Acceptability, Safety
Conditions
Keywords
Vagina, Film, Extended Release
Brief summary
This is a double-blinded crossover study to evaluate whether Eudragit® content impacts the ability to self-insert placebo vaginal films. Thirty women will self-insert one high and and one low Eudragit® content film. The insertion order will be randomized in a 1:1 ratio. After inserting each film, participants will complete a survey reporting their perceptions and experience. The primary endpoint is successful insertion defined as all of the film inside the vagina upon visual assessment by a study clinician. Secondary outcomes include preference for the low level or high level Eudragit® formulation film with respect to insertion and participants' description of identified challenges.
Detailed description
This is a double-blinded crossover study to evaluate whether ammonio methacrylate copolymer dispersion type B (Eudragit®) content impacts the ability to self-insert placebo vaginal films. Eudragit® is a commonly used pharmaceutical excipient, present in several FDA approved products. This hydrophobic excipient is used in vaginal film formulations to increase disintegration time and impart extended drug release property. The presence of Eudragit and its concentration level affects film disintegration and spreadability in the vaginal environment, and are likely to affect tactile properties. Consequently, these attributes may impact ease of film administration, acceptability, and user preferences for specific film type. Thirty pre-menopausal women, 18 - 45 years of age, will self-insert one high and and one low Eudragit® content film. High and low Eudragit films correspond to 12.8% and 6.4% of Eudragit® added during the formulation blending stage. The insertion order will be randomized in a 1:1 ratio. Within 10 minutes of the insertion, clinical staff will perform a speculum exam to assess the location of the film and remove the residual film. After inserting each film, participants will complete a survey reporting their perceptions and experience. The primary endpoint is successful insertion defined as all of the film inside the vagina upon visual assessment by a study clinician. Secondary outcomes include preference for the low level or high level Eudragit® formulation film with respect to insertion and participants' description of identified challenges.
Interventions
DEVICEHigh Eudragit® Content Vaginal Film
High (12.8%) Eudragit® Content Vaginal Film
DEVICELow Eudragit® Content Vaginal Film
Low (6.4%) Eudragit® Content Vaginal Film
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Katherine Bunge
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
The participants, clinicians, and assessors of the study outcomes will be blinded to Eudragit® content of the film.
Intervention model description
Each participant will self-insert one low level Eudragit® and one high level Eudragit® formulation film. The sequence of insertion will be randomized in a 1:1 ratio.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 18-45 * Intact uterus by participant report * Agrees to abstain from inserting anything into the vagina for 24 hours prior to the study visit
Exclusion criteria
* Menopausal (as defined as amenorrhea for one year or more without an alternative etiology) * Hysterectomy (including total and supracervical) * Currently pregnant or pregnancy within 90 days of enrollment * Lactating * Symptoms of a urogenital infection including vaginal discharge, pain, odor, or itching * Menses at the time of enrollment * Known allergy or hypersensitivity to any of the components of the placebo film * Any condition that, in the opinion of the Investigator, would preclude provision of consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Successfully Insert Vaginal Film | Approximately 30 minutes | Number of participants that successfully insert each vaginal film defined as the film location being completely inside the vagina upon visual assessment by a clinician |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Report Self-Insertion of Vaginal Film Was Easy | Approximately 30 minutes | Participants that report that self-insertion of the placebo vaginal film was not difficult at all as assessed on a Likert scale from 1 (not difficult at all) to 4 (very difficult) |
| Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | Approximately 1 hour | Number of participants that report that they would prefer to use the high Eudragit® content vaginal film over the low Eudragit® content vaginal film. This outcome was analyzed by order of film product use (high then low vs low then high) as this may influence product preference. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Eudragit® Film, Then Low Eudragit® Film High (12.8%) Eudragit® content vaginal film, then low (6.4%) Eudragit® content vaginal film
High Eudragit® Content Vaginal Film: High (12.8%) Eudragit® Content Vaginal Film
Low Eudragit® Content Vaginal Film: Low (6.4%) Eudragit® Content Vaginal Film | 15 |
| Low Eudragit® Film, Then High Eudragit® Film Low (6.4%) Eudragit® content vaginal film, then high (12.8%) Eudragit® content vaginal film
High Eudragit® Content Vaginal Film: High (12.8%) Eudragit® Content Vaginal Film
Low Eudragit® Content Vaginal Film: Low (6.4%) Eudragit® Content Vaginal Film | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Low Eudragit® Film, Then High Eudragit® Film | High Eudragit® Film, Then Low Eudragit® Film |
|---|---|---|---|
| Age, Continuous | 29.8 years STANDARD_DEVIATION 7.2 | 28.1 years STANDARD_DEVIATION 5.3 | 31.5 years STANDARD_DEVIATION 8.6 |
| Body Mass Index | 29.7 kg/m^2 STANDARD_DEVIATION 8.2 | 28.2 kg/m^2 STANDARD_DEVIATION 5.6 | 31.3 kg/m^2 STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 15 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Prior participation in vaginal film studies | 7 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 8 Participants | 8 Participants |
| Region of Enrollment United States | 30 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 30 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sexually Active | 23 Participants | 14 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Number of Participants That Successfully Insert Vaginal Film
Number of participants that successfully insert each vaginal film defined as the film location being completely inside the vagina upon visual assessment by a clinician
Time frame: Approximately 30 minutes
Population: All participants who attempted insertion of both vaginal film products which included the entire cohort of 30 enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Eudragit® Film | Number of Participants That Successfully Insert Vaginal Film | Successful Insertion | 8 Participants |
| High Eudragit® Film | Number of Participants That Successfully Insert Vaginal Film | Unsuccessful insertion | 22 Participants |
| Low Eudragit® Film | Number of Participants That Successfully Insert Vaginal Film | Successful Insertion | 8 Participants |
| Low Eudragit® Film | Number of Participants That Successfully Insert Vaginal Film | Unsuccessful insertion | 22 Participants |
Comparison: This was a paired analysis comparing successful insertion of the high and low Eudragit® Films. The McNemar's test statistic is based on the discordant pairs (number of participants with high successful, low unsuccessful versus low successful, high unsuccessful).p-value: >0.99McNemar
Secondary
Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film
Number of participants that report that they would prefer to use the high Eudragit® content vaginal film over the low Eudragit® content vaginal film. This outcome was analyzed by order of film product use (high then low vs low then high) as this may influence product preference.
Time frame: Approximately 1 hour
Population: All participants that attempted insertion of both vaginal film products; this included the entire cohort of 30 enrolled.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Eudragit® Film | Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | Preferred High Eudragit® Film | 5 Participants |
| High Eudragit® Film | Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | Preferred Low Eudragit® Film | 5 Participants |
| High Eudragit® Film | Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | No Preference | 5 Participants |
| Low Eudragit® Film | Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | Preferred High Eudragit® Film | 9 Participants |
| Low Eudragit® Film | Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | Preferred Low Eudragit® Film | 2 Participants |
| Low Eudragit® Film | Number of Participants That Prefer the High Over the Low Eudragit® Content Vaginal Film | No Preference | 4 Participants |
p-value: 0.26Fisher Exact
Secondary
Number of Participants That Report Self-Insertion of Vaginal Film Was Easy
Participants that report that self-insertion of the placebo vaginal film was not difficult at all as assessed on a Likert scale from 1 (not difficult at all) to 4 (very difficult)
Time frame: Approximately 30 minutes
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Eudragit® Film | Number of Participants That Report Self-Insertion of Vaginal Film Was Easy | Not Difficult To Insert | 11 Participants |
| High Eudragit® Film | Number of Participants That Report Self-Insertion of Vaginal Film Was Easy | At Least Some Difficulty Inserting Film | 19 Participants |
| Low Eudragit® Film | Number of Participants That Report Self-Insertion of Vaginal Film Was Easy | Not Difficult To Insert | 8 Participants |
| Low Eudragit® Film | Number of Participants That Report Self-Insertion of Vaginal Film Was Easy | At Least Some Difficulty Inserting Film | 22 Participants |
p-value: 0.45McNemar