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

• Sponsor: Duramed Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00394771
• Collaborator: (none)
• Enrollment: 567
• Locations: 50
• Arms: 4
• Duration (Months): 17
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Breakthrough Bleeding	Drug: DR-1031; Drug: Seasonale®; Drug: Portia®	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 567 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• 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
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

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: 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 ; 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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

Other Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duramed Investigational Site	Huntsville	Alabama	United States	35801
2	Duramed Investigational Site	Tucson	Arizona	United States	85741
3	Duramed Investigational Site	Little Rock	Arkansas	United States	72205
4	Duramed Investigational Site	San Diego	California	United States	92108
5	Duramed Investigational Site	San Francisco	California	United States	94102
6	Duramed Investigational Site	Santa Ana	California	United States	92705
7	Duramed Investigational Site	Vista	California	United States	92083
8	Duramed Investigational Site	Pueblo	Colorado	United States	81001
9	Duramed Investigational Site	Stratford	Connecticut	United States	06615
10	Duramed Investigational Site	Deland	Florida	United States	32720
11	Duramed Investigational Site	Jacksonville	Florida	United States	32207
12	Duramed Investigational Site	Melbourne	Florida	United States	32935
13	Duramed Investigational Site	Miami	Florida	United States	33186
14	Duramed Investigational Site	Tampa	Florida	United States	33607
15	Duramed Investigational Site	West Palm Beach	Florida	United States	33401
16	Duramed Investigational Site	West Palm Beach	Florida	United States	33407
17	Duramed Investigational Site	Alpharetta	Georgia	United States	30005
18	Duramed Investigational Site	Douglasville	Georgia	United States	30134
19	Duramed Investigational Site	Savannah	Georgia	United States	31406
20	Duramed Investigational Site	Boise	Idaho	United States	83712
21	Duramed Investigational Site	Meridian	Idaho	United States	83642
22	Duramed Investigational Site	Fort Wayne	Indiana	United States	46825
23	Duramed Investigational Site	Wichita	Kansas	United States	67205
24	Duramed Investigational Site	Baton Rouge	Louisiana	United States	70808
25	Duramed Investigational Site	Metairie	Louisiana	United States	70006
26	Duramed Investigational Site	Shreveport	Louisiana	United States	71106
27	Duramed Investigational Site	Riverdale	Maryland	United States	20737
28	Duramed Investigational Site	Kansas City	Missouri	United States	64114
29	Duramed Investigational Site	Las Vegas	Nevada	United States	89109
30	Duramed Investigational Site	Las Vegas	Nevada	United States	89128
31	Duramed Investigational Site	N. Las Vegas	Nevada	United States	89030
32	Duramed Investigational Site	Lebanon	New Hampshire	United States	03756
33	Duramed Investigational Site	Cary	North Carolina	United States	27511
34	Duramed Investigational Site	New Bern	North Carolina	United States	28562
35	Duramed Investigational Site	Winston-Salem	North Carolina	United States	27103
36	Duramed Investigational Site	Cleveland	Ohio	United States	44122
37	Duramed Investigational Site	Mayfield Heights	Ohio	United States	44124
38	Duramed Investigational Site	Eugene	Oregon	United States	97401
39	Duramed Investigational Site	Medford	Oregon	United States	97504
40	Duramed Investigational Site	Pittsburgh	Pennsylvania	United States	15206
41	Duramed Investigational Site	Charleston	South Carolina	United States	29425
42	Duramed Investigational Site	Columbia	South Carolina	United States	29201
43	Duramed Investigational Site	Hilton Head Island	South Carolina	United States	29926
44	Duramed Investigational Site	Jackson	Tennessee	United States	38305
45	Duramed Investigational Site	Austin	Texas	United States	78737
46	Duramed Investigational Site	Dallas	Texas	United States	75390
47	Duramed Investigational Site	Houston	Texas	United States	77024
48	Duramed Investigational Site	San Antonio	Texas	United States	78229
49	Duramed Investigational Site	Salt Lake City	Utah	United States	84102
50	Duramed Investigational Site	Williston	Vermont	United States	05495

Sponsors and Collaborators

• Duramed Research

Investigators

• Principal Investigator: Duramed Medical Monitor, Duramed Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duramed Research
• ClinicalTrials.gov Identifier: NCT00394771
• Other Study ID Numbers: DR-ASC-201
• First Posted: Nov 1, 2006
• Last Update Posted: Jul 26, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Duramed Research: oral contraceptives; breakthrough bleeding; spotting
• Additional relevant MeSH terms: Metrorrhagia; Hemorrhage; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Levonorgestrel; Ethinyl Estradiol; Estradiol; Polyestradiol phosphate

Study Results

Participant Flow

Pre-assignment Detail	A total of 988 subjects were screened for participation in this study, and 567 took at least one dose of investigational product (Safety population).

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Period Title: Overall Study
STARTED	140	136	143	148
Intent to Treat (ITT) Population	110	110	108	120
COMPLETED	99	102	96	109
NOT COMPLETED	41	34	47	39

Baseline Characteristics

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale	Total
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.	Total of all reporting groups
Overall Participants	110	110	108	120	448
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.1 (6.88)	30.5 (7.02)	30.7 (7.61)	30.6 (6.90)	30.5 (7.08)
Sex: Female, Male (Count of Participants)
Female	110 100%	110 100%	108 100%	120 100%	448 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
African-American	21 19.1%	20 18.2%	18 16.7%	17 14.2%	76 17%
Asian	1 0.9%	4 3.6%	1 0.9%	3 2.5%	9 2%
Caucasian	72 65.5%	68 61.8%	69 63.9%	82 68.3%	291 65%
Hispanic	13 11.8%	17 15.5%	19 17.6%	16 13.3%	65 14.5%
Other	3 2.7%	1 0.9%	1 0.9%	2 1.7%	7 1.6%
Weight (lbs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lbs]	156.6 (28.84)	153.6 (27.18)	156.0 (30.79)	151.9 (30.03)	154.4 (29.22)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.6 (4.13)	25.7 (4.24)	26.0 (4.59)	25.5 (4.41)	25.9 (4.35)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	114.2 (10.74)	114.4 (10.34)	115.6 (9.31)	112.8 (10.23)	114.2 (10.19)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	72.3 (8.85)	72.9 (7.46)	71.8 (7.72)	71.4 (8.44)	72.1 (8.14)
Heart Rate (beats/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/minute]	73.9 (9.85)	73.7 (8.90)	73.7 (9.17)	71.9 (9.07)	73.3 (9.26)
Smoking Status (participants) [Number]
Current Smoker	13 11.8%	16 14.5%	11 10.2%	11 9.2%	51 11.4%
Past Smoker	20 18.2%	11 10%	12 11.1%	21 17.5%	64 14.3%
Non-Smoker	77 70%	83 75.5%	85 78.7%	88 73.3%	333 74.3%
Oral Contraceptive Use History (participants) [Number]
Missing	1 0.9%	0 0%	0 0%	0 0%	1 0.2%
Continuous User	44 40%	46 41.8%	42 38.9%	49 40.8%	181 40.4%
Prior User	44 40%	45 40.9%	49 45.4%	52 43.3%	190 42.4%
Fresh-Start	21 19.1%	19 17.3%	17 15.7%	19 15.8%	76 17%

Outcome Measures

1. Primary Outcome

Title	Days With Bleeding and/or Spotting During Active Cycle 1 (Day 1-84)
Description	Bleeding is defined as a flow heavy enough to require sanitary protection. Spotting does not require sanitary protection.
Time Frame	Day 1-84

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	110	110	108	120
Median (Full Range) [days]	13	13.5	15	15

2. Secondary Outcome

Title	Days With Bleeding During Active Cycle 1 (Day 1-84)
Description	Bleeding is defined as a flow heavy enough to require sanitary protection.
Time Frame	Day 1-84

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	110	110	108	120
Median (Full Range) [days]	3.5	2.5	4	2

3. Secondary Outcome

Title	Days With Bleeding During Active Cycle 2 (Day 92-176)
Description	Bleeding is defined as a flow heavy enough to require sanitary protection.
Time Frame	Day 92-176

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	109	108	107	120
Median (Full Range) [days]	1	2	1	2

4. Secondary Outcome

Title	Time to First Bleeding Day
Description	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

Outcome Measure Data

Analysis Population Description

ITT population. However this data was not summarized due to limitations in the diary data.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Maximum Bleeding Severity During Active Cycle 1 (Day 1-84)
Description	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

Outcome Measure Data

Analysis Population Description

ITT population. However data was not summarized due to limitations in the diary data.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	0	0	0	0

6. Primary Outcome

Title	Days With Bleeding and/or Spotting During Active Cycle 2 (Day 92-176)
Description	Bleeding is defined as a flow heavy enough to require sanitary protection. Spotting does not require sanitary protection.
Time Frame	Day 92-176

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	109	108	107	120
Median (Full Range) [days]	6	7	5	6

7. Secondary Outcome

Title	Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 1 (Day 85-91)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	109	108	106	120
0 day	14 12.7%	28 25.5%	25 23.1%	27 22.5%
1-3 days	36 32.7%	17 15.5%	27 25%	18 15%
4-7 days	59 53.6%	63 57.3%	54 50%	75 62.5%

8. Secondary Outcome

Title	Participants With Bleeding and/or Spotting Days During the 7-day Withdrawal During Cycle 2 (Day 177-183)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	97	96	94	105
0 day	15 13.6%	20 18.2%	23 21.3%	21 17.5%
1-3 days	32 29.1%	32 29.1%	26 24.1%	24 20%
4-7 days	50 45.5%	44 40%	45 41.7%	60 50%

9. Secondary Outcome

Title	Participants Reporting Hormone-Related Symptoms During Active Cycle 1 (Day 1-84)
Description	Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time Frame	Day 1-84

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	110	110	108	120
Breast tenderness/pain	58 52.7%	57 51.8%	50 46.3%	64 53.3%
Headache	83 75.5%	84 76.4%	86 79.6%	92 76.7%
Bloating	80 72.7%	76 69.1%	72 66.7%	84 70%
Pelvic pain	72 65.5%	65 59.1%	61 56.5%	67 55.8%
Anxiety	42 38.2%	43 39.1%	34 31.5%	59 49.2%
Depression	51 46.4%	40 36.4%	36 33.3%	52 43.3%
Irritability	72 65.5%	69 62.7%	66 61.1%	78 65%

10. Secondary Outcome

Title	Participants Reporting Hormone-Related Symptoms During Active Cycle 2 (Day 92-176)
Description	Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time Frame	Day 92-176

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	109	108	107	120
Breast tenderness/pain	46 41.8%	47 42.7%	44 40.7%	44 36.7%
Headache	74 67.3%	72 65.5%	72 66.7%	78 65%
Bloating	64 58.2%	64 58.2%	57 52.8%	70 58.3%
Pelvic pain	58 52.7%	57 51.8%	45 41.7%	57 47.5%
Anxiety	40 36.4%	40 36.4%	31 28.7%	47 39.2%
Depression	41 37.3%	39 35.5%	30 27.8%	44 36.7%
Irritability	55 50%	63 57.3%	54 50%	65 54.2%

11. Secondary Outcome

Title	Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 1 (Day 85-91)
Description	Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time Frame	Day 85-91

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	110	110	108	120
Breast tenderness/pain	33 30%	28 25.5%	17 15.7%	33 27.5%
Headache	57 51.8%	50 45.5%	57 52.8%	50 41.7%
Bloating	61 55.5%	51 46.4%	46 42.6%	62 51.7%
Pelvic pain	50 45.5%	49 44.5%	37 34.3%	53 44.2%
Anxiety	26 23.6%	17 15.5%	14 13%	22 18.3%
Depression	25 22.7%	21 19.1%	17 15.7%	23 19.2%
Irritability	44 40%	43 39.1%	23 21.3%	36 30%

12. Secondary Outcome

Title	Participants Reporting Hormone-Related Symptoms During the 7-day Withdrawal Cycle 2 (Day 177-183)
Description	Hormone-related symptoms include breast tenderness/pain, headache, bloating, pelvic pain, anxiety, depression, and irritability.
Time Frame	Day 177-183

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	97	96	94	105
Breast tenderness/pain	29 26.4%	25 22.7%	15 13.9%	25 20.8%
Headache	39 35.5%	42 38.2%	37 34.3%	48 40%
Bloating	51 46.4%	53 48.2%	38 35.2%	60 50%
Pelvic pain	52 47.3%	42 38.2%	31 28.7%	51 42.5%
Anxiety	21 19.1%	22 20%	13 12%	22 18.3%
Depression	18 16.4%	21 19.1%	15 13.9%	17 14.2%
Irritability	39 35.5%	37 33.6%	25 23.1%	39 32.5%

13. Other Pre-specified Outcome

Title	Number of Moderate to Heavy Bleeding Days During Active Cycle 1 (Day 1-84)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population of participants who completed the relevant pages in the patient diary.

Arm/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	110	110	108	120
Median (Full Range) [days]	0	0	0	0

14. Other Pre-specified Outcome

Title	Number of Moderate to Heavy Bleeding Days During Active Cycle 2 (Day 92-176)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Low Dose DR-1031	Midrange Dose DR-1031	High Dose DR-1031	Seasonale
Arm/Group Description	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.	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.	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.	84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
Measure Participants	109	108	107	120
Median (Full Range) [days]	0	0	0	0

Adverse Events

Time Frame	Day 1 up to Day 256 (longest treatment plus 14 days)
Arm/Group Title	Low Dose DR-1031		Midrange Dose DR-1031		High Dose DR-1031		Seasonale
Arm/Group Description	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.		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.		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.		84 days of combination active tablets, each containing 30 mcg EE and 150 mcg LNG, followed by 7 days of placebo tablets.
All Cause Mortality
	Low Dose DR-1031		Midrange Dose DR-1031		High Dose DR-1031		Seasonale
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Dose DR-1031		Midrange Dose DR-1031		High Dose DR-1031		Seasonale
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/140 (0.7%)		2/136 (1.5%)		3/143 (2.1%)		5/148 (3.4%)
Gastrointestinal disorders
Small intestinal obstruction	0/140 (0%)		0/136 (0%)		0/143 (0%)		1/148 (0.7%)
Vomiting	0/140 (0%)		0/136 (0%)		0/143 (0%)		1/148 (0.7%)
Hepatobiliary disorders
Cholecystitis	0/140 (0%)		1/136 (0.7%)		0/143 (0%)		0/148 (0%)
Infections and infestations
Pyelonephritis	0/140 (0%)		1/136 (0.7%)		0/143 (0%)		0/148 (0%)
Injury, poisoning and procedural complications
Road traffic accident	0/140 (0%)		0/136 (0%)		0/143 (0%)		2/148 (1.4%)
Multiple fractures	0/140 (0%)		0/136 (0%)		0/143 (0%)		1/148 (0.7%)
Polytraumatism	0/140 (0%)		0/136 (0%)		0/143 (0%)		1/148 (0.7%)
Post procedural bile leak	0/140 (0%)		1/136 (0.7%)		0/143 (0%)		0/148 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/140 (0%)		0/136 (0%)		1/143 (0.7%)		0/148 (0%)
Nervous system disorders
Hemiparesis	1/140 (0.7%)		0/136 (0%)		0/143 (0%)		0/148 (0%)
Hypoaesthesia	1/140 (0.7%)		0/136 (0%)		0/143 (0%)		0/148 (0%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/140 (0%)		0/136 (0%)		0/143 (0%)		1/148 (0.7%)
Abortion spontaneous	0/140 (0%)		0/136 (0%)		2/143 (1.4%)		0/148 (0%)
Other (Not Including Serious) Adverse Events
	Low Dose DR-1031		Midrange Dose DR-1031		High Dose DR-1031		Seasonale
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/140 (43.6%)		44/136 (32.4%)		49/143 (34.3%)		53/148 (35.8%)
Infections and infestations
Nasopharyngitis	15/140 (10.7%)		7/136 (5.1%)		8/143 (5.6%)		8/148 (5.4%)
Upper respiratory tract infection	9/140 (6.4%)		7/136 (5.1%)		5/143 (3.5%)		9/148 (6.1%)
Sinusitis	10/140 (7.1%)		6/136 (4.4%)		2/143 (1.4%)		6/148 (4.1%)
Urinary tract infection	8/140 (5.7%)		1/136 (0.7%)		5/143 (3.5%)		2/148 (1.4%)
Investigations
Weight increased	6/140 (4.3%)		4/136 (2.9%)		9/143 (6.3%)		8/148 (5.4%)
Musculoskeletal and connective tissue disorders
Back pain	7/140 (5%)		7/136 (5.1%)		5/143 (3.5%)		6/148 (4.1%)
Nervous system disorders
Headache	19/140 (13.6%)		19/136 (14%)		23/143 (16.1%)		19/148 (12.8%)
Migraine	2/140 (1.4%)		7/136 (5.1%)		1/143 (0.7%)		2/148 (1.4%)
Reproductive system and breast disorders
Dysmenorrhoea	13/140 (9.3%)		6/136 (4.4%)		5/143 (3.5%)		7/148 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Details of the study and its results shall not be publicized or published in any form to cooperative publication without prior, written consent of sponsor. Such approval is necessary to prevent premature disclosure of trade secrets and other confidential information.