Safety and Efficacy of Boric Acid Inserts for Treatment of Vulvovaginal Candidiasis

Inclusion Criteria

1. Patients who are postmenarcheal, nonpregnant biological females, 12 years of age andolder, at Screening;

2. Patients with acute symptomatic VVC infection at Screening, defined as meeting allof the following criteria:

• A potassium hydroxide (KOH) wet mount or saline wet mount preparation performedfrom the inflamed vaginal mucosa or secretions demonstrating yeast forms (hyphae or pseudohyphae) of or budding yeast;

• Vaginal pH ≤4.5; and

• Total Vulvar Signs and Symptoms (VSS) Scale score of ≥4: vulvovaginal signs (edema, erythema, and excoriation/fissures) and symptoms (vulvovaginal burning,itching, and irritation) as rated using the VSS Scale.

3. Patients aged 21 and older must have cervical cancer screening results meeting thefollowing criteria for inclusion at Screening or within the 1 year prior toScreening: negative for intraepithelial lesion or malignancy or clinicallyinsignificant findings not requiring any further surveillance or treatment beyond arepeat cervical cytology test;

• Patients between 21 and 29 years of age must have a cervical cancer screeningtest (Papanicolaou [Pap] smear) performed at Screening or have a documented Papsmear result within 1 year of Screening which must be available for theassessment by the PI or qualified designee at the Screening Visit; and

• Patients 30 years of age and older must have documented cervical cancerscreening tests (Pap smear and high-risk human papillomavirus [HPV]) performedat Screening or have documented results within 1 year of Screening which mustbe available for the assessment by the PI or qualified designee at theScreening Visit.

4. Patients must be suitable candidates for vaginal treatment, able to insert the studydrug, and are comfortable undergoing pelvic exams;

5. Patients willing and able to provide written informed consent or assent (for those 12 to 17 years of age);

6. Patients willing and able to comply with Protocol requirements, instructions, andProtocol-stated restrictions, as determined by the PI;

7. Patients willing and able to give authorization for use of protected healthinformation;

8. Patients of childbearing potential (as defined in Inclusion Criterion 1) must use 1of the following contraceptive options described below through Day 28 (Visit 5):

• Copper intrauterine device used continuously and successfully for at least 90days prior to the first dose of study drug;

• Levonorgestrel-releasing intrauterine system used successfully for at least 90days prior to the first dose of study drug;

• Progestin implant used successfully for at least 90 days prior to the firstdose of study drug;

• Monogamy with a vasectomized male partner (medical assessment of the surgicalsuccess of the vasectomy must have occurred at least 6 months prior to thefirst dose of study drug);

• Abstinence; or

• Use of 1 of the following hormonal methods in combination with 1 of thefollowing barrier methods:

• Hormonal methods

• Barrier methods

9. Patients must be willing to avoid tampon or menstrual cup use during the TreatmentPeriod (ie, Day 1 to Day 14); and

10. Patients must be willing to abstain from receiving oral intercourse during theTreatment Period (ie, Day 1 to Day 14).

Exclusion Criteria:

1. Patients with known or suspected other active infectious causes of cervicitis,vaginitis, or vulvitis (eg, BV, Chlamydia trachomatis, Neisseria gonorrhoeae, T.vaginalis, or genital lesions consistent with HPV, herpes simplex, syphilis,chancroid, etc) based on the results of clinical assessments, in-clinic microscopicassessments (eg, clue cells or trichomonads detected on saline wet mount), and/orrapid diagnostic tests (RDTs) performed prior to enrollment (eg, OSOM® test, etc);

2. Patients who have undergone any vaginal rejuvenation procedure (ie, laser) within 4weeks prior to Screening or plan to undergo a vaginal rejuvenation procedure priorto completion of the last planned assessment;

3. Patients who will undergo evaluation or treatment during the clinical study forabnormal cytology or findings from high-risk HPV testing or Pap test finding;

4. Patients diagnosed with BV, determined by meeting 3 of the 4 Amsel's criteria:

• A fishy odor of the vaginal discharge before or after the addition of a drop of 10% KOH (ie, a positive whiff test);

• Homogenous, thin discharge (milk-like consistency) that smoothly coats thevaginal walls;

• At least 20% of epithelial cells are clue cells (eg, vaginal epithelial cellsstudded with adherent bacteria) on saline wet mount microscopic evaluation ofvaginal discharge; or

• pH of vaginal fluid >4.5.

5. Patients currently undergoing treatment for or with a history of treatment forcervical, vaginal, or vulvar cancer;

6. Patients using any systemic (eg, oral or injectable) corticosteroid treatment duringthe study or within 30 days prior to Screening;

7. Patients using topical steroids applied to the vulvar or vaginal regions during thestudy or within 7 days prior to Screening;

8. Patients using any systemic (eg, oral or injectable) or topical (applied to thevulvar or vaginal regions) antimicrobials including antifungal, antiviral,antibacterial, or anti-trichomonal drugs during the clinical study or within 14 daysprior to Screening;

9. Patients using any prescription (eg, vaginal estrogen, ospemifene, prasterone) ornon-prescription intravaginal or vulvar product (eg, vitamin E gel capsules [vaginalinserts], lubricants, moisturizers, douches, creams, or spermicides) within 7 daysprior to Screening and through Day 28 (Visit 5);

10. Patients unwilling to refrain from the use of intravaginal products (eg, douches,creams, spermicides, yoni eggs, tampons, menstrual cups, and any other suchintravaginal product that, in the opinion of the PI, would be consideredexclusionary) during the Treatment Period, inclusive of Day 14;

11. Patients with a current immunocompromising condition (ie, HIV, end-stage renaldisease);

12. Patients using any immunosuppressive medication (included, but not limited to,carbamazepine, cyclosporine, tacrolimus, methotrexate, 6 mercaptopurine, ormycophenolate) or radiation treatment within 3 months prior to Screening or duringthe clinical study;

13. Patients with a history of pelvic radiation treatment;

14. Patients with a clinically significant major organ disease, cancer, infection (except acute VVC), or other condition that may affect the clinical assessment ofVVC or render the patient a poor study candidate, per the PI's judgment;

15. Patients with any comorbid condition that would preclude the safe participation ofthe patient in the clinical study or would prevent the patient from meeting theclinical study requirements, per the PI's judgment;

16. Patients with diabetes mellitus type I, use of insulin (current or anticipated needduring the study), or poorly-controlled diabetes mellitus type II, defined as (hemoglobin A1c [(HbA1c]) of 10% or higher result within the prior 6 months) or atScreening;

17. Patients with any laboratory abnormality that, in the opinion of the PI, wouldlikely introduce additional risk to the patient or might interfere with datainterpretation. The findings noted below are particularly exclusionary:

• Serum alanine aminotransferase ≥2.5 × the upper limit of normal (ULN) of thereference range;

• Serum aspartate aminotransferase ≥2.5 × the ULN of the reference range; or

• Serum total bilirubin ≥2 × the ULN of the reference range, unless the elevationis consistent with Gilbert's syndrome

18. Patients with a known history of HIV, hepatitis B, or hepatitis C virus (HCV), or apositive test for HIV antibody, hepatitis B surface antigen, or HCV antibody;

19. Patients who are pregnant (ie, a positive pregnancy test at Screening), lactating,or planning to become pregnant during the clinical study period;

20. Patients with a planned surgery or other medical procedure that would impactcompliance with the Protocol, per the PI's discretion;

21. Patients with a current or recent history (eg, the past 12 months) of substanceabuse (including alcohol) or any other medical, psychiatric, or other conditionthat, in the PI's opinion, would preclude compliance with the Protocol;

22. Patients currently participating or had participated in another clinical studywithin the 30 days prior to Screening;

23. Patients currently have or expect, within the Treatment Period, to have heavymenstrual bleeding (defined as "flooding" or bleeding through ≥1 tampon or sanitarypad in 2 hours or less with most periods) or a menstrual duration >7 days; or

24. Patients currently have or suspect to have an active urinary tract infection (UTI)based on urinalysis and clinical assessment.