Trial Outcomes & Findings for Efficacy and Safety Study of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing DRSP/EE (292002)(P05722) (NCT NCT00413062)

NCT ID: NCT00413062

Last Updated: 2022-02-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2281 participants

Primary outcome timeframe

1 year (13 cycles)

Results posted on

2022-02-09

Participant Flow

This study recruited participants from North America and South America

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).

Participant milestones

Participant milestones
Measure
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).
Overall Study
STARTED
1666
554
Overall Study
COMPLETED
988
344
Overall Study
NOT COMPLETED
678
210

Reasons for withdrawal

Reasons for withdrawal
Measure
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).
Overall Study
Adverse event/serious adverse event
289
56
Overall Study
Pre-treatment (serious) adverse event
1
0
Overall Study
Withdrawal of informed consent
111
36
Overall Study
Pregnancy
15
5
Overall Study
Pregnancy wish
17
6
Overall Study
Lost to Follow-up
175
73
Overall Study
Other reason
70
34

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
NOMAC-E2
n=1666 Participants
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
n=554 Participants
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
n=2220 Participants
Total of all reporting groups
Age, Continuous
27.6 years
STANDARD_DEVIATION 7.2 • n=5 Participants
27.8 years
STANDARD_DEVIATION 7.0 • n=7 Participants
27.7 years
STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male
Female
1666 Participants
n=5 Participants
554 Participants
n=7 Participants
2220 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 1 year (13 cycles)

Population: 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).

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.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=684 woman years (rounded to nearest integer)
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
n=233 woman years (rounded to nearest integer)
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).
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Overall group
1.754 Pregnancies per 100 woman years
Interval 0.9061 to 3.0632
3.005 Pregnancies per 100 woman years
Interval 1.2082 to 6.1917
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
=<35 years old (n=1158; n=378)
1.963 Pregnancies per 100 woman years
Interval 0.9798 to 3.5119
3.092 Pregnancies per 100 woman years
Interval 1.1347 to 6.7299
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
>35 years old (n=212; n=66)
0.807 Pregnancies per 100 woman years
Interval 0.0204 to 4.4977
2.572 Pregnancies per 100 woman years
Interval 0.0651 to 14.33

PRIMARY outcome

Timeframe: 1 year (13 cycles)

Population: 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).

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.

Outcome measures

Outcome measures
Measure
NOMAC-E2
n=684 woman years (rounded to nearest integer)
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
n=233 woman years (rounded to nearest integer)
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).
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Overall group
2.192 Pregnancies per 100 woman years
Interval 1.2268 to 3.6154
4.293 Pregnancies per 100 woman years
Interval 2.0587 to 7.8951
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
=<35 years old (n=1158; n=378)
2.498 Pregnancies per 100 woman years
Interval 1.3657 to 4.1913
4.638 Pregnancies per 100 woman years
Interval 2.1208 to 8.8042
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
>35 years old (n=212; n=66)
0.807 Pregnancies per 100 woman years
Interval 0.0204 to 4.4977
2.572 Pregnancies per 100 woman years
Interval 0.0651 to 14.33

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 12 cycles

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Every 28-day cycle for 13 cycles (one year total)

Population: 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.

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.

Outcome measures

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

Adverse Events

NOMAC-E2

Serious events: 32 serious events
Other events: 720 other events
Deaths: 0 deaths

DRSP-EE

Serious events: 6 serious events
Other events: 162 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
NOMAC-E2
n=1666 participants at risk
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
n=554 participants at risk
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).
Blood and lymphatic system disorders
Anaemia
0.06%
1/1666 • Number of events 1
0.00%
0/554
Cardiac disorders
Cardiac aneurysm
0.06%
1/1666 • Number of events 1
0.00%
0/554
Congenital, familial and genetic disorders
Venous angioma of brain
0.06%
1/1666 • Number of events 1
0.00%
0/554
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/1666
0.18%
1/554 • Number of events 1
Gastrointestinal disorders
Gastritis
0.06%
1/1666 • Number of events 1
0.00%
0/554
Hepatobiliary disorders
Cholecystitis
0.12%
2/1666 • Number of events 2
0.00%
0/554
Hepatobiliary disorders
Cholelithiasis
0.30%
5/1666 • Number of events 5
0.00%
0/554
Infections and infestations
Appendicitis
0.12%
2/1666 • Number of events 2
0.36%
2/554 • Number of events 2
Infections and infestations
Bacterial diarrhoea
0.06%
1/1666 • Number of events 1
0.00%
0/554
Infections and infestations
Pneumonia
0.06%
1/1666 • Number of events 1
0.00%
0/554
Infections and infestations
Pyelonephritis
0.06%
1/1666 • Number of events 1
0.00%
0/554
Injury, poisoning and procedural complications
Ankle fracture
0.06%
1/1666 • Number of events 1
0.00%
0/554
Injury, poisoning and procedural complications
Femur fracture
0.06%
1/1666 • Number of events 1
0.00%
0/554
Injury, poisoning and procedural complications
Joint dislocation
0.00%
0/1666
0.18%
1/554 • Number of events 1
Injury, poisoning and procedural complications
Post procedural complication
0.06%
1/1666 • Number of events 1
0.00%
0/554
Injury, poisoning and procedural complications
Post procedural haemorrhage
0.06%
1/1666 • Number of events 1
0.00%
0/554
Injury, poisoning and procedural complications
Road traffic accident
0.12%
2/1666 • Number of events 2
0.00%
0/554
Injury, poisoning and procedural complications
Spinal cord injury cervical
0.06%
1/1666 • Number of events 1
0.00%
0/554
Musculoskeletal and connective tissue disorders
Back pain
0.06%
1/1666 • Number of events 1
0.00%
0/554
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm
0.00%
0/1666
0.18%
1/554 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.06%
1/1666 • Number of events 1
0.00%
0/554
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoid tumor of the appendix
0.06%
1/1666 • Number of events 1
0.00%
0/554
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Degeneration of uterine fibroid
0.06%
1/1666 • Number of events 1
0.00%
0/554
Nervous system disorders
Migraine
0.06%
1/1666 • Number of events 1
0.00%
0/554
Nervous system disorders
Optic neuritis
0.06%
1/1666 • Number of events 2
0.00%
0/554
Pregnancy, puerperium and perinatal conditions
Premature separation of placenta
0.06%
1/1666 • Number of events 1
0.00%
0/554
Psychiatric disorders
Major depression
0.06%
1/1666 • Number of events 1
0.00%
0/554
Psychiatric disorders
Psychotic disorder
0.06%
1/1666 • Number of events 1
0.00%
0/554
Reproductive system and breast disorders
Endometriosis
0.06%
1/1666 • Number of events 1
0.00%
0/554
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis
0.00%
0/1666
0.18%
1/554 • Number of events 1
Surgical and medical procedures
Breast cosmetic surgery
0.06%
1/1666 • Number of events 1
0.00%
0/554

Other adverse events

Other adverse events
Measure
NOMAC-E2
n=1666 participants at risk
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
n=554 participants at risk
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).
Investigations
Weight increased
12.6%
210/1666 • Number of events 215
6.9%
38/554 • Number of events 38
Nervous system disorders
Headache
7.3%
121/1666 • Number of events 162
8.3%
46/554 • Number of events 69
Reproductive system and breast disorders
Cervical dysplasia
4.6%
77/1666 • Number of events 78
6.1%
34/554 • Number of events 35
Reproductive system and breast disorders
Metrorrhagia
6.1%
102/1666 • Number of events 120
3.1%
17/554 • Number of events 18
Reproductive system and breast disorders
Withdrawal bleeding irregular
9.2%
154/1666 • Number of events 293
0.54%
3/554 • Number of events 6
Skin and subcutaneous tissue disorders
Acne
19.6%
327/1666 • Number of events 390
10.8%
60/554 • Number of events 69

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER