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

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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:
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
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
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 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
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 1591 535 2126
Hide 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%
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)
Hide Outcome Measure Data
Hide 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
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 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)
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)
Hide Outcome Measure Data
Hide 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
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 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
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)
Hide 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 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
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)
Hide 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 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
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: 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)
Hide 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 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)
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)
Hide 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 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
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)
Hide 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 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
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
Hide 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 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
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)
Hide 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 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
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)
Hide 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 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)
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   38/1591 (2.39%)      13/535 (2.43%)    
Ear and labyrinth disorders     
Vestibular neuronitis  1/1591 (0.06%)  1 0/535 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1/1591 (0.06%)  1 1/535 (0.19%)  1
Anal fissure  1/1591 (0.06%)  1 0/535 (0.00%)  0
Constipation  1/1591 (0.06%)  1 0/535 (0.00%)  0
Enteritis  1/1591 (0.06%)  1 0/535 (0.00%)  0
Haemorrhoids  1/1591 (0.06%)  1 0/535 (0.00%)  0
Mesenteric vein thrombosis  1/1591 (0.06%)  1 0/535 (0.00%)  0
Nausea  0/1591 (0.00%)  0 1/535 (0.19%)  1
General disorders     
Fatigue  0/1591 (0.00%)  0 1/535 (0.19%)  1
Pyrexia  1/1591 (0.06%)  1 0/535 (0.00%)  0
Hepatobiliary disorders     
Cholelithiasis  2/1591 (0.13%)  2 0/535 (0.00%)  0
Portal vein thrombosis  1/1591 (0.06%)  1 0/535 (0.00%)  0
Infections and infestations     
Appendicitis  1/1591 (0.06%)  1 1/535 (0.19%)  1
Cellulitis  0/1591 (0.00%)  0 1/535 (0.19%)  1
Cryptosporidiosis infection  0/1591 (0.00%)  0 1/535 (0.19%)  1
Encephalitis viral  1/1591 (0.06%)  1 0/535 (0.00%)  0
Epiglottitis  0/1591 (0.00%)  0 1/535 (0.19%)  1
Gastroenteritis  3/1591 (0.19%)  3 0/535 (0.00%)  0
Giardiasis  0/1591 (0.00%)  0 1/535 (0.19%)  1
Peritonsillar abscess  2/1591 (0.13%)  2 0/535 (0.00%)  0
Pilonidal cyst  1/1591 (0.06%)  1 0/535 (0.00%)  0
Pyelonephritis  1/1591 (0.06%)  1 1/535 (0.19%)  1
Injury, poisoning and procedural complications     
Alcohol poisoning  0/1591 (0.00%)  0 1/535 (0.19%)  1
Fibula fracture  1/1591 (0.06%)  1 0/535 (0.00%)  0
Ligament injury  1/1591 (0.06%)  1 0/535 (0.00%)  0
Limb injury  0/1591 (0.00%)  0 1/535 (0.19%)  1
Multiple injuries  1/1591 (0.06%)  1 0/535 (0.00%)  0
Tibia fracture  1/1591 (0.06%)  1 0/535 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Exostosis  0/1591 (0.00%)  0 1/535 (0.19%)  1
Intervertebral disc disorder  1/1591 (0.06%)  1 0/535 (0.00%)  0
Intervertebral disc protrusion  3/1591 (0.19%)  3 1/535 (0.19%)  1
Myalgia  1/1591 (0.06%)  1 0/535 (0.00%)  0
Osteonecrosis  1/1591 (0.06%)  1 0/535 (0.00%)  0
Systemic lupus erythematosus  0/1591 (0.00%)  0 1/535 (0.19%)  1
Tenosynovitis  0/1591 (0.00%)  0 1/535 (0.19%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1/1591 (0.06%)  1 0/535 (0.00%)  0
Colon cancer metastatic  1/1591 (0.06%)  1 0/535 (0.00%)  0
Metastatic gastric cancer  1/1591 (0.06%)  1 0/535 (0.00%)  0
Nervous system disorders     
Headache  0/1591 (0.00%)  0 1/535 (0.19%)  1
Multiple Sclerosis  1/1591 (0.06%)  1 0/535 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Hyperemesis gravidarum  1/1591 (0.06%)  1 0/535 (0.00%)  0
Psychiatric disorders     
Depression  1/1591 (0.06%)  1 0/535 (0.00%)  0
Reproductive system and breast disorders     
Haematosalpinx  1/1591 (0.06%)  1 0/535 (0.00%)  0
Menorrhagia  1/1591 (0.06%)  1 0/535 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1/1591 (0.06%)  1 0/535 (0.00%)  0
Hyperventilation  1/1591 (0.06%)  1 0/535 (0.00%)  0
Nasal septum deviation  2/1591 (0.13%)  2 0/535 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  0/1591 (0.00%)  0 1/535 (0.19%)  1
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   849/1591 (53.36%)      242/535 (45.23%)    
Infections and infestations     
Influenza  55/1591 (3.46%)  61 30/535 (5.61%)  36
Nasopharyngitis  144/1591 (9.05%)  190 53/535 (9.91%)  66
Vaginal candidiasis  127/1591 (7.98%)  143 45/535 (8.41%)  53
Investigations     
Weight increased  158/1591 (9.93%)  162 37/535 (6.92%)  38
Nervous system disorders     
Headache  217/1591 (13.64%)  405 72/535 (13.46%)  123
Reproductive system and breast disorders     
Cervical dysplasia  111/1591 (6.98%)  112 39/535 (7.29%)  40
Withdrawal bleeding irregular  188/1591 (11.82%)  424 2/535 (0.37%)  2
Skin and subcutaneous tissue disorders     
Acne  280/1591 (17.60%)  335 47/535 (8.79%)  53
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
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
EMail: ClinicalTrialsDisclosure@merck.com
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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