Trial Outcomes & Findings for Effects on Bone Mineral Density (BMD) of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG/EE (292005)(P05765)(COMPLETED) (NCT NCT00511342)
NCT ID: NCT00511342
Last Updated: 2022-02-09
Results Overview
BMD was measured by a Dual Energy X-ray Absorptiometry (DEXA) machine. The Z-score measures the distance of the measured BMD value from the appropriate normal age matched population mean value in units of standard deviation of this population. More negative scores indicate less BMD compared to age matched population, \& more positive scores indicate higher BMD compared to age matched population. The adjusted mean change from baseline to the after Cycle 26 visit of the Z-scores is estimated using a baseline-adjusted analysis of covariance (ANCOVA).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
110 participants
Primary outcome timeframe
Baseline and after cycle 26 (2 years)
Results posted on
2022-02-09
Participant Flow
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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Overall Study
STARTED
|
56
|
54
|
|
Overall Study
COMPLETED
|
43
|
32
|
|
Overall Study
NOT COMPLETED
|
13
|
22
|
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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Overall Study
Unacceptable vaginal bleeding
|
2
|
1
|
|
Overall Study
Other Adverse Event (AE)/ Serious AE
|
8
|
12
|
|
Overall Study
Pregnancy
|
0
|
1
|
|
Overall Study
Pregnancy wish
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
5
|
|
Overall Study
Other Reason
|
2
|
2
|
Baseline Characteristics
Effects on Bone Mineral Density (BMD) of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG/EE (292005)(P05765)(COMPLETED)
Baseline characteristics by cohort
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=54 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
Total
n=110 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
23.0 years
STANDARD_DEVIATION 3.2 • n=39 Participants
|
22.1 years
STANDARD_DEVIATION 2.0 • n=41 Participants
|
22.6 years
STANDARD_DEVIATION 2.7 • n=35 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=39 Participants
|
54 Participants
n=41 Participants
|
110 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Baseline Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck
Lumbar Spine
|
0.351 score on a scale
n=39 Participants
|
-0.106 score on a scale
n=41 Participants
|
0.127 score on a scale
n=35 Participants
|
|
Baseline Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck
Femoral Neck
|
0.321 score on a scale
n=39 Participants
|
0.035 score on a scale
n=41 Participants
|
0.181 score on a scale
n=35 Participants
|
PRIMARY outcome
Timeframe: Baseline and after cycle 26 (2 years)Population: All-Subjects-Treated (AST) group consisted of all randomized participants who took at least one dose of trial medication. The number of participants in the AST group with a baseline value and a Week 26 value is presented.
BMD was measured by a Dual Energy X-ray Absorptiometry (DEXA) machine. The Z-score measures the distance of the measured BMD value from the appropriate normal age matched population mean value in units of standard deviation of this population. More negative scores indicate less BMD compared to age matched population, \& more positive scores indicate higher BMD compared to age matched population. The adjusted mean change from baseline to the after Cycle 26 visit of the Z-scores is estimated using a baseline-adjusted analysis of covariance (ANCOVA).
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=54 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Mean Change From Baseline in Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck
Lumbar Spine (n=42/ n=34)
|
0.019 score on a scale
Standard Deviation 0.242 • Interval -0.049 to 0.108
|
0.121 score on a scale
Standard Deviation 0.269 • Interval 0.02 to 0.195
|
|
Mean Change From Baseline in Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck
Femoral Neck (n=42/ n=34 )
|
-0.007 score on a scale
Standard Deviation 0.228 • Interval -0.068 to 0.073
|
0.044 score on a scale
Standard Deviation 0.253 • Interval -0.045 to 0.111
|
SECONDARY outcome
Timeframe: 2 years (26 cycles)Population: Restricted Intent-To-Treat (ITT) analysis set included all participants treated, and further excluded non-pregnant participants without at least one cycle expected to be at risk for pregnancy(with recorded use of condoms or without confirmed sexual intercourse, as determined from the electronic diary data).
Contraceptive efficacy parameter of this trial was the Pearl Index. 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
| Measure |
NOMAC-E2
n=72 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=58 Woman years (rounded to nearest integer)
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
|
0.000 Pregnancies per 100 woman years
Interval 0.0 to 5.1276
|
1.734 Pregnancies per 100 woman years
Interval 0.0439 to 9.6621
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. 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: 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.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE)
|
22 participants
|
14 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE)
|
12 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE)
|
11 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE)
|
10 participants
|
5 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE)
|
9 participants
|
8 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE)
|
7 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE)
|
2 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE)
|
2 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE)
|
6 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE)
|
3 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE)
|
12 participants
|
6 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE)
|
15 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE)
|
6 participants
|
5 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE)
|
4 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE)
|
6 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE)
|
5 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE)
|
6 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE)
|
3 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE)
|
6 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE)
|
4 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE)
|
1 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE)
|
2 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE)
|
4 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE)
|
4 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE)
|
2 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE)
|
4 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. 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: LNG-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2 group: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE)
|
9 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE)
|
9 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE)
|
4 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE)
|
16 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE)
|
10 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE)
|
13 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE)
|
14 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE)
|
16 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE)
|
12 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE)
|
11 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE)
|
12 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE)
|
21 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE)
|
17 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE)
|
18 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE)
|
13 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE)
|
18 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE)
|
20 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE)
|
17 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE)
|
14 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE)
|
15 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE)
|
12 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE)
|
17 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE)
|
16 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE)
|
19 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE)
|
15 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE)
|
24 participants
|
11 participants
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. 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.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE)
|
3 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE)
|
0 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE)
|
1 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE)
|
6 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE)
|
2 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE)
|
2 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE)
|
2 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE)
|
2 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE)
|
1 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE)
|
2 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE)
|
1 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE)
|
1 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE)
|
2 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE)
|
2 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE)
|
1 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE)
|
0 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE)
|
0 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Bleeding
Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE)
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. 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: 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.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE)
|
3 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE)
|
4 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE)
|
2 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE)
|
4 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE)
|
9 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE)
|
11 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE)
|
9 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE)
|
6 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE)
|
8 participants
|
8 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE)
|
6 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE)
|
6 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE)
|
5 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE)
|
2 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE)
|
1 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE)
|
5 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE)
|
2 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE)
|
1 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE)
|
1 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE)
|
2 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE)
|
3 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE)
|
2 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE)
|
6 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE)
|
3 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE)
|
17 participants
|
13 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE)
|
10 participants
|
5 participants
|
|
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE)
|
14 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. 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: LNG-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2 group: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE)
|
5 participants
|
7 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE)
|
3 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE)
|
3 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE)
|
1 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE)
|
3 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE)
|
1 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE)
|
4 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE)
|
1 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE)
|
0 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE)
|
1 participants
|
4 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE)
|
1 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE)
|
2 participants
|
3 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE)
|
1 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE)
|
0 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE)
|
0 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE)
|
0 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE)
|
0 participants
|
0 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE)
|
0 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE)
|
1 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE)
|
0 participants
|
1 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE)
|
1 participants
|
2 participants
|
|
Number of Participants With an Occurrence of Early Withdrawal Bleeding
Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE)
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years total) including one week after stopping treatmentPopulation: 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 diary cards. 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: 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.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE)
|
10 participants
|
24 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE)
|
14 participants
|
19 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 3 (n=53 Nomac-E2/ n=45 LNG-EE)
|
14 participants
|
17 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 4 (n=51 Nomac-E2/ n=43 LNG-EE)
|
9 participants
|
19 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE)
|
9 participants
|
18 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 6 (n=50 Nomac-E2/ n=43 LNG-EE)
|
11 participants
|
14 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 7 (n=48 Nomac-E2/ n=41 LNG-EE)
|
7 participants
|
15 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE)
|
10 participants
|
16 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE)
|
11 participants
|
9 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 10 (n=44 Nomac-E2/ n=39 LNG-EE)
|
5 participants
|
13 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 11 (n=43 Nomac-E2/ n=40 LNG-EE)
|
5 participants
|
16 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE)
|
6 participants
|
18 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 13 (n=41 Nomac-E2/ n=38 LNG-EE)
|
8 participants
|
9 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 14 (n=42 Nomac-E2/ n=38 LNG-EE)
|
10 participants
|
12 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE)
|
6 participants
|
10 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE)
|
4 participants
|
11 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE)
|
6 participants
|
14 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE)
|
4 participants
|
14 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 19 (n=43 Nomac-E2/ n=36 LNG-EE)
|
7 participants
|
15 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE)
|
3 participants
|
13 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 21 (n=41 Nomac-E2/ n=34 LNG-EE)
|
6 participants
|
16 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE)
|
7 participants
|
13 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE)
|
4 participants
|
12 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE)
|
3 participants
|
10 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE)
|
3 participants
|
7 participants
|
|
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Cycle 26 (n=4Nomac-E2/ n=1 LNG-EE)
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. Participants documented whether vaginal bleeding was present, and if so, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any bleeding/spotting episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: LNG-EE: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 14 (n=3 Nomac-E2/ n=3 LNG-EE)
|
1.3 days
Standard Deviation 0.6
|
2.7 days
Standard Deviation 1.5
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 20 (n=4 Nomac-E2/ n=2 LNG-EE)
|
3.5 days
Standard Deviation 2.1
|
4.0 days
Standard Deviation 4.2
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 23 (n=4 Nomac-E2/ n=5 LNG-EE)
|
3.8 days
Standard Deviation 2.9
|
3.4 days
Standard Deviation 1.8
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 26 (n=3 Nomac-E2/ n=0 LNG-EE)
|
2.3 days
Standard Deviation 2.3
|
NA days
Standard Deviation NA
Mean and Standard Deviation does not apply for 0 participants.
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 1 (n=22 Nomac-E2/ n=14 LNG-EE)
|
4.1 days
Standard Deviation 3.1
|
2.2 days
Standard Deviation 1.9
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 2 (n=12 Nomac-E2/ n=6 LNG-EE)
|
3.8 days
Standard Deviation 3.1
|
4.8 days
Standard Deviation 1.9
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 3 (n=15 Nomac-E2/ n=3 LNG-EE)
|
4.1 days
Standard Deviation 3.8
|
4.0 days
Standard Deviation 1.7
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 4 (n=12 Nomac-E2/ n=2 LNG-EE)
|
4.0 days
Standard Deviation 2.8
|
1.5 days
Standard Deviation 0.7
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 5 (n=11 Nomac-E2/ n=2 LNG-EE)
|
3.7 days
Standard Deviation 2.3
|
6.5 days
Standard Deviation 6.4
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 6 (n=10 Nomac-E2/ n=5 LNG-EE)
|
2.0 days
Standard Deviation 1.2
|
2.6 days
Standard Deviation 1.8
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 7 (n=6 Nomac-E2/ n=5 LNG-EE)
|
3.0 days
Standard Deviation 1.9
|
2.6 days
Standard Deviation 0.9
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 8 (n=4 Nomac-E2/ n=3 LNG-EE)
|
2.3 days
Standard Deviation 1.5
|
2.0 days
Standard Deviation 1.0
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 9 (n=9 Nomac-E2/ n=8 LNG-EE)
|
2.2 days
Standard Deviation 1.4
|
2.1 days
Standard Deviation 1.0
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 10 (n=7 Nomac-E2/ n=1 LNG-EE)
|
2.0 days
Standard Deviation 0.8
|
2.0 days
Standard Deviation NA
Value for one participant, therefore, standard deviation does not apply.
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 11 (n=6 Nomac-E2/ n=3 LNG-EE)
|
2.0 days
Standard Deviation 1.1
|
2.3 days
Standard Deviation 1.2
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 12 (n=5 Nomac-E2/ n=4 LNG-EE)
|
3.2 days
Standard Deviation 0.8
|
4.0 days
Standard Deviation 2.4
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 13 (n=6 Nomac-E2/ n=4 LNG-EE)
|
3.0 days
Standard Deviation 2.1
|
3.0 days
Standard Deviation 2.2
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 15 (n=2 Nomac-E2/ n=2 LNG-EE)
|
2.0 days
Standard Deviation 1.4
|
7.5 days
Standard Deviation 2.1
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 16 (n=6 Nomac-E2/ n=2 LNG-EE)
|
1.5 days
Standard Deviation 0.5
|
1.5 days
Standard Deviation 0.7
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 17 (n=4 Nomac-E2/ n=2 LNG-EE)
|
1.8 days
Standard Deviation 1.0
|
2.0 days
Standard Deviation 1.4
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 18 (n=1 Nomac-E2/ n=3 LNG-EE)
|
3.0 days
Standard Deviation NA
Value for one participant, therefore, standard deviation does not apply.
|
3.0 days
Standard Deviation 2.0
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 19 (n=2 Nomac-E2/ n=2 LNG-EE)
|
2.0 days
Standard Deviation 1.4
|
6.0 days
Standard Deviation 1.4
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 21 (n=4 Nomac-E2/ n=1 LNG-EE)
|
2.3 days
Standard Deviation 1.3
|
5.0 days
Standard Deviation NA
Value for one participant, therefore, standard deviation does not apply.
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 22 (n=2 Nomac-E2/ n=1 LNG-EE)
|
3.0 days
Standard Deviation 1.4
|
6.0 days
Standard Deviation NA
Value for one participant, therefore, standard deviation does not apply.
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 24 (n=2 Nomac-E2/ n=3 LNG-EE)
|
2.0 days
Standard Deviation 1.4
|
4.7 days
Standard Deviation 3.2
|
|
Average Number of Breakthrough Bleeding-Spotting Days
Cycle 25 (n=6 Nomac-E2/ n=2 LNG-EE)
|
2.2 days
Standard Deviation 1.3
|
3.5 days
Standard Deviation 3.5
|
SECONDARY outcome
Timeframe: Every 28-day cycle for 26 cycles (2 years 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 diary cards. 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: LNG-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2 group: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Outcome measures
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=52 Participants
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 18 (n=30 Nomac-E2/ n=34 LNG-EE)
|
3.2 days
Standard Deviation 1.3
|
4.8 days
Standard Deviation 1.3
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 25 (n=27 Nomac-E2/ n=31 LNG-EE)
|
3.4 days
Standard Deviation 2.0
|
5.2 days
Standard Deviation 3.2
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 1 (n=49 Nomac-E2/ n=50 LNG-EE)
|
4.7 days
Standard Deviation 2.7
|
6.7 days
Standard Deviation 4.0
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 2 (n=44 Nomac-E2/ n=47 LNG-EE)
|
4.7 days
Standard Deviation 2.1
|
5.3 days
Standard Deviation 1.8
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 3 (n=46 Nomac-E2/ n=47 LNG-EE)
|
4.4 days
Standard Deviation 2.0
|
5.2 days
Standard Deviation 1.6
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 4 (n=37 Nomac-E2/ n=44 LNG-EE)
|
4.3 days
Standard Deviation 2.0
|
5.5 days
Standard Deviation 2.1
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 5 (n=40 Nomac-E2/ n=44 LNG-EE)
|
4.1 days
Standard Deviation 2.7
|
5.6 days
Standard Deviation 2.9
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 6 (n=37 Nomac-E2/ n=44 LNG-EE)
|
4.0 days
Standard Deviation 1.7
|
5.0 days
Standard Deviation 1.5
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 7 (n=33 Nomac-E2/ n=41 LNG-EE)
|
4.0 days
Standard Deviation 1.8
|
5.1 days
Standard Deviation 1.6
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 8 (n=35 Nomac-E2/ n=41 LNG-EE)
|
3.5 days
Standard Deviation 1.5
|
5.1 days
Standard Deviation 1.5
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 9 (n=34 Nomac-E2/ n=37 LNG-EE)
|
3.6 days
Standard Deviation 1.3
|
5.4 days
Standard Deviation 2.5
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 10 (n=31 Nomac-E2/ n=39 LNG-EE)
|
3.5 days
Standard Deviation 1.2
|
5.4 days
Standard Deviation 2.4
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 11 (n=28 Nomac-E2/ n=40 LNG-EE)
|
3.9 days
Standard Deviation 1.5
|
5.1 days
Standard Deviation 1.5
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 12 (n=30 Nomac-E2/ n=40 LNG-EE)
|
3.8 days
Standard Deviation 1.9
|
5.1 days
Standard Deviation 1.5
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 13 (n=30 Nomac-E2/ n=39 LNG-EE)
|
3.4 days
Standard Deviation 1.5
|
4.8 days
Standard Deviation 1.8
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 14 (n=30 Nomac-E2/ n=37 LNG-EE)
|
3.8 days
Standard Deviation 1.6
|
4.9 days
Standard Deviation 1.2
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 15 (n=22 Nomac-E2/ n=36 LNG-EE)
|
3.6 days
Standard Deviation 1.6
|
4.8 days
Standard Deviation 1.2
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 16 (n=26 Nomac-E2/ n=37 LNG-EE)
|
3.2 days
Standard Deviation 1.1
|
4.9 days
Standard Deviation 2.1
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 17 (n=25 Nomac-E2/ n=36 LNG-EE)
|
4.0 days
Standard Deviation 1.9
|
4.6 days
Standard Deviation 1.3
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 19 (n=25 Nomac-E2/ n=35 LNG-EE)
|
3.7 days
Standard Deviation 1.5
|
4.9 days
Standard Deviation 1.6
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 20 (n=22 Nomac-E2/ n=34 LNG-EE)
|
3.4 days
Standard Deviation 1.2
|
5.0 days
Standard Deviation 1.4
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 21 (n=24 Nomac-E2/ n=33 LNG-EE)
|
3.4 days
Standard Deviation 1.8
|
4.8 days
Standard Deviation 1.6
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 22 (n=26 Nomac-E2/ n=32 LNG-EE)
|
3.7 days
Standard Deviation 1.5
|
5.1 days
Standard Deviation 1.9
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 23 (n=26 Nomac-E2/ n=31 LNG-EE)
|
3.5 days
Standard Deviation 1.6
|
5.0 days
Standard Deviation 1.4
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 24 (n=24 Nomac-E2/ n=32 LNG-EE)
|
3.7 days
Standard Deviation 2.2
|
4.9 days
Standard Deviation 1.5
|
|
Average Number of Withdrawal Bleeding-spotting Days
Cycle 26 (n=8 Nomac-E2/ n=10 LNG-EE)
|
3.1 days
Standard Deviation 1.4
|
4.2 days
Standard Deviation 0.6
|
Adverse Events
NOMAC-E2
Serious events: 1 serious events
Other events: 42 other events
Deaths: 0 deaths
LNG-EE
Serious events: 1 serious events
Other events: 43 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=54 participants at risk
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/56
|
1.9%
1/54 • Number of events 1
|
|
Infections and infestations
Appendicitis
|
1.8%
1/56 • Number of events 1
|
0.00%
0/54
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/56
|
1.9%
1/54 • Number of events 1
|
Other adverse events
| Measure |
NOMAC-E2
n=56 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 26 consecutive 28-day cycles (2 years).
|
LNG-EE
n=54 participants at risk
Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (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 26 consecutive 28-day cycles (2 years).
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
5.4%
3/56 • Number of events 4
|
1.9%
1/54 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
3.6%
2/56 • Number of events 2
|
5.6%
3/54 • Number of events 3
|
|
Infections and infestations
Bronchitis
|
5.4%
3/56 • Number of events 3
|
1.9%
1/54 • Number of events 1
|
|
Infections and infestations
Chlamydial cervicitis
|
0.00%
0/56
|
5.6%
3/54 • Number of events 4
|
|
Infections and infestations
Gastroenteritis
|
1.8%
1/56 • Number of events 1
|
5.6%
3/54 • Number of events 4
|
|
Infections and infestations
Influenza
|
17.9%
10/56 • Number of events 13
|
16.7%
9/54 • Number of events 11
|
|
Infections and infestations
Nasopharyngitis
|
30.4%
17/56 • Number of events 26
|
33.3%
18/54 • Number of events 28
|
|
Infections and infestations
Sinusitis
|
3.6%
2/56 • Number of events 2
|
5.6%
3/54 • Number of events 4
|
|
Infections and infestations
Vaginitis bacterial
|
0.00%
0/56
|
5.6%
3/54 • Number of events 3
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
5.4%
3/56 • Number of events 3
|
7.4%
4/54 • Number of events 4
|
|
Investigations
Weight increased
|
8.9%
5/56 • Number of events 5
|
1.9%
1/54 • Number of events 1
|
|
Nervous system disorders
Headache
|
1.8%
1/56 • Number of events 2
|
13.0%
7/54 • Number of events 15
|
|
Psychiatric disorders
Libido decreased
|
5.4%
3/56 • Number of events 3
|
0.00%
0/54
|
|
Psychiatric disorders
Mood altered
|
10.7%
6/56 • Number of events 6
|
11.1%
6/54 • Number of events 6
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
1.8%
1/56 • Number of events 1
|
5.6%
3/54 • Number of events 3
|
|
Reproductive system and breast disorders
Dyspareunia
|
5.4%
3/56 • Number of events 3
|
0.00%
0/54
|
|
Skin and subcutaneous tissue disorders
Acne
|
10.7%
6/56 • Number of events 6
|
7.4%
4/54 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.4%
3/56 • Number of events 3
|
0.00%
0/54
|
|
Vascular disorders
Hot flush
|
5.4%
3/56 • Number of events 3
|
0.00%
0/54
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
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 written consent, which shall not be withheld unreasonably.
- Publication restrictions are in place
Restriction type: OTHER