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

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00413062
First received: December 18, 2006
Last updated: November 20, 2013
Last verified: November 2013
Results First Received: April 27, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Contraception
Interventions: Drug: NOMAC-E2
Drug: DRSP-EE

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study recruited participants from North America and South America

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In total, 2281 participants were randomized (NOMAC-E2 n=1710; DRSP-EE n=571) but 2220 participants were treated (NOMAC-E2 n=1666; DRSP-EE n=554).

Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Participant Flow:   Overall Study
    NOMAC-E2     DRSP-EE  
STARTED     1666     554  
COMPLETED     988     344  
NOT COMPLETED     678     210  
Adverse event/serious adverse event                 289                 56  
Pre-treatment (serious) adverse event                 1                 0  
Withdrawal of informed consent                 111                 36  
Pregnancy                 15                 5  
Pregnancy wish                 17                 6  
Lost to Follow-up                 175                 73  
Other reason                 70                 34  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
Total Total of all reporting groups

Baseline Measures
    NOMAC-E2     DRSP-EE     Total  
Number of Participants  
[units: participants]
  1666     554     2220  
Age  
[units: years]
Mean ± Standard Deviation
  27.6  ± 7.2     27.8  ± 7.0     27.7  ± 7.1  
Gender  
[units: participants]
     
Female     1666     554     2220  
Male     0     0     0  



  Outcome Measures
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1.  Primary:   Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)   [ Time Frame: 1 year (13 cycles) ]

Measure Type Primary
Measure Title Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Measure Description In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a maximum of two days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 women years) that the women were under risk of becoming pregnant.
Time Frame 1 year (13 cycles)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The "restricted ITT" set included all participants treated except for 27 nonpregnant participants whose exposure was excluded due to limited credibility of diary data, & also excluded nonpregnant participants without >= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse, based on e-diary data).

Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values
    NOMAC-E2     DRSP-EE  
Number of Participants Analyzed  
[units: participants]
  1370     444  
Number of woman years (rounded to nearest integer) Analyzed  
[units: woman years (rounded to nearest integer)]
  684     233  
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)  
[units: Pregnancies per 100 woman years]
Number ( 95% Confidence Interval )
   
Overall group     1.754  
  ( 0.9061 to 3.0632 )  
  3.005  
  ( 1.2082 to 6.1917 )  
=<35 years old (n=1158; n=378)     1.963  
  ( 0.9798 to 3.5119 )  
  3.092  
  ( 1.1347 to 6.7299 )  
>35 years old (n=212; n=66)     0.807  
  ( 0.0204 to 4.4977 )  
  2.572  
  ( 0.0651 to 14.33 )  

No statistical analysis provided for Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)



2.  Primary:   Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)   [ Time Frame: 1 year (13 cycles) ]

Measure Type Primary
Measure Title Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Measure Description In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a period of 14 days. Each 13 cycles (28 days per cycle) of exposure constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 women years) that the women were under risk of becoming pregnant.
Time Frame 1 year (13 cycles)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The "restricted ITT" set included all participants treated except for 27 nonpregnant participants whose exposure was excluded due to limited credibility of diary data, & also excluded nonpregnant participants without >= 1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse, based on e-diary data).

Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

Measured Values
    NOMAC-E2     DRSP-EE  
Number of Participants Analyzed  
[units: participants]
  1370     444  
Number of woman years (rounded to nearest integer) Analyzed  
[units: woman years (rounded to nearest integer)]
  684     233  
Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)  
[units: Pregnancies per 100 woman years]
Number ( 95% Confidence Interval )
   
Overall group     2.192  
  ( 1.2268 to 3.6154 )  
  4.293  
  ( 2.0587 to 7.8951 )  
=<35 years old (n=1158; n=378)     2.498  
  ( 1.3657 to 4.1913 )  
  4.638  
  ( 2.1208 to 8.8042 )  
>35 years old (n=212; n=66)     0.807  
  ( 0.0204 to 4.4977 )  
  2.572  
  ( 0.0651 to 14.33 )  

No statistical analysis provided for Number of In-treatment Pregnancies (With +14 Day Window) Per 100 Woman Years of Exposure (Pearl Index)



3.  Secondary:   Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
Measure Description Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting



4.  Secondary:   Number of Participants With an Occurrence of Absence of Withdrawal Bleeding   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
Measure Description Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Number of Participants With an Occurrence of Absence of Withdrawal Bleeding



5.  Secondary:   Number of Participants With an Occurrence of Breakthrough Bleeding   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Number of Participants With an Occurrence of Breakthrough Bleeding
Measure Description

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding.

Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.

Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Number of Participants With an Occurrence of Breakthrough Bleeding



6.  Secondary:   Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
Measure Description

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding.

Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.

Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)



7.  Secondary:   Number of Participants With an Occurrence of Early Withdrawal Bleeding   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Number of Participants With an Occurrence of Early Withdrawal Bleeding
Measure Description

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period".

Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.

Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Number of Participants With an Occurrence of Early Withdrawal Bleeding



8.  Secondary:   Number of Participants With an Occurrence of Continued Withdrawal Bleeding   [ Time Frame: Every 28-day cycle for 12 cycles ]

Measure Type Secondary
Measure Title Number of Participants With an Occurrence of Continued Withdrawal Bleeding
Measure Description

Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle.

Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.

Time Frame Every 28-day cycle for 12 cycles  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
NOMAC-E2

Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).

DRSP-EE

Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).


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

No statistical analysis provided for Number of Participants With an Occurrence of Continued Withdrawal Bleeding



9.  Secondary:   Average Number of Breakthrough Bleeding/Spotting Days   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Average Number of Breakthrough Bleeding/Spotting Days
Measure Description Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: DRSP-EE group: 21-day period starting on Day 1 of the cycle; NOMAC-E2: 21-day period starting on Day 4 of the cycle.
Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

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.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Average Number of Breakthrough Bleeding/Spotting Days



10.  Secondary:   Average Number of Withdrawal Bleeding/Spotting Days   [ Time Frame: Every 28-day cycle for 13 cycles (one year total) ]

Measure Type Secondary
Measure Title Average Number of Withdrawal Bleeding/Spotting Days
Measure Description Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using e-diaries. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding was defined as bleeding/spotting episode that started during or continued into the "expected bleeding period". Expected bleeding period: DRSP-EE group: 7-day period starting on Day 22 of the cycle; NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle.
Time Frame Every 28-day cycle for 13 cycles (one year total)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.

n= number of participants who had withdrawal bleeding/spotting for the respective cycle.


Reporting Groups
  Description
NOMAC-E2 Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).
DRSP-EE Monophasic COC tablets containing 3 mg Drospirenone (DRSP) and 30 mcg Ethinyl Estradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 13 consecutive 28-day menstrual cycles (1 year).

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

No statistical analysis provided for Average Number of Withdrawal Bleeding/Spotting Days




  Serious Adverse Events


  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp.
e-mail: ClinicalTrialsDisclosure@merck.com


No publications provided by Merck Sharp & Dohme Corp.

Publications automatically indexed to this study:

Responsible Party: Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00413062     History of Changes
Other Study ID Numbers: P05722, 292002
Study First Received: December 18, 2006
Results First Received: April 27, 2011
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration