Trial Outcomes & Findings for Study of the Safety, Efficacy and Cycle Control of a Contraceptive Vaginal Ring (NCT NCT00455156)

NCT ID: NCT00455156

Last Updated: 2026-01-23

Results Overview

The Pearl Index derived from using all cycles for which back up contraception is not used will be the primary efficacy endpoint. The Pearl Index is used to indicate how many women out of 100 would get pregnant using a specific birth control method over a year. It uses the formula: (Pregnancies x 12 x 100) / (Women x Months of study). The lower the Pearl Index, the more effective the contraceptive.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1200 participants

Primary outcome timeframe

12 Months

Results posted on

2026-01-23

Participant Flow

Participant milestones

Participant milestones
Measure
150/15 NES/EE CVR
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Overall Study
STARTED
1143
Overall Study
COMPLETED
585
Overall Study
NOT COMPLETED
558

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of the Safety, Efficacy and Cycle Control of a Contraceptive Vaginal Ring

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
150/15 NES/EE CVR
n=1143 Participants
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Age, Categorical
<=18 years
0 Participants
n=270 Participants
Age, Categorical
Between 18 and 65 years
1143 Participants
n=270 Participants
Age, Categorical
>=65 years
0 Participants
n=270 Participants
Age, Continuous
26.0 years
STANDARD_DEVIATION 5.01 • n=270 Participants
Sex: Female, Male
Female
1143 Participants
n=270 Participants
Sex: Female, Male
Male
0 Participants
n=270 Participants
Region of Enrollment
United States
1143 participants
n=270 Participants

PRIMARY outcome

Timeframe: 12 Months

Population: All cycles with documented backup contraception are excluded unless the subject became pregnant in that cycle. All cycles after conception for women who became pregnant are excluded.

The Pearl Index derived from using all cycles for which back up contraception is not used will be the primary efficacy endpoint. The Pearl Index is used to indicate how many women out of 100 would get pregnant using a specific birth control method over a year. It uses the formula: (Pregnancies x 12 x 100) / (Women x Months of study). The lower the Pearl Index, the more effective the contraceptive.

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=9212 Cycles
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Contraceptive Efficacy Using the Pearl Index for All Subjects
2.96 Number of pregnancies per 100 women mths
Interval 1.93 to 4.55

PRIMARY outcome

Timeframe: Visit 0 and Visit 5, up to 13 months

Population: Subjects that were treated and had a pap smear performed at the respective timepoints were analyzed

Changes from Baseline in Pap Smear results as measured at Screening (Baseline) and at Visit 5 (Cycle 13)

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=1139 Participants
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Changes From Baseline in Pap Smear
Visit 0/Baseline: Normal Pap
1060 Participants
Changes From Baseline in Pap Smear
Visit 0/Baseline: ASCUS HPV Negative Pap
47 Participants
Changes From Baseline in Pap Smear
Visit 0/Baseline: Abnormal, Other Pap
32 Participants
Changes From Baseline in Pap Smear
Visit 5/Cycle 13: Normal Pap
629 Participants
Changes From Baseline in Pap Smear
Visit 5/Cycle 13: ASCUS HPV Negative Pap
48 Participants
Changes From Baseline in Pap Smear
Visit 5/Cycle 13: Abnormal, Other Pap
67 Participants

PRIMARY outcome

Timeframe: 12 Months

Population: Only subjects less than or equal to 35 years of age are included in this analysis. All cycles with documented backup contraception are excluded unless the subject became pregnant in that cycle. All cycles after conception for women who became pregnant are excluded.

The Pearl Index derived from using all cycles for which back up contraception is not used will be the primary efficacy endpoint and analyzed for subjects that are less than or equal to 35 years of age. The Pearl Index is used to indicate how many women out of 100 would get pregnant using a specific birth control method over a year. It uses the formula: (Pregnancies x 12 x 100) / (Women x Months of study). The lower the Pearl Index, the more effective the contraceptive.

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=7636 Cycles
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Contraceptive Efficacy Using the Pearl Index for Subjects Less Than or Equal to 35 Years of Age
3.92 Number of pregnancies per 100 women mths
Interval 2.6 to 5.89

SECONDARY outcome

Timeframe: Cycles 1-13, up to 13 months

Population: subjects that completed diaries during the respective cycles are included.

Scheduled bleeding is any bleeding or spotting that occurs during the CVR-free intervals, regardless of the duration of the regimen. The bleeding may continue into days 1-4 of the subsequent cycle. Bleeding days are assessed based on subject diaries completed during Cycles 1-13.

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=1143 Participants
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 12
4.4 Days
Standard Deviation 1.97
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 13
4.1 Days
Standard Deviation 2.20
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 1
4.3 Days
Standard Deviation 1.75
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 2
4.6 Days
Standard Deviation 2.04
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 3
4.5 Days
Standard Deviation 2.02
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 4
4.5 Days
Standard Deviation 2.00
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 5
4.4 Days
Standard Deviation 2.05
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 6
4.4 Days
Standard Deviation 2.07
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 7
4.4 Days
Standard Deviation 1.96
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 8
4.3 Days
Standard Deviation 2.01
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 9
4.4 Days
Standard Deviation 2.01
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 10
4.4 Days
Standard Deviation 2.04
Bleeding Patterns Assessed by Number of Scheduled Bleeding Days
Cycle 11
4.5 Days
Standard Deviation 2.06

SECONDARY outcome

Timeframe: Cycles 1-13, up to 13 months

Population: subjects that completed diaries during the respective cycles are included.

Unscheduled bleeding or spotting is any bleeding or spotting that occurs while taking active hormones with 2 exceptions: 1) Bleeding/spotting that occurs during a CVR-free interval and continues to Days 1-4 of the next active cycle is not considered unscheduled and 2) Bleeding/spotting reported during Days 1-7 of the first cycle of study CVR insertion is not considered unscheduled. Bleeding days are assessed based on subject diaries completed during Cycles 1-13.

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=1143 Participants
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 13
1.1 Days
Standard Deviation 2.53
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 1
1.3 Days
Standard Deviation 2.91
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 2
0.8 Days
Standard Deviation 2.33
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 3
0.7 Days
Standard Deviation 2.05
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 4
0.8 Days
Standard Deviation 2.24
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 5
0.8 Days
Standard Deviation 2.05
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 6
0.8 Days
Standard Deviation 2.05
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 7
1.0 Days
Standard Deviation 2.42
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 8
0.9 Days
Standard Deviation 2.16
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 9
1.0 Days
Standard Deviation 2.20
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 10
1.0 Days
Standard Deviation 2.35
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 11
1.1 Days
Standard Deviation 2.59
Bleeding Patterns Assessed by Number of Unscheduled Bleeding Days
Cycle 12
1.1 Days
Standard Deviation 2.73

SECONDARY outcome

Timeframe: Up to 6 Months

Population: Women who state, during the course of the study, that they wish to discontinue to become pregnant and women who indicate, at the end of the study, that they plan to become pregnant as soon as possible will be followed for up to six months or until earlier pregnancy. Only subjects that wanted to become pregnant are included in this analysis.

Women who state, during the course of the study, that they wish to discontinue to become pregnant and women who indicate, at the end of the study, that they plan to become pregnant as soon as possible will be followed for up to six months or until earlier pregnancy.

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=18 Participants
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Return to Fertility Assessed by Intended Pregnancies
11 Participants

SECONDARY outcome

Timeframe: Up to 6 Months

Population: Women, who do not wish to become pregnant at the time of termination or end of treatment, will be followed until the time of their first post-treatment menses. Only subjects that did not want to become pregnant or use hormonal contraception are included in this analysis.

Women, who do not wish to become pregnant at the time of termination or end of treatment, will be followed until the time of their first post-treatment menses.

Outcome measures

Outcome measures
Measure
150/15 NES/EE CVR
n=145 Participants
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Number of Participants With Return of Post-Treatment Menses Within 6 Months
138 Participants

Adverse Events

150/15 NES/EE CVR

Serious events: 21 serious events
Other events: 1007 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
150/15 NES/EE CVR
n=1143 participants at risk
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Infections and infestations
PNEUMONIA
0.17%
2/1143 • Number of events 2 • Enrollment through follow-up, up to 18 months
Infections and infestations
PYELONEPHRITIS
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
ABDOMINAL PAIN
0.17%
2/1143 • Number of events 2 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
DIARRHOEA
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
NAUSEA
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
VOMITING
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Psychiatric disorders
BIPOLAR DISORDER
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Psychiatric disorders
BIPOLAR I DISORDER
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Immune system disorders
DRUG HYPERSENSITIVITY
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Immune system disorders
FOOD ALLERGY
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Immune system disorders
HYPERSENSITIVITY
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MELANOMA
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SALIVARY GLAND ADENOMA
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Nervous system disorders
HEADACHE
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Vascular disorders
DEEP VEIN THROMBOSIS
0.17%
2/1143 • Number of events 2 • Enrollment through follow-up, up to 18 months
Blood and lymphatic system disorders
LYMPHADENITIS
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Ear and labyrinth disorders
VERTIGO
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Cardiac disorders
ATRIAL FIBRILLATION
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
General disorders
INFUSION SITE PHLEBITIS
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Hepatobiliary disorders
CHOLELITHIASIS
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Reproductive system and breast disorders
UTERINE SPASM
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Skin and subcutaneous tissue disorders
URTICARIA
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months
Social circumstances
DRUG ABUSER
0.09%
1/1143 • Number of events 1 • Enrollment through follow-up, up to 18 months

Other adverse events

Other adverse events
Measure
150/15 NES/EE CVR
n=1143 participants at risk
150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year. 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR): 150 mg of Nestorone and 15 mg of ethinyl estradiol (150/15 NES/EE CVR), administered via vaginal ring, used on a 21/7 days in/out schedule for no more than one year.
Reproductive system and breast disorders
VAGINAL DISCHARGE
6.6%
75/1143 • Number of events 75 • Enrollment through follow-up, up to 18 months
Reproductive system and breast disorders
METTRORRHAGIA
5.1%
58/1143 • Number of events 58 • Enrollment through follow-up, up to 18 months
Respiratory, thoracic and mediastinal disorders
BREAST TENDERNESS
6.0%
69/1143 • Number of events 69 • Enrollment through follow-up, up to 18 months
Reproductive system and breast disorders
GENITAL PRURITUS FEMALE
5.2%
60/1143 • Number of events 60 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
NAUSEA
21.3%
244/1143 • Number of events 244 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
VOMITING
10.2%
117/1143 • Number of events 117 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
DIARRHOEA
10.5%
120/1143 • Number of events 120 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
8.0%
92/1143 • Number of events 92 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
DYSPEPSIA
5.7%
65/1143 • Number of events 65 • Enrollment through follow-up, up to 18 months
Gastrointestinal disorders
STOMACH DISCOMFORT
5.2%
59/1143 • Number of events 59 • Enrollment through follow-up, up to 18 months
Nervous system disorders
HEADACHE
43.4%
496/1143 • Number of events 496 • Enrollment through follow-up, up to 18 months
Nervous system disorders
MIGRAINE
5.1%
58/1143 • Number of events 58 • Enrollment through follow-up, up to 18 months
Musculoskeletal and connective tissue disorders
BACK PAIN
10.0%
114/1143 • Number of events 114 • Enrollment through follow-up, up to 18 months
Musculoskeletal and connective tissue disorders
MYALGIA
7.2%
82/1143 • Number of events 82 • Enrollment through follow-up, up to 18 months
Musculoskeletal and connective tissue disorders
NECK PAIN
4.9%
56/1143 • Number of events 56 • Enrollment through follow-up, up to 18 months
Psychiatric disorders
INSOMNIA
6.3%
72/1143 • Number of events 72 • Enrollment through follow-up, up to 18 months
Respiratory, thoracic and mediastinal disorders
PHARYNGOLARYNGEAL PAIN
8.3%
95/1143 • Number of events 95 • Enrollment through follow-up, up to 18 months
Immune system disorders
SEASONAL ALLERGY
5.9%
67/1143 • Number of events 67 • Enrollment through follow-up, up to 18 months
Reproductive system and breast disorders
Dysmenorrhoea
12.6%
144/1143 • Number of events 144 • Enrollment through follow-up, up to 18 months
Infections and infestations
SINUSITIS
6.2%
71/1143 • Number of events 71 • Enrollment through follow-up, up to 18 months
Infections and infestations
URINARY TRACT INFECTION
8.5%
97/1143 • Number of events 97 • Enrollment through follow-up, up to 18 months
Infections and infestations
INFLUENZA
8.6%
98/1143 • Number of events 98 • Enrollment through follow-up, up to 18 months
Infections and infestations
VULVOVAGINAL MYCOTIC INFECTION
12.4%
142/1143 • Number of events 142 • Enrollment through follow-up, up to 18 months
Infections and infestations
NASOPHARYNGITIS
18.5%
212/1143 • Number of events 212 • Enrollment through follow-up, up to 18 months
Infections and infestations
UPPER RESPIRATORY TRACK INFECTION
17.8%
204/1143 • Number of events 204 • Enrollment through follow-up, up to 18 months

Additional Information

Kimberly Myer

Premier Research

Phone: 9842381297

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place