Duration of Effect of Acidform Gel on Vaginal pH

Study Overview
=================
Brief Summary
-----------------
The objective of this study was to determine the magnitude and duration of the reduction in pH (acidification) following a single dose of Acidform vaginal gel containing 3, 4, or 5 g compared with hydroxyethylcellulose placebo gel (4 g) or no treatment. Vaginal pH was measured 1 h, 6 h, 12 h, 24 h, then once daily for 7 days. In addition, the participants were assessed for an exploratory endpoint to the determine effect of one dose of Acidform gel (3, 4 or 5 g) or placebo gel (4 g) or no treatment, on asymptomatic bacterial vaginosis (BV).

Detailed Description
-----------------
One hundred healthy volunteer women, 20 per each treatment arm, were treated with either Intravaginal Acidform Gel(IVAG), 5 g dose (GROUP A), Acidform gel, 4 g dose (GROUP B), Acidform gel, 3 g dose (GROUP C), Universal Placebo Gel (UPG), 4 g (GROUP D) or no treatment (GROUP E). For GROUPS A, B, C and D, treatment is defined as speculum exam plus instillation of Investigational Product (IP) or placebo gel. For GROUP E (control), no treatment is defined as speculum exam and no gel instillation. At least 15 women in each group were of either African American or Hispanic ethnicity. Routine screening tests were performed on admission; and subjects assessed for BV via vaginal swabs obtained for grading by Amsel criteria. A direct vaginal pH reading by research staff- was obtained before the speculum exam, as well as one hour, and six hours post-treatment (Day 0). At the one hour and six hour post treatment time points, the direct vaginal pH readings were taken on specimens collected from two different positions in the vagina, in case of incomplete distribution of the IP soon after administration. Both readings are included as data points. At the six hour timepoint, subjects were trained on self-collecting vaginal swabs and performing the vaginal pH test. At 12 hours post-treatment, subjects performed the vaginal pH test themselves using self-obtained swabs, and record their results for clinician review. Subjects stayed overnight in the domiciliary unit, and vaginal pH and Amsel criteria was measured again by research staff at 24 (+/- 2) hours post-treatment before discharge on Day 1. The subjects were discharged with the appropriate pH testing supplies and diary. All women agreed to abstain from sexual intercourse, douching and use of any intravaginally applied products or devices until after their final study visit on Day 7. Subjects measured their vaginal pH at 24 (+/-2) hour intervals for 5 days (Days 2-6) as outpatients and recorded the pH test results, and any change in vaginal comfort, in a provided diary. Subjects also recorded any activities engaged in from the abstinence criteria in the study exclusion list, if applicable, each day. On Day 7, subjects returned to the clinic with their diaries, had their vaginal pH and Amsel criteria determined by the clinic staff, and queried as to any vaginal discomfort (vaginal comfort assessment) over the course of the study, as self-recorded in their diaries.

Official Title
-----------------
A Randomized, Placebo Controlled Pilot Study to Determine the Effect and Duration of Acidform Gel on Vaginal pH

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Acidform 5 g
* Drug: Placebo 4 g
* Drug: Acidform 4 g
* Drug: Acidform 3 g


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy female subjects between 18 and 45 years, inclusive Ability to understand the consent process and procedures Subjects agree to be available for all study visits Written informed consent in accordance with institutional guidelines Negative pregnancy test Able and willing to comply with all study procedures Have not engaged in sexual intercourse, douching or used of any form of vaginal suppository or intravaginal device for 24 hours prior to enrollment. Agree to abstain from sexual intercourse, douching or any form of vaginal suppository or intravaginal device use during course of study Report menstrual cycle regularity (25- to 35- day menstrual cycles) Exclusion Criteria: Participation in any study with an investigational compound or device within 30 days prior to signing informed consent Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study protocol Any other medical condition(s) that, in the judgment of the investigator, might interfere with the study or require treatment that might interfere with the study Family member of the investigation study staff Pregnant or breast-feeding Inability to provide informed consent A subject with a history or expectation of noncompliance with medications or treatment protocol Women with symptoms of Urinary Tract Infection (UTI) or Sexually Transmitted Infection (STI) reported or observed during examination, at screening*. Women who regularly use douches, vaginal medications or suppositories, feminine sprays, genital wipes or contraceptive spermicides, or report abnormal vaginal discharge in the past 48 hours prior to screening Women who are menstruating or who would expect to menstruate during the study Women who are currently using contraceptives that are directly delivered to the vaginal mucosa, such as NuvaRing Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acidform Gel, Group A<br>Administration of a single vaginal dose of Acidform gel (5 g) | Drug: Acidform 5 g<br>* Effect of 5 g vaginally administered Acidform on pH over 7 days<br>|
| Experimental: Acidform Gel, Group B<br>Administration of a single vaginal dose of Acidform gel (4 g) | Drug: Acidform 4 g<br>* Effect of 4 g vaginally administered Acidform on pH over 7 days<br>|
| Experimental: Acidform Gel, Group C<br>Administration of a single vaginal dose of Acidform gel (3 g) | Drug: Acidform 3 g<br>* Effect of 3 g vaginally administered Acidform on pH over 7 days<br>|
| Placebo Comparator: Placebo Gel, Group D<br>Administration of a single dose of hydroxyethylcellulose (HEC) placebo gel (4 g) | Drug: Placebo 4 g<br>* Effect of 4 g of vaginally administered HEC placebo gel on pH over 7 days<br>* Other names: Natrasol 250 HX Pharm;|
| No Intervention: No intervention, Group E<br>No vaginal product administered | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vaginal pH Following a Single Dose of Acidform (3, 4, and 5 g), HEC Placebo (4 g), or no Intervention. | Vaginal swabs were used to collect samples from the vagina of women dosed with Acidform, HEC placebo, or no treatment. The pH of the samples was measured at pre-determined time points over the course of 7 days. | Baseline (Day 0), 1, 6 & 12 hours post treatment, and Days 1, 2, 3, 4, 5, 6 & 7. |