A Study to Evaluate the Efficacy and Safety of DR-102 for the Prevention of Pregnancy

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01178125
• Collaborator: (none)
• Enrollment: 2,858
• Locations: 62
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 46.1
• Patients Per Site Per Month: 1.6

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-102. Study participants will receive physical and gynecological exams, including Pap smear. During the study, all participants will be required to complete a daily diary.

Condition or Disease	Intervention/Treatment	Phase
Contraception; Female Contraception	Drug: DR-102	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2858 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-102) for the Prevention of Pregnancy in Women
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DR-102 desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	Drug: DR-102

Outcome Measures

Primary Outcome Measures

1. All Users Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight, Using the 7-Day Rule [thirteen 28-day cycles]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI) and the 7-day rule (a standardized process for calculating pregnancy rates). 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-102 or > 7 days after stopping the combination desogestrel/ethinyl estradiol (DSG/EE) or ethinyl estradiol (EE) treatment of DR-102.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). Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.

2. Typical-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight, Using the 7-Day Rule [thirteen 28-day cycles]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI) and the 7-day rule (a standardized process for calculating pregnancy rates). 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-102 or > 7 days after stopping the combination DSG/EE or EE treatment of DR-102.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). Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.

3. Compliant-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight, Using the 7-Day Rule [thirteen 28-day cycles]

   Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI) and the 7-day rule (a standardized process for calculating pregnancy rates). 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-102 or > 7 days after stopping the combination DSG/EE or EE treatment of DR-102.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). Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.

Secondary Outcome Measures

1. All Users Life-Table Estimates of Pregnancy Rates Based on 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight [thirteen 28-day cycles]

   A life table approach was used to estimate the cumulative pregnancy rate on a cycle-by-cycle basis for each of the thirteen 28-day treatment cycles.

2. Compliant-Use Life-Table Estimates of Pregnancy Rates Based on 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight [thirteen 28-day cycles]

   A life table approach was used to estimate the cumulative pregnancy rate on a cycle-by-cycle basis for each of the thirteen 28-day treatment cycles. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.

3. Percentage of On-Drug Pregnancies in All Users, by Body Weight Decile Groups Using the 7-Day Rule [thirteen 28-day cycles]

   Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body weight decile (weight range, in kilograms). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.

4. Percentage of On-Drug Pregnancies in Typical-Use, by Body Weight Decile Groups Using the 7-Day Rule [thirteen 28-day cycles]

   Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body weight decile (weight range, in kilograms). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.

5. Percentage of On-Drug Pregnancies in Compliant-Use, by Body Weight Decile Groups Using the 7-Day Rule [thirteen 28-day cycles]

   Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body weight decile (weight range, in kilograms). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.

6. Percentage of On-Drug Pregnancies in All Users, by Body Mass Index (BMI) Decile Groups Using the 7-Day Rule [thirteen 28-day cycles]

   Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body mass index (BMI) decile (BMI range, in kg/m^2). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.

7. Percentage of On-Drug Pregnancies in Typical-Use, by Body Mass Index (BMI) Decile Groups Using the 7-Day Rule [thirteen 28-day cycles]

   Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body mass index (BMI) decile (BMI range, in kg/m^2). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.

8. Percentage of On-Drug Pregnancies in Compliant-Use, by Body Mass Index (BMI) Decile Groups Using the 7-Day Rule [thirteen 28-day cycles]

   Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body mass index (BMI) decile (BMI range, in kg/m^2). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.

Other Outcome Measures

1. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs [Serious adverse Event (SAE) reporting period began upon signed informed consent and ended at the Final Study or the Early Withdrawal Visit. AEs were reported at each study visit (Weeks 0 through Week 53). Treatment duration with IP was up to one year.]

   AEs summarized are those that began or worsened after treatment with investigational product (IP). An AE is any untoward medical occurrence in a subject or clinical investigation subject participating in a clinical study and which does not necessarily have to have a causal relationship with this treatment or clinical study. Severity of AEs was assessed as mild, moderate or severe. A severe AE was defined as incapacitating, with inability to perform usual activity. An AE was defined as treatment-related when there is reasonable possibility that the AE was caused by or attributed to the IP and/or a causal relationship cannot be ruled out. An SAE was defined as one that meets any one of the following criteria: fatal or life-threatening; requires or prolongs in-patient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical event.

2. Endometrial Biopsy Classification Results for Endometrial Tissue/Glands at Baseline and Endpoint [Baseline (at Enrollment), Endpoint (Week 51/Early Withdrawal)]

   A subset of study participants agreed to have baseline and endpoint (Week 51/Early Withdrawal) endometrial biopsies. Results were provided for assessment of endometrial tissue/glands. Atrophic: scant or moderate amount of tissue, consists of tiny strips and wisps of surface endometrium or small tubular glands with scant or absent luminal secretions. Inactive: tubular glands lined by epithelial cells with mild pseudostratified and elongated nuclei. Proliferative: tubular or elongated glands lined by cells with elongated, dense, pseudostratified nuclei. Secretory: glands are tortuous or coiled with subnuclear vacuolation, secretion, and intraluminal tufts. Hyperplasia: proliferative type of glands showing glandular crowding with irregular shapes and sizes of enlargement, budding, and branching. Menstrual: glandular and stromal breakdown with fibrin thrombi in small vessels, condensed and collapsed stroma, and necrotic debris.

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 oral contraceptive 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 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 greater than or equal to 35 years

• Others as dictated by protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 10007	Montgomery	Alabama	United States
2	Teva Investigational Site 10013	Phoenix	Arizona	United States
3	Teva Investigational Site 10017	Phoenix	Arizona	United States
4	Teva Investigational Site 10032	Little Rock	Arkansas	United States
5	Teva Investigational Site 10026	San Diego	California	United States
6	Teva Investigational Site 10056	San Diego	California	United States
7	Teva Investigational Site 10002	Colorado Springs	Colorado	United States
8	Teva Investigational Site 10033	Colorado Springs	Colorado	United States
9	Teva Investigational Site 10057	Washington	District of Columbia	United States
10	Teva Investigational Site 10052	Clearwater	Florida	United States
11	Teva Investigational Site 10021	Jacksonville	Florida	United States
12	Teva Investigational Site 10036	Leesburg	Florida	United States
13	Teva Investigational Site 10012	Miami	Florida	United States
14	Teva Investigational Site 10015	Miami	Florida	United States
15	Teva Investigational Site 10055	Palm Beach Gardens	Florida	United States
16	Teva Investigational Site 10001	West Palm Beach	Florida	United States
17	Teva Investigational Site 10031	Decatur	Georgia	United States
18	Teva Investigational Site 10041	Roswell	Georgia	United States
19	Teva Investigational Site 10050	Savannah	Georgia	United States
20	Teva Investigational Site 10008	Louisville	Kentucky	United States
21	Teva Investigational Site 10023	Mount Sterling	Kentucky	United States
22	Teva Investigational Site 10048	Lawrenceville	New Jersey	United States
23	Teva Investigational Site 10030	Moorestown	New Jersey	United States
24	Teva Investigational Site 10014	Albuquerque	New Mexico	United States
25	Teva Investigational Site 10006	Rochester	New York	United States
26	Teva Investigational Site 10044	Cary	North Carolina	United States
27	Teva Investigational Site 10040	Charlotte	North Carolina	United States
28	Teva Investigational Site 10034	New Bern	North Carolina	United States
29	Teva Investigational Site 10018	Winston-Salem	North Carolina	United States
30	Teva Investigational Site 10046	Winston-Salem	North Carolina	United States
31	Teva Investigational Site 10022	Columbus	Ohio	United States
32	Teva Investigational Site 10039	Columbus	Ohio	United States
33	Teva Investigational Site 10028	Oklahoma City	Oklahoma	United States
34	Teva Investigational Site 10043	Philadelphia	Pennsylvania	United States
35	Teva Investigational Site 10003	Pittsburgh	Pennsylvania	United States
36	Teva Investigational Site 10049	Bluffton	South Carolina	United States
37	Teva Investigational Site 10037	Columbia	South Carolina	United States
38	Teva Investigational Site 10035	Greenville	South Carolina	United States
39	Teva Investigational Site 10047	Mount Pleasant	South Carolina	United States
40	Teva Investigational Site 10016	Jackson	Tennessee	United States
41	Teva Investigational Site 10045	Knoxville	Tennessee	United States
42	Teva Investigational Site 10005	Memphis	Tennessee	United States
43	Teva Investigational Site 10042	Nashville	Tennessee	United States
44	Teva Investigational Site 10054	Dallas	Texas	United States
45	Teva Investigational Site 10019	Houston	Texas	United States
46	Teva Investigational Site 10020	San Antonio	Texas	United States
47	Teva Investigational Site 10038	Arlington	Virginia	United States
48	Teva Investigational Site 10024	Norfolk	Virginia	United States
49	Teva Investigational Site 10051	Norfolk	Virginia	United States
50	Teva Investigational Site 10053	Richmond	Virginia	United States
51	Teva Investigational Site 10027	Seattle	Washington	United States
52	Teva Investigational Site 10029	Tacoma	Washington	United States
53	Teva Investigational Site 80108	Beer Sheva		Israel
54	Teva Investigational Site 80109	Givataim		Israel
55	Teva Investigational Site 80104	Haifa		Israel
56	Teva Investigational Site 80107	Haifa		Israel
57	Teva Investigational Site 80101	Modi'in		Israel
58	Teva Investigational Site 80103	Or-Yehuda		Israel
59	Teva Investigational Site 80100	Petach-Tikva		Israel
60	Teva Investigational Site 80105	RishonLe'zio		Israel
61	Teva Investigational Site 80102	Tel-Aviv		Israel
62	Teva Investigational Site 80106	Tel-Aviv		Israel

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Chair: Teva Women's Health Research Protocol Chair, Teva Women's Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01178125
• Other Study ID Numbers: DSG-PPS-303
• First Posted: Aug 9, 2010
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: Pregnancy Prevention; Oral Contraceptives

Study Results

Participant Flow

Recruitment Details	A total of 3691 women desiring pregnancy prevention were screened for enrollment into this study. Of the 3691 subjects screened, 2858 subjects at 53 centers in the US and 9 centers in Israel met entry criteria and were considered to be eligible for enrollment into the study.
Pre-assignment Detail	Of the 2858 enrolled, 93 participants withdrew from study before taking any investigational product, for the following reasons: lost to follow-up (n=34), consent withdrawn (n=17), sponsor request (n=13), withdrawn due to pregnancy (n=11), noncompliance (n=6), other (n=6), protocol violation (n=3), adverse event(n=2), investigator request (n=2).

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Period Title: Overall Study
STARTED	2858
Safety Population	2765
Intent to Treat (ITT) Population	2607
Pregnancy ITT (PITT) Population	2401
COMPLETED	1680
NOT COMPLETED	1178

Baseline Characteristics

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Overall Participants	2765
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.7 (5.44)
Sex: Female, Male (Count of Participants)
Female	2765 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	1798 65%
Black	428 15.5%
Asian	72 2.6%
Hispanic	393 14.2%
Other	74 2.7%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	72.4 (18.62)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.9 (6.54)

Outcome Measures

1. Primary Outcome

Title	All Users Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight, Using the 7-Day Rule
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI) and the 7-day rule (a standardized process for calculating pregnancy rates). 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-102 or > 7 days after stopping the combination desogestrel/ethinyl estradiol (DSG/EE) or ethinyl estradiol (EE) treatment of DR-102.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). Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'All Users' set included PITT participants who completed at least one 28-day cycle.

Arm/Group Title	DR-102: Total	DR-102: Baseline Body Weight <90 kg	DR-102: Baseline Body Weight ≥90 kg
Arm/Group Description	All participants taking desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	Subpopulation of total participants with a Baseline body weight <90 kg	Subpopulation of total participants with a Baseline body weight ≥90 kg
Measure Participants	2401	2034	367
Measure Treatment Cycles	24631	21050	3581
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	2.43	2.35	2.90

2. Other Pre-specified Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs
Description	AEs summarized are those that began or worsened after treatment with investigational product (IP). An AE is any untoward medical occurrence in a subject or clinical investigation subject participating in a clinical study and which does not necessarily have to have a causal relationship with this treatment or clinical study. Severity of AEs was assessed as mild, moderate or severe. A severe AE was defined as incapacitating, with inability to perform usual activity. An AE was defined as treatment-related when there is reasonable possibility that the AE was caused by or attributed to the IP and/or a causal relationship cannot be ruled out. An SAE was defined as one that meets any one of the following criteria: fatal or life-threatening; requires or prolongs in-patient hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical event.
Time Frame	Serious adverse Event (SAE) reporting period began upon signed informed consent and ended at the Final Study or the Early Withdrawal Visit. AEs were reported at each study visit (Weeks 0 through Week 53). Treatment duration with IP was up to one year.

Outcome Measure Data

Analysis Population Description

Safety population (received at least 1 dose of DR-102)

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2765
Any AE	1778 64.3%
Severe AEs	173 6.3%
Treatment-related AEs	608 22%
Deaths	0 0%
Other SAEs	46 1.7%
Withdrawn From Study Due to AEs	234 8.5%

3. Other Pre-specified Outcome

Title	Endometrial Biopsy Classification Results for Endometrial Tissue/Glands at Baseline and Endpoint
Description	A subset of study participants agreed to have baseline and endpoint (Week 51/Early Withdrawal) endometrial biopsies. Results were provided for assessment of endometrial tissue/glands. Atrophic: scant or moderate amount of tissue, consists of tiny strips and wisps of surface endometrium or small tubular glands with scant or absent luminal secretions. Inactive: tubular glands lined by epithelial cells with mild pseudostratified and elongated nuclei. Proliferative: tubular or elongated glands lined by cells with elongated, dense, pseudostratified nuclei. Secretory: glands are tortuous or coiled with subnuclear vacuolation, secretion, and intraluminal tufts. Hyperplasia: proliferative type of glands showing glandular crowding with irregular shapes and sizes of enlargement, budding, and branching. Menstrual: glandular and stromal breakdown with fibrin thrombi in small vessels, condensed and collapsed stroma, and necrotic debris.
Time Frame	Baseline (at Enrollment), Endpoint (Week 51/Early Withdrawal)

Outcome Measure Data

Analysis Population Description

Subset of participants with sufficient tissue at both Baseline and Endpoint biopsies.

Arm/Group Title	DR-102: Baseline	DR-102: Endpoint
Arm/Group Description	prior to starting desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	at Week 51 of treatment with desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	72	72
Atrophic	10 0.4%	47 NaN
Inactive	13 0.5%	6 NaN
Proliferative	11 0.4%	9 NaN
Secretory	38 1.4%	10 NaN
Hyperplasia	0 0%	0 NaN
Menstrual Endometrium	0 0%	0 NaN

4. Secondary Outcome

Title	All Users Life-Table Estimates of Pregnancy Rates Based on 28-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 thirteen 28-day treatment cycles.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'All Users' set included PITT participants who completed at least one 28-day cycle.

Arm/Group Title	DR-102: Total	DR-102: Baseline Body Weight <90 kg	DR-102: Baseline Body Weight ≥90 kg
Arm/Group Description	All participants taking desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	Subpopulation of total participants with a Baseline body weight <90 kg	Subpopulation of total participants with a Baseline body weight ≥90 kg
Measure Participants	2401	2034	367
Cycle 1	0.0004	0.0005	0
Cycle 2	0.0013	0.0010	0.0028
Cycle 3	0.0031	0.0031	0.0028
Cycle 4	0.0073	0.0070	0.0091
Cycle 5	0.0078	0.0070	0.0125
Cycle 6	0.0088	0.0082	0.0125
Cycle 7	0.0104	0.0094	0.0163
Cycle 8	0.0132	0.0120	0.0202
Cycle 9	0.0161	0.0153	0.0202
Cycle 10	0.0184	0.0174	0.0243
Cycle 11	0.0190	0.0181	0.0243
Cycle 12	0.0209	0.0195	0.0287
Cycle 13	0.0247	0.0240	0.0287

5. Primary Outcome

Title	Typical-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight, Using the 7-Day Rule
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI) and the 7-day rule (a standardized process for calculating pregnancy rates). 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-102 or > 7 days after stopping the combination DSG/EE or EE treatment of DR-102.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). Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'Typical-use' set included PITT participants who completed at least one 28-day cycle and in which no other birth control method (BCM), including condoms, were used.

Arm/Group Title	DR-102: Total	DR-102: Baseline Body Weight <90 kg	DR-102: Baseline Body Weight ≥90 kg
Arm/Group Description	All participants taking desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	Subpopulation of total participants with a Baseline body weight <90 kg	Subpopulation of total participants with a Baseline body weight ≥90 kg
Measure Participants	2333	1977	356
Measure Treatment Cycles	22309	19086	3223
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	2.68	2.59	3.23

6. Primary Outcome

Title	Compliant-Use Pregnancy Rates Based on Pearl Index (PI) Analyses for 28-Day Cycles and Broken Out by Subpopulations Defined by Participant Weight, Using the 7-Day Rule
Description	Contraceptive failure is measured by the pregnancy rate calculated using the Pearl Index (PI) and the 7-day rule (a standardized process for calculating pregnancy rates). 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-102 or > 7 days after stopping the combination DSG/EE or EE treatment of DR-102.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). Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. 'Compliant-use' set included PITT participants who completed at least one 28-day cycle and in which no other birth control method (BCM), including condoms, were used, and who were deemed to be compliant, per protocol.

Arm/Group Title	DR-102: Total	DR-102: Baseline Body Weight <90 kg	DR-102: Baseline Body Weight ≥90 kg
Arm/Group Description	All participants taking desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	Subpopulation of total participants with a Baseline body weight <90 kg	Subpopulation of total participants with a Baseline body weight ≥90 kg
Measure Participants	2317	1961	356
Measure Treatment Cycles	22085	18886	3199
Number (95% Confidence Interval) [pregnancies / 100 woman years exposure]	2.00	1.79	3.25

7. Secondary Outcome

Title	Compliant-Use Life-Table Estimates of Pregnancy Rates Based on 28-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 thirteen 28-day treatment cycles. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'Compliant-use' set included PITT participants who completed at least one 28-day cycle and in which no other BCMs, including condoms, were used, and who were deemed to be compliant, per protocol.

Arm/Group Title	DR-102: Total	DR-102: Baseline Body Weight <90 kg	DR-102: Baseline Body Weight ≥90 kg
Arm/Group Description	All participants taking desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days	Subpopulation of total participants with a Baseline body weight <90 kg	Subpopulation of total participants with a Baseline body weight ≥90 kg
Measure Participants	2317	1961	356
Cycle 1	0	0	0
Cycle 2	0.0015	0.0009	0.0047
Cycle 3	0.0038	0.0037	0.0047
Cycle 4	0.0063	0.0046	0.0154
Cycle 5	0.0063	0.0046	0.0154
Cycle 6	0.0063	0.0046	0.0154
Cycle 7	0.0072	0.0057	0.0154
Cycle 8	0.0102	0.0080	0.0224
Cycle 9	0.0152	0.0139	0.0224
Cycle 10	0.0163	0.0139	0.0298
Cycle 11	0.0163	0.0139	0.0298
Cycle 12	0.0174	0.0152	0.0298
Cycle 13	0.0208	0.0191	0.0298

8. Secondary Outcome

Title	Percentage of On-Drug Pregnancies in All Users, by Body Weight Decile Groups Using the 7-Day Rule
Description	Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body weight decile (weight range, in kilograms). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'All Users' set included PITT participants who completed at least one 28-day cycle. n=number of participants in the body weight decile group.

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2401
≤53.1 kg (n=249)	0.40
>53.1 to ≤57.1 kg (n=248)	2.42
>57.1 to ≤60.8 kg (n=249)	1.61
>60.8 to ≤64.0 kg (n=234)	1.28
>64.0 to ≤67.6 kg (n=222)	4.05
>67.6 to ≤72.1 kg (n=249)	1.20
>72.1 to ≤77.4 kg (n=230)	2.17
>77.4 to ≤85.3 kg (n=251)	1.99
>85.3 to ≤97.5 kg (n=236)	2.12
>97.5 to ≤181.4 kg (n=233)	2.15

9. Secondary Outcome

Title	Percentage of On-Drug Pregnancies in Typical-Use, by Body Weight Decile Groups Using the 7-Day Rule
Description	Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body weight decile (weight range, in kilograms). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'Typical-use' set included PITT participants who completed at least one 28-day cycle and in which no other birth control method (BCM), including condoms, were used. n=number of participants in body weight decile group.

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2333
≤53.1 kg (n=240)	0.42
>53.1 to ≤57.1 kg (n=240)	2.50
>57.1 to ≤60.8 kg (n=245)	1.63
>60.8 to ≤64.0 kg (n=227)	1.32
>64.0 to ≤67.6 kg (n=217)	4.15
>67.6 to ≤72.1 kg (n=240)	1.25
>72.1 to ≤77.5 kg (n=226)	2.21
>77.5 to ≤85.3 kg (n=242)	2.07
>85.3 to ≤97.1 kg (n=223)	2.24
>97.1 to ≤181.4 kg (n=233)	2.15

10. Secondary Outcome

Title	Percentage of On-Drug Pregnancies in Compliant-Use, by Body Weight Decile Groups Using the 7-Day Rule
Description	Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body weight decile (weight range, in kilograms). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. 'Compliant-use' set included PITT participants who completed at least 1 28-day cycle in which no other BCMs were used, and who were deemed to be compliant, per protocol. n=number of participants in body weight decile group.

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2317
≤53.1 kg (n=238)	0.42
>53.1 to ≤57.1 kg (n=240)	1.67
>57.1 to ≤60.8 kg (n=244)	1.23
>60.8 to ≤64.0 kg (n=225)	0.89
>64.0 to ≤67.6 kg (n=215)	2.79
>67.6 to ≤72.1 kg (n=237)	0.84
>72.1 to ≤77.5 kg (n=223)	2.24
>77.5 to ≤85.3 kg (n=241)	0.83
>85.3 to ≤97.5 kg (n=228)	1.75
>97.5 to ≤181.4 kg (n=226)	2.21

11. Secondary Outcome

Title	Percentage of On-Drug Pregnancies in All Users, by Body Mass Index (BMI) Decile Groups Using the 7-Day Rule
Description	Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body mass index (BMI) decile (BMI range, in kg/m^2). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'All Users' set included PITT participants who completed at least one 28-day cycle. n=number of participants in BMI decile group.

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2401
≤20.1 kg/m^2 (n=243)	1.65
>20.1 to ≤21.5 kg/m^2 (n=238)	1.68
>21.5 to ≤22.7 kg/m^2 (n=240)	1.67
>22.7 to ≤23.8 kg/m^2 (n=241)	0.83
>23.8 to ≤25.2 kg/m^2 (n=240)	1.25
>25.2 to ≤26.6 kg/m^2 (n=242)	2.07
>26.6 to ≤28.7 kg/m^2 (n=237)	2.11
>28.7 to ≤31.4 kg/m^2 (n=240)	3.33
>31.4 to ≤35.6 kg/m^2 (n=241)	2.49
>35.6 to ≤68.0 kg/m^2 (n=239)	2.09

12. Secondary Outcome

Title	Percentage of On-Drug Pregnancies in Typical-Use, by Body Mass Index (BMI) Decile Groups Using the 7-Day Rule
Description	Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body mass index (BMI) decile (BMI range, in kg/m^2). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. The 'Typical-use' set included PITT participants who completed at least one 28-day cycle and in which no other birth control method (BCM), including condoms, were used. n=number of participants in BMI decile group.

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2333
≤20.1 kg/m^2 (n=235)	1.70
>20.1 to ≤21.5 kg/m^2 (n=233)	1.72
>21.5 to ≤22.7 kg/m^2 (n=232)	1.72
>22.7 to ≤23.8 kg/m^2 (n=235)	0.85
>23.8 to ≤25.2 kg/m^2 (n=232)	1.29
>25.2 to ≤26.6 kg/m^2 (n=233)	2.15
>26.6 to ≤28.7 kg/m^2 (n=234)	2.14
>28.7 to ≤31.4 kg/m^2 (n=233)	3.43
>31.4 to ≤35.7 kg/m^2 (n=233)	2.58
>35.7 to ≤68.0 kg/m^2 (n=233)	2.15

13. Secondary Outcome

Title	Percentage of On-Drug Pregnancies in Compliant-Use, by Body Mass Index (BMI) Decile Groups Using the 7-Day Rule
Description	Crude pregnancy rate is defined as the percentage of on-drug pregnancies per number of participants in each body mass index (BMI) decile (BMI range, in kg/m^2). The 7-day rule is a standardized process for calculating pregnancy rates. Seven-day rule: a pregnancy was considered "on drug" if the date of conception was on or after the date of first dose of investigational product (IP), but no more than 7 days after the last tablet was taken; last tablet included combination hormonal or EE tablets. Compliant use: did not skip 2 or more consecutive pills, had an overall compliance with IP administration of at least 80%, and did not use a prohibited medication.
Time Frame	thirteen 28-day cycles

Outcome Measure Data

Analysis Population Description

Pregnancy Intent-to-Treat Population (PITT) of participants who were 18 to 35 years of age, inclusive, at the Screening Visit. 'Compliant-use' set included PITT participants who completed at least 1 28-day cycle and in which no other BCMs were used, and who were deemed to be compliant, per protocol. n=number of participants in BMI decile group.

Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
Measure Participants	2317
≤20.1 kg/m^2 (n=233)	0.86
>20.1 to ≤21.5 kg/m^2 (n=231)	1.30
>21.5 to ≤22.7 kg/m^2 (n=239)	0.84
>22.7 to ≤23.8 kg/m^2 (n=225)	0.89
>23.8 to ≤25.2 kg/m^2 (n=232)	0.86
>25.2 to ≤26.6 kg/m^2 (n=233)	1.29
>26.6 to ≤28.7 kg/m^2 (n=229)	2.18
>28.7 to ≤31.4 kg/m^2 (n=232)	2.59
>31.4 to ≤35.7 kg/m^2 (n=233)	1.72
>35.7 to ≤68.0 kg/m^2 (n=230)	2.17

Adverse Events

Time Frame	Serious adverse Event (SAE) reporting period began upon signed informed consent and ended at the Final Study or the Early Withdrawal Visit. AEs were reported at each study visit (Weeks 0 through Week 53). Treatment duration with IP was up to one year.
Arm/Group Title	DR-102
Arm/Group Description	desogestrel/ethinyl estradiol 0.15/0.02 mg for 21 days then ethinyl estradiol 0.01 mg for 7 days
All Cause Mortality
	DR-102
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	DR-102
	Affected / at Risk (%)	# Events
Total	46/2765 (1.7%)
Blood and lymphatic system disorders
Anaemia	1/2765 (0%)
Gastrointestinal disorders
Pancreatitis	1/2765 (0%)
General disorders
Non-cardiac chest pain	1/2765 (0%)
Hepatobiliary disorders
Cholecystitis	3/2765 (0.1%)
Biliary dyskinesia	1/2765 (0%)
Cholecystitis acute	1/2765 (0%)
Immune system disorders
Anaphylactic shock	1/2765 (0%)
Food allergy	1/2765 (0%)
Infections and infestations
Appendicitis	3/2765 (0.1%)
Pneumonia	2/2765 (0.1%)
Meningitis viral	1/2765 (0%)
Rectal abscess	1/2765 (0%)
Sepsis	1/2765 (0%)
Toxic shock syndrome streptococcal	1/2765 (0%)
Injury, poisoning and procedural complications
Avulsion fracture	1/2765 (0%)
Burns second degree	1/2765 (0%)
Cervical vertebral fracture	1/2765 (0%)
Exposure to toxic agent	1/2765 (0%)
Intentional overdose	1/2765 (0%)
Joint dislocation	1/2765 (0%)
Road traffic accident	1/2765 (0%)
Skull fracture	1/2765 (0%)
Spinal fracture	1/2765 (0%)
Splenic rupture	1/2765 (0%)
Sternal fracture	1/2765 (0%)
Traumatic liver injury	1/2765 (0%)
Investigations
Alpha 1 foetoprotein increased	1/2765 (0%)
Foetal heart rate decreased	1/2765 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/2765 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0	2/2765 (0.1%)
Phyllodes tumour	1/2765 (0%)
Thyroid cancer	1/2765 (0%)
Nervous system disorders
Cerebrovascular accident	1/2765 (0%)
Migraine	1/2765 (0%)
Narcolepsy	1/2765 (0%)
Polyneuropathy	1/2765 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	5/2765 (0.2%)
Foetal death	1/2765 (0%)
Psychiatric disorders
Depression	2/2765 (0.1%)
Adjustment disorder with depressed mood	1/2765 (0%)
Bipolar disorder	1/2765 (0%)
Panic disorder with agoraphobia	1/2765 (0%)
Suicide attempt	1/2765 (0%)
Renal and urinary disorders
Nephrolithiasis	1/2765 (0%)
Reproductive system and breast disorders
Cervical dysplasia	2/2765 (0.1%)
Haemorrhagic ovarian cyst	1/2765 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	3/2765 (0.1%)
Acute respiratory distress syndrome	1/2765 (0%)
Bronchospasm	1/2765 (0%)
Asthma	1/2765 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/2765 (0%)
Vascular disorders
Deep vein thrombosis	1/2765 (0%)
Other (Not Including Serious) Adverse Events
	DR-102
	Affected / at Risk (%)	# Events
Total	1319/2765 (47.7%)
Gastrointestinal disorders
Nausea	130/2765 (4.7%)
Vomiting	47/2765 (1.7%)
Infections and infestations
Nasopharyngitis	247/2765 (8.9%)
Upper respiratory infection	172/2765 (6.2%)
Sinusitus	152/2765 (5.5%)
Urinary tract infection	130/2765 (4.7%)
Vulvovaginal mycotic infection	128/2765 (4.6%)
Vaginitis bacterial	105/2765 (3.8%)
Bronchitis	67/2765 (2.4%)
Pharyngitis streptococcal	55/2765 (2%)
Gastroenteritis viral	53/2765 (1.9%)
Influenza	42/2765 (1.5%)
Investigations
Weight increased	108/2765 (3.9%)
Human papilloma virus test positive	43/2765 (1.6%)
Nervous system disorders
Headache	132/2765 (4.8%)
Migraine	51/2765 (1.8%)
Psychiatric disorders
Anxiety	54/2765 (2%)
Depression	43/2765 (1.6%)
Reproductive system and breast disorders
Metrorrhagia	121/2765 (4.4%)
Cervical dysplasia	114/2765 (4.1%)
Dysmenorrhea	82/2765 (3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	46/2765 (1.7%)
Skin and subcutaneous tissue disorders
Acne	72/2765 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigator/Institution must submit proposed publication to Sponsor for review within a prespecified number of days before submission for publication. If Sponsor's review shows that potentially patentable subject matter would be disclosed, publication/public disclosure shall be delayed to enable Sponsor, or Sponsor's designees, to file necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.