All Cause Mortality 

NOMACE2  DRSPEE  
Affected / at Risk (%)  # Events  Affected / at Risk (%)  # Events  
Total  / (NaN)  / (NaN)  
Serious Adverse Events 

NOMACE2  DRSPEE  
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 

NOMACE2  DRSPEE  
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