A Study to Evaluate the Efficacy and Safety of DR-103 for the Prevention of Pregnancy

• Sponsor: Teva Women's Health (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00996580
• Collaborator: (none)
• Enrollment: 3,597
• Locations: 94
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 38.3
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This is an open-label, single-treatment study. All subjects will receive 12 months of oral contraceptive therapy with DR-103. 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
Pregnancy Prevention	Drug: DR-103	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3597 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of a Combination Oral Contraceptive Regimen (DR-103) for the Prevention of Pregnancy in Women
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DR-103 Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Drug: DR-103; One tablet daily. Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.; Other Names: levonorgestrel/ethinyl estradiol Quartette®

Outcome Measures

Primary Outcome Measures

1. All Users Pregnancy Rates Based on Pearl Index (PI) Analyses for 91-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(4)/(total number of 91-day cycles)

2. Typical-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 91-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(4)/(total number of 91-day cycles)

3. Compliant-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 91-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(4)/(total number of 91-day cycles)

4. All Users Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycle-Equivalents and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. In order to compare the efficacy of extended treatment with DR-103 to conventional 28-day cyclic oral contraceptive treatment, the 91-day DR-103 treatment cycle was separated into three 28-day cycle-equivalents, derived from the 84-day active combination (EE/LNG) pill period of each 91-day extended cycle. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(13)/(total number of 28-day cycles)

5. Typical-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycle-Equivalents and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. In order to compare the efficacy of extended treatment with DR-103 to conventional 28-day cyclic oral contraceptive treatment, the 91-day DR-103 treatment cycle was separated into three 28-day cycle-equivalents, derived from the 84-day active combination (EE/LNG) pill period of each 91-day extended cycle. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(13)/(total number of 28-day cycles)

6. Compliant-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycle-Equivalents and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. In order to compare the efficacy of extended treatment with DR-103 to conventional 28-day cyclic oral contraceptive treatment, the 91-day DR-103 treatment cycle was separated into three 28-day cycle-equivalents, derived from the 84-day active combination (EE/LNG) pill period of each 91-day extended cycle. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(13)/(total number of 28-day cycles)

7. Summary of Participants With Treatment-emergent Adverse Events [Day 1 up to 13 months]

   The on-treatment time frame spanned the time during which study drug was administered until 3 weeks beyond the last study drug date. Relationship to study drug was assessed by the investigator. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention.

Secondary Outcome Measures

1. All Users Life-Table Estimates of Pregnancy Rates Based on 91-day Cycles and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   A life table approach was used to estimate the cumulative pregnancy rate on a cycle-by-cycle basis for each of the four 91-day treatment cycles.

2. Compliant-Use Life-Table Estimates of Pregnancy Rates Based on 91-day Cycles and Broken Out by Subpopulations Defined by Participant Weight [Day 1 up to year 1]

   A life table approach was used to estimate the cumulative pregnancy rate on a cycle-by-cycle basis for each of the four 91-day treatment cycles.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Sexually active at risk for pregnancy

• Agreement to use study OC therapy as their only method of birth control during the study

• history of regular spontaneous menstrual cycles or withdrawal bleeding episodes

• Others as dictated by FDA-approved protocol

Exclusion Criteria:

• Any contraindication to the use of oral contraceptives

• Pregnancy or plans to become pregnant in the next 14 months

• Smoker and age ≥ 35 years

• Others as dictated by FDA-approved protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Women's Health Research Investigational Site	Montgomery	Alabama	United States	36116
2	Teva Women's Health Research Investigational Site	Phoenix	Arizona	United States	85015
3	Teva Women's Health Research Investigational Site	Phoenix	Arizona	United States	85037
4	Teva Women's Health Research Investigational Site	Tucson	Arizona	United States	85741
5	Teva Women's Health Research Investigational Site	Little Rock	Arkansas	United States	72205
6	Teva Women's Health Research Investigational Site	Anaheim	California	United States	92801
7	Teva Women's Health Research Investigational Site	Irvine	California	United States	92618
8	Teva Women's Health Research Investigational Site	Los Angeles	California	United States	90033
9	Teva Women's Health Research Investigational Site	National City	California	United States	91950
10	Teva Women's Health Research Investigational Site	San Diego	California	United States	29103
11	Teva Women's Health Research Investigational Site	San Diego	California	United States	92108
12	Teva Women's Health Research Investigational Site	San Diego	California	United States	92123
13	Teva Women's Health Research Investigational Site	San Francisco	California	United States	92103
14	Teva Women's Health Research Investigational Site	Torrance	California	United States	90502
15	Teva Women's Health Research Investigational Site	Colorado Springs	Colorado	United States	80909
16	Teva Women's Health Research Investigational Site	Pueblo	Colorado	United States	81001
17	Teva Women's Health Research Investigational Site	Washington	District of Columbia	United States	20036
18	Teva Women's Health Research Investigational Site	Clearwater	Florida	United States	33759
19	Teva Women's Health Research Investigational Site	Jacksonville	Florida	United States	32207
20	Teva Women's Health Research Investigational Site	Leesburg	Florida	United States	34748
21	Teva Women's Health Research Investigational Site	Miami	Florida	United States	33143
22	Teva Women's Health Research Investigational Site	Miami	Florida	United States	33186
23	Teva Women's Health Research Investigational Site	New Port Richey	Florida	United States	34652
24	Teva Women's Health Research Investigational Site	Palm Beach	Florida	United States	33409
25	Teva Women's Health Research Investigational Site	St. Petersburg	Florida	United States	33709
26	Teva Women's Health Research Investigational Site	Tampa	Florida	United States	33613
27	Teva Women's Health Research Investigational Site	West Palm Beach	Florida	United States	33401
28	Teva Women's Health Research Investigational Site	Atlanta	Georgia	United States	30303
29	Teva Women's Health Research Investigational Site	Decatur	Georgia	United States	30034
30	Teva Women's Health Research Investigational Site	Roswell	Georgia	United States	30075
31	Teva Women's Health Research Investigational Site	Sandy Springs	Georgia	United States	30328
32	Teva Women's Health Research Investigational Site	Savannah	Georgia	United States	31406
33	Teva Women's Health Research Investigational Site	Meridian	Idaho	United States	83642
34	Teva Women's Health Research Investigational Site	Champaign	Illinois	United States	61820
35	Teva Women's Health Research Investigational Site	Wichita	Kansas	United States	67207
36	Teva Women's Health Research Investigational Site	Lexington	Kentucky	United States	40509
37	Teva Women's Health Research Investigational Site	Louisville	Kentucky	United States	40291
38	Teva Women's Health Research Investigational Site	Mt Sterling	Kentucky	United States	40353
39	Teva Women's Health Research Investigational Site	Baton Rouge	Louisiana	United States	70808
40	Teva Women's Health Research Investigational Site	Metairie	Louisiana	United States	70006
41	Teva Women's Health Research Investigational Site	Baltimore	Maryland	United States	21201
42	Teva Women's Health Research Investigational Site	Kansas City	Missouri	United States	64108
43	Teva Women's Health Research Investigational Site	St. Louis	Missouri	United States	63117
44	Teva Women's Health Research Investigational Site	Lincoln	Nebraska	United States	68510
45	Teva Women's Health Research Investigational Site	Las Vegas	Nevada	United States	89146
46	Teva Women's Health Research Investigational Site	Berlin	New Jersey	United States	08009
47	Teva Women's Health Research Investigational Site	Lawrenceville	New Jersey	United States	08648
48	Teva Women's Health Research Investigational Site	Moorestown	New Jersey	United States	08057
49	Teva Women's Health Research Investigational Site	New Brunswick	New Jersey	United States	08901
50	Teva Women's Health Research Investigational Site	Albuquerque	New Mexico	United States	87102
51	Teva Women's Health Research Investigational Site	Port Jefferson	New York	United States	11777
52	Teva Women's Health Research Investigational Site	Rochester	New York	United States	14609
53	Teva Women's Health Research Investigational Site	Cary	North Carolina	United States	27518
54	Teva Women's Health Research Investigational Site	Charlotte	North Carolina	United States	28209
55	Teva Women's Health Research Investigational Site	New Bern	North Carolina	United States	28562
56	Teva Women's Health Research Investigational Site	Raleigh	North Carolina	United States	27609
57	Teva Women's Health Research Investigational Site	Raleigh	North Carolina	United States	27612
58	Teva Women's Health Research Investigational Site	Salisbury	North Carolina	United States	28144
59	Teva Women's Health Research Investigational Site	Wilmington	North Carolina	United States	28401
60	Teva Women's Health Research Investigational Site	Winston-Salem	North Carolina	United States	27103
61	Teva Women's Health Research Investigational Site	Columbus	Ohio	United States	43210
62	Teva Women's Health Research Investigational Site	Columbus	Ohio	United States	43213
63	Teva Women's Health Research Investigational Site	Edmond	Oklahoma	United States	73013
64	Teva Women's Health Research Investigational Site	Oklahoma City	Oklahoma	United States	73112
65	Teva Women's Health Research Investigational Site	Eugene	Oregon	United States	97401
66	Teva Women's Health Research Investigational Site	Medford	Oregon	United States	97504
67	Teva Women's Health Research Investigational Site	Philadelphia	Pennsylvania	United States	19114
68	Teva Women's Health Research Investigational Site	Pittsburgh	Pennsylvania	United States	15206
69	Teva Women's Health Research Investigational Site	Charleston	South Carolina	United States	29425
70	Teva Women's Health Research Investigational Site	Columbia	South Carolina	United States	29201
71	Teva Women's Health Research Investigational Site	Goose Creek	South Carolina	United States	29445
72	Teva Women's Health Research Investigational Site	Greenville	South Carolina	United States	29605
73	Teva Women's Health Research Investigational Site	Greer	South Carolina	United States	29651
74	Teva Women's Health Research Investigational Site	Hilton Head Island	South Carolina	United States	29926
75	Teva Women's Health Research Investigational Site	Bristol	Tennessee	United States	37620
76	Teva Women's Health Research Investigational Site	Jackson	Tennessee	United States	38305
77	Teva Women's Health Research Investigational Site	Knoxville	Tennessee	United States	37920
78	Teva Women's Health Research Investigational Site	Memphis	Tennessee	United States	38120
79	Teva Women's Health Research Investigational Site	Nashville	Tennessee	United States	37203
80	Teva Women's Health Research Investigational Site	Austin	Texas	United States	78759
81	Teva Women's Health Research Investigational Site	Dallas	Texas	United States	75234
82	Teva Women's Health Research Investigational Site	Dallas	Texas	United States	75390
83	Teva Women's Health Research Investigational Site	Ft. Worth	Texas	United States	76135
84	Teva Women's Health Research Investigational Site	Houston	Texas	United States	77054
85	Teva Women's Health Research Investigational Site	San Antonio	Texas	United States	78229
86	Teva Women's Health Research Investigational Site	Waco	Texas	United States	76712
87	Teva Women's Health Research Investigational Site	Salt Lake City	Utah	United States	84107
88	Teva Women's Health Research Investigational Site	Arlington	Virginia	United States	22203
89	Teva Women's Health Research Investigational Site	Newport News	Virginia	United States	23602
90	Teva Women's Health Research Investigational Site	Norfolk	Virginia	United States	23502
91	Teva Women's Health Research Investigational Site	Norfolk	Virginia	United States	23507
92	Teva Women's Health Research Investigational Site	Richmond	Virginia	United States	23233
93	Teva Women's Health Research Investigational Site	Seattle	Washington	United States	98105
94	Teva Women's Health Research Investigational Site	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Teva Women's Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Women's Health
• ClinicalTrials.gov Identifier: NCT00996580
• Other Study ID Numbers: DR-103-301
• First Posted: Oct 16, 2009
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Teva Women's Health: Contraception; Oral contraceptives
• Additional relevant MeSH terms: Levonorgestrel; Ethinyl Estradiol; Estradiol

Study Results

Participant Flow

Pre-assignment Detail	A total of 4,962 subjects were screened for participation in this study, and 3,597 took at least one dose of investigational product (Safety population).

Arm/Group Title	DR-103
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.
Period Title: Overall Study
STARTED	3597
Pregnancy Intent-to-Treat Population	3019
COMPLETED	2144
NOT COMPLETED	1453

Baseline Characteristics

Arm/Group Title	DR-103
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.
Overall Participants	3597
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.4 (7.0)
Sex: Female, Male (Count of Participants)
Female	3597 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	14 0.4%
Asian	78 2.2%
Native Hawaiian or Other Pacific Islander	10 0.3%
Black or African American	696 19.3%
White	2324 64.6%
Hispanic or Latino	404 11.2%
Other	71 2%
Height (inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [inches]	64.6 (2.7)
Weight (pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pounds]	162.5 (43.2)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.4 (7.0)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	113.1 (10.4)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	72.3 (8.3)
Heart Rate (beats/minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/minute]	74.6 (10.0)
Oral Contraceptive Use History (participants) [Number]
Continuous user	1570 43.6%
New Start	619 17.2%
Prior User	1408 39.1%
Smoking Status (participants) [Number]
Current Smoker	602 16.7%
Former Smoker	636 17.7%
Never Smoked	2359 65.6%

Outcome Measures

1. Primary Outcome

Title	All Users Pregnancy Rates Based on Pearl Index (PI) Analyses for 91-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(4)/(total number of 91-day cycles)
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age when study treatment started. The 'All Users' set included PITT participants who completed at least one 91-day cycle.

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2769	2276	493
Measure Treatment cycles	9217	7633	1584
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	2.82	2.46	4.54

2. Primary Outcome

Title	Typical-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 91-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(4)/(total number of 91-day cycles)
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age when study treatment started. The 'Typical-Use' set included PITT participants who completed at least one 91-day cycle and no other birth control methods including condoms were used.

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2606	2149	457
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	3.25	2.83	5.32

3. Primary Outcome

Title	Compliant-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 91-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(4)/(total number of 91-day cycles)
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

'Compliant-Use' set included PITT participants who completed at least one 91-day cycle and no other birth control methods were used. Cycles were excluded if a subject 1) skipped 2 or more consecutive combination pills, 2) had a pattern of substantial non-compliance with treatment, or 3) used a prohibited concomitant medication

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2505	2067	438
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	3.71	3.23	6.04

4. Secondary Outcome

Title	All Users Life-Table Estimates of Pregnancy Rates Based on 91-day Cycles and Broken Out by Subpopulations Defined by Participant Weight
Description	A life table approach was used to estimate the cumulative pregnancy rate on a cycle-by-cycle basis for each of the four 91-day treatment cycles.
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age when study treatment started. The 'All Users' set included PITT participants who completed at least one 91-day cycle.

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2769	2276	493
Cycle 1	0.0074	0.0060	0.0139
Cycle 2	0.0134	0.0114	0.0231
Cycle 3	0.0212	0.0185	0.0339
Cycle 4	0.0272	0.0239	0.0429

5. Primary Outcome

Title	All Users Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycle-Equivalents and Broken Out by Subpopulations Defined by Participant Weight
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. In order to compare the efficacy of extended treatment with DR-103 to conventional 28-day cyclic oral contraceptive treatment, the 91-day DR-103 treatment cycle was separated into three 28-day cycle-equivalents, derived from the 84-day active combination (EE/LNG) pill period of each 91-day extended cycle. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(13)/(total number of 28-day cycles)
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age when study treatment started. The 'All Users' set included PITT participants who completed at least one 28-day cycle.

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	3019	2479	540
Measure Treatment cycles	30785	25487	5298
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	2.74	2.40	4.42

6. Primary Outcome

Title	Typical-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycle-Equivalents and Broken Out by Subpopulations Defined by Participant Weight
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. In order to compare the efficacy of extended treatment with DR-103 to conventional 28-day cyclic oral contraceptive treatment, the 91-day DR-103 treatment cycle was separated into three 28-day cycle-equivalents, derived from the 84-day active combination (EE/LNG) pill period of each 91-day extended cycle. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(13)/(total number of 28-day cycles)
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age when study treatment started. The 'Typical-Use' set included PITT participants who completed at least one 28-day cycle and no other birth control methods including condoms were used.

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2972	2436	536
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	2.92	2.55	4.72

7. Primary Outcome

Title	Compliant-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycle-Equivalents and Broken Out by Subpopulations Defined by Participant Weight
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI). PI used all pregnancies, as determined by a positive urine and/or serum pregnancy test, except those for which the date of conception was before starting DR-103 or > 7 days after stopping the combination EE/LNG treatment of DR-103. The estimated date of conception and gestational age of the fetus was determined by transvaginal or abdominal ultrasound. In order to compare the efficacy of extended treatment with DR-103 to conventional 28-day cyclic oral contraceptive treatment, the 91-day DR-103 treatment cycle was separated into three 28-day cycle-equivalents, derived from the 84-day active combination (EE/LNG) pill period of each 91-day extended cycle. The PI is defined as number of contraceptive failures per 100 women-years of exposure: (100)*(total number of pregnancies)*(13)/(total number of 28-day cycles)
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

'Compliant-Use' set included PITT participants who completed at least one 28-day cycle and no other birth control methods were used. Cycles were excluded if a subject 1) skipped 2 or more consecutive combination pills, 2) had a pattern of substantial non-compliance with treatment, or 3) used a prohibited concomitant medication

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2941	2531	531
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	3.07	2.68	4.94

8. Primary Outcome

Title	Summary of Participants With Treatment-emergent Adverse Events
Description	The on-treatment time frame spanned the time during which study drug was administered until 3 weeks beyond the last study drug date. Relationship to study drug was assessed by the investigator. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention.
Time Frame	Day 1 up to 13 months

Outcome Measure Data

Analysis Population Description

Safety population of treated participants

Arm/Group Title	DR-103
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.
Measure Participants	3597
Treatment-emergent AEs (TEAEs)	2605 72.4%
Treatment-related AEs	1086 30.2%
Serious AEs	58 1.6%
TEAEs leading to discontinuation	463 12.9%

9. Secondary Outcome

Title	Compliant-Use Life-Table Estimates of Pregnancy Rates Based on 91-day Cycles and Broken Out by Subpopulations Defined by Participant Weight
Description	A life table approach was used to estimate the cumulative pregnancy rate on a cycle-by-cycle basis for each of the four 91-day treatment cycles.
Time Frame	Day 1 up to year 1

Outcome Measure Data

Analysis Population Description

'Compliant-Use' set included PITT participants who completed at least one 91-day cycle and no other birth control methods were used. Cycles were excluded if a subject 1) skipped 2 or more consecutive combination pills, 2) had a pattern of substantial non-compliance with treatment, or 3) used a prohibited concomitant medication

Arm/Group Title	DR-103: Total	DR-103: <90 kg Subpopulation	DR-103: >=90kg Subpopulation
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.	Subpopulation of the total participants who weighed <90 kg during the screening visit.	Subpopulation of the total participants who weighed >=90 kg during the screening visit.
Measure Participants	2505	2067	438
Cycle 1	0.0080	0.0062	0.0164
Cycle 2	0.0134	0.0116	0.0215
Cycle 3	0.0236	0.0203	0.0392
Cycle 4	0.0291	0.0256	0.0457

Adverse Events

Time Frame	Day 1 - one year and three weeks
Arm/Group Title	DR-103
Arm/Group Description	Four 91-day cycles of the DR-103 regimen: 42 days combination therapy of 20 mcg ethinyl estradiol (EE) /150 mcg levonorgestrel (LNG) followed by; 21 days combination therapy of 25 mcg EE/150 mcg LNG followed by; 21 days combination therapy of 30 mcg EE/150 mcg LNG followed by; 7 days of 10 mcg EE.
All Cause Mortality
	DR-103
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	DR-103
	Affected / at Risk (%)	# Events
Total	58/3597 (1.6%)
Blood and lymphatic system disorders
Anemia	1/3597 (0%)
Cardiac disorders
Supraventricular tachycardia	1/3597 (0%)
Atrial fibrillation	1/3597 (0%)
Angina pectoris	1/3597 (0%)
Congenital, familial and genetic disorders
Hip dysplasia	1/3597 (0%)
Gastrointestinal disorders
Colitis	1/3597 (0%)
Abdominal pain	3/3597 (0.1%)
Gastrointestinal haemorrhage	1/3597 (0%)
Ileitis	1/3597 (0%)
Hepatobiliary disorders
Cholecystitis	2/3597 (0.1%)
Cholelithiasis	2/3597 (0.1%)
Cholecystitis acute	1/3597 (0%)
Infections and infestations
Pneumonia	2/3597 (0.1%)
Staphylococcal infection	1/3597 (0%)
Pelvic inflammatory disease	1/3597 (0%)
Pharyngitis	1/3597 (0%)
Hepatitis C	1/3597 (0%)
Viral infection	1/3597 (0%)
Rectal abscess	1/3597 (0%)
Appendicitis	2/3597 (0.1%)
Urinary tract infection	1/3597 (0%)
Pyelonephritis	2/3597 (0.1%)
Salpingitis	1/3597 (0%)
Helicobacter gastritis	1/3597 (0%)
Injury, poisoning and procedural complications
Injury	1/3597 (0%)
Overdose	2/3597 (0.1%)
Lower limb fracture	1/3597 (0%)
Spinal fracture	1/3597 (0%)
Joint injury	1/3597 (0%)
Multiple drug overdose	1/3597 (0%)
Musculoskeletal and connective tissue disorders
Bursitis	1/3597 (0%)
Pain in extremity	1/3597 (0%)
Intervertebral disc protrusion	1/3597 (0%)
Nervous system disorders
Convulsion	2/3597 (0.1%)
Convulsion	1/3597 (0%)
Syncope	1/3597 (0%)
Headache	1/3597 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	5/3597 (0.1%)
Abortion missed	1/3597 (0%)
Premature separation of placenta	1/3597 (0%)
Blighted ovum	1/3597 (0%)
Ectopic pregnancy	2/3597 (0.1%)
Psychiatric disorders
Depression suicidal	1/3597 (0%)
Depression	1/3597 (0%)
Suicide attempt	5/3597 (0.1%)
Anxiety	1/3597 (0%)
Mental status changes	1/3597 (0%)
Drug dependence	1/3597 (0%)
Reproductive system and breast disorders
Uterine inflammation	1/3597 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/3597 (0%)
Pleural effusion	1/3597 (0%)
Vascular disorders
Deep vein thrombosis	3/3597 (0.1%)
Other (Not Including Serious) Adverse Events
	DR-103
	Affected / at Risk (%)	# Events
Total	1567/3597 (43.6%)
Gastrointestinal disorders
Nausea	241/3597 (6.7%)
Infections and infestations
Nasopharyngitis	342/3597 (9.5%)
Upper respiratory tract infection	323/3597 (9%)
Sinusitis	246/3597 (6.8%)
Urinary tract infection	214/3597 (5.9%)
Nervous system disorders
Headache	420/3597 (11.7%)
Reproductive system and breast disorders
Metrorrhagia	216/3597 (6%)
Dysmenorrhoea	188/3597 (5.2%)
Skin and subcutaneous tissue disorders
Acne	193/3597 (5.4%)

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.