A Study to Evaluate Bleeding Patterns With Three Different Doses of DR-1031 Compared to Seasonale

Study Overview
=================
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.

Official Title
-----------------
A Prospective, Multicenter, Double-Blinded, Randomized Study to Evaluate Bleeding Patterns in Women Using One of Three Different Doses of DR-1031 Oral Contraceptive Compared to Seasonale Oral Contraceptive Regimen

Conditions
-----------------
Breakthrough Bleeding

Intervention / Treatment
-----------------
* Drug: DR-1031
* Drug: Seasonale®
* Drug: Portia®


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose DR-1031<br>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. | Drug: DR-1031<br>* 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.<br>* Other names: Quartette®;Drug: Portia®<br>* 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.<br>* Other names: levonorgestrel/ethinyl estradiol;|
| Experimental: Midrange Dose DR-1031<br>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. | Drug: DR-1031<br>* 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.<br>* Other names: Quartette®;Drug: Portia®<br>* 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.<br>* Other names: levonorgestrel/ethinyl estradiol;|
| Experimental: High Dose DR-1031<br>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. | Drug: DR-1031<br>* 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.<br>* Other names: Quartette®;Drug: Portia®<br>* 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.<br>* Other names: levonorgestrel/ethinyl estradiol;|
| Active Comparator: Seasonale<br>84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets. | Drug: Seasonale®<br>* 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.<br>* Other names: levonorgestrel/ethinyl estradiol;Drug: Portia®<br>* 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.<br>* Other names: levonorgestrel/ethinyl estradiol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1-84 | 
| 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. | Day 92-176 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days With Bleeding During Active Cycle 1 (Day 1-84) | Bleeding is defined as a flow heavy enough to require sanitary protection. | Day 1-84 | 
| Days With Bleeding During Active Cycle 2 (Day 92-176) | Bleeding is defined as a flow heavy enough to require sanitary protection. | Day 92-176 | 
| 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. | Day 1-84 | 
| 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. | Day 1-84 | 
| 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. | Day 85-91 | 
| 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. | Day 177-183 | 
| 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. | Day 1-84 | 
| 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. | Day 92-176 | 
| 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. | Day 85-91 | 
| 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. | Day 177-183 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oral contraceptives, breakthrough bleeding, spotting