A Functional Performance Study of The Wondaleaf Female Condom

This research study will determine how well two female condoms perform when used during sex. One of these condoms (FC2) is already commercially available in South Africa. The other female condom, "Wondaleaf Condom" is a new female condom. Participants will use both condoms. The study aims to determine how well these condoms work comparatively. Study visits include a screening/enrolment visit and 2 follow up visits.

This research study will determine how well two female condoms perform when used during sex. One of these condoms (FC2) is already commercially available in South Africa. The other female condom, "Wondaleaf Condom" is a new female condom. Participants will use both condoms. The study aims to determine how well these condoms work comparatively.

The Wondaleaf female condom is a new female condom (FC) design made of polyurethane with no external or internal rings. The body of the condom is fitted by an exterior adhesive shield which also displays the condom when removed from the condom packaging.

Purpose: To ascertain the functional performance of the Wondaleaf FC. This research study will be a two-period, cross-over randomized controlled trial to compare the functional performance, safety and acceptability of two FC types.

Study Design: The study will enrol 220 women, anticipating that 200 participants complete the study. The age range of these participants is from 18-45 years. Each participant will be asked to use five Wondaleaf FCs and five FC2 female condoms (available in the South African public sector).

Primary endpoints will be total clinical failure and total device failure for each condom type. Secondary endpoints will include rates of invagination, complete slippage, misdirection, and breakage.

Function, safety, and acceptability will be assessed at two follow-up visits approximately one month apart after enrollment. Participants will complete a Condom Log at home which gathers data on experience after use of each condom.

Female clients of the Commercial City Clinic will be told about the study. If a potential participant expresses interest in participating, the participant will be given the study information to read, which will describe the study requirements and the potential role in the study. If the participant agrees to take part in the research, the participant will be asked to provide written consent. The participant will be screened to ensure that the requirements for study participation are met.

Enrolled participants will be asked to use five FC2 and five Wondaleaf FCs. Participants will be asked to return to the clinic for follow-up after using each type of device. During the 1st follow-up visit, participants will be interviewed about the first assigned condom type and will receive the next condom packet within their second assigned (randomized) use sequence. In the second follow-up visit, participants will be interviewed about use of the condoms and will be discontinued from study participation. Data on device function, safety and acceptability for each condom type will be collected during follow-up visits.

At enrolment, baseline data will be gathered on participant demographics and past FC use via the baseline questionnaire. Using a pelvic model, the study staff will demonstrate female condom insertion and train the participants in the proper use of the first assigned female condom. Further, study staff will re- emphasize the instructions on how to complete the condom use log. Participants will be told that they do not have to use the FCs during consecutive acts of intercourse. The study staff will discuss with the participant an approximate timeframe for use of all 5 condoms and a suitable follow-up date will be scheduled. This date will be noted on an appointment slip. Participants will be encouraged to come back if condoms are finished before the due date and will be given the research study contact details to call for any appointment changes.

Follow-up visits: There will be two follow-up visits. During the first follow-up visit, study staff will review the information on the Condom Use Logs for completeness and accuracy. Further, the participants will be asked questions from a follow-up survey about the experiences using the FCs. Participants will be trained in the use of the second condom type, and given appropriate written condom use instructions. Staff will schedule the second follow-up visit, and participants will obtain the next condom packet in the assigned use sequence. At the end of the second follow-up visit the discontinuation form will be completed. Participation period for study participants is expected to last between 2-4 months.

The study will be registered on the South African clinical trials registry (SANCTR) and on clinicaltrials.gov.

The study will be monitored by an independent monitor contracted by the study investigator. The monitoring visit schedule includes an initiation visit, one interim visit and a close out visit. Risk based monitoring will be conducted for the study. The following study records will be reviewed:

* 100% of informed consent forms
* 100% of 100 enrolled participant files for source data verification
* 100% of serious adverse events and protocol deviations
* Investigator site file
* Study product No audits are planned for the study. The study has employed data staff to complete daily quality control of documents to ensure accuracy and completeness of data and electronic case report forms.

The site has Standard Operating Procedures in place to ensure consistency of site operations and study procedures. In addition, a source document guide and Manual of Procedures will be developed to ensure conformity.

Statistical Considerations:

The hypothesis for the primary endpoints, total clinical failure and total failure of a female condom and their components, is that the new condom WC2 is 'non-inferior' to FC2 with regard to the rate of events within a margin of 3.0%. That is, that the rate of events of each of the new condoms is not worse than that of the FC2 by more than 3.0%.

To demonstrate non-inferiority at a 5% significance level, the study will require the upper limit of the one-sided 95% confidence interval or equivalently the upper limit of the two-sided 90% confidence interval for the difference in the occurrence of events (New - FC2) to be below 3.0%.

It was calculated that the power to demonstrate non-inferiority obtained for different sample sizes, starting by the minimum of 200 couples completing the study recommended by ISO standards. It was assumed a total failure rate of 4% for the FC2 as reported from past research. It was assumed a correlation between uses of 0.15, as reported for male condoms. This assumption is more conservative than the maximum of 0.20 recommended by International Organization for Standardization (ISO) standards for female condoms.

For acceptability, scores ranging from 1 (lowest) to 5 (highest) to be compared across condom types using Friedman test, the proposed sample size will provide more than 99% power to detect a minimum difference of 1 in the scores of any two condom types, in a 5% significance level two-sided test. This calculation assumes a standard error of 1 and adjusts for multiple inferences using Bonferroni criterion, but ignores clustering (condoms within couples).

Data Analysis All analyses for primary and secondary endpoints will be performed according to the assigned condom use sequence among the subset of participants who provide relevant follow-up data on at least one condom of each type, no matter if they followed the assigned sequence. This will be the main analysis. An additional analysis will be performed with protocol compliers (i.e. participants who follow the assigned condom use sequence). All analyses for secondary endpoints will use a nominal 5% significance level.

A detailed analysis plan will be developed prior to the initiation of study enrollment. Any deviations to be made from this summary will be documented in the detailed analysis plan.

Condom Function The failure rates, or proportions of condom uses with clinical breakage, total breakage, slippage, misdirection, invagination, total clinical failure, and total FC failure will be summarized by condom type according to endpoint definitions. 95% confidence intervals for the proportion of each endpoint will be calculated using the exact method based on the binomial distribution.

Safety Data The proportion of participants with symptoms of genitourinary irritation during or immediately after any of the 5 separate uses and medical and serious adverse events, classified by relatedness to condom type, expectedness and severity will be reported.

Product Acceptability The key acceptability endpoints (listed below) will be summarized.

* comfort in use;
* ease of insertion and removal;
* like or dislike of product attributes and adequacy and feel of lubrication.

Eligibility Criteria:
Inclusion Criteria:

1. Be between the ages of 18 and 45 years (inclusive);
2. Be literate (able to read a newspaper or letter easily);
3. Be sexually active (defined as having at least two vaginal coital acts per week and not being abstinent in the month prior to enrolment);
4. Be in an exclusive (monogamous) sexual relationship with her spouse or partner while participating in this research study;
5. Have been in a sexual relationship with this partner for at least 6 months;
6. Not be a sex worker;
7. Not be pregnant (as determined by pregnancy testing) or planning a pregnancy during the time of the research study;
8. Be without observable evidence of Sexually Transmitted Infections (STI) as determined through syndromic diagnosis and vaginal examination;
9. Be using hormonal or other non-barrier contraception (e.g. Oral Contraception (OCs), injectable, implant, Intra Uterine Device (IUD), or have had a tubal sterilization);
10. Not be menopausal (defined as 12 months without menstruation);
11. Not have had a hysterectomy;
12. Not have known sensitivities or allergies to latex, polyurethane, vaginal/sexual lubricants or the lubricants used on condoms;
13. Willing to give informed consent;
14. Willing to complete the FC coital use logs;
15. Willing to use the study condoms as directed;
16. Willing to adhere to the follow-up schedule and all study procedures;
17. Willing to provide research study staff with an address, phone number or other locator information while participating in the study; and,
18. Willing to participate in the study for the duration of 10 condom uses (approximately 2-4 months.
19. Willing to have fingerprint scan to check for co-enrolment in other research projects

Exclusion Criteria:

* None specified