A Study to Evaluate the Effectiveness of NuvaRing® to Prevent Pregnancies in Chinese Women (P06450)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01277211
• Collaborator: (none)
• Enrollment: 983
• Arms: 2
• Actual Duration (Months): 24

Study Details

Study Description

Brief Summary

This is a study to assess the effectiveness of NuvaRing® (SCH 900702) for the prevention of pregnancy in fertile Chinese women. The acceptability and safety of NuvaRing® will also be assessed and compared with that of Yasmin.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: ENG 120 µg + EE 15 µg intravaginal ring; Drug: DRSP 3 mg + EE 30 µg	Phase 3

Detailed Description

The purpose of this study is to assess the contraceptive efficacy of NuvaRing in fertile Chinese women; to assess vaginal bleeding pattern (cycle control), general safety, and acceptability of NuvaRing; and to evaluate the NuvaRing's effect on dysmenorrhea.

Study Design

• Study Type: Interventional
• Actual Enrollment: 983 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomized, Open-Label, Controlled, Multi-Center Trial to Evaluate the Contraceptive Efficacy, Cycle Control, Safety and Acceptability of NuvaRing® (SCH 900702) in Chinese Women
• Actual Study Start Date: Sep 19, 2011
• Actual Primary Completion Date: Sep 18, 2013
• Actual Study Completion Date: Sep 18, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ENG-EE (NuvaRing) Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.	Drug: ENG 120 µg + EE 15 µg intravaginal ring; 13 cycles of ENG-EE (NuvaRing) vaginal ring use. Each cycle 28 days, with a 21-day active treatment period followed by 7-day ring-free period. One ring per cycle, each ring containing 11.7 mg ENG and 2.7 mg EE, and releasing on average 120 mcg/day of ENG and 15 mcg/day of EE.; Other Names: NuvaRing
Active Comparator: DRSP-EE Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.	Drug: DRSP 3 mg + EE 30 µg; 13 cycles of DRSP-EE tablet use. Each cycle 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received total of 21 tablets per cycle, each tablet contained 3 mg DRSP and 30 μg EE.; Other Names: Yasmin

Outcome Measures

Primary Outcome Measures

1. Pearl Index, by Treatment Group [Up to 1 year]

   Primary Efficacy Outcome measure for this study was contraceptive efficacy, or the prevention of in-treatment pregnancy. The total incidence of in-treatment pregnancies was expressed as the Pearl Index, which is defined as the number of in-treatment pregnancies per 100 woman-years of exposure (one woman-year defined as a period of 365.25 days).

Secondary Outcome Measures

1. Percentage of Participants With Intermenstrual (Breakthrough) Bleeding/Spotting, by Cycle [Up to 1 year]

   Participants kept diaries to record vaginal bleeding events. They were asked to record, on a daily basis, whether they experienced vaginal bleeding, which included BLEEDING or SPOTTING, at any time during a cycle other than normal menstruation while in the study. (This is also known as "breakthough" bleeding.) Vaginal bleeding that required >=2 pads/tampons per day was classified as BLEEDING. Vaginal bleeding that required <=1 pad/tampon per day was classified as SPOTTING.

2. Percentage of Participants With Absence of Withdrawal Bleeding, by Cycle [Up to 1 year]

   Participants kept diaries to record vaginal bleeding events. They were asked to record, on a daily basis, whether vaginal bleeding was present. Absence of withdrawal bleeding was defined as no bleeding/spotting during the expected bleeding period.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Sexually active Chinese women, at risk for pregnancy and not planning to use condoms during trial medication use

• Women in need for contraception and willing to use a hormonal contraceptive method for 13 cycles

• Body mass index ≥18 and ≤29 kg/m^2

Key Exclusion Criteria:

• Contraindications for contraceptive steroids

• Abnormal cervical smear corresponding to indeterminate changes at screening

• Clinically relevant abnormal laboratory result at screening as judged by the investigator.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01277211
• Other Study ID Numbers: P06450
• First Posted: Jan 14, 2011
• Last Update Posted: Feb 4, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Organon and Co: Contraception; NuvaRing
• Additional relevant MeSH terms: NuvaRing

Study Results

Participant Flow

Pre-assignment Detail	Of the 983 participants randomized, 946 received treatment and 37 discontinued prior to receiving treatment.

Arm/Group Title	ENG-EE (NuvaRing)	DRSP-EE
Arm/Group Description	Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.	Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.
Period Title: Overall Study
STARTED	738	245
Treated	714	232
COMPLETED	588	182
NOT COMPLETED	150	63

Baseline Characteristics

Arm/Group Title	ENG-EE (NuvaRing)	DRSP-EE	Total
Arm/Group Description	Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.	Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.	Total of all reporting groups
Overall Participants	714	232	946
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.8 (4.0)	31.2 (3.9)	31.7 (4.0)
Sex: Female, Male (Count of Participants)
Female	714 100%	232 100%	946 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Pearl Index, by Treatment Group
Description	Primary Efficacy Outcome measure for this study was contraceptive efficacy, or the prevention of in-treatment pregnancy. The total incidence of in-treatment pregnancies was expressed as the Pearl Index, which is defined as the number of in-treatment pregnancies per 100 woman-years of exposure (one woman-year defined as a period of 365.25 days).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Restricted Intent-to-Treat (R-ITT) Group, which consisted of all participants from the Intent-to-Treat (ITT) Group who had at least one cycle at risk (no condom use and confirmed intercourse).

Arm/Group Title	ENG-EE (NuvaRing)	DRSP-EE
Arm/Group Description	Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.	Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.
Measure Participants	662	216
Mean (95% Confidence Interval) [Pregnancies per 100 woman-years]	1.92	3.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	Differences between the two treatment groups (ENG-EE vs. DRSP-EE) were explored using an exact 95% CI for the Ratio of the two Pearl Indices based on the Poisson distribution.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.531
	Comments
	Method	Poisson distribution method
	Comments	Differences between treatment groups was explored using an exact 95% CI for the ratio of the two Pearl Indices based on the Poisson distribution.
Method of Estimation	Estimation Parameter	Ratio of Pearl Indices
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.19 to 2.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Intermenstrual (Breakthrough) Bleeding/Spotting, by Cycle
Description	Participants kept diaries to record vaginal bleeding events. They were asked to record, on a daily basis, whether they experienced vaginal bleeding, which included BLEEDING or SPOTTING, at any time during a cycle other than normal menstruation while in the study. (This is also known as "breakthough" bleeding.) Vaginal bleeding that required >=2 pads/tampons per day was classified as BLEEDING. Vaginal bleeding that required <=1 pad/tampon per day was classified as SPOTTING.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

ITT Group, which consisted of all randomized participants who used at least one ring/pill.

Arm/Group Title	ENG-EE (NuvaRing)	DRSP-EE
Arm/Group Description	Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.	Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.
Measure Participants	714	232
Cycle 1 (n=598,199)	18.6 2.6%	21.6 9.3%
Cycle 2 (n=604,195)	12.3 1.7%	18.5 8%
Cycle 3 (n=578,196)	8.5 1.2%	14.3 6.2%
Cycle 4 (n=587,194)	7.5 1.1%	15.5 6.7%
Cycle 5 (n=592,187)	6.8 1%	8.0 3.4%
Cycle 6 (n=590,185)	6.9 1%	10.8 4.7%
Cycle 7 (n=583,186)	7.5 1.1%	11.3 4.9%
Cycle 8 (n=585,188)	6.3 0.9%	10.6 4.6%
Cycle 9 (n=576,187)	6.9 1%	8.0 3.4%
Cycle 10 (n=572,183)	5.9 0.8%	10.4 4.5%
Cycle 11 (n=578,177)	4.2 0.6%	7.9 3.4%
Cycle 12 (n=569,176)	5.3 0.7%	9.7 4.2%
Cycle 13 (n=544,173)	6.4 0.9%	11.0 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 1, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.346
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 1
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -9.9 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 2, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 2
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -12.7 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 3, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 3
	Estimated Value	-5.8
	Confidence Interval	(2-Sided) 95%; -11.8 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 4, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 4
	Estimated Value	-8.0
	Confidence Interval	(2-Sided) 95%; -14.0 to -2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 5, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.556
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 5
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -6.4 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 6, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.089
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 6
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) 95%; -9.5 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 7, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 7
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -9.4 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 8, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 8
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95%; -9.8 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 9, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.621
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 9
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -6.2 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 10, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 10
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -10.0 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 11, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 11
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -8.9 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 12, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 12
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -9.9 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 13, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 13
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -10.4 to -0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Absence of Withdrawal Bleeding, by Cycle
Description	Participants kept diaries to record vaginal bleeding events. They were asked to record, on a daily basis, whether vaginal bleeding was present. Absence of withdrawal bleeding was defined as no bleeding/spotting during the expected bleeding period.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

ITT Group, which consisted of all randomized participants who used at least one ring/pill.

Arm/Group Title	ENG-EE (NuvaRing)	DRSP-EE
Arm/Group Description	Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.	Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.
Measure Participants	714	232
Cycle 1 (n=596,199)	8.6 1.2%	14.6 6.3%
Cycle 2 (n=602,195)	4.8 0.7%	9.7 4.2%
Cycle 3 (n=577,196)	5.2 0.7%	11.7 5%
Cycle 4 (n=586,194)	4.1 0.6%	7.7 3.3%
Cycle 5 (n=590,187)	5.4 0.8%	6.4 2.8%
Cycle 6 (n=588,185)	5.8 0.8%	9.7 4.2%
Cycle 7 (n=581,186)	3.4 0.5%	7.5 3.2%
Cycle 8 (n=583,188)	5.0 0.7%	6.9 3%
Cycle 9 (n=575,187)	4.3 0.6%	8.6 3.7%
Cycle 10 (n=571,183)	3.7 0.5%	6.6 2.8%
Cycle 11 (n=576,177)	3.0 0.4%	7.3 3.1%
Cycle 12 (n=568,176)	4.0 0.6%	10.2 4.4%
Cycle 13 (n=543,173)	5.9 0.8%	10.4 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 1, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 1
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -12.0 to -1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 2, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 2
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -10.1 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 3, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 3
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -12.0 to -2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 4, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 4
	Estimated Value	-3.6
	Confidence Interval	(2-Sided) 95%; -8.5 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 5, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.609
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 5
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -5.7 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 6, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 6
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) 95%; -9.3 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 7, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 7
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -9.0 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 8, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.308
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 8
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -6.7 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 9, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 9
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -9.3 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 10, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 10
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -7.6 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 11, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 11
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -9.4 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 12, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 12
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -11.7 to -2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ENG-EE (NuvaRing), DRSP-EE
	Comments	For Cycle 13, a two-sided 95% CI for the difference in percentage between the treatment groups (ENG-EE vs. DRSP-EE) was calculated using the method of Miettinen and Nurminen.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages, Cycle 13
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -10.2 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to 1 year
Arm/Group Title	ENG-EE (NuvaRing)		DRSP-EE
Arm/Group Description	Participants were to complete 13 cycles of etonogestrel (ENG) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day ring-free period. Participants used one ring per cycle. Each ring contained 11.7 mg ENG and 2.7 mg EE, and released on average 120 mcg/day of ENG and 15 mcg/day of EE.		Participants were to complete 13 cycles of drospirenone (DRSP) and ethinylestradiol (EE) use. Each cycle was 28 days, with a 21-day active treatment period followed by a 7-day tablet-free period. Participants received a total of 21 tablets of DRSP-EE per cycle. Each tablet contained 3 mg DRSP and 30 μg EE.
All Cause Mortality
	ENG-EE (NuvaRing)		DRSP-EE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ENG-EE (NuvaRing)		DRSP-EE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/714 (0.3%)		4/232 (1.7%)
Infections and infestations
Sinusitis	1/714 (0.1%)	1	0/232 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion	1/714 (0.1%)	1	0/232 (0%)	0
Invasive ductal breast carcinoma	0/714 (0%)	0	1/232 (0.4%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/714 (0%)	0	2/232 (0.9%)	2
Vascular disorders
Deep vein thrombosis	0/714 (0%)	0	1/232 (0.4%)	1
Other (Not Including Serious) Adverse Events
	ENG-EE (NuvaRing)		DRSP-EE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/714 (0%)		0/232 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The sponsor must have the opportunity to review and comment on data analysis and presentation for all abstracts, manuscripts, and slide presentations that report any results of this trial 45 days prior to the submission for publication or presentation.