Efficacy and Safety Study of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing DRSP/EE (292002)(COMPLETED)(P05722)

This study has been completed.

Sponsor:

Information provided by:

Merck

ClinicalTrials.gov Identifier:

NCT00413062

First received: December 18, 2006

Last updated: March 27, 2013

Last verified: March 2013

History of Changes

Results First Received: April 27, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Prevention
Condition:	Contraception
Interventions:	Drug: NOMAC-E2 Drug: DRSP-EE

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study recruited participants from North America and South America

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In total, 2281 participants were randomized (NOMAC-E2 n=1710; DRSP-EE n=571) but 2220 participants were treated (NOMAC-E2 n=1666; DRSP-EE n=554).

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Participant Flow: Overall Study

	NOMAC-E2	DRSP-EE
STARTED	1666	554
COMPLETED	988	344
NOT COMPLETED	678	210
Adverse event/serious adverse event	289	56
Pre-treatment (serious) adverse event	1	0
Withdrawal of informed consent	111	36
Pregnancy	15	5
Pregnancy wish	17	6
Lost to Follow-up	175	73
Other reason	70	34

Baseline Characteristics

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Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Total	Total of all reporting groups

Baseline Measures

	NOMAC-E2	DRSP-EE	Total
Number of Participants [units: participants]	1666	554	2220
Age [units: years] Mean ± Standard Deviation	27.6 ± 7.2	27.8 ± 7.0	27.7 ± 7.1
Gender [units: participants]
Female	1666	554	2220
Male	0	0	0

Outcome Measures

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1. Primary:

Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: 1 year (13 cycles) ]

Measure Type	Primary
Measure Title	Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The "restricted ITT" set included all participants treated except for 27 nonpregnant participants whose exposure was excluded due to limited credibility of diary data, & also excluded nonpregnant participants without >= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse, based on e-diary data).

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1370	444
Number of woman years (rounded to nearest integer) Analyzed [units: woman years (rounded to nearest integer)]	684	233
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [units: Pregnancies per 100 woman years] Number ( 95% Confidence Interval )
Overall group	1.754 ( 0.9061 to 3.0632 )	3.005 ( 1.2082 to 6.1917 )
=<35 years old (n=1158; n=378)	1.963 ( 0.9798 to 3.5119 )	3.092 ( 1.1347 to 6.7299 )
>35 years old (n=212; n=66)	0.807 ( 0.0204 to 4.4977 )	2.572 ( 0.0651 to 14.33 )

No statistical analysis provided for Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)

2. Primary:

Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [ Time Frame: 1 year (13 cycles) ]

Measure Type	Primary
Measure Title	Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The "restricted ITT" set included all participants treated except for 27 nonpregnant participants whose exposure was excluded due to limited credibility of diary data, & also excluded nonpregnant participants without >= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse, based on e-diary data).

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1370	444
Number of woman years (rounded to nearest integer) Analyzed [units: woman years (rounded to nearest integer)]	684	233
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [units: Pregnancies per 100 woman years] Number ( 95% Confidence Interval )
Overall group	2.192 ( 1.2268 to 3.6154 )	4.293 ( 2.0587 to 7.8951 )
=<35 years old (n=1158; n=378)	2.498 ( 1.3657 to 4.1913 )	4.638 ( 2.1208 to 8.8042 )
>35 years old (n=212; n=66)	0.807 ( 0.0204 to 4.4977 )	2.572 ( 0.0651 to 14.33 )

No statistical analysis provided for Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)

3. Secondary:

Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting [units: participants]
Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE)	370	84
Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE)	243	55
Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE)	196	40
Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE)	152	34
Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE)	139	29
Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE)	125	18
Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE)	104	25
Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE)	97	23
Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE)	85	30
Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE)	93	29
Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE)	83	27
Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE)	70	15
Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE)	62	20

No statistical analysis provided for Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting

4. Secondary:

Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

n= number of participants with evaluable cycles.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [units: participants]
Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE)	216	23
Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE)	167	15
Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE)	178	15
Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE)	184	16
Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE)	169	13
Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE)	166	9
Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE)	139	13
Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE)	152	16
Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE)	151	8
Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE)	147	8
Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE)	156	6
Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE)	141	10
Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE)	187	7

No statistical analysis provided for Number of Participants With an Occurrence of Absence of Withdrawal Bleeding

5. Secondary:

Number of Participants With an Occurrence of Breakthrough Bleeding [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Number of Participants With an Occurrence of Breakthrough Bleeding
Measure 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: 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

n= number of participants with evaluable cycles.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Number of Participants With an Occurrence of Breakthrough Bleeding [units: participants]
Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE)	100	19
Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE)	47	5
Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE)	43	5
Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE)	39	7
Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE)	30	4
Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE)	29	4
Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE)	31	5
Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE)	25	5
Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE)	24	7
Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE)	27	9
Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE)	19	5
Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE)	16	3
Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE)	16	2

No statistical analysis provided for Number of Participants With an Occurrence of Breakthrough Bleeding

6. Secondary:

Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

n= number of participants with evaluable cycles.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [units: participants]
Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE)	306	72
Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE)	211	50
Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE)	168	36
Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE)	126	30
Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE)	114	25
Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE)	102	16
Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE)	85	20
Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE)	78	18
Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE)	64	23
Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE)	71	21
Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE)	67	22
Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE)	59	12
Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE)	46	18

No statistical analysis provided for Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)

7. Secondary:

Number of Participants With an Occurrence of Early Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Number of Participants With an Occurrence of Early Withdrawal Bleeding
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

n= number of participants with evaluable cycles.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Number of Participants With an Occurrence of Early Withdrawal Bleeding [units: participants]
Cycle 1 (n=1202 NOMAC-E2; n=398 DRSP-EE)	175	46
Cycle 2 (n=950 NOMAC-E2; n=308 DRSP-EE)	68	14
Cycle 3 (n=812 NOMAC-E2; n=256 DRSP-EE)	66	24
Cycle 4 (n=739 NOMAC-E2; n=236 DRSP-EE)	48	9
Cycle 5 (n=671 NOMAC-E2; n=229 DRSP-EE)	36	11
Cycle 6 (n=628 NOMAC-E2; n=207 DRSP-EE)	28	11
Cycle 7 (n=565 NOMAC-E2; n=196 DRSP-EE)	22	11
Cycle 8 (n=543 NOMAC-E2; n=189 DRSP-EE)	29	13
Cycle 9 (n=507 NOMAC-E2; n=173 DRSP-EE)	17	9
Cycle 10 (n=491 NOMAC-E2; n=170 DRSP-EE)	27	13
Cycle 11 (n=456 NOMAC-E2; n=160 DRSP-EE)	17	7
Cycle 12 (n=428 NOMAC-E2; n=152 DRSP-EE)	10	6
Cycle 13 (n=383 NOMAC-E2; n=133 DRSP-EE)	9	6

No statistical analysis provided for Number of Participants With an Occurrence of Early Withdrawal Bleeding

8. Secondary:

Number of Participants With an Occurrence of Continued Withdrawal Bleeding [ Time Frame: Every 28-day cycle for 12 cycles ]

Measure Type	Secondary
Measure Title	Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Measure 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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year). n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year). n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).

Description

NOMAC-E2

Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).

DRSP-EE

Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Number of Participants With an Occurrence of Continued Withdrawal Bleeding [units: participants]
Cycle 1 (n=1179 NOMAC-E2; n=393 DRSP-EE)	367	216
Cycle 2 (n=939 NOMAC-E2; n=304 DRSP-EE)	309	174
Cycle 3 (n=794 NOMAC-E2; n=254 DRSP-EE)	225	149
Cycle 4 (n=730 NOMAC-E2; n=235 DRSP-EE)	192	145
Cycle 5 (n=659 NOMAC-E2; n=227 DRSP-EE)	171	135
Cycle 6 (n=617 NOMAC-E2; n=207 DRSP-EE)	149	122
Cycle 7 (n=555 NOMAC-E2; n=194 DRSP-EE)	142	111
Cycle 8 (n=540 NOMAC-E2; n=188 DRSP-EE)	128	107
Cycle 9 (n=503 NOMAC-E2; n=171 DRSP-EE)	116	106
Cycle 10 (n=486 NOMAC-E2; n=169 DRSP-EE)	121	95
Cycle 11 (n=455 NOMAC-E2; n=159 DRSP-EE)	90	94
Cycle 12 (n=421 NOMAC-E2; n=149 DRSP-EE)	95	78

No statistical analysis provided for Number of Participants With an Occurrence of Continued Withdrawal Bleeding

9. Secondary:

Average Number of Breakthrough Bleeding/Spotting Days [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Average Number of Breakthrough Bleeding/Spotting Days
Measure 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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

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.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Average Number of Breakthrough Bleeding/Spotting Days [units: days] Mean ± Standard Deviation
Cycle 1 (n=370 NOMAC-E2; n=84 DRSP-EE)	4.5 ± 3.6	4.0 ± 2.9
Cycle 2 (n=243 NOMAC-E2; n=55 DRSP-EE)	3.5 ± 2.7	2.7 ± 2.3
Cycle 3 (n=196 NOMAC-E2; n=40 DRSP-EE)	3.2 ± 2.5	2.6 ± 2.0
Cycle 4 (n=152 NOMAC-E2; n=34 DRSP-EE)	3.5 ± 2.7	3.2 ± 2.5
Cycle 5 (n=139 NOMAC-E2; n=29 DRSP-EE)	3.6 ± 3.0	2.6 ± 2.1
Cycle 6 (n=125 NOMAC-E2; n=18 DRSP-EE)	3.2 ± 2.7	3.0 ± 1.7
Cycle 7 (n=104 NOMAC-E2; n=25 DRSP-EE)	3.9 ± 2.9	2.9 ± 2.0
Cycle 8 (n=97 NOMAC-E2; n=23 DRSP-EE)	3.4 ± 2.4	2.6 ± 2.4
Cycle 9 (n=85 NOMAC-E2; n=30 DRSP-EE)	3.5 ± 3.2	3.2 ± 2.2
Cycle 10 (n=93 NOMAC-E2; n=29 DRSP-EE)	2.6 ± 2.1	3.2 ± 2.1
Cycle 11 (n=83 NOMAC-E2; n=27 DRSP-EE)	3.6 ± 2.5	2.9 ± 2.0
Cycle 12 (n=70 NOMAC-E2; n=15 DRSP-EE)	2.9 ± 2.4	3.1 ± 2.9
Cycle 13 (n=62 NOMAC-E2; n=20 DRSP-EE)	2.8 ± 2.2	3.0 ± 1.9

No statistical analysis provided for Average Number of Breakthrough Bleeding/Spotting Days

10. Secondary:

Average Number of Withdrawal Bleeding/Spotting Days [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type	Secondary
Measure Title	Average Number of Withdrawal Bleeding/Spotting Days
Measure 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)
Safety Issue	No

Population Description

n= number of participants who had withdrawal bleeding/spotting for the respective cycle.

Reporting Groups

	Description
NOMAC-E2	Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE	Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values

	NOMAC-E2	DRSP-EE
Number of Participants Analyzed [units: participants]	1312	436
Average Number of Withdrawal Bleeding/Spotting Days [units: days] Mean ± Standard Deviation
Cycle 1 (n=986 NOMAC-E2; n=375 DRSP-EE)	5.7 ± 5.0	6.0 ± 3.5
Cycle 2 (n=783 NOMAC-E2; n=293 DRSP-EE)	5.0 ± 4.6	6.2 ± 17.1
Cycle 3 (n=634 NOMAC-E2; n=241 DRSP-EE)	4.8 ± 4.4	6.6 ± 18.9
Cycle 4 (n=555 NOMAC-E2; n=220 DRSP-EE)	4.5 ± 2.9	6.5 ± 19.8
Cycle 5 (n=502 NOMAC-E2; n=216 DRSP-EE)	4.5 ± 3.5	6.6 ± 19.9
Cycle 6 (n=462 NOMAC-E2; n=198 DRSP-EE)	4.1 ± 2.5	6.6 ± 20.8
Cycle 7 (n=426 NOMAC-E2; n=183 DRSP-EE)	4.2 ± 3.4	6.5 ± 21.6
Cycle 8 (n=391 NOMAC-E2; n=173 DRSP-EE)	4.1 ± 2.4	6.8 ± 22.3
Cycle 9 (n=356 NOMAC-E2; n=165 DRSP-EE)	3.9 ± 2.2	6.9 ± 22.8
Cycle 10 (n=344 NOMAC-E2; n=162 DRSP-EE)	4.2 ± 2.8	6.8 ± 23.0
Cycle 11 (n=300 NOMAC-E2; n=154 DRSP-EE)	3.8 ± 1.9	6.8 ± 23.6
Cycle 12 (n=287 NOMAC-E2; n=142 DRSP-EE)	3.8 ± 2.5	6.9 ± 24.6
Cycle 13 (n=196 NOMAC-E2; n=126 DRSP-EE)	2.8 ± 2.3	4.3 ± 1.6

No statistical analysis provided for Average Number of Withdrawal Bleeding/Spotting Days

Serious Adverse Events

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Other Adverse Events

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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 agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp.
e-mail: ClinicalTrialsDisclosure@merck.com

No publications provided by Merck

Publications automatically indexed to this study:

Westhoff C, Kaunitz AM, Korver T, Sommer W, Bahamondes L, Darney P, Verhoeven C. Efficacy, safety, and tolerability of a monophasic oral contraceptive containing nomegestrol acetate and 17β-estradiol: a randomized controlled trial. Obstet Gynecol. 2012 May;119(5):989-99.

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT00413062 History of Changes
Other Study ID Numbers:	Organon protocol 292002, P05722
Study First Received:	December 18, 2006
Results First Received:	April 27, 2011
Last Updated:	March 27, 2013
Health Authority:	United States: Food and Drug Administration

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