Breakthrough Bleeding
Conditions
Keywords
oral contraceptives, breakthrough bleeding, spotting
Brief summary
This is a 4-arm study to evaluate and compare bleeding patterns between three different doses of DR-1031 oral contraceptive with Seasonale oral contraceptive. Study participants will receive physical and gynecological exams, including Pap smear. During the study, all participants will be required to complete a diary
Detailed description
This Phase 2, prospective, multicenter, double-blinded, randomized study is designed to evaluate and compare bleeding patterns in women using one of three different doses of DR-1031 oral contraceptive with Seasonale oral contraceptive. Patients who meet all study entrance criteria will be randomly assigned to one of four treatment groups, The overall study duration will be approximately 9 months; this will include a screening period of approximately 4 weeks, a run-in period of 4 weeks, a treatment period of approximately 6 months (two,91-day cycles) and a final study visit occurring 14-21 days after completion of study drug.
Interventions
DRUGDR-1031
Active therapy cycle of 84 days taking combination tablets containing ascending doses of ethinyl estradiol (EE) and 150 mcg levonorgestrel (LNG), followed by a 7-day withdrawal cycle of 10 mcg EE. The total extended cycle was 91 days and participants were to complete two extended cycles. Active therapy dosage of EE varied by treatment arm.
DRUGSeasonale®
84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets for two consecutive 91-day cycles.
DRUGPortia®
Portia® 28 consists of 21 pink active tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg of ethinyl estradiol, and seven white inert tablets. Portia was taken as a pre-study run-in medication.
Sponsors
Duramed Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Premenopausal * Not pregnant or breastfeeding * Agree to use back-up non-hormonal contraception for study period
Exclusion criteria
* Any contraindication to the use of oral contraceptives * Pregnancy within the last 3 months * Smoking \>10 cigarettes per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176) | Day 92-176 | Bleeding is defined as a flow heavy enough to require sanitary protection. Spotting does not require sanitary protection. |
| Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84) | Day 1-84 | Bleeding is defined as a flow heavy enough to require sanitary protection. Spotting does not require sanitary protection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days With Bleeding During Active Cycle 2 (Day 92-176) | Day 92-176 | Bleeding is defined as a flow heavy enough to require sanitary protection. |
| Time to First Bleeding Day | Day 1-84 | Time to first bleeding day was defined as the time between the start of intervention until the first day when bleeding was heavy enough to require the use of sanitary protection. Data are not summarized due to limitations in the diary data and an inability to accurately determine a participant's first day of bleeding. |
| Maximum Bleeding Severity During Active Cycle 1 (Day 1-84) | Day 1-84 | Bleeding is defined as a flow heavy enough to require sanitary protection. Participants recorded in the diary days when they had bleeding, and whether they considered the bleeding to be light, moderate or heavy. Data was not summarized due to limitations in the diary data, and an inability to accurately determine the maximum bleeding severity. See pre-specified analyses for Number of Moderate to Heavy Bleeding Days. |
| Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | Day 85-91 | Participants are categorized by the duration of bleeding that occurred during the scheduled 7-day withdrawal period for Cycle 1. |
| Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Day 1-84 | Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability. |
| Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Day 92-176 | Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability. |
| Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Day 85-91 | Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability. |
| Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Day 177-183 | Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability. |
| Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | Day 177-183 | Participants are categorized by the duration of bleeding that occurred during the scheduled 7-day withdrawal period for Cycle 2. |
| Days With Bleeding During Active Cycle 1 (Day 1-84) | Day 1-84 | Bleeding is defined as a flow heavy enough to require sanitary protection. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84) | Day 1-84 | Bleeding is defined as a flow heavy enough to require sanitary protection. Participants recorded in the diary days when they had bleeding, and whether they considered the bleeding to be light, moderate or heavy. |
| Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176) | Day 92-176 | Bleeding is defined as a flow heavy enough to require sanitary protection. Participants recorded in the diary days when they had bleeding, and whether they considered the bleeding to be light, moderate or heavy. |
Countries
United States
Participant flow
Pre-assignment details
A total of 988 subjects were screened for participation in this study, and 567 took at least one dose of investigational product (Safety population).
Participants by arm
| Arm | Count |
|---|---|
| Low Dose DR-1031 42 days combination active tablets (20 mcg EE /150 mcg LNG) followed by 21 days combination active tablets (25 mcg EE/150 mcg LNG) followed by 21 days combination active tablets (30 mcg EE/ 150 mcg LNG) followed by 7 days of 10 mcg EE tablets. | 110 |
| Midrange Dose DR-1031 21 days combination active tablets (20 mcg EE /150 mcg LNG) followed by 42 days combination active tablets (25 mcg EE/ 150 mcg LNG) followed by 21 days combination active tablets (30 mcg EE/ 150 mcg LNG) followed by 7 days of 10 mcg EE tablets. | 110 |
| High Dose DR-1031 21 days combination active tablets (20 mcg EE /150 mcg LNG) followed by 21 days combination active tablets (25 mcg EE/150 mcg LNG) followed by 42 days combination active tablets (30 mcg EE/ 150 mcg LNG) followed by 7 days of 10 mcg EE tablets. | 108 |
| Seasonale 84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets. | 120 |
| Total | 448 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 | 12 | 8 |
| Overall Study | Did not meet protocol requirements | 1 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 15 | 15 | 13 | 10 |
| Overall Study | Other | 3 | 3 | 1 | 0 |
| Overall Study | Participant pregnant | 0 | 1 | 2 | 2 |
| Overall Study | Protocol Violation | 2 | 4 | 9 | 7 |
| Overall Study | Withdrawal by Subject | 10 | 6 | 8 | 12 |
Baseline characteristics
| Characteristic | Midrange Dose DR-1031 | Low Dose DR-1031 | Total | Seasonale | High Dose DR-1031 |
|---|---|---|---|---|---|
| Age Continuous | 30.5 years STANDARD_DEVIATION 7.02 | 30.1 years STANDARD_DEVIATION 6.88 | 30.5 years STANDARD_DEVIATION 7.08 | 30.6 years STANDARD_DEVIATION 6.9 | 30.7 years STANDARD_DEVIATION 7.61 |
| Body Mass Index | 25.7 kg/m^2 STANDARD_DEVIATION 4.24 | 26.6 kg/m^2 STANDARD_DEVIATION 4.13 | 25.9 kg/m^2 STANDARD_DEVIATION 4.35 | 25.5 kg/m^2 STANDARD_DEVIATION 4.41 | 26.0 kg/m^2 STANDARD_DEVIATION 4.59 |
| Diastolic Blood Pressure | 72.9 mmHg STANDARD_DEVIATION 7.46 | 72.3 mmHg STANDARD_DEVIATION 8.85 | 72.1 mmHg STANDARD_DEVIATION 8.14 | 71.4 mmHg STANDARD_DEVIATION 8.44 | 71.8 mmHg STANDARD_DEVIATION 7.72 |
| Heart Rate | 73.7 beats/minute STANDARD_DEVIATION 8.9 | 73.9 beats/minute STANDARD_DEVIATION 9.85 | 73.3 beats/minute STANDARD_DEVIATION 9.26 | 71.9 beats/minute STANDARD_DEVIATION 9.07 | 73.7 beats/minute STANDARD_DEVIATION 9.17 |
| Oral Contraceptive Use History Continuous User | 46 participants | 44 participants | 181 participants | 49 participants | 42 participants |
| Oral Contraceptive Use History Fresh-Start | 19 participants | 21 participants | 76 participants | 19 participants | 17 participants |
| Oral Contraceptive Use History Missing | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Oral Contraceptive Use History Prior User | 45 participants | 44 participants | 190 participants | 52 participants | 49 participants |
| Race/Ethnicity, Customized African-American | 20 participants | 21 participants | 76 participants | 17 participants | 18 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 1 participants | 9 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 68 participants | 72 participants | 291 participants | 82 participants | 69 participants |
| Race/Ethnicity, Customized Hispanic | 17 participants | 13 participants | 65 participants | 16 participants | 19 participants |
| Race/Ethnicity, Customized Other | 1 participants | 3 participants | 7 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 110 Participants | 110 Participants | 448 Participants | 120 Participants | 108 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Smoking Status Current Smoker | 16 participants | 13 participants | 51 participants | 11 participants | 11 participants |
| Smoking Status Non-Smoker | 83 participants | 77 participants | 333 participants | 88 participants | 85 participants |
| Smoking Status Past Smoker | 11 participants | 20 participants | 64 participants | 21 participants | 12 participants |
| Systolic Blood Pressure | 114.4 mmHg STANDARD_DEVIATION 10.34 | 114.2 mmHg STANDARD_DEVIATION 10.74 | 114.2 mmHg STANDARD_DEVIATION 10.19 | 112.8 mmHg STANDARD_DEVIATION 10.23 | 115.6 mmHg STANDARD_DEVIATION 9.31 |
| Weight | 153.6 lbs STANDARD_DEVIATION 27.18 | 156.6 lbs STANDARD_DEVIATION 28.84 | 154.4 lbs STANDARD_DEVIATION 29.22 | 151.9 lbs STANDARD_DEVIATION 30.03 | 156.0 lbs STANDARD_DEVIATION 30.79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 61 / 140 | 44 / 136 | 49 / 143 | 53 / 148 |
| serious Total, serious adverse events | 1 / 140 | 2 / 136 | 3 / 143 | 5 / 148 |
Outcome results
Primary
Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84)
Bleeding is defined as a flow heavy enough to require sanitary protection. Spotting does not require sanitary protection.
Time frame: Day 1-84
Population: Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose DR-1031 | Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84) | 13 days |
| Midrange Dose DR-1031 | Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84) | 13.5 days |
| High Dose DR-1031 | Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84) | 15 days |
| Seasonale | Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84) | 15 days |
Primary
Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176)
Bleeding is defined as a flow heavy enough to require sanitary protection. Spotting does not require sanitary protection.
Time frame: Day 92-176
Population: Intent to treat (ITT) population of participants who were still active in the study and who completed the relevant pages in the patient diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose DR-1031 | Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176) | 6 days |
| Midrange Dose DR-1031 | Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176) | 7 days |
| High Dose DR-1031 | Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176) | 5 days |
| Seasonale | Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176) | 6 days |
Secondary
Days With Bleeding During Active Cycle 1 (Day 1-84)
Bleeding is defined as a flow heavy enough to require sanitary protection.
Time frame: Day 1-84
Population: Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose DR-1031 | Days With Bleeding During Active Cycle 1 (Day 1-84) | 3.5 days |
| Midrange Dose DR-1031 | Days With Bleeding During Active Cycle 1 (Day 1-84) | 2.5 days |
| High Dose DR-1031 | Days With Bleeding During Active Cycle 1 (Day 1-84) | 4 days |
| Seasonale | Days With Bleeding During Active Cycle 1 (Day 1-84) | 2 days |
Secondary
Days With Bleeding During Active Cycle 2 (Day 92-176)
Bleeding is defined as a flow heavy enough to require sanitary protection.
Time frame: Day 92-176
Population: Intent to treat (ITT) population of participants who were still active in the study and who completed the relevant pages in the patient diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose DR-1031 | Days With Bleeding During Active Cycle 2 (Day 92-176) | 1 days |
| Midrange Dose DR-1031 | Days With Bleeding During Active Cycle 2 (Day 92-176) | 2 days |
| High Dose DR-1031 | Days With Bleeding During Active Cycle 2 (Day 92-176) | 1 days |
| Seasonale | Days With Bleeding During Active Cycle 2 (Day 92-176) | 2 days |
Secondary
Maximum Bleeding Severity During Active Cycle 1 (Day 1-84)
Bleeding is defined as a flow heavy enough to require sanitary protection. Participants recorded in the diary days when they had bleeding, and whether they considered the bleeding to be light, moderate or heavy. Data was not summarized due to limitations in the diary data, and an inability to accurately determine the maximum bleeding severity. See pre-specified analyses for Number of Moderate to Heavy Bleeding Days.
Time frame: Day 1-84
Population: ITT population. However data was not summarized due to limitations in the diary data.
Secondary
Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84)
Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time frame: Day 1-84
Population: Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Depression | 51 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Anxiety | 42 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Irritability | 72 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Headache | 83 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Breast tenderness/pain | 58 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Bloating | 80 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Pelvic pain | 72 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Anxiety | 43 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Bloating | 76 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Breast tenderness/pain | 57 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Depression | 40 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Pelvic pain | 65 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Irritability | 69 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Headache | 84 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Pelvic pain | 61 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Headache | 86 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Anxiety | 34 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Breast tenderness/pain | 50 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Depression | 36 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Bloating | 72 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Irritability | 66 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Irritability | 78 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Breast tenderness/pain | 64 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Headache | 92 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Bloating | 84 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Anxiety | 59 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Depression | 52 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84) | Pelvic pain | 67 participants |
Secondary
Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176)
Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time frame: Day 92-176
Population: Intent to treat (ITT) population of participants who were still active in the study and who completed the relevant pages in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Breast tenderness/pain | 46 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Depression | 41 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Anxiety | 40 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Headache | 74 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Irritability | 55 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Bloating | 64 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Pelvic pain | 58 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Depression | 39 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Pelvic pain | 57 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Bloating | 64 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Anxiety | 40 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Irritability | 63 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Headache | 72 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Breast tenderness/pain | 47 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Pelvic pain | 45 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Breast tenderness/pain | 44 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Headache | 72 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Bloating | 57 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Anxiety | 31 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Depression | 30 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Irritability | 54 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Bloating | 70 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Irritability | 65 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Depression | 44 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Headache | 78 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Breast tenderness/pain | 44 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Anxiety | 47 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176) | Pelvic pain | 57 participants |
Secondary
Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91)
Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time frame: Day 85-91
Population: Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Breast tenderness/pain | 33 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Depression | 25 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Anxiety | 26 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Headache | 57 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Irritability | 44 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Bloating | 61 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Pelvic pain | 50 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Depression | 21 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Pelvic pain | 49 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Bloating | 51 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Anxiety | 17 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Irritability | 43 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Headache | 50 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Breast tenderness/pain | 28 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Pelvic pain | 37 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Breast tenderness/pain | 17 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Headache | 57 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Bloating | 46 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Anxiety | 14 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Depression | 17 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Irritability | 23 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Bloating | 62 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Irritability | 36 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Depression | 23 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Headache | 50 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Breast tenderness/pain | 33 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Anxiety | 22 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91) | Pelvic pain | 53 participants |
Secondary
Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183)
Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time frame: Day 177-183
Population: Intent to treat (ITT) population of participants who were still active in the study and who completed the relevant pages in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Breast tenderness/pain | 29 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Depression | 18 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Anxiety | 21 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Headache | 39 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Irritability | 39 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Bloating | 51 participants |
| Low Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Pelvic pain | 52 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Depression | 21 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Pelvic pain | 42 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Bloating | 53 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Anxiety | 22 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Irritability | 37 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Headache | 42 participants |
| Midrange Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Breast tenderness/pain | 25 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Pelvic pain | 31 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Breast tenderness/pain | 15 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Headache | 37 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Bloating | 38 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Anxiety | 13 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Depression | 15 participants |
| High Dose DR-1031 | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Irritability | 25 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Bloating | 60 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Irritability | 39 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Depression | 17 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Headache | 48 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Breast tenderness/pain | 25 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Anxiety | 22 participants |
| Seasonale | Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183) | Pelvic pain | 51 participants |
Secondary
Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91)
Participants are categorized by the duration of bleeding that occurred during the scheduled 7-day withdrawal period for Cycle 1.
Time frame: Day 85-91
Population: Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 0 day | 14 participants |
| Low Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 4-7 days | 59 participants |
| Low Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 1-3 days | 36 participants |
| Midrange Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 0 day | 28 participants |
| Midrange Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 4-7 days | 63 participants |
| Midrange Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 1-3 days | 17 participants |
| High Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 1-3 days | 27 participants |
| High Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 0 day | 25 participants |
| High Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 4-7 days | 54 participants |
| Seasonale | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 0 day | 27 participants |
| Seasonale | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 4-7 days | 75 participants |
| Seasonale | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91) | 1-3 days | 18 participants |
Secondary
Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183)
Participants are categorized by the duration of bleeding that occurred during the scheduled 7-day withdrawal period for Cycle 2.
Time frame: Day 177-183
Population: Intent to treat (ITT) population of participants who were still active in the study and who completed the relevant pages in the patient diary.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 0 day | 15 participants |
| Low Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 4-7 days | 50 participants |
| Low Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 1-3 days | 32 participants |
| Midrange Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 0 day | 20 participants |
| Midrange Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 4-7 days | 44 participants |
| Midrange Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 1-3 days | 32 participants |
| High Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 1-3 days | 26 participants |
| High Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 0 day | 23 participants |
| High Dose DR-1031 | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 4-7 days | 45 participants |
| Seasonale | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 0 day | 21 participants |
| Seasonale | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 4-7 days | 60 participants |
| Seasonale | Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183) | 1-3 days | 24 participants |
Secondary
Time to First Bleeding Day
Time to first bleeding day was defined as the time between the start of intervention until the first day when bleeding was heavy enough to require the use of sanitary protection. Data are not summarized due to limitations in the diary data and an inability to accurately determine a participant's first day of bleeding.
Time frame: Day 1-84
Population: ITT population. However this data was not summarized due to limitations in the diary data.
Other Pre-specified
Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84)
Bleeding is defined as a flow heavy enough to require sanitary protection. Participants recorded in the diary days when they had bleeding, and whether they considered the bleeding to be light, moderate or heavy.
Time frame: Day 1-84
Population: Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose DR-1031 | Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84) | 0 days |
| Midrange Dose DR-1031 | Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84) | 0 days |
| High Dose DR-1031 | Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84) | 0 days |
| Seasonale | Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84) | 0 days |
Other Pre-specified
Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176)
Bleeding is defined as a flow heavy enough to require sanitary protection. Participants recorded in the diary days when they had bleeding, and whether they considered the bleeding to be light, moderate or heavy.
Time frame: Day 92-176
Population: Intent to treat (ITT) population of participants who were still active in the study and who completed the relevant pages in the patient diary.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Dose DR-1031 | Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176) | 0 days |
| Midrange Dose DR-1031 | Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176) | 0 days |
| High Dose DR-1031 | Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176) | 0 days |
| Seasonale | Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176) | 0 days |