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

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ClinicalTrials.gov Identifier: NCT00413062
Recruitment Status : Completed
First Posted : December 19, 2006
Results First Posted : August 29, 2011
Last Update Posted : August 27, 2015
Sponsor:
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 2281
Recruitment Details This study recruited participants from North America and South America
Pre-assignment Details 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).
Arm/Group Title NOMAC-E2 DRSP-EE
Hide 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 1666 554
Completed 988 344
Not Completed 678 210
Reason Not Completed
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
Arm/Group Title NOMAC-E2 DRSP-EE Total
Hide 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 1666 554 2220
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1666 participants 554 participants 2220 participants
27.6  (7.2) 27.8  (7.0) 27.7  (7.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1666 participants 554 participants 2220 participants
Female
1666
 100.0%
554
 100.0%
2220
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title NOMAC-E2 DRSP-EE
Hide 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 1370 444
Overall Number of Units Analyzed
Type of Units Analyzed: Woman years (rounded to nearest integer)
684 233
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Pregnancies per 100 woman years
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)
2.Primary Outcome
Title Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title NOMAC-E2 DRSP-EE
Hide 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 1370 444
Overall Number of Units Analyzed
Type of Units Analyzed: Woman years (rounded to nearest integer)
684 233
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Pregnancies per 100 woman years
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)
3.Secondary Outcome
Title Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Measure Type: Number
Unit of Measure: 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
4.Secondary Outcome
Title Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Measure Type: Number
Unit of Measure: 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
5.Secondary Outcome
Title Number of Participants With an Occurrence of Breakthrough Bleeding
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Measure Type: Number
Unit of Measure: 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
6.Secondary Outcome
Title Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Measure Type: Number
Unit of Measure: 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
7.Secondary Outcome
Title Number of Participants With an Occurrence of Early Withdrawal Bleeding
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Measure Type: Number
Unit of Measure: 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
8.Secondary Outcome
Title Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Measure Type: Number
Unit of Measure: 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
9.Secondary Outcome
Title Average Number of Breakthrough Bleeding/Spotting Days
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Mean (Standard Deviation)
Unit of Measure: days
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)
10.Secondary Outcome
Title Average Number of Withdrawal Bleeding/Spotting Days
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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 1312 436
Mean (Standard Deviation)
Unit of Measure: days
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)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NOMAC-E2 DRSP-EE
Hide 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   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
NOMAC-E2 DRSP-EE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/1666 (1.92%)      6/554 (1.08%)    
Blood and lymphatic system disorders     
Anaemia  1/1666 (0.06%)  1 0/554 (0.00%)  0
Cardiac disorders     
Cardiac aneurysm  1/1666 (0.06%)  1 0/554 (0.00%)  0
Congenital, familial and genetic disorders     
Venous angioma of brain  1/1666 (0.06%)  1 0/554 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain upper  0/1666 (0.00%)  0 1/554 (0.18%)  1
Gastritis  1/1666 (0.06%)  1 0/554 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  2/1666 (0.12%)  2 0/554 (0.00%)  0
Cholelithiasis  5/1666 (0.30%)  5 0/554 (0.00%)  0
Infections and infestations     
Appendicitis  2/1666 (0.12%)  2 2/554 (0.36%)  2
Bacterial diarrhoea  1/1666 (0.06%)  1 0/554 (0.00%)  0
Pneumonia  1/1666 (0.06%)  1 0/554 (0.00%)  0
Pyelonephritis  1/1666 (0.06%)  1 0/554 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture  1/1666 (0.06%)  1 0/554 (0.00%)  0
Femur fracture  1/1666 (0.06%)  1 0/554 (0.00%)  0
Joint dislocation  0/1666 (0.00%)  0 1/554 (0.18%)  1
Post procedural complication  1/1666 (0.06%)  1 0/554 (0.00%)  0
Post procedural haemorrhage  1/1666 (0.06%)  1 0/554 (0.00%)  0
Road traffic accident  2/1666 (0.12%)  2 0/554 (0.00%)  0
Spinal cord injury cervical  1/1666 (0.06%)  1 0/554 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1/1666 (0.06%)  1 0/554 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign breast neoplasm  0/1666 (0.00%)  0 1/554 (0.18%)  1
Breast cancer  1/1666 (0.06%)  1 0/554 (0.00%)  0
Carcinoid tumor of the appendix  1/1666 (0.06%)  1 0/554 (0.00%)  0
Degeneration of uterine fibroid  1/1666 (0.06%)  1 0/554 (0.00%)  0
Nervous system disorders     
Migraine  1/1666 (0.06%)  1 0/554 (0.00%)  0
Optic neuritis  1/1666 (0.06%)  2 0/554 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Premature separation of placenta  1/1666 (0.06%)  1 0/554 (0.00%)  0
Psychiatric disorders     
Major depression  1/1666 (0.06%)  1 0/554 (0.00%)  0
Psychotic disorder  1/1666 (0.06%)  1 0/554 (0.00%)  0
Reproductive system and breast disorders     
Endometriosis  1/1666 (0.06%)  1 0/554 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthmatic crisis  0/1666 (0.00%)  0 1/554 (0.18%)  1
Surgical and medical procedures     
Breast cosmetic surgery  1/1666 (0.06%)  1 0/554 (0.00%)  0
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide 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   720/1666 (43.22%)      162/554 (29.24%)    
Investigations     
Weight increased  210/1666 (12.61%)  215 38/554 (6.86%)  38
Nervous system disorders     
Headache  121/1666 (7.26%)  162 46/554 (8.30%)  69
Reproductive system and breast disorders     
Cervical dysplasia  77/1666 (4.62%)  78 34/554 (6.14%)  35
Metrorrhagia  102/1666 (6.12%)  120 17/554 (3.07%)  18
Withdrawal bleeding irregular  154/1666 (9.24%)  293 3/554 (0.54%)  6
Skin and subcutaneous tissue disorders     
Acne  327/1666 (19.63%)  390 60/554 (10.83%)  69
1
Term from vocabulary, MedDRA (11.0)
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.
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00413062     History of Changes
Other Study ID Numbers: P05722
292002
First Submitted: December 18, 2006
First Posted: December 19, 2006
Results First Submitted: April 27, 2011
Results First Posted: August 29, 2011
Last Update Posted: August 27, 2015