Healthy
Conditions
Brief summary
This is a multi-center study to evaluate hormone levels with the oral contraceptive regimen DR-1021.
Detailed description
Female volunteers, aged 18-35 years old who met all Inclusion and no Exclusion Criteria, were enrolled in this study. All participants were current users of a standard 21/7 oral contraceptive regimen (21 days of combination progestin/estrogen followed by 7 days placebo) and had completed at least one 28-day cycle prior to beginning the Cycle 1 baseline cycle. After completing screening, all enrolled participants continued to receive the same regimen of 150 μg DSG /20 μg EE combination pills once daily for 21 days followed by placebo once daily for 7 days during Cycle 1 (the Run-In phase). Following completion of Cycle 1, participants were randomly assigned to receive either DR-1021 or Mircette during Cycle 2. All participants who completed Cycle 2 were to receive Kariva during Cycle 3; however, participants were only followed for the first 21 days of this 28-day regimen, after which they were considered study completers.
Interventions
DRUGDR-1021
Twenty-one 150 μg desogestrel/20 μg ethinyl estradiol (EE) combination tablets plus seven 10 μg EE tablets.
DRUGMircette®
Twenty-one 150 μg desogestrel/20 μg ethinyl estradiol (EE) combination tablets plus two placebo tablets plus five 10 μg EE tablets.
DRUGKariva®
Twenty-one 150 μg desogestrel/20 μg ethinyl estradiol (EE) combination tablets plus two placebo tablets plus five 10 μg EE tablets.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Premenopausal * Weight \<200 lbs * Currently taking or willing to be treated with an oral contraceptive with a standard 21/7 regimen for one cycle prior to starting Study Cycle 1 * Others as dictated by protocol
Exclusion criteria
* Any contraindication to the use of oral contraceptives * Breast feeding * Smoking \> 10 cigarettes per day * Use of drugs that require simultaneous use of contraceptives (e.g., isotretinoin \[Accutane\]) * Others as dictated by protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Estradiol Levels by Cycle Day | Cycle 2, Day 2 (Baseline), and Days 4, 6, 19-20, 23, 24, 25, 27, 28, Cycle 3, Days 2, 4 and 6. | Levels of estradiol were measured throughout the study from blood samples. |
| Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2, Day 2 (Baseline), and Days 4, 6, 19-20, 23, 24, 25, 27, 28, Cycle 3, Days 2, 4 and 6. | Levels of follicle stimulating hormone were measured throughout the study from blood samples. |
| Serum Inhibin-B Levels by Cycle Day | Cycle 2, Day 2 (Baseline), and Days 4, 6, 19-20, 23, 24, 25, 27, 28, Cycle 3, Days 2, 4 and 6. | Levels of inhibin-B were measured throughout the study from blood samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21 | The percentage of participants with unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding or spotting was derived from participant diaries. |
| Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1, Days 11, 19-20, 23, 25, 27, Cycle 2, Days 4, 11, 19-20, 23, 25, 27, Cycle 3, Day 4. | Ovarian follicles were measured by trans-vaginal ultrasound. The size of the 3 largest follicles was documented for each participant, and the percentage of follicles greater than 5 mm in diameter was calculated based on the total number follicles present (indicated by n for each time point). |
| Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21 | The percentage of participants with unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding (not including spotting) was derived from participant diaries. |
| Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21 | The total number of days of unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding (not including spotting) was derived from participant diaries. |
| Change From Cycle 2 Days 1 - 20 to Cycle 2 Days 21 - 28 in Maximum Follicle Size | Cycle 2, Days 1-20 and Cycle 2, Days 21-28 | The change in the size of the largest documented follicle during combination therapy (Days 1 to 21) and during monotherapy/placebo (Days 21-28) measured by trans-vaginal ultrasound. |
| Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21 | The total number of days of unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding or spotting was derived from participant diaries. |
Countries
United States
Participant flow
Recruitment details
Female volunteers, aged 18-35 years old who were current users of a standard 21/7 oral contraceptive regimen (21 days of combination progestin/estrogen followed by 7 days placebo) were enrolled at 4 investigative sites in the United States.
Pre-assignment details
67 women were screened for participation in this study; 61 were enrolled and took at least 1 dose of their current regimen of oral contraceptive in Cycle 1 (the Run-in Cycle). Of the 61 enrolled, 3 participants discontinued the study prior to completing the Run-in Cycle and were therefore not randomly assigned to study drug in Cycle 2.
Participants by arm
| Arm | Count |
|---|---|
| DR-1021 After randomization, participants received DR-1021 consisting of 150 μg desogestrel (DSG)/20 μg ethinyl estradiol (EE) administered orally as a combination tablet once daily for 21 days followed by EE 10 μg tablet once daily for 7 days (Cycle 2). Participants who completed Cycle 2 then received Kariva, consisting of 150 μg DSG/20 μg EE administered orally as a combination tablet taken once daily for 21 days followed by placebo tablet once daily for 2 days followed by 10 μg EE taken once daily for 5 days (Cycle 3). | 28 |
| Mircette After randomization, participants received Mircette consisting of 150 μg desogestrel (DSG)/20 μg ethinyl estradiol (EE) administered orally as a combination tablet once daily for 21 days followed by placebo tablet once daily for 2 days followed by 10 μg EE tablet once daily for 5 days (Cycle 2). Participants who completed Cycle 2 then received Kariva, consisting of 150 μg DSG/20 μg EE administered orally as a combination tablet taken once daily for 21 days followed by placebo tablet once daily for 2 days followed by 10 μg EE taken once daily for 5 days (Cycle 3). | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Cycle 1: Run-in Cycle | Adverse Event | 1 | 0 | 0 |
| Cycle 1: Run-in Cycle | Withdrawal by Subject | 2 | 0 | 0 |
| Cycle 2: Randomized Treatment Cycle | Noncompliance | 0 | 0 | 1 |
| Cycle 2: Randomized Treatment Cycle | Withdrawal by Subject | 0 | 1 | 0 |
| Cycle 3: Follow-up | Noncompliance | 0 | 1 | 0 |
| Cycle 3: Follow-up | Pregnancy | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Mircette | Total | DR-1021 |
|---|---|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 4.38 | 27.7 years STANDARD_DEVIATION 4.51 | 27.3 years STANDARD_DEVIATION 4.68 |
| Race/Ethnicity, Customized African-American | 6 participants | 10 participants | 4 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 20 participants | 40 participants | 20 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 28 participants | 56 participants | 28 participants |
| Sex: Female, Male Female | 28 Participants | 56 Participants | 28 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 28 | 7 / 28 |
| serious Total, serious adverse events | 0 / 28 | 1 / 28 |
Outcome results
Primary
Serum Estradiol Levels by Cycle Day
Levels of estradiol were measured throughout the study from blood samples.
Time frame: Cycle 2, Day 2 (Baseline), and Days 4, 6, 19-20, 23, 24, 25, 27, 28, Cycle 3, Days 2, 4 and 6.
Population: Intent-to-treat population with available data at each time point (as indicated by n).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 2 (n=28, 28) | 47.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 25 (n=27, 28) | 24.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 6 (n=27, 27) | 43.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 27 (n=25, 28) | 30.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 23 (n=27, 28) | 24.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 28 (n=26, 28) | 36.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Days 19-20 (n=26, 28) | 19.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 3 - Day 2 (n=27, 28) | 34.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 3 - Day 4 (n=27, 27) | 66.00 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 4 (n=28, 28) | 62.50 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 3 - Day 6 (n=24, 26) | 28.50 pg/mL |
| DR-1021 | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 24 (n=25, 28) | 25.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 3 - Day 6 (n=24, 26) | 32.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 23 (n=27, 28) | 19.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 2 (n=28, 28) | 51.50 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 4 (n=28, 28) | 34.50 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 6 (n=27, 27) | 29.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Days 19-20 (n=26, 28) | 20.50 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 24 (n=25, 28) | 26.50 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 25 (n=27, 28) | 26.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 27 (n=25, 28) | 20.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 2 - Day 28 (n=26, 28) | 27.50 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 3 - Day 4 (n=27, 27) | 27.00 pg/mL |
| Mircette | Serum Estradiol Levels by Cycle Day | Cycle 3 - Day 2 (n=27, 28) | 43.00 pg/mL |
Comparison: Comparison of treatment groups at Cycle 2 - Day 2 time point. p-values \< 0.05 were considered statistically significant.p-value: 0.6346Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 4 time point.p-value: 0.2757Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 6 time point.p-value: 0.1321Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Days 19-20 time point.p-value: 0.5543Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 23 time point.p-value: 0.394Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 24 time point.p-value: 0.7891Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 25 time point.p-value: 0.4829Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 27 time point.p-value: 0.4526Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 28 time point.p-value: 0.2485Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 2 time point.p-value: 0.6252Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 4 time point.p-value: 0.4003Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 6 time point.p-value: 0.8841Wilcoxon (Mann-Whitney)
Primary
Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day
Levels of follicle stimulating hormone were measured throughout the study from blood samples.
Time frame: Cycle 2, Day 2 (Baseline), and Days 4, 6, 19-20, 23, 24, 25, 27, 28, Cycle 3, Days 2, 4 and 6.
Population: Intent-to-treat population with available data at each time point (as indicated by n).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 27 (n=25, 28) | 3.70 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 2 (n=28, 28) | 4.00 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 4 (n=28, 28) | 3.55 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 6 (n=28, 27) | 3.70 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Days 19-20 (n=26, 28) | 1.45 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 23 (n=27, 28) | 2.70 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 24 (n=25, 28) | 2.80 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 25 (n=27, 28) | 2.90 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 28 (n=26, 28) | 5.05 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 3 - Day 2 (n=27, 28) | 4.90 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 3 - Day 4 (n=27, 28) | 3.70 mIU/mL |
| DR-1021 | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 3 - Day 6 (n=24, 26) | 2.50 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 3 - Day 4 (n=27, 28) | 3.60 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 27 (n=25, 28) | 3.90 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 24 (n=25, 28) | 3.70 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 2 (n=28, 28) | 4.00 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 3 - Day 2 (n=27, 28) | 4.05 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 4 (n=28, 28) | 3.70 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 25 (n=27, 28) | 3.90 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 6 (n=28, 27) | 3.50 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 3 - Day 6 (n=24, 26) | 2.50 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Days 19-20 (n=26, 28) | 1.55 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 28 (n=26, 28) | 4.70 mIU/mL |
| Mircette | Serum Follicle Stimulating Hormone (FSH) Levels by Cycle Day | Cycle 2 - Day 23 (n=27, 28) | 2.35 mIU/mL |
Comparison: Comparison of treatment groups at Cycle 2 - Day 2 time point. p-values \< 0.05 were considered statistically significant.p-value: 0.8892Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 4 time point.p-value: 0.7678Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 6 time point.p-value: 0.5782Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Days 19-20 time point.p-value: 0.8083Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 23 time point.p-value: 1Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 24 time point.p-value: 0.4122Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 25 time point.p-value: 0.6675Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 27 time point.p-value: 0.8445Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 28 time point.p-value: 0.3772Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 2 time point.p-value: 0.1918Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 4 time point.p-value: 0.6675Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 6 time point.p-value: 0.9226Wilcoxon (Mann-Whitney)
Primary
Serum Inhibin-B Levels by Cycle Day
Levels of inhibin-B were measured throughout the study from blood samples.
Time frame: Cycle 2, Day 2 (Baseline), and Days 4, 6, 19-20, 23, 24, 25, 27, 28, Cycle 3, Days 2, 4 and 6.
Population: Intent-to-treat population with available data at each time point (as indicated by n).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 25 (n=27, 28) | 35.20 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Days 19-20 (n=26, 28) | 23.15 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 27 (n=25, 28) | 39.60 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 4 (n=28, 28) | 42.80 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 28 (n=26, 28) | 41.95 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 23 (n=27, 28) | 28.10 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 3 - Day 2 (n=27, 28) | 54.70 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 6 (n=28, 27) | 46.35 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 3 - Day 4 (n=27, 28) | 51.10 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 24 (n=25, 28) | 36.80 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 3 - Day 6 (n=24, 26) | 36.15 pg/mL |
| DR-1021 | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 2 (n=28, 28) | 92.30 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 3 - Day 6 (n=24, 26) | 29.55 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 2 (n=28, 28) | 99.00 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 6 (n=28, 27) | 41.20 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Days 19-20 (n=26, 28) | 28.85 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 23 (n=27, 28) | 32.15 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 24 (n=25, 28) | 55.00 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 25 (n=27, 28) | 62.30 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 27 (n=25, 28) | 49.20 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 28 (n=26, 28) | 55.05 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 3 - Day 2 (n=27, 28) | 57.95 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 3 - Day 4 (n=27, 28) | 52.25 pg/mL |
| Mircette | Serum Inhibin-B Levels by Cycle Day | Cycle 2 - Day 4 (n=28, 28) | 64.45 pg/mL |
Comparison: Comparison of treatment groups at Cycle 2 - Day 2 time point. p-values \< 0.05 were considered statistically significant.p-value: 0.0979Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 4 time point.p-value: 0.0629Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 6 time point.p-value: 0.8464Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Days 19-20 time point.p-value: 0.6316Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 23 time point.p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 24 time point.p-value: 0.0955Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 25 time point.p-value: 0.1523Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 2 - Day 27 time point.p-value: 0.2809Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 28 time point.p-value: 0.8829Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 2 time point.p-value: 0.9262Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 -Day 4 time point.p-value: 0.7811Wilcoxon (Mann-Whitney)
Comparison: Comparison of treatment groups at Cycle 3 - Day 6 time point.p-value: 0.3703Wilcoxon (Mann-Whitney)
Secondary
Change From Cycle 2 Days 1 - 20 to Cycle 2 Days 21 - 28 in Maximum Follicle Size
The change in the size of the largest documented follicle during combination therapy (Days 1 to 21) and during monotherapy/placebo (Days 21-28) measured by trans-vaginal ultrasound.
Time frame: Cycle 2, Days 1-20 and Cycle 2, Days 21-28
Population: Intent-to-treat population with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DR-1021 | Change From Cycle 2 Days 1 - 20 to Cycle 2 Days 21 - 28 in Maximum Follicle Size | -2.02 mm | Standard Deviation 6.076 |
| Mircette | Change From Cycle 2 Days 1 - 20 to Cycle 2 Days 21 - 28 in Maximum Follicle Size | -1.79 mm | Standard Deviation 3.081 |
Secondary
Number of Days of Bleeding During Unscheduled and Scheduled Study Periods
The total number of days of unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding (not including spotting) was derived from participant diaries.
Time frame: Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DR-1021 | Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 0.70 days | Standard Deviation 2.127 |
| DR-1021 | Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 2.30 days | Standard Deviation 1.793 |
| DR-1021 | Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 0.70 days | Standard Deviation 1.436 |
| Mircette | Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 0.71 days | Standard Deviation 1.607 |
| Mircette | Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 0.52 days | Standard Deviation 0.935 |
| Mircette | Number of Days of Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 2.63 days | Standard Deviation 1.843 |
Secondary
Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods
The total number of days of unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding or spotting was derived from participant diaries.
Time frame: Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DR-1021 | Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 2.19 days | Standard Deviation 3.732 |
| DR-1021 | Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 3.19 days | Standard Deviation 2.167 |
| DR-1021 | Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 1.96 days | Standard Deviation 2.808 |
| Mircette | Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 1.41 days | Standard Deviation 1.551 |
| Mircette | Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 3.67 days | Standard Deviation 1.754 |
| Mircette | Number of Days of Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 1.64 days | Standard Deviation 2.614 |
Secondary
Percentage of Follicles Greater Than 5 mm in Diameter
Ovarian follicles were measured by trans-vaginal ultrasound. The size of the 3 largest follicles was documented for each participant, and the percentage of follicles greater than 5 mm in diameter was calculated based on the total number follicles present (indicated by n for each time point).
Time frame: Cycle 1, Days 11, 19-20, 23, 25, 27, Cycle 2, Days 4, 11, 19-20, 23, 25, 27, Cycle 3, Day 4.
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 19-20 (n= 47, 94) | 29.8 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 11 (n=63, 48) | 30.2 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 23 (n= 30, 76) | 50.0 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 25 (n= 85, 106) | 32.9 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 27 (n=135, 145) | 29.6 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 4 (n=154, 156) | 35.1 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 11 (n=76, 54) | 27.6 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Days 19-20 (n=143, 148) | 17.5 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 23 (n=91, 62) | 24.2 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 25 (n=69, 80) | 30.4 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 27 (n=94, 132) | 23.4 percentage of follicles |
| DR-1021 | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 3 - Day 4 (n=138, 117) | 25.4 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 27 (n=94, 132) | 20.5 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 11 (n=76, 54) | 31.5 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 11 (n=63, 48) | 29.2 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 19-20 (n= 47, 94) | 27.7 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 25 (n=69, 80) | 18.8 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 23 (n= 30, 76) | 26.3 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Days 19-20 (n=143, 148) | 18.9 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 25 (n= 85, 106) | 31.1 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 3 - Day 4 (n=138, 117) | 27.4 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 1 - Day 27 (n=135, 145) | 35.2 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 23 (n=91, 62) | 24.2 percentage of follicles |
| Mircette | Percentage of Follicles Greater Than 5 mm in Diameter | Cycle 2 - Day 4 (n=154, 156) | 31.4 percentage of follicles |
Secondary
Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods
The percentage of participants with unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding (not including spotting) was derived from participant diaries.
Time frame: Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DR-1021 | Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 18.5 percentage of participants |
| DR-1021 | Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 77.8 percentage of participants |
| DR-1021 | Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 29.6 percentage of participants |
| Mircette | Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 33.3 percentage of participants |
| Mircette | Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 77.8 percentage of participants |
| Mircette | Percentage of Participants With Bleeding During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 25.0 percentage of participants |
Secondary
Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods
The percentage of participants with unscheduled (Day 1 to Day 21 of each cycle) and scheduled (ie,withdrawal \[Day 22 to Day 28 of each cycle\]) bleeding or spotting was derived from participant diaries.
Time frame: Cycle 2, Days 1-21, Cycle 2, Days 22-28 and Cycle 3, Days 1-21
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DR-1021 | Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 48.1 percentage of participants |
| DR-1021 | Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 77.8 percentage of participants |
| DR-1021 | Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 55.6 percentage of participants |
| Mircette | Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Unscheduled (Day 1-21) | 59.3 percentage of participants |
| Mircette | Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 2 - Scheduled (Day 22-28) | 92.6 percentage of participants |
| Mircette | Percentage of Participants With Bleeding or Spotting During Unscheduled and Scheduled Study Periods | Cycle 3 - Unscheduled (Day 1-21) | 53.6 percentage of participants |