Evaluation of Non-hormonal Intravaginal Rings in Female Sheep

The IVR technology under investigation is hypothesized to offer sustained vaginal administration of non-hormonal APls to prevent unintended pregnancy and sexually transmitted infections. The study to be performed under this research plan will test a total of 6 different ring types. The non-hormonal APls consist of copper, zinc, and lactide salts.

Sheep are the animal model of choice for this study because the anatomy and histology of the sheep cervix and vagina are similar to those of women thereby allowing for the testing of a full-sized human IVR without the need for scaling. Moreover, the postcoital contraceptive efficacy  assay in sheep has previously been developed and published.

The costs associated with the manufacture and supply of the IVRs will be outside the scope of this research plan. The IVRs will be individually supplied in sealed foil pouches with ID numbers assigned and supplied to the test facility ready-for-use.

Technical requirements for the laboratory conducting the in-life portion of the study include:
1. Experience with toxicity, pharmacokinetic , and postcoital efficacy studies in female sheep
2. Specialized equipment and experienced staff to perform colposcopy and optical coherence tomography (OCT).
3. Experience conducting postcoital tests in sheep, the ability to obtain and use fresh human sperm, and experience performing sperm motility assessments .

To support the pharmacokinetic (PK) goals, concentration determination of (a) copper and zinc ions in cervicovaginal swab and plasma samples and (b) lactic acid in cervicovaginal swab samples will be needed. The copper and zinc ion quantifications will require ICP-MS or ICP-OES capabilities. Reverse phase HPLC will be used to quantify lactic acid levels. These bioanalytical assays could be conducted at an organization separate from the in-life portion of the study, if necessary. Analytical methods will be provided but may need adaptation for use with the sheep vaginal fluid and plasma matricies.