Trial Outcomes & Findings for Safety and Acceptability Study of a Non-Hormonal Ring (NCT NCT03598088)

Results Overview

All participants had fewer than 5 progressively motile sperm per high power field (PMS/HPF) in all cycles during Ovaprene use.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

38 participants

Primary outcome timeframe

Baseline to OVP PCTa at 175 Days

Results posted on

2022-06-08

Participant Flow

Participant milestones

Participant milestones
Measure	Healthy Sexually Active Women Healthy, sexually active women who are not at risk for pregnancy due to previous female tubal sterilization will receive both Ovaprene (3 rings over 3 cycles (1 ring per cycle)) and the Caya diaphragm (to be used for intercourse at 1 time for 1 cycle) throughout the course of the trial. Each cycle was 28-35 days long. The purpose of the Caya PCT cycle is to ensure that in this study population and at these sites, results that are expected to be observed in a PCT cycle with an approved vaginal barrier can be replicated. Ovaprene: non-hormonal contraceptive ring
Screening/Baseline PCT Visits 1-4 STARTED	38
Screening/Baseline PCT Visits 1-4 COMPLETED	38
Screening/Baseline PCT Visits 1-4 NOT COMPLETED	0
Caya PCT Cycle, Visit 5 & 6 STARTED	38
Caya PCT Cycle, Visit 5 & 6 COMPLETED	35
Caya PCT Cycle, Visit 5 & 6 NOT COMPLETED	3
OVP Safety Cycle Visits 7-11 STARTED	33
OVP Safety Cycle Visits 7-11 Used the OVP Device During the Study	33
OVP Safety Cycle Visits 7-11 COMPLETED	28
OVP Safety Cycle Visits 7-11 NOT COMPLETED	5
OVP PCT Cycle A Visits 12-16 STARTED	28
OVP PCT Cycle A Visits 12-16 Completed 1 OVP PCT Cycle	26
OVP PCT Cycle A Visits 12-16 COMPLETED	24
OVP PCT Cycle A Visits 12-16 NOT COMPLETED	4
OVP PCT Cycle B Visits 17-21 STARTED	24
OVP PCT Cycle B Visits 17-21 COMPLETED	23
OVP PCT Cycle B Visits 17-21 NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Acceptability Study of a Non-Hormonal Ring

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Enrolled Population n=38 Participants Healthy, sexually active women who are not at risk for pregnancy due to previous female tubal sterilization will receive both Ovaprene and the Caya diaphragm throughout the course of the trial. The purpose of the Caya PCT cycle is to ensure that in this study population and at these sites, results that are expected to be observed in a PCT cycle with an approved vaginal barrier can be replicated.
Age, Continuous	34.8 years STANDARD_DEVIATION 6.83 • n=93 Participants
Sex: Female, Male Female	38 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants
Race (NIH/OMB) White	30 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	38 participants n=93 Participants
BMI	29.93 kg/m^2 STANDARD_DEVIATION 8.723 • n=93 Participants

PRIMARY outcome

Timeframe: Baseline to OVP PCTa at 175 Days

All participants had fewer than 5 progressively motile sperm per high power field (PMS/HPF) in all cycles during Ovaprene use.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=26 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Changes From Baseline in the Post Coital Test Results (PCT) Due to Device Use. Number of participants with an Average of Fewer than 5 PMS/HPF in Cervical Mucus at Baseline	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in the Post Coital Test Results (PCT) Due to Device Use. Number of participants with an Average of Fewer than 5 PMS/HPF in Cervical Mucus at OVP3A	26 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-Intercourse (Baseline Visit 1) and Post-Intercourse (Baseline Visit 2) (24hrs)

Population: There were 7 subjects that did not have an evaluable result for pH in Cervicovaginal Fluid at these timepoints.

Evaluating the change in CVF pH before and after sex with no device present.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=26 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Changes in Cervicovaginal pH Pre-coitus and Post-coitus in the Absence of the Study Device. Pre-Intercourse Visit 1	6.42 pH Standard Deviation 0.804	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes in Cervicovaginal pH Pre-coitus and Post-coitus in the Absence of the Study Device. Post-Intercourse Visit 2	6.92 pH Standard Deviation 0.417	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: OVP Cycle A Visit 13 (Day 121) to Visit 14 (Day 122) and OVP Cycle B Visit 18 (Day 156) to Visit 19 (Day 157).

Evaluating the change in CVF pH before and after intercourse when the Ovaprene device was being worn during intercourse.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=26 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B n=23 Participants All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Changes in Cervicovaginal pH Pre-coitus and Post-coitus in the Presence of the Study Device. Pre-Intercourse Visit 13 (A) Visit 18 (B)	6.15 pH Standard Deviation 1.147	5.94 pH Standard Deviation 1.266	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes in Cervicovaginal pH Pre-coitus and Post-coitus in the Presence of the Study Device. Post-Intercourse Visit 14 (A); Visit 19 (B)	6.57 pH Standard Deviation 0.890	6.40 pH Standard Deviation 1.011	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 175 days

Number of participants within the Ovaprene population that experienced a Urogenital treatment emergent adverse event (AE).

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) During Use of the Device.	21 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 175 days

Pelvic exams were completed at all 21 visits via a vaginal Colposcopy procedure.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Number of Participants With Changes in Pelvic Exam Findings From Baseline	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 175 days

Population: Baseline was defined as the first visit of the Ovaprene Cycle (OS1 (Visit 7), OP1a (Visit 12), OP1b (Visit 17)) For Nugent Scores. The OS Cycle (Safety cycle) was the 3rd cycle for each participant approximately Days 84 to 105. OPa was the 4th cycle (approximately Days 112 to 140) and OPb was the 5th cycle (approximately days 140 to 175).

Nugent scores were calculated prior to the insertion of each Ovaprene device and then after the device was removed at the end of each cycle. Nugent score is a gram stain storage system assessing vaginal bacteria present on a scale of 0-10. Scores ranging from 7-10 are indicative of bacterial vaginosis.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Changes From Baseline in Nugent Score Change from OP1A to OP5A	-0.2 Score (0-10) Standard Deviation 2.63	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Nugent Score Change from OP1B to OP5B	1.1 Score (0-10) Standard Deviation 2.59	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Nugent Score Change from OS1 to OS2	0.8 Score (0-10) Standard Deviation 1.79	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Nugent Score Change from OS1 to OS3	1.3 Score (0-10) Standard Deviation 3.16	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Nugent Score Change from OS1 to OS4	1.3 Score (0-10) Standard Deviation 2.75	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Nugent Score Change from OS1 to OS5	0.9 Score (0-10) Standard Deviation 2.03	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre Baseline (Day 1) to Post Baseline (Day 2); OVP PCTa Pre Intercourse (Visit 13, Day 121) to Post Intercourse (Visit 14, Day 122) and PCTb Pre Intercourse (Visit 18, Day 156) to Post Intercourse (Visit 19, Day 157).

Population: The number of participants analyzed is based on the number of viable samples collected at each timepoint.

Measuring the E.coli inhibition (%) pre and post intercourse

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. Baseline Pre-Intercourse (Visit 3)	29.81 % inhibition of vaginal bacterial growth Standard Deviation 40.16	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. Baseline Post-Intercourse (Visit 4)	-7.42 % inhibition of vaginal bacterial growth Standard Deviation 37.54	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. OVPa Pre-Intercourse (Visit 13)	27.23 % inhibition of vaginal bacterial growth Standard Deviation 47.47	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. OVPa Post-Intercourse (Visit 14)	15.66 % inhibition of vaginal bacterial growth Standard Deviation 46.41	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. OVPb Pre-Intercourse (Visit 18)	28.10 % inhibition of vaginal bacterial growth Standard Deviation 40.85	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. OVPb Post-Intercourse (Visit 19)	10.62 % inhibition of vaginal bacterial growth Standard Deviation 37.70	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre Baseline (Day 1) to Post Baseline (Day 2); OVP PCTa Pre Intercourse (Visit 13, Day 121) to Post Intercourse (Visit 14, Day 122) and PCTb Pre Intercourse (Visit 18, Day 156) to Post Intercourse (Visit 19, Day 157).

Population: The number of participants analyzed corresponds to the number of viable samples received for analysis.

Measurement of Interleukin-1 Beta (pg IL-1Beta/ug Protein), Interleukin-8 (pg IL-8/ug Protein), Secretory leukocyte Peptidase Inhibitor (SLPI)

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B n=33 Participants All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI n=33 Participants All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. Baseline Pre-Intercourse (Visit 2)	0.075 pg/ug Standard Deviation 0.144	2.6563 pg/ug Standard Deviation 7.3156	2640.005 pg/ug Standard Deviation 2708.657	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. Baseline Post-Intercourse (Visit 3)	0.093 pg/ug Standard Deviation 0.192	3.3688 pg/ug Standard Deviation 7.9979	2175.645 pg/ug Standard Deviation 1895.113	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. OVPa Pre-Intercourse (Visit 13)	0.101 pg/ug Standard Deviation 0.134	1.2470 pg/ug Standard Deviation 0.8429	282.344 pg/ug Standard Deviation 248.081	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. OVPa Post-Intercourse (Visit 14)	0.111 pg/ug Standard Deviation 0.223	0.7870 pg/ug Standard Deviation 0.7914	1706.977 pg/ug Standard Deviation 2856.200	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. OVPb Pre-Intercourse (Visit 18)	0.119 pg/ug Standard Deviation 0.264	1.5135 pg/ug Standard Deviation 1.3988	309.313 pg/ug Standard Deviation 411.673	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. OVPb Post-Intercourse (Visit 19)	0.141 pg/ug Standard Deviation 0.342	0.4291 pg/ug Standard Deviation 0.300	700.894 pg/ug Standard Deviation 416.64	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 35 days (one complete cycle)

Population: Analysis was performed on rings worn for one full cycle.

Vaginal samples and swabs of the used Ovaprene devices were tested for growth of staphylococcus aureus.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Number of Participants With a Study Devices That Has Been Worn for One Cycle With Staphylococcus Aureus Presence on Study Device.	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 35 days (one full cyle)

Vaginal samples and swabs of the used Ovaprene devices were tested for group A Streptococcus.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=33 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Number of Devices With Presence of Group A Streptococcus That Have Been Worn for One Cycle.	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 175 days

Population: Each participant could answer the questionnaire 3 times, one for each Ovaprene cycle therefore one participant could have made the same comment 3 times. The results display the number of times a comment was made. All comments were pooled together in this table.

Summary of Open-Ended Acceptability Questionnaire

Outcome measures

Outcome measures
Measure	Ovaprene Population n=199 Comments Received All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Summary of the Acceptability of the Study Device Among Male and Female Participants. At home removal and insertion	2 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Easy to use/insert/convenient	48 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Not Pericoital	29 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Does not slip out	2 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Comfortable/cannot tell it is there	52 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Lack of side effects	9 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Hormone-free	32 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Discreet, small, light, soft	17 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Altruism	4 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Iron supplementation	1 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Easy for the doctor to take out and put back in	1 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. Learning about how my body changes through different cycles	1 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Summary of the Acceptability of the Study Device Among Male and Female Participants. I believe its effective	1 participant comments	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening or BP3 Visit (2 days)

Outcome measures

Outcome measures
Measure	Ovaprene Population n=32 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Participants Who Could be Fitted With the Ovaprene Device	32 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Visit 3 (BP3, Day 15-20); Visit 7 (OS1, Day 84); Visit 12 (OP1a, Day 112); Visit 13 (OP2a, Day 122-132); Visit 17 (OP1b, Day 140); UNS could occur at any point during the 175 day study duration

Population: The sites were reminded during a site call on 2/11/2019 that they were to allow patients to try to insert, position, and remove the device using only written instructions. After that point, there were 20 patients who were given the opportunity to do this. Not all participants attempted this at all visits.

Number of participants that required written instructions, those who required written and verbal instructions and those who needed physical assistance.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=15 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B n=12 Participants All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI n=12 Participants All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A n=1 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B n=13 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit n=1 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B All Enrolled Participants that used the Ovaprene device
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Position - written only	12 Participants	11 Participants	12 Participants	1 Participants	13 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Remove - written and verbal instructions	4 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Insert - written only	13 Participants	12 Participants	12 Participants	1 Participants	13 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Insert - written and verbal instructions	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Insert - physical assistance needed	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Position - written and verbal instructions	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Position - physical assistance required	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Remove - written only	11 Participants	9 Participants	0 Participants	0 Participants	9 Participants	1 Participants	—	—	—	—	—	—	—	—	—	—	—
Participants That Could Correctly Insert, Position and Remove the Ovaprene Device Remove - physical assistance required	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 175 days

Population: The examinations at Screening were amended to occur at BP3, so later participants only had a check at BP3.

Location was determined digitally and visually by the investigators.

Outcome measures

Outcome measures
Measure	Ovaprene Population n=15 Participants All Enrolled Participants that used the Ovaprene device during the study for one PCT cycle.	Ovaprene Population, PCT B n=17 Participants All Enrolled Participants that used the Ovaprene device during OVP PCT Cycle B.	Ovaprene Population, SLPI n=21 Participants All Enrolled Participants that used the Ovaprene device.	Ovaprene Population at OP2A n=33 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B n=32 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at Unscheduled Visit n=27 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OS5 n=28 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1A n=26 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP2A n=27 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3A n=26 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4A n=26 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5A n=24 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP1B n=23 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population At OP2B n=24 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP3B n=24 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP4B n=24 Participants All Enrolled Participants that used the Ovaprene device	Ovaprene Population at OP5B n=24 Participants All Enrolled Participants that used the Ovaprene device
Location of Ovaprene in Relation to Cervix Digital: Not over cervical os/not on anterior vaginal wall	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Location of Ovaprene in Relation to Cervix Digital Exam: Over cervical os	15 Participants	17 Participants	21 Participants	33 Participants	29 Participants	26 Participants	28 Participants	26 Participants	25 Participants	24 Participants	25 Participants	23 Participants	23 Participants	24 Participants	24 Participants	24 Participants	22 Participants
Location of Ovaprene in Relation to Cervix Digital: not over cervical os - on anterior vaginal wall	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Location of Ovaprene in Relation to Cervix Visual: Over cervical os	15 Participants	17 Participants	21 Participants	33 Participants	30 Participants	26 Participants	28 Participants	26 Participants	25 Participants	24 Participants	25 Participants	23 Participants	23 Participants	24 Participants	23 Participants	24 Participants	22 Participants
Location of Ovaprene in Relation to Cervix Visual: not over cervical os - on anterior vaginal wall	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Location of Ovaprene in Relation to Cervix Visual: Not over cervical os/not on anterior vaginal wall	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants

Adverse Events

Ovaprene Device

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Caya Cycle

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jessica Hatheway VP, Clinical Operations

Dare Bioscience, Inc.

Phone: 858-926-7655

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PIs are restricted from publishing results without prior approval from the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ovaprene Device n=33 participants at risk All Enrolled Participants that used the Ovaprene device	Caya Cycle n=35 participants at risk All Enrolled Participants that used the Caya diaphragm.
Infections and infestations Bacterial Vaginosis	24.2% 8/33 • Number of events 9 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Infections and infestations Urinary Tract Infection	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Infections and infestations Vulvovaginal mycotic infection	6.1% 2/33 • Number of events 2 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Adnexa uteri pain	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Dyspareunia	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Merorrhagia	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Pelvic Pain	9.1% 3/33 • Number of events 3 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Pruritus genital	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Uterine spasm	6.1% 2/33 • Number of events 2 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Vaginal Discharge	6.1% 2/33 • Number of events 2 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Post procedural hemorrhage	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Vaginal Odor	27.3% 9/33 • Number of events 11 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Vulvar Erosion	3.0% 1/33 • Number of events 2 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Vulvovaginal dryness	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Reproductive system and breast disorders Vulvovaginal pruritus	6.1% 2/33 • Number of events 2 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Renal and urinary disorders dysuria	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.
Vascular disorders Hemorrhage	3.0% 1/33 • Number of events 1 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.	0.00% 0/35 • Adverse Event information was collected from time of consent (Screening Visit/Baseline) to Completion (Visit 21); 175 days. The Caya diaphragm was set up as a control (not a comparator device) to ensure participants could perform a successful Post-Coital Test using a marketed device. The Caya device was only used for 1 act of sexual activity whereas Ovaprene was worn continuously for three 28-day cycles, so the comparison of Adverse Events is not a valid one.