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

• ClinicalTrials.gov Identifier: NCT00511199
• Recruitment Status: Completed
• First Posted: August 3, 2007
• Results First Posted: August 29, 2011
• Last Update Posted: June 6, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Contraception
• Interventions: Drug: NOMAC-E2; Drug: DRSP-EE
• Enrollment: 2152

Participant Flow

Recruitment Details	This study recruited participants from Europe, Asia and Australia.
Pre-assignment Details	In total, 2152 subjects were randomized, of which 1613 subjects to NOMAC-E2 and 539 subjects to DRSP-EE. A total of 2126 subjects were randomized and treated, of which 1591 subjects on NOMAC-E2 and 535 subjects on DRSP-EE.

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Period Title: Overall Study
Started	1591	535
Completed	1142	410
Not Completed	449	125
Reason Not Completed
Unacceptable Vaginal Bleeding	63	4
Other Adverse Event (AE)/ Serious AE	227	52
Withdrawal of Informed Consent	19	4
Pregnancy	6	3
Pregnancy Wish	16	8
Lost to Follow-up	40	17
Other Reason	78	37

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).	Total of all reporting groups
Overall Number of Baseline Participants		1591	535	2126
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1591 participants	535 participants	2126 participants
		28.1 (7.0)	27.6 (7.0)	28.0 (7.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1591 participants	535 participants	2126 participants
	Female	1591 100.0%	535 100.0%	2126 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

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 women years) that the women were under risk of becoming pregnant.
Time Frame	1 year (13 cycles)

Outcome Measure Data

Analysis Population Description

Restricted ITT set included all participants treated except for 2 nonpregnant participants whose exposure was excluded due to limited credibility of diary data & also excluded nonpregnant participants without >= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o confirmed sexual intercourse, based on e-diary data).

Arm/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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1442	486
Overall Number of Units Analyzed; Type of Units Analyzed: Woman years (rounded to nearest integer)	857	295
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Pregnancies per 100 woman years
Overall group	0.467; (0.1271 to 1.1948)	1.017; (0.2097 to 2.971)
=<35 years old (n= 1193; n=402)	0.571; (0.1555 to 1.4614)	1.261; (0.2601 to 3.6858)
>35 years old (n= 249; n=84)	0.000; (0 to 2.3594)	0.000; (0 to 6.4466)

2. Primary Outcome

Title	Number of In-treatment Pregnancies (With +14 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 period of 14 days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 women years) that the women were under risk of becoming pregnant.
Time Frame	1 year (13 cycles)

Outcome Measure Data

Analysis Population Description

Restricted ITT set included all participants treated except for 2 nonpregnant participants whose exposure was excluded due to limited credibility of diary data & also excluded nonpregnant participants without >= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o confirmed sexual intercourse, based on e-diary data).

Arm/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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1442	486
Overall Number of Units Analyzed; Type of Units Analyzed: Woman years (rounded to nearest integer)	857	295
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Pregnancies per 100 woman years
Overall group	0.817; (0.3283 to 1.6826)	1.356; (0.3693 to 3.4707)
=<35 years old (n=1193; n=402)	0.999; (0.4016 to 2.058)	1.682; (0.4582 to 4.3056)
>35 years old (n=249; n=84)	0.000; (0 to 2.3594)	0.000; (0 to 6.4466)

3. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Measure Type: Number; Unit of Measure: participants
Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE)	483	130
Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE)	289	75
Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE)	297	54
Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE)	231	59
Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE)	221	62
Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE)	182	53
Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE)	165	45
Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE)	127	47
Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE)	129	47
Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE)	121	32
Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE)	125	29
Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE)	110	30
Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE)	94	33

4. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Measure Type: Number; Unit of Measure: participants
Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE)	284	14
Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE)	237	17
Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE)	258	18
Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE)	244	20
Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE)	245	17
Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE)	249	10
Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE)	245	11
Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE)	235	9
Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE)	245	13
Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE)	245	12
Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE)	232	17
Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE)	227	12
Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE)	279	14

5. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: LNG-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Measure Type: Number; Unit of Measure: Participants
Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE)	129	24
Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE)	63	20
Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE)	61	16
Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE)	54	11
Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE)	52	12
Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE)	43	8
Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE)	41	7
Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE)	28	5
Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE)	32	7
Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE)	23	7
Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE)	27	7
Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE)	30	13
Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE)	21	12

6. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Measure Type: Number; Unit of Measure: Participants
Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE)	408	118
Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE)	244	58
Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE)	257	42
Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE)	186	51
Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE)	180	52
Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE)	148	45
Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE)	135	40
Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE)	104	43
Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE)	106	40
Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE)	105	27
Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE)	100	22
Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE)	87	18
Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE)	76	22

7. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Measure Type: Number; Unit of Measure: Participants
Cycle 1 (n=1466 NOMAC-E2; n=470 DRSP-EE)	142	52
Cycle 2 (n=1339 NOMAC-E2; n=440 DRSP-EE)	93	29
Cycle 3 (n=1233 NOMAC-E2; n=398 DRSP-EE)	80	22
Cycle 4 (n=1135 NOMAC-E2; n=389 DRSP-EE)	69	20
Cycle 5 (n=1064 NOMAC-E2; n=368 DRSP-EE)	55	22
Cycle 6 (n=982 NOMAC-E2; n=349 DRSP-EE)	34	16
Cycle 7 (n=931 NOMAC-E2; n=320 DRSP-EE)	36	18
Cycle 8 (n=874 NOMAC-E2; n=298 DRSP-EE)	31	12
Cycle 9 (n=861 NOMAC-E2; n=295 DRSP-EE)	33	11
Cycle 10 (n=809 NOMAC-E2; n=271 DRSP-EE)	19	9
Cycle 11 (n=770 NOMAC-E2; n=277 DRSP-EE)	27	9
Cycle 12 (n=743 NOMAC-E2; n=259 DRSP-EE)	18	9
Cycle 13 (n=666 NOMAC-E2; n=241 DRSP-EE)	17	8

8. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame	Every 28-day cycle for 12 cycles

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 13 consecutive 28-day menstrual cycles (1 year). 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 (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year). n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).
Overall Number of Participants Analyzed	1524	503
Measure Type: Number; Unit of Measure: Participants
Cycle 1 (n=1455 NOMAC-E2; n=466 DRSP-EE)	412	283
Cycle 2 (n=1320 NOMAC-E2; n=437 DRSP-EE)	406	274
Cycle 3 (n=1201 NOMAC-E2; n=397 DRSP-EE)	364	243
Cycle 4 (n=1120 NOMAC-E2; n=387 DRSP-EE)	321	222
Cycle 5 (n=1051 NOMAC-E2; n=365 DRSP-EE)	280	203
Cycle 6 (n=965 NOMAC-E2; n=348 DRSP-EE)	285	190
Cycle 7 (n=920 NOMAC-E2; n=318 DRSP-EE)	247	190
Cycle 8 (n=868 NOMAC-E2; n=296 DRSP-EE)	224	170
Cycle 9 (n=854 NOMAC-E2; n=291 DRSP-EE)	228	176
Cycle 10 (n=806 NOMAC-E2; n=269 DRSP-EE)	191	158
Cycle 11 (n=766 NOMAC-E2; n=276 DRSP-EE)	195	162
Cycle 12 (n=725 NOMAC-E2; n=257 DRSP-EE)	184	153

9. Secondary Outcome

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 e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Mean (Standard Deviation); Unit of Measure: days
Cycle 1 (n=483 NOMAC-E2; n=130 DRSP-EE)	4.6 (3.6)	4.2 (3.0)
Cycle 2 (n=289 NOMAC-E2; n=75 DRSP-EE)	3.5 (2.8)	3.2 (2.5)
Cycle 3 (n=297 NOMAC-E2; n=54 DRSP-EE)	3.4 (2.6)	3.6 (2.8)
Cycle 4 (n=231 NOMAC-E2; n=59 DRSP-EE)	3.1 (2.5)	2.9 (2.5)
Cycle 5 (n=221 NOMAC-E2; n=62 DRSP-EE)	3.2 (2.5)	2.9 (2.8)
Cycle 6 (n=182 NOMAC-E2; n=53 DRSP-EE)	3.3 (2.5)	2.4 (2.0)
Cycle 7 (n=165 NOMAC-E2; n=45 DRSP-EE)	3.2 (2.5)	3.0 (2.8)
Cycle 8 (n=127 NOMAC-E2; n=47 DRSP-EE)	3.1 (2.4)	2.7 (1.9)
Cycle 9 (n=129 NOMAC-E2; n=47 DRSP-EE)	3.4 (2.6)	2.6 (2.2)
Cycle 10 (n=121 NOMAC-E2; n=32 DRSP-EE)	3.1 (2.5)	3.1 (2.6)
Cycle 11 (n=125 NOMAC-E2; n=29 DRSP-EE)	2.8 (2.4)	2.6 (2.5)
Cycle 12 (n=110 NOMAC-E2; n=30 DRSP-EE)	3.1 (2.2)	2.6 (2.3)
Cycle 13 (n=94 NOMAC-E2; n=33 DRSP-EE)	2.7 (2.0)	3.2 (2.6)

10. Secondary Outcome

Title	Average Number of Withdrawal Bleeding/Spotting Days
Description	Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding was defined as bleeding/spotting episode that started during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Time Frame	Every 28-day cycle for 13 cycles (one year total)

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 13 consecutive 28-day menstrual cycles (1 year).	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Overall Number of Participants Analyzed	1524	503
Mean (Standard Deviation); Unit of Measure: days
Cycle 1 (n=1182 NOMAC-E2; n=456 DRSP-EE)	5.7 (11.2)	6.0 (3.3)
Cycle 2 (n=1102 NOMAC-E2; n=423 DRSP-EE)	5.6 (15.1)	5.5 (2.2)
Cycle 3 (n=975 NOMAC-E2; n=380 DRSP-EE)	5.9 (19.0)	5.4 (2.4)
Cycle 4 (n=891 NOMAC-E2; n=369 DRSP-EE)	6.0 (19.9)	5.4 (3.5)
Cycle 5 (n=819 NOMAC-E2; n=351 DRSP-EE)	6.0 (20.8)	5.3 (3.4)
Cycle 6 (n=733 NOMAC-E2; n=339 DRSP-EE)	5.8 (21.8)	5.2 (2.8)
Cycle 7 (n=686 NOMAC-E2; n=309 DRSP-EE)	5.8 (22.4)	5.2 (2.5)
Cycle 8 (n=639 NOMAC-E2; n=289 DRSP-EE)	5.6 (22.3)	5.7 (8.5)
Cycle 9 (n=616 NOMAC-E2; n=282 DRSP-EE)	5.7 (21.9)	5.7 (8.5)
Cycle 10 (n=564 NOMAC-E2; n=259 DRSP-EE)	5.7 (23.5)	5.5 (8.2)
Cycle 11 (n=538 NOMAC-E2; n=260 DRSP-EE)	6.0 (24.1)	5.6 (8.3)
Cycle 12 (n=516 NOMAC-E2; n=247 DRSP-EE)	5.6 (21.3)	5.7 (8.9)
Cycle 13 (n=387 NOMAC-E2; n=227 DRSP-EE)	4.9 (23.9)	4.2 (3.8)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
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 13 consecutive 28-day menstrual cycles (1 year).		Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
All-Cause Mortality
	NOMAC-E2		DRSP-EE
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	NOMAC-E2		DRSP-EE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/1591 (2.39%)		13/535 (2.43%)
Ear and labyrinth disorders
Vestibular neuronitis 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Gastrointestinal disorders
Abdominal pain 1	1/1591 (0.06%)	1	1/535 (0.19%)	1
Anal fissure 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Constipation 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Enteritis 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Haemorrhoids 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Mesenteric vein thrombosis 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Nausea 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
General disorders
Fatigue 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Pyrexia 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Hepatobiliary disorders
Cholelithiasis 1	2/1591 (0.13%)	2	0/535 (0.00%)	0
Portal vein thrombosis 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Infections and infestations
Appendicitis 1	1/1591 (0.06%)	1	1/535 (0.19%)	1
Cellulitis 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Cryptosporidiosis infection 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Encephalitis viral 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Epiglottitis 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Gastroenteritis 1	3/1591 (0.19%)	3	0/535 (0.00%)	0
Giardiasis 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Peritonsillar abscess 1	2/1591 (0.13%)	2	0/535 (0.00%)	0
Pilonidal cyst 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Pyelonephritis 1	1/1591 (0.06%)	1	1/535 (0.19%)	1
Injury, poisoning and procedural complications
Alcohol poisoning 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Fibula fracture 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Ligament injury 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Limb injury 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Multiple injuries 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Tibia fracture 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Musculoskeletal and connective tissue disorders
Exostosis 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Intervertebral disc disorder 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Intervertebral disc protrusion 1	3/1591 (0.19%)	3	1/535 (0.19%)	1
Myalgia 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Osteonecrosis 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Systemic lupus erythematosus 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Tenosynovitis 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Colon cancer metastatic 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Metastatic gastric cancer 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Nervous system disorders
Headache 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
Multiple Sclerosis 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Psychiatric disorders
Depression 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Reproductive system and breast disorders
Haematosalpinx 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Menorrhagia 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Hyperventilation 1	1/1591 (0.06%)	1	0/535 (0.00%)	0
Nasal septum deviation 1	2/1591 (0.13%)	2	0/535 (0.00%)	0
Vascular disorders
Deep vein thrombosis 1	0/1591 (0.00%)	0	1/535 (0.19%)	1
1 Term from vocabulary, MedDRA (11.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	NOMAC-E2		DRSP-EE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	849/1591 (53.36%)		242/535 (45.23%)
Infections and infestations
Influenza 1	55/1591 (3.46%)	61	30/535 (5.61%)	36
Nasopharyngitis 1	144/1591 (9.05%)	190	53/535 (9.91%)	66
Vaginal candidiasis 1	127/1591 (7.98%)	143	45/535 (8.41%)	53
Investigations
Weight increased 1	158/1591 (9.93%)	162	37/535 (6.92%)	38
Nervous system disorders
Headache 1	217/1591 (13.64%)	405	72/535 (13.46%)	123
Reproductive system and breast disorders
Cervical dysplasia 1	111/1591 (6.98%)	112	39/535 (7.29%)	40
Withdrawal bleeding irregular 1	188/1591 (11.82%)	424	2/535 (0.37%)	2
Skin and subcutaneous tissue disorders
Acne 1	280/1591 (17.60%)	335	47/535 (8.79%)	53
1 Term from vocabulary, MedDRA (11.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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 consent, which shall not be withheld unreasonably.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Mansour D, Verhoeven C, Sommer W, Weisberg E, Taneepanichskul S, Melis GB, Sundström-Poromaa I, Korver T. Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen. Eur J Contracept Reprod Health Care. 2011 Dec;16(6):430-43. doi: 10.3109/13625187.2011.614029. Epub 2011 Oct 13.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Witjes H, Creinin MD, Sundström-Poromaa I, Martin Nguyen A, Korver T. Comparative analysis of the effects of nomegestrol acetate/17 β-estradiol and drospirenone/ethinylestradiol on premenstrual and menstrual symptoms and dysmenorrhea. Eur J Contracept Reprod Health Care. 2015;20(4):296-307. doi: 10.3109/13625187.2015.1016154. Epub 2015 Feb 25.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00511199 History of Changes
• Other Study ID Numbers: P05724; Organon Protocol No. 292001
• First Submitted: August 2, 2007
• First Posted: August 3, 2007
• Results First Submitted: July 28, 2011
• Results First Posted: August 29, 2011
• Last Update Posted: June 6, 2018