Effects on Bone Mineral Density (BMD) of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG/EE (292005)(P05765)(COMPLETED)
Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT00511342
Collaborator
(none)
110
2
33
Study Details
Study Description
Brief Summary
The primary purpose of this study is to evaluate the effects of the NOMAC-E2 combined oral contraceptive (COC) on bone mineral density (BMD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
110 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
An Open-Label, Randomized, Single Center Trial in Healthy Young Women, to Evaluate the Effects of a Monophasic Combined Oral Contraceptive (COC) Containing 2.5 mg NOMAC and 1.5 mg E2 on Bone Mineral Density (BMD) Compared to a Monophasic COC Containing 0.150 mg Levonorgestrel and 0.030 mg Ethinyl Estradiol
Study Start Date
:
Sep 1, 2006
Actual Primary Completion Date
:
Jun 1, 2009
Actual Study Completion Date
:
Jun 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NOMAC-E2 Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic COC |
Drug: NOMAC-E2
Nomegestrol Acetate and Estradiol Tablets, 2.5 mg NOMAC and 1.5 mg E2 taken once daily from Day 1 of menstrual period up to and including Day 28 for 26 consecutive 28-day menstrual cycles (2 years).
Other Names:
|
| Active Comparator: LNG-EE Levonorgestrel (LNG) and Ethinyl Estradiol (EE), 0.150 mg LNG and 0.030 mg EE monophasic COC |
Drug: LNG-EE
Levonorgestrel and Ethinyl Estradiol Tablets, 0.150 mg Levonorgestrel and 0.030 mg Ethinyl Estradiol taken once daily from Day 1 of menstrual period up to and including Day 28 for 26 consecutive 28-day menstrual cycles (2 years).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Change From Baseline in Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck [Baseline and after cycle 26 (2 years)]
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).
Secondary Outcome Measures
- Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) [2 years (26 cycles)]
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.
- Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting [Every 28-day cycle for 26 cycles (2 years total)]
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.
- Number of Participants With an Occurrence of Absence of Withdrawal Bleeding [Every 28-day cycle for 26 cycles (2 years total)]
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.
- Number of Participants With an Occurrence of Breakthrough Bleeding [Every 28-day cycle for 26 cycles (2 years total)]
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.
- Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) [Every 28-day cycle for 26 cycles (2 years total)]
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.
- Number of Participants With an Occurrence of Early Withdrawal Bleeding [Every 28-day cycle for 26 cycles (2 years total)]
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.
- Number of Participants With an Occurrence of Continued Withdrawal Bleeding [Every 28-day cycle for 26 cycles (2 years total) including one week after stopping treatment]
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.
- Average Number of Breakthrough Bleeding-Spotting Days [Every 28-day cycle for 26 cycles (2 years total)]
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.
- Average Number of Withdrawal Bleeding-spotting Days [Every 28-day cycle for 26 cycles (2 years total)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 35 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
- Sexually active women, at risk for pregnancy and not planning to use condoms
during treatment;
-
At least 20 but not older than 35 years of age at the time of screening;
-
BMI = 17 and = 35;
-
Good physical and mental health;
-
Willing to give informed consent in writing;
-
Willing to take part in the trial for two years.
Exclusion criteria:
-
Family history of osteoporotic fracture below the age of 70;
-
Postgastrectomy;
-
History of eating disorder, viz. anorexia nervosa, bulimia;
-
Endocrine disorder (including controlled diabetes, [para]thyroid disease, Cushing's disease);
-
Rheumatoid arthritis;
-
Significant scoliosis;
-
Fasting parathyroid hormone (PTH) outside the reference range at screening;
-
Fasting calcitonin outside the reference range at screening;
-
Prolactin above the reference range (hyperprolactinemia) at screening;
-
Fasting cholesterol and/or triglycerides above the reference range for age at screening (treatment with lipid lowering drugs not allowed);
-
Engaging in vigorous exercise such as marathon, competitive swimming, triathlon;
-
Smoking more than ten cigarettes/day;
-
Use of more than two units of alcohol a day;
-
Use of one or more of the following drugs:
-
gonadotropin releasing hormone (GnRH) analogues (also past use for more than six months at any time, or for any period of time less than six months ago is a contraindication);
-
systemic or inhaled administration of corticosteroids (also past use for more than one year, less than five years ago or any period of time in the past year is a contraindication);
-
thiazide diuretics;
-
thyroid hormone;
-
bisphosphonates;
-
calcium supplementation in combination with vitamin D supplementation/
calcitonin;
-
ever treatment after childhood with fluorides;
-
Contraindications for contraceptive steroids
-
An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia[CIN], squamous intraepithelial lesion [SIL], carcinoma in situ, invasive carcinoma) at screening;
-
Clinically relevant abnormal laboratory result at screening as judged by the investigator;
-
Use of an injectable hormonal method of contraception; within 6 months of an injection with a 3-month duration, within 4 months of an injection with a 2-month duration, within 2 months of an injection with a 1-month duration;
-
Within 12 months after a pregnancy prior to the start of trial medication;
-
Breastfeeding or within 12 months after stopping breastfeeding prior to the start of trial medication;
-
Present use or use within 2 months prior to the start of the trial medication of the following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (other than pre- and post-treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St John's Wort);
-
Administration of investigational drugs and/or participation in another clinical trial within 2 months prior to the start of the trial medication or during the trial period.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT00511342
Other Study ID Numbers:
- P05765
- Organon Protocol No. 292005
First Posted:
Aug 3, 2007
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Period Title: Overall Study | ||
| STARTED | 56 | 54 |
| COMPLETED | 43 | 32 |
| NOT COMPLETED | 13 | 22 |
Baseline Characteristics
| Arm/Group Title | NOMAC-E2 | LNG-EE | Total |
|---|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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 of all reporting groups |
| Overall Participants | 56 | 54 | 110 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
23.0
(3.2)
|
22.1
(2.0)
|
22.6
(2.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
56
100%
|
54
100%
|
110
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Baseline Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck (score on a scale) [Mean (Full Range) ] | |||
| Lumbar Spine |
0.351
|
-0.106
|
0.127
|
| Femoral Neck |
0.321
|
0.035
|
0.181
|
Outcome Measures
| Title | Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) |
|---|---|
| Description | 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. |
| Time Frame | 2 years (26 cycles) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 54 | 48 |
| Measure Woman years (rounded to nearest integer) | 72 | 58 |
| Number (95% Confidence Interval) [Pregnancies per 100 woman years] |
0.000
|
1.734
|
| Title | Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= Number of participants with evaluable cycles. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE) |
22
39.3%
|
14
25.9%
|
| Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE) |
12
21.4%
|
6
11.1%
|
| Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE) |
15
26.8%
|
3
5.6%
|
| Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE) |
12
21.4%
|
2
3.7%
|
| Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE) |
11
19.6%
|
2
3.7%
|
| Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE) |
10
17.9%
|
5
9.3%
|
| Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE) |
6
10.7%
|
5
9.3%
|
| Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE) |
4
7.1%
|
3
5.6%
|
| Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE) |
9
16.1%
|
8
14.8%
|
| Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE) |
7
12.5%
|
1
1.9%
|
| Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE) |
6
10.7%
|
3
5.6%
|
| Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE) |
5
8.9%
|
4
7.4%
|
| Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE) |
6
10.7%
|
4
7.4%
|
| Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE) |
3
5.4%
|
3
5.6%
|
| Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE) |
2
3.6%
|
2
3.7%
|
| Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE) |
6
10.7%
|
2
3.7%
|
| Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE) |
4
7.1%
|
2
3.7%
|
| Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE) |
1
1.8%
|
3
5.6%
|
| Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE) |
2
3.6%
|
2
3.7%
|
| Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE) |
4
7.1%
|
2
3.7%
|
| Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE) |
4
7.1%
|
1
1.9%
|
| Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE) |
2
3.6%
|
1
1.9%
|
| Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE) |
4
7.1%
|
5
9.3%
|
| Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE) |
2
3.6%
|
3
5.6%
|
| Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE) |
6
10.7%
|
2
3.7%
|
| Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE) |
3
5.4%
|
0
0%
|
| Title | Mean Change From Baseline in Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck |
|---|---|
| Description | 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). |
| Time Frame | Baseline and after cycle 26 (2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 54 |
| Lumbar Spine (n=42/ n=34) |
0.019
(0.242)
|
0.121
(0.269)
|
| Femoral Neck (n=42/ n=34 ) |
-0.007
(0.228)
|
0.044
(0.253)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | NOMAC-E2, LNG-EE |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.19 |
| Comments | No corrections for multiple comparisons were made for these safety parameters. The a-priori threshold for statistical significance was 0.05. | |
| Method | ANCOVA | |
| Comments | The ANCOVA included the Z-score values at baseline as adjusted factor. | |
| Method of Estimation | Estimation Parameter | Difference of adjusted means |
| Estimated Value | -0.078 | |
| Confidence Interval |
(2-Sided) 95% -0.198 to 0.041 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | NOMAC-E2 minus LNG-EE for lumbar spine (L2-L4) | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | NOMAC-E2, LNG-EE |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.57 |
| Comments | No corrections for multiple comparisons were made for these safety parameters. The a-priori threshold for statistical significance was 0.05. | |
| Method | ANCOVA | |
| Comments | The ANCOVA included the Z-score values at baseline as adjusted factor. | |
| Method of Estimation | Estimation Parameter | Difference of adjusted means |
| Estimated Value | -0.030 | |
| Confidence Interval |
(2-Sided) 95% -0.136 to 0.075 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | NOMAC-E2 minus LNG-EE for femoral neck | |
| Title | Number of Participants With an Occurrence of Absence of Withdrawal Bleeding |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= Number of participants with evaluable cycles. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE) |
4
7.1%
|
2
3.7%
|
| Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE) |
9
16.1%
|
2
3.7%
|
| Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE) |
9
16.1%
|
1
1.9%
|
| Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE) |
16
28.6%
|
0
0%
|
| Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE) |
10
17.9%
|
0
0%
|
| Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE) |
14
25%
|
0
0%
|
| Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE) |
15
26.8%
|
1
1.9%
|
| Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE) |
12
21.4%
|
0
0%
|
| Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE) |
13
23.2%
|
3
5.6%
|
| Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE) |
14
25%
|
1
1.9%
|
| Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE) |
16
28.6%
|
0
0%
|
| Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE) |
12
21.4%
|
0
0%
|
| Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE) |
11
19.6%
|
0
0%
|
| Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE) |
12
21.4%
|
2
3.7%
|
| Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE) |
21
37.5%
|
2
3.7%
|
| Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE) |
17
30.4%
|
1
1.9%
|
| Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE) |
18
32.1%
|
1
1.9%
|
| Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE) |
13
23.2%
|
3
5.6%
|
| Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE) |
18
32.1%
|
2
3.7%
|
| Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE) |
20
35.7%
|
2
3.7%
|
| Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE) |
17
30.4%
|
2
3.7%
|
| Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE) |
16
28.6%
|
2
3.7%
|
| Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE) |
17
30.4%
|
4
7.4%
|
| Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE) |
19
33.9%
|
3
5.6%
|
| Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE) |
15
26.8%
|
2
3.7%
|
| Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE) |
24
42.9%
|
11
20.4%
|
| Title | Number of Participants With an Occurrence of Breakthrough Bleeding |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= Number of participants with evaluable cycles. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE) |
6
10.7%
|
1
1.9%
|
| Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE) |
2
3.6%
|
1
1.9%
|
| Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE) |
2
3.6%
|
1
1.9%
|
| Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE) |
3
5.4%
|
0
0%
|
| Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE) |
2
3.6%
|
1
1.9%
|
| Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE) |
2
3.6%
|
0
0%
|
| Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE) |
1
1.8%
|
0
0%
|
| Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE) |
2
3.6%
|
1
1.9%
|
| Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE) |
1
1.8%
|
0
0%
|
| Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE) |
2
3.6%
|
0
0%
|
| Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE) |
0
0%
|
0
0%
|
| Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE) |
1
1.8%
|
0
0%
|
| Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE) |
2
3.6%
|
0
0%
|
| Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE) |
1
1.8%
|
0
0%
|
| Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE) |
0
0%
|
0
0%
|
| Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE) |
1
1.8%
|
1
1.9%
|
| Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE) |
0
0%
|
0
0%
|
| Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE) |
0
0%
|
0
0%
|
| Title | Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= Number of participants with evaluable cycles. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE) |
17
30.4%
|
13
24.1%
|
| Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE) |
10
17.9%
|
5
9.3%
|
| Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE) |
14
25%
|
2
3.7%
|
| Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE) |
9
16.1%
|
2
3.7%
|
| Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE) |
11
19.6%
|
1
1.9%
|
| Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE) |
9
16.1%
|
4
7.4%
|
| Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE) |
6
10.7%
|
4
7.4%
|
| Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE) |
3
5.4%
|
2
3.7%
|
| Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE) |
8
14.3%
|
8
14.8%
|
| Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE) |
6
10.7%
|
1
1.9%
|
| Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE) |
6
10.7%
|
3
5.6%
|
| Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE) |
4
7.1%
|
3
5.6%
|
| Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE) |
5
8.9%
|
3
5.6%
|
| Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE) |
2
3.6%
|
2
3.7%
|
| Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE) |
1
1.8%
|
2
3.7%
|
| Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE) |
5
8.9%
|
2
3.7%
|
| Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE) |
2
3.6%
|
2
3.7%
|
| Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE) |
1
1.8%
|
3
5.6%
|
| Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE) |
1
1.8%
|
2
3.7%
|
| Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE) |
2
3.6%
|
2
3.7%
|
| Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE) |
3
5.4%
|
1
1.9%
|
| Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE) |
2
3.6%
|
1
1.9%
|
| Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE) |
4
7.1%
|
4
7.4%
|
| Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE) |
2
3.6%
|
2
3.7%
|
| Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE) |
6
10.7%
|
2
3.7%
|
| Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE) |
3
5.4%
|
0
0%
|
| Title | Number of Participants With an Occurrence of Early Withdrawal Bleeding |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= Number of participants with evaluable cycles. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE) |
5
8.9%
|
7
13%
|
| Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE) |
3
5.4%
|
4
7.4%
|
| Cycle 3 (n=55 Nomac-E2/ n=48 LNG-EE) |
3
5.4%
|
3
5.6%
|
| Cycle 4 (n=53 Nomac-E2/ n=44 LNG-EE) |
1
1.8%
|
4
7.4%
|
| Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE) |
3
5.4%
|
3
5.6%
|
| Cycle 6 (n=51 Nomac-E2/ n=44 LNG-EE) |
1
1.8%
|
3
5.6%
|
| Cycle 7 (n=48 Nomac-E2/ n=42 LNG-EE) |
4
7.1%
|
4
7.4%
|
| Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE) |
1
1.8%
|
3
5.6%
|
| Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE) |
0
0%
|
3
5.6%
|
| Cycle 10 (n=45 Nomac-E2/ n=40 LNG-EE) |
1
1.8%
|
4
7.4%
|
| Cycle 11 (n=44 Nomac-E2/ n=40 LNG-EE) |
1
1.8%
|
3
5.6%
|
| Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE) |
2
3.6%
|
3
5.6%
|
| Cycle 13 (n=41 Nomac-E2/ n=39 LNG-EE) |
1
1.8%
|
2
3.7%
|
| Cycle 14 (n=42 Nomac-E2/ n=39 LNG-EE) |
0
0%
|
0
0%
|
| Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE) |
0
0%
|
2
3.7%
|
| Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE) |
0
0%
|
0
0%
|
| Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE) |
0
0%
|
0
0%
|
| Cycle 19 (n=43 Nomac-E2/ n=37 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 21 (n=41 Nomac-E2/ n=35 LNG-EE) |
0
0%
|
2
3.7%
|
| Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE) |
1
1.8%
|
2
3.7%
|
| Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE) |
0
0%
|
1
1.9%
|
| Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE) |
1
1.8%
|
2
3.7%
|
| Cycle 26 (n=32 Nomac-E2/ n=21 LNG-EE) |
1
1.8%
|
0
0%
|
| Title | Number of Participants With an Occurrence of Continued Withdrawal Bleeding |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) including one week after stopping treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= Number of participants with evaluable cycles. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=53 Nomac-E2/ n=52 LNG-EE) |
10
17.9%
|
24
44.4%
|
| Cycle 2 (n=53 Nomac-E2/ n=49 LNG-EE) |
14
25%
|
19
35.2%
|
| Cycle 3 (n=53 Nomac-E2/ n=45 LNG-EE) |
14
25%
|
17
31.5%
|
| Cycle 4 (n=51 Nomac-E2/ n=43 LNG-EE) |
9
16.1%
|
19
35.2%
|
| Cycle 5 (n=50 Nomac-E2/ n=44 LNG-EE) |
9
16.1%
|
18
33.3%
|
| Cycle 6 (n=50 Nomac-E2/ n=43 LNG-EE) |
11
19.6%
|
14
25.9%
|
| Cycle 7 (n=48 Nomac-E2/ n=41 LNG-EE) |
7
12.5%
|
15
27.8%
|
| Cycle 8 (n=47 Nomac-E2/ n=41 LNG-EE) |
10
17.9%
|
16
29.6%
|
| Cycle 9 (n=47 Nomac-E2/ n=40 LNG-EE) |
11
19.6%
|
9
16.7%
|
| Cycle 10 (n=44 Nomac-E2/ n=39 LNG-EE) |
5
8.9%
|
13
24.1%
|
| Cycle 11 (n=43 Nomac-E2/ n=40 LNG-EE) |
5
8.9%
|
16
29.6%
|
| Cycle 12 (n=42 Nomac-E2/ n=40 LNG-EE) |
6
10.7%
|
18
33.3%
|
| Cycle 13 (n=41 Nomac-E2/ n=38 LNG-EE) |
8
14.3%
|
9
16.7%
|
| Cycle 14 (n=42 Nomac-E2/ n=38 LNG-EE) |
10
17.9%
|
12
22.2%
|
| Cycle 15 (n=43 Nomac-E2/ n=38 LNG-EE) |
6
10.7%
|
10
18.5%
|
| Cycle 16 (n=43 Nomac-E2/ n=38 LNG-EE) |
4
7.1%
|
11
20.4%
|
| Cycle 17 (n=43 Nomac-E2/ n=37 LNG-EE) |
6
10.7%
|
14
25.9%
|
| Cycle 18 (n=43 Nomac-E2/ n=37 LNG-EE) |
4
7.1%
|
14
25.9%
|
| Cycle 19 (n=43 Nomac-E2/ n=36 LNG-EE) |
7
12.5%
|
15
27.8%
|
| Cycle 20 (n=42 Nomac-E2/ n=36 LNG-EE) |
3
5.4%
|
13
24.1%
|
| Cycle 21 (n=41 Nomac-E2/ n=34 LNG-EE) |
6
10.7%
|
16
29.6%
|
| Cycle 22 (n=42 Nomac-E2/ n=34 LNG-EE) |
7
12.5%
|
13
24.1%
|
| Cycle 23 (n=43 Nomac-E2/ n=35 LNG-EE) |
4
7.1%
|
12
22.2%
|
| Cycle 24 (n=43 Nomac-E2/ n=35 LNG-EE) |
3
5.4%
|
10
18.5%
|
| Cycle 25 (n=42 Nomac-E2/ n=33 LNG-EE) |
3
5.4%
|
7
13%
|
| Cycle 26 (n=4Nomac-E2/ n=1 LNG-EE) |
0
0%
|
0
0%
|
| Title | Average Number of Breakthrough Bleeding-Spotting Days |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= number of participants who had breakthrough bleeding/spotting for the respective cycle. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=22 Nomac-E2/ n=14 LNG-EE) |
4.1
(3.1)
|
2.2
(1.9)
|
| Cycle 2 (n=12 Nomac-E2/ n=6 LNG-EE) |
3.8
(3.1)
|
4.8
(1.9)
|
| Cycle 3 (n=15 Nomac-E2/ n=3 LNG-EE) |
4.1
(3.8)
|
4.0
(1.7)
|
| Cycle 4 (n=12 Nomac-E2/ n=2 LNG-EE) |
4.0
(2.8)
|
1.5
(0.7)
|
| Cycle 5 (n=11 Nomac-E2/ n=2 LNG-EE) |
3.7
(2.3)
|
6.5
(6.4)
|
| Cycle 6 (n=10 Nomac-E2/ n=5 LNG-EE) |
2.0
(1.2)
|
2.6
(1.8)
|
| Cycle 7 (n=6 Nomac-E2/ n=5 LNG-EE) |
3.0
(1.9)
|
2.6
(0.9)
|
| Cycle 8 (n=4 Nomac-E2/ n=3 LNG-EE) |
2.3
(1.5)
|
2.0
(1.0)
|
| Cycle 9 (n=9 Nomac-E2/ n=8 LNG-EE) |
2.2
(1.4)
|
2.1
(1.0)
|
| Cycle 10 (n=7 Nomac-E2/ n=1 LNG-EE) |
2.0
(0.8)
|
2.0
(NA)
|
| Cycle 11 (n=6 Nomac-E2/ n=3 LNG-EE) |
2.0
(1.1)
|
2.3
(1.2)
|
| Cycle 12 (n=5 Nomac-E2/ n=4 LNG-EE) |
3.2
(0.8)
|
4.0
(2.4)
|
| Cycle 13 (n=6 Nomac-E2/ n=4 LNG-EE) |
3.0
(2.1)
|
3.0
(2.2)
|
| Cycle 14 (n=3 Nomac-E2/ n=3 LNG-EE) |
1.3
(0.6)
|
2.7
(1.5)
|
| Cycle 15 (n=2 Nomac-E2/ n=2 LNG-EE) |
2.0
(1.4)
|
7.5
(2.1)
|
| Cycle 16 (n=6 Nomac-E2/ n=2 LNG-EE) |
1.5
(0.5)
|
1.5
(0.7)
|
| Cycle 17 (n=4 Nomac-E2/ n=2 LNG-EE) |
1.8
(1.0)
|
2.0
(1.4)
|
| Cycle 18 (n=1 Nomac-E2/ n=3 LNG-EE) |
3.0
(NA)
|
3.0
(2.0)
|
| Cycle 19 (n=2 Nomac-E2/ n=2 LNG-EE) |
2.0
(1.4)
|
6.0
(1.4)
|
| Cycle 20 (n=4 Nomac-E2/ n=2 LNG-EE) |
3.5
(2.1)
|
4.0
(4.2)
|
| Cycle 21 (n=4 Nomac-E2/ n=1 LNG-EE) |
2.3
(1.3)
|
5.0
(NA)
|
| Cycle 22 (n=2 Nomac-E2/ n=1 LNG-EE) |
3.0
(1.4)
|
6.0
(NA)
|
| Cycle 23 (n=4 Nomac-E2/ n=5 LNG-EE) |
3.8
(2.9)
|
3.4
(1.8)
|
| Cycle 24 (n=2 Nomac-E2/ n=3 LNG-EE) |
2.0
(1.4)
|
4.7
(3.2)
|
| Cycle 25 (n=6 Nomac-E2/ n=2 LNG-EE) |
2.2
(1.3)
|
3.5
(3.5)
|
| Cycle 26 (n=3 Nomac-E2/ n=0 LNG-EE) |
2.3
(2.3)
|
NA
(NA)
|
| Title | Average Number of Withdrawal Bleeding-spotting Days |
|---|---|
| Description | 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. |
| Time Frame | Every 28-day cycle for 26 cycles (2 years total) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n= number of participants who had breakthrough bleeding/spotting for the respective cycle. |
| Arm/Group Title | NOMAC-E2 | LNG-EE |
|---|---|---|
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). |
| Measure Participants | 56 | 52 |
| Cycle 1 (n=49 Nomac-E2/ n=50 LNG-EE) |
4.7
(2.7)
|
6.7
(4.0)
|
| Cycle 2 (n=44 Nomac-E2/ n=47 LNG-EE) |
4.7
(2.1)
|
5.3
(1.8)
|
| Cycle 3 (n=46 Nomac-E2/ n=47 LNG-EE) |
4.4
(2.0)
|
5.2
(1.6)
|
| Cycle 4 (n=37 Nomac-E2/ n=44 LNG-EE) |
4.3
(2.0)
|
5.5
(2.1)
|
| Cycle 5 (n=40 Nomac-E2/ n=44 LNG-EE) |
4.1
(2.7)
|
5.6
(2.9)
|
| Cycle 6 (n=37 Nomac-E2/ n=44 LNG-EE) |
4.0
(1.7)
|
5.0
(1.5)
|
| Cycle 7 (n=33 Nomac-E2/ n=41 LNG-EE) |
4.0
(1.8)
|
5.1
(1.6)
|
| Cycle 8 (n=35 Nomac-E2/ n=41 LNG-EE) |
3.5
(1.5)
|
5.1
(1.5)
|
| Cycle 9 (n=34 Nomac-E2/ n=37 LNG-EE) |
3.6
(1.3)
|
5.4
(2.5)
|
| Cycle 10 (n=31 Nomac-E2/ n=39 LNG-EE) |
3.5
(1.2)
|
5.4
(2.4)
|
| Cycle 11 (n=28 Nomac-E2/ n=40 LNG-EE) |
3.9
(1.5)
|
5.1
(1.5)
|
| Cycle 12 (n=30 Nomac-E2/ n=40 LNG-EE) |
3.8
(1.9)
|
5.1
(1.5)
|
| Cycle 13 (n=30 Nomac-E2/ n=39 LNG-EE) |
3.4
(1.5)
|
4.8
(1.8)
|
| Cycle 14 (n=30 Nomac-E2/ n=37 LNG-EE) |
3.8
(1.6)
|
4.9
(1.2)
|
| Cycle 15 (n=22 Nomac-E2/ n=36 LNG-EE) |
3.6
(1.6)
|
4.8
(1.2)
|
| Cycle 16 (n=26 Nomac-E2/ n=37 LNG-EE) |
3.2
(1.1)
|
4.9
(2.1)
|
| Cycle 17 (n=25 Nomac-E2/ n=36 LNG-EE) |
4.0
(1.9)
|
4.6
(1.3)
|
| Cycle 18 (n=30 Nomac-E2/ n=34 LNG-EE) |
3.2
(1.3)
|
4.8
(1.3)
|
| Cycle 19 (n=25 Nomac-E2/ n=35 LNG-EE) |
3.7
(1.5)
|
4.9
(1.6)
|
| Cycle 20 (n=22 Nomac-E2/ n=34 LNG-EE) |
3.4
(1.2)
|
5.0
(1.4)
|
| Cycle 21 (n=24 Nomac-E2/ n=33 LNG-EE) |
3.4
(1.8)
|
4.8
(1.6)
|
| Cycle 22 (n=26 Nomac-E2/ n=32 LNG-EE) |
3.7
(1.5)
|
5.1
(1.9)
|
| Cycle 23 (n=26 Nomac-E2/ n=31 LNG-EE) |
3.5
(1.6)
|
5.0
(1.4)
|
| Cycle 24 (n=24 Nomac-E2/ n=32 LNG-EE) |
3.7
(2.2)
|
4.9
(1.5)
|
| Cycle 25 (n=27 Nomac-E2/ n=31 LNG-EE) |
3.4
(2.0)
|
5.2
(3.2)
|
| Cycle 26 (n=8 Nomac-E2/ n=10 LNG-EE) |
3.1
(1.4)
|
4.2
(0.6)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | NOMAC-E2 | LNG-EE | ||
| Arm/Group Description | Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 26 consecutive 28-day cycles (2 years). | 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). | ||
All Cause Mortality |
||||
| NOMAC-E2 | LNG-EE | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| NOMAC-E2 | LNG-EE | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/56 (1.8%) | 1/54 (1.9%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 |
| Infections and infestations | ||||
| Appendicitis | 1/56 (1.8%) | 1 | 0/54 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/56 (0%) | 0 | 1/54 (1.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| NOMAC-E2 | LNG-EE | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/56 (75%) | 43/54 (79.6%) | ||
| Cardiac disorders | ||||
| Palpitations | 3/56 (5.4%) | 4 | 1/54 (1.9%) | 1 |
| Gastrointestinal disorders | ||||
| Nausea | 2/56 (3.6%) | 2 | 3/54 (5.6%) | 3 |
| Infections and infestations | ||||
| Bronchitis | 3/56 (5.4%) | 3 | 1/54 (1.9%) | 1 |
| Chlamydial cervicitis | 0/56 (0%) | 0 | 3/54 (5.6%) | 4 |
| Gastroenteritis | 1/56 (1.8%) | 1 | 3/54 (5.6%) | 4 |
| Influenza | 10/56 (17.9%) | 13 | 9/54 (16.7%) | 11 |
| Nasopharyngitis | 17/56 (30.4%) | 26 | 18/54 (33.3%) | 28 |
| Sinusitis | 2/56 (3.6%) | 2 | 3/54 (5.6%) | 4 |
| Vaginitis bacterial | 0/56 (0%) | 0 | 3/54 (5.6%) | 3 |
| Vulvovaginal mycotic infection | 3/56 (5.4%) | 3 | 4/54 (7.4%) | 4 |
| Investigations | ||||
| Weight increased | 5/56 (8.9%) | 5 | 1/54 (1.9%) | 1 |
| Nervous system disorders | ||||
| Headache | 1/56 (1.8%) | 2 | 7/54 (13%) | 15 |
| Psychiatric disorders | ||||
| Libido decreased | 3/56 (5.4%) | 3 | 0/54 (0%) | 0 |
| Mood altered | 6/56 (10.7%) | 6 | 6/54 (11.1%) | 6 |
| Reproductive system and breast disorders | ||||
| Cervical dysplasia | 1/56 (1.8%) | 1 | 3/54 (5.6%) | 3 |
| Dyspareunia | 3/56 (5.4%) | 3 | 0/54 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Acne | 6/56 (10.7%) | 6 | 4/54 (7.4%) | 4 |
| Eczema | 3/56 (5.4%) | 3 | 0/54 (0%) | 0 |
| Vascular disorders | ||||
| Hot flush | 3/56 (5.4%) | 3 | 0/54 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT00511342
Other Study ID Numbers:
- P05765
- Organon Protocol No. 292005
First Posted:
Aug 3, 2007
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022