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

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

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

Study Overview

• Status: Completed
• Conditions: Breakthrough Bleeding
• Intervention / Treatment: Drug: DR-1031; Drug: Portia®; Drug: Seasonale®

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.

• Study Type: Interventional
• Enrollment (Actual): 567
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Duramed Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Duramed Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Duramed Investigational Site
  • California
    • San Diego, California, United States, 92108
      • Duramed Investigational Site
    • San Francisco, California, United States, 94102
      • Duramed Investigational Site
    • Santa Ana, California, United States, 92705
      • Duramed Investigational Site
    • Vista, California, United States, 92083
      • Duramed Investigational Site
  • Colorado
    • Pueblo, Colorado, United States, 81001
      • Duramed Investigational Site
  • Connecticut
    • Stratford, Connecticut, United States, 06615
      • Duramed Investigational Site
  • Florida
    • Deland, Florida, United States, 32720
      • Duramed Investigational Site
    • Jacksonville, Florida, United States, 32207
      • Duramed Investigational Site
    • Melbourne, Florida, United States, 32935
      • Duramed Investigational Site
    • Miami, Florida, United States, 33186
      • Duramed Investigational Site
    • Tampa, Florida, United States, 33607
      • Duramed Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Duramed Investigational Site
    • West Palm Beach, Florida, United States, 33407
      • Duramed Investigational Site
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Duramed Investigational Site
    • Douglasville, Georgia, United States, 30134
      • Duramed Investigational Site
    • Savannah, Georgia, United States, 31406
      • Duramed Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83712
      • Duramed Investigational Site
    • Meridian, Idaho, United States, 83642
      • Duramed Investigational Site
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Duramed Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Duramed Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Duramed Investigational Site
    • Metairie, Louisiana, United States, 70006
      • Duramed Investigational Site
    • Shreveport, Louisiana, United States, 71106
      • Duramed Investigational Site
  • Maryland
    • Riverdale, Maryland, United States, 20737
      • Duramed Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Duramed Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Duramed Investigational Site
    • Las Vegas, Nevada, United States, 89128
      • Duramed Investigational Site
    • N. Las Vegas, Nevada, United States, 89030
      • Duramed Investigational Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Duramed Investigational Site
  • North Carolina
    • Cary, North Carolina, United States, 27511
      • Duramed Investigational Site
    • New Bern, North Carolina, United States, 28562
      • Duramed Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Duramed Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Duramed Investigational Site
    • Mayfield Heights, Ohio, United States, 44124
      • Duramed Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Duramed Investigational Site
    • Medford, Oregon, United States, 97504
      • Duramed Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Duramed Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Duramed Investigational Site
    • Columbia, South Carolina, United States, 29201
      • Duramed Investigational Site
    • Hilton Head Island, South Carolina, United States, 29926
      • Duramed Investigational Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Duramed Investigational Site
  • Texas
    • Austin, Texas, United States, 78737
      • Duramed Investigational Site
    • Dallas, Texas, United States, 75390
      • Duramed Investigational Site
    • Houston, Texas, United States, 77024
      • Duramed Investigational Site
    • San Antonio, Texas, United States, 78229
      • Duramed Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Duramed Investigational Site
  • Vermont
    • Williston, Vermont, United States, 05495
      • Duramed Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: DR-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.; Other Names: levonorgestrel/ethinyl estradiol; Quartette®; Drug: Portia®; 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.; Other Names: levonorgestrel/ethinyl estradiol
Experimental: 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.	Drug: DR-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.; Other Names: levonorgestrel/ethinyl estradiol; Quartette®; Drug: Portia®; 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.; Other Names: levonorgestrel/ethinyl estradiol
Experimental: 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.	Drug: DR-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.; Other Names: levonorgestrel/ethinyl estradiol; Quartette®; Drug: Portia®; 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.; Other Names: levonorgestrel/ethinyl estradiol
Active Comparator: Seasonale; 84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.	Drug: Portia®; 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.; Other Names: levonorgestrel/ethinyl estradiol; Drug: Seasonale®; 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.; 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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Duramed Research
• Investigators: Principal Investigator: Duramed Medical Monitor, Duramed Research

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: October 30, 2006
• First Submitted That Met QC Criteria: October 30, 2006
• First Posted (Estimate): November 1, 2006

Study Record Updates

• Last Update Posted (Estimate): July 26, 2013
• Last Update Submitted That Met QC Criteria: July 12, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: oral contraceptives; breakthrough bleeding; spotting
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Uterine Hemorrhage; Hemorrhage; Metrorrhagia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Levonorgestrel; Estradiol; Ethinyl Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: DR-ASC-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No