Multi-Center Study of New Medications to Treat Vaginal Infections

• Terconazole (Drug)
• Metronidazole (Drug)
• Terconazole/metronidazole (Drug)

Primary outcomes

• Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit [7-14 days after beginning treatment]: The percentage of participants with clinical cure of both bacterial vaginosis (BV) AND vulvovaginal candidiasis (VVC) was compared between the combination therapy and the two single entity treatments. Clinical cure of BV is defined as: discharge has returned to normal/physiologic, negative whiff test, and saline wet mount is <20% clue cells. Clinical cure of VVC is defined as resolution of all signs and symptoms attributable to vulvovaginal candidiasis

Secondary outcomes

• Cure of the BV Component of Mixed Infection [7-14 days after beginning treatment]: The percentage of participants with both BV and VVC who had clinical cure of bacterial vaginosis (BV) was compared between the combination therapy and the two single entity treatments. Clinical cure of BV was defined as: 1. discharge has returned to normal/physiologic, 2. the whiff test is negative for any amine "fishy" odor, 3. the saline wet mount is <20% clue cells
• Cure of the VVC Component of Mixed Infection [7-14 days after beginning treatment]: The percentage of participants with both BV and VVC who had clinical cure of VVC was compared between the combination therapy and the two single entity treatments.Clinical cure of VVC was defined as complete resolution of all signs and symptoms attributable to VVC
• Microbiologic and Mycologic Cure [7-14 days after beginning treatment]: The percentage of participants with both microbiologic and mycologic cure was compared between the combination therapy and the two single entity treatments. Yeast cultures were performed and Gram stains of vaginal fluid were graded according to Nugent's criteria. Microbiologic cure requires normal Nugent gram stain score and mycologic cure requires negative yeast culture.
• Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit [7-14 days after beginning treatment]: Subjects reported if symptoms completely resolved and the date of resolution. The percentage of participants reporting complete resolution of symptoms was compared between arms.
• Number of Participants With Treatment Emergent Adverse Events [Any time during study participation (up to 30 days)]: Adverse events were collected at study visits, from subject diaries and from spontaneous reports

Sex: Female, ages: 12 Years to any

Inclusion Criteria:

* A clinical diagnosis of vaginal infection that is confirmed by laboratory testing and:
* Capable of providing written informed consent or assent
* Currently not menstruating and not anticipating menses during treatment
* If heterosexually active, subject must be post-menopausal for ≥ 1 year, surgically sterile, or practicing an acceptable form of birth control
* Negative pregnancy test
* Other criteria as identified in the protocol

Exclusion Criteria:

* Other infectious causes of vulvovaginitis
* Subject has recently used, or is expected to require the concomitant use of prohibited medications/products
* Nursing mother
* Use of any investigational drug within 30 days of enrollment
* History of hypersensitivity to any ingredient/component of the formulations
* Other criteria as identified in the protocol

Participant flow

Outcome results

• Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit (Primary), Count of participants, Participants: Terconazole Vaginal Gel 31; Metronidazole Vaginal Gel 29; Terconazole/Metronidazole Vaginal Gel 43 (p 0.030)
• Cure of the BV Component of Mixed Infection (Secondary), Count of participants, Participants: Terconazole Vaginal Gel 38; Metronidazole Vaginal Gel 46; Terconazole/Metronidazole Vaginal Gel 54 (p 0.015)
• Cure of the VVC Component of Mixed Infection (Secondary), Count of participants, Participants: Terconazole Vaginal Gel 52; Metronidazole Vaginal Gel 37; Terconazole/Metronidazole Vaginal Gel 53 (p 0.012)
• Microbiologic and Mycologic Cure (Secondary), Count of participants, Participants: Terconazole Vaginal Gel 19; Metronidazole Vaginal Gel 5; Terconazole/Metronidazole Vaginal Gel 24
• Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit (Secondary), Count of participants, Participants: Terconazole Vaginal Gel 49; Metronidazole Vaginal Gel 44; Terconazole/Metronidazole Vaginal Gel 49
• Number of Participants With Treatment Emergent Adverse Events (Secondary), Count of participants, Participants: Terconazole Vaginal Gel 44; Metronidazole Vaginal Gel 40; Terconazole/Metronidazole Vaginal Gel 44

Adverse events

Time frame: The safety population includes all participants randomized to treatment and administered at least one dose of study drug, and includes subjects who had a negative yeast culture and/or normal gram stain at the baseline visit. Adverse events were collected over the entire course of the study (up to 30 days after beginning treatment).

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2015-03-12)
• Statistical Analysis Plan (PDF, 2018-05-01)

• Robert J Borgman, Ph.D., Study director, Curatek Pharmaceuticals