A Randomized Double-Blind Cross-Over Study of Self-Insertion of Two Formulations of a Placebo Vaginal Film
Phase: NA
Conditions: Safety, Acceptability
Sponsor: Katherine Bunge

  
 
 
   
FAME-103B: A Randomized Double-Blind Cross-Over Study of Self-Insertion of Two 
Formulations of a Placebo Vaginal Film 
 
 
 
 
Funding Agency: 
National Institutes of Health 
 
Protocol Chair: 
Sharon Hillier, PhD 
University of Pittsburgh 
Pittsburgh, PA USA 
 
 
Protocol Co-Chair 
Katherine Bunge, MD MPH  
University of Pittsburgh 
Pittsburgh, PA USA 
 
 
Study Site: 
University of Pittsburgh Medical Center 
Magee-Womens Hospital 
Pittsburgh, PA 
Phone:  412-641-6435 
Fax:  412-641-1133 
 
07Apr2020 
 
Version 1.0 
 
ClincalTrials.gov ID: NCT04391036

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FAME-103B 
Table of Contents 
 Protocol Signature Page......................................................................................................... 4 
LIST OF ABBREVIATIONS ....................................................................................................... 5 
PROTOCOL TEAM ROSTER .................................................................................................... 6 
PROTOCOL SUMMARY ........................................................................................................... 8 
1 
Key Roles .......................................................................................................................... 9 
1.1 
Protocol Identification ........................................................................................ 9 
1.2 
Sponsor and Monitor Identification .................................................................... 9 
1.3 
Protocol Chair ................................................................................................... 9 
1.4 
Laboratory ......................................................................................................... 9 
2 
Introduction .....................................................................................................................10 
2.1 
Vaginal films for HIV prevention ...................................................................... 10 
2.2 
Integrated Preclinical/Clinical Program ........................................................... 10 
2.3 
FAME-103 ....................................................................................................... 11 
2.4 
FAME-103B Rationale .................................................................................... 11 
2.5 
Safety Data: Eudragit® platform ..................................................................... 11 
3 
Study Objectives .............................................................................................................12 
3.1 
Primary Objective: ........................................................................................... 12 
3.2 
Primary Endpoint: ........................................................................................... 12 
3.3 
Secondary Objectives: .................................................................................... 12 
3.4 
Secondary Endpoints ...................................................................................... 12 
4 
Study Population .............................................................................................................13 
4.1 
Selection of the Study Population ................................................................... 13 
4.2 
Recruitment ..................................................................................................... 13 
4.3 
Study Design Summary .................................................................................. 13 
4.4 
Inclusion Criteria ............................................................................................. 14 
4.5 
Exclusion Criteria ............................................................................................ 14 
5 
Study Procedures ............................................................................................................14 
5.1 
Pre-screening .................................................................................................. 14 
5.2 
Study visit........................................................................................................ 15 
5.3 
Telephone follow-up ........................................................................................ 16 
6 
Study Product ..................................................................................................................16 
6.1 
Regimen.......................................................................................................... 16 
6.2 
Administration ................................................................................................. 16 
6.3 
Study Product Formulation.............................................................................. 17 
6.4 
Study Product Supply and Accountability ....................................................... 17 
6.5 
Study Product Dispensing ............................................................................... 17 
7 
Laboratory Evaluations ...................................................................................................17 
7.1 
Laboratories .................................................................................................... 17 
7.2 
Specimen Collection and Processing .............................................................. 18 
7.3 
Biohazard Containment .................................................................................. 18 
8 
Assessment of Safety and Clinical Management ..........................................................18 
8.1 
Safety Monitoring ............................................................................................ 18 
8.2 
Adverse Events Definitions ............................................................................. 18 

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8.3 
Criteria for Early Termination of Study Participation ....................................... 19 
9 
Statistical Considerations ..............................................................................................19 
9.1 
Sample Size and Accrual ................................................................................ 19 
9.2 
Statistical analyses ......................................................................................... 20 
9.3 
Blinding ........................................................................................................... 20 
9.4 
Random assignment ....................................................................................... 20 
 
 
Table 1: Study Visit Procedures .................................................................................... 16 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Signature Page 
 
 
Protocol Title:  FAME-103B: A Randomized Double-Blind Cross-Over Study of Self-Insertion 
of Two Formulations of a Placebo Vaginal Film 
  
 
 
Protocol Version:   Version 1.0 
 
 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in compliance with 
United States (US) Health and Human Service regulations (45 CFR 46); applicable U.S. 
Food and Drug Administration regulations; standards of the International Conference on 
Harmonization Guideline for Good Clinical Practice (E6); Institutional Review 
Board/Ethics Committee determinations; all applicable in-country, state, and local laws 
and regulations; and other applicable requirements (e.g., US National Institutes of 
Health, Division of AIDS) and institutional policies.  
 
 
_______________________________________________ 
Protocol Chair (PRINT NAME)  
 
___________________________________________ 
Signature of Protocol Chair  
 
________________________ 
Date (Month/Day/Year) 
 
 
 
_______________________________________________ 
Protocol Co-Chair (PRINT NAME)  
 
___________________________________________ 
Signature of Protocol Co-Chair  
 
______________________ 
Date (Month/Day/Year) 

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FAME-103B 
LIST OF ABBREVIATIONS 
 
AE 
 
 
adverse event 
ARV                            Antiretroviral 
CRF 
 
 
case report form 
HIV 
 
 
Human Immunodeficiency Virus 
IRB 
 
 
Institutional Review Board 
STI 
 
 
sexually transmitted infection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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FAME-103B 
PROTOCOL TEAM ROSTER 
 
Sharon Hillier, PhD 
Protocol Chair 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
Magee-Womens Hospital 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-6435 
Fax: 412-641-6170 
Email: shillier@mail.magee.edu 
 
Katherine Bunge, MD MPH 
Protocol Co-Chair 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-6967 
Fax: 412-641-1133 
Email: kbunge@mail.magee.edu 
 
 
Lisa Rohan, PhD 
Co-Investigator 
Department of Pharmaceutical Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-6108 
Fax: 12-641-6170 
Email:  lrohan@mwri.magee.edu 
Pittsburgh, PA 15213 USA 
Phone: 412-641- 6108 
Fax: 412-641-6170 
Email: lrohan@mwri.magee.edu 
 
Julie S. Downs, PhD 
Co-investigator 
Dept. of Social and Decision Sciences 
Carnegie Mellon University 
208 Porter Hall (SDS) 
Pittsburgh, PA 15213-3890 
Office:  219-C Porter Hall 
Phone:  412-268-1862 
Fax:  412-268-6938 
Email:  downs@cmu.edu 
 
Ingrid Macio, PA-C 
Co-Investigator  
Magee-Womens Hospital 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-641-5455 
Fax: 412-641-2319 
Email: imacio@mail.magee.edu 
 
Leslie Meyn, PhD 
Co-Investigator 
Biostatistician/Assistant Professor  
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone:  42-641-4233 
Fax: 412-641-1133 
Email:  lmeyn@mail.magee.edu  
 
 
 
Danielle Litzinger, CRNP 
Co-Investigator  
Magee-Womens Hospital 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-641-3424 
Fax: 412-641-2319 
Email: litzingerda@mail.magee.edu 
 
 
 
 
 

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NIH 
Hans M.L. Spiegel, MD 
Sr. Medical Officer,  
PMPRB/Prevention Sciences Program,  
Contractor, Kelly Government Solutions 
DAIDS, NIAID, NIH 
5601 Fishers Lane Room 8B51A 
Rockville, MD 20852 
Tel:  240-292-4633 
Fax: 240-627-3465 
Email: hans.spiegel@nih.gov 
 
Jeanna Piper, MD 
Sr. Medical Officer 
Clinical Microbicide Research Branch 
PSP/DAIDS/NIAID/NIH 
5601 Fishers Lane 
Room 8B68 
Rockville, MD 20852 
Tel: 240-292-4798 
E-mail: piperj@niaid.nih.gov 
 
Jim A. Turpin, PhD  
Branch Chief 
Preclinical Microbicides and Prevention Research Branch (PMPRB)  
NIAID/DAIDS  
Room 8B31/MSC 9831 
5601 Fishers Lane 
Rockville, MD 20852-9831 
Phone   (301) 451-2732 
Fax (240) 627-3465 
Email: jturpin@niaid.nih.gov  
 
Cherlynn Mathias, RN, BSN 
Program Officer/Nurse Consultant 
Prevention Science Program, NIH/DAIDS/PSP 
5601 Fishers Lane, 8B51B MSC 9831 
Rockville, MD 20852 
Phone: 240-292-4791 
Fax: 240-627-3465 
Email: cmathias@niaid.nih.gov  
 
 
 
 
 
 
 
 
 

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FAME-103B 
PROTOCOL SUMMARY 
 
Short Title: 
 
      FAME-103B 
 
Chairs : 
Sharon Hillier, PhD; Katherine Bunge, MD MPH  
 
Sample Size: 
30 pre-menopausal women without urogenital complaints 
 
Study Population:  
The recruitment strategy is likely to capture a diverse population as 
this community is comprised of approximately 48% White, 48% 
African-American and 4% other ethnicities including Hispanic, Asian, 
Indian and Native American. Persons below the age of 18 will not be 
recruited.  
 
Study Sites: 
UPMC Magee-Womens Hospital, Pittsburgh, PA 
 
 
Study Design: 
Randomized cross-over study of self-insertion of two formulations of a 
placebo vaginal film 
 
Study Duration:  
One study visit lasting approximately 90 minutes 
 
Study Film Products: 
Two formulations of a placebo vaginal film (high and low level 
ammonio-methacrylate copolymer type B (Eudragit®) 

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Key Roles 
 
1.1 
Protocol Identification 
 
Protocol Title:   
FAME-103B 
 
 
 
1.2 
Sponsor and Monitor Identification 
 
Funding Agency:   
DAIDS/NIAID/NIH 
 
 
             
5601 Fishers Lane 
                                    
Rockville, MD 20892-9831 
 
  
1.3 
Protocol Chair 
Protocol Chair: 
Sharon L. Hillier, PhD 
 
 
 
 
University of Pittsburgh School of Medicine 
 
 
 
 
Magee-Womens Hospital 
 
 
 
 
300 Halket Street 
 
 
 
 
Pittsburgh, PA 15213 
 
 
 
 
Phone: 412-641-6435 
 
 
 
 
Fax: 412-641-1133 
 
 
 
 
Email:  shillier@mail.magee.edu 
  
Protocol Co-Chair: 
Katherine Bunge, MD MPH 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-6967 
Fax: 412-641-1133 
Email: kbunge@mail.magee.edu   
 
1.4 
Laboratory 
Magee-Womens Research Institute 
204 Craft Avenue Rm A520 and A530 
Pittsburgh, PA  15213    
CLIA:  39D1004688 
 
UPMC Presbyterian/Shadyside CP PUH 
UPMC Clinical Laboratory Building 
3477 Euler Way 
Pittsburgh, PA  15213 
CLIA:  39D0911193 
  
Clinical and Translational Research Center 
University of Pittsburgh Medical Center 
300 Halket Street Rm 5521 
Pittsburgh, PA  15213 
CLIA:  39D1031322 
 

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2 
Introduction 
 
2.1 
Vaginal films for HIV prevention 
 
Sexual transmission accounts for the majority of new HIV infections worldwide. While most 
cases of sexual transmission involve both a male partner and a female partner, women are 
disproportionately impacted by the sexual transmission of HIV1. This disproportionate impact 
arises from a combination of biologic, social, and economic factors. Women at risk face 
formidable challenges in protecting themselves from HIV infection, including power differentials, 
gender norms, and economic dependence.  
 
 
Topical microbicides are agents designed to prevent or substantially reduce the acquisition and 
transmission of HIV when applied to the genital or gastrointestinal mucosa. In addition to 
preventing HIV infection, topical microbicides may satisfy two critical needs: affordability and 
female control. Topical microbicides also have the potential for high acceptability for both male 
and female partners. Acceptability and utility of topical microbicides can be maximized by the 
development of an array of dosing formulations.   
 
Vaginal films are an attractive dosing option for several reasons. In terms of manufacturing, 
films are inexpensive, scalable, physically and chemically stable, uniform with regards to 
product content, and amenable to combinations of active ingredients. In terms of use, films are 
discreet, portable, and easy to store. Vaginal films can deliver fixed doses of microbicidal agents 
with minimal mess and without an applicator. The small volume of vaginal films may also result 
in less dilution of endogenous antiviral or antibacterial properties of vaginal fluids compared to 
vaginal gels. In studies of spermicidal film, women have found vaginal films to be 
acceptable2,3,4. When Vaginal Contraceptive Film (VCF) was compared to foaming tablets 
containing nonoxynol-9 (N-9), contraceptive film was preferred in three different countries2. 
Ninety-seven percent of 59 Mexican women, 60 percent of 52 Dominican women, and 86 
percent of 51 Kenyan women reported liking contraceptive film.  In particular, they cited the 
following favorable characteristics: ease of use, general feel or comfort, additional lubrication, 
and lack of side effects. Over eighty percent of Cameroonian sex workers, who participated in a 
large randomized placebo-controlled trial of N-9 film, reported that they would use the film were 
it found to be effective against HIV3. In Zambian focus groups, placebo vaginal film was 
preferred over placebo vaginal tablets and soft-gel capsules after each product was used once 
daily for one week 4.  In a study evaluating the acceptability of placebo microbicidal film, soft gel 
capsule and tablet, African women were instructed to use each of the three products once daily 
for 7 consecutive days. The film and soft-gel capsule were chosen significantly more often than 
the tablet as the preferred dosage form (39%, 37% and 25%, respectively). In this particular 
study, film and soft gel were preferred because of faster dissolving time and easier insertion4.  In 
other studies, participants found vaginal films to be less messy than foaming tablets or gel2,5.  
 
2.2 
Integrated Preclinical/Clinical Program 
 
The Film Antiretroviral Microbicide Evaluation (FAME) program brings together an inter-
disciplinary group of research scientists from four academic institutions: University of Pittsburgh, 
University of Washington, Carnegie Mellon University, and the University of Colorado. The long-
term goal of the program is to develop and evaluate an extended delivery vaginal film containing 
an integrase inhibitor which could provide protection from HIV for one week or more following a 
single application. The first iteration of the FAME IPCP established proof of concept that vaginal 
films containing the antiretrovirals (ARVs) dapivirine and tenofovir could deliver drug to target 

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tissues as effectively as gel formulations of those same ARVs. The second iteration strives to 
develop an extended release formulation of an integrase inhibitor MK-2048 which will provide 
coverage for 7 days after each use. FAME-103 is the backbone of this effort. 
 
2.3 
FAME-103 
 
FAME-103 is clinical study of a vaginal film containing the integrase inhibitor MK-2048 in a 
formulation containing either high or low concentrations of the extended release polymer 
Eudragit®.  MK-2048 is a potent 2nd generation integrase inhibitor; the extended platform film to 
be used in FAME-103 is intended to provide 7 days of protection.  The primary objective of 
FAME-103 is to evaluate the safety of the two formulations of MK-2048 vaginal film. A key 
secondary objective is to evaluate the pharmacokinetics of the two film formulations.   
 
Because safety and pharmacokinetics are key study outcomes, the active vaginal film will be 
inserted by a clinician.  Product misplacement was noted in the last four clinical trials of vaginal 
film previously conducted at the University of Pittsburgh. While most participants could 
successfully insert the vaginal films, incorrect film placement was noted for some. In some 
instances, the vaginal film stuck to the finger after attempted insertion and in other instances the 
film was visualized on the external genitalia.    
 
2.4 
FAME-103B Rationale 
 
The objective of the FAME-103B study is to evaluate whether study participants can self-insert   
the high and low Eudragit® content placebo films. In previous vaginal film trials conducted at the 
University of Pittsburgh, participants have had variable success with self-insertion. As the 
Eudragit® film formulation as an extended platform moves forward with other active 
pharmaceutical ingredients in clinical trials, understanding whether the level of Eudragit® in the 
film impacts ease of insertion is vitally important.  
 
In order to evaluate whether Eudragit® content impacts ease of self-insertion, participants will 
be asked to self-insert each placebo film and complete a survey reporting their perceptions and 
experience. 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. This study poses minimal risks to 
participants as the safety of the high Eudragit® placebo film has already been evaluated in 
FAME-101 and found to be safe. The risk to study participants will also be minimized because 
the film will be removed immediately after insertion thereby limiting exposure to under 10 
minutes for each film. The feasibility of easy film removal after self-insertion has been 
established by the clinical staff at the Reproductive Infectious Disease Unit at Magee-Womens 
Hospital who have removed film within 15 minutes of insertion in at least 40 prior participants. 
Thus, no technical or safety issues with film removal are anticipated. 
 
 
2.5 
Safety Data: Eudragit® platform 
 
The Eudragit® film has a proven safety record. 
 
Pre-Clinical Safety Data 
Safety evaluation of the extended release placebo film was performed in a nonhuman primate 
model.  Six pigtailed macaques were exposed to two films per week for two weeks, which is 
double the proposed human dosing (intended dosing is one film per week). In total, four films 
were delivered to each macaque over fourteen days. The vaginal microbiota, vaginal pH, and 

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number of PMNs on gram stained vaginal smears were assessed before the first film placement 
and after the fourth film placement.  The integrity of the cervicovaginal tissues was assessed by 
colposcopy at each film placement. Of note, there was visible film in the vagina with each film 
placement. No adverse events were noted by colposcopy; microbiota remained stable with no 
effect noted on the beneficial H202 producing microorganisms; vaginal pH remained within 
normal range; and PMN counts remained within the normal range even after more frequent 
administration than intended for use (Patton, personal communication). The entire study report 
is presented in Appendix IV. 
 
Clinical Safety Data 
FAME-101 was a safety and acceptability study of the higher Eudragit® level. Sixty-four HIV 
uninfected, healthy women were enrolled. At enrollment the participants were randomized to 
timing of the follow-up visit. They then attempted self-insertion of the film. Immediately after this 
attempt, a clinician performed a visual inspection. If most of the film was visualized outside of 
the introitus, the film was removed by the clinician and a second film placed by the clinician 
during a speculum examination. Participants returned either 3,7,10 or 14 days after film 
placement depending on their randomization and then all participants returned for a final safety 
assessment three weeks after enrollment. Safety assessments, acceptability parameters, and 
changes to the vaginal microenvironment were assessed at each visit. The persistence of the 
film was noted. 
 
 
Eighty-four participants were screened and 64 enrolled. The median age was 26.5 years; 56% 
were white and 27% non-Hispanic black. The primary endpoint was Grade 2 or higher AEs. 
There were 6 Grade 2 events; these included bacterial vaginosis, vaginal itching, pelvic 
cramping (2), friable cervix and adnexal pain. Of these, only bacterial vaginosis and vaginal 
itching were attributed to study product use.  Forty-seven AEs were reported amongst 64 
participants. Thirty-one participants (48.5%) reported at least one AE; 22 reported at least one 
urogenital event. For the women randomized to the 3 and 7 day follow up visit approximately 
50% of the participants had visible film on speculum exam (44% and 56%). In summary, the 
high Eudragit® film was very well tolerated with no concerning safety signals. 
 
3 
Study Objectives 
 
3.1 
Primary Objective: 
• To assess women’s ability to successfully insert two formulations of a vaginal          
placebo film containing differing concentrations of Eudragit® 
 
3.2 
Primary Endpoint: 
• 
Visual assessment of film location after insertion attempt (completely inserted, 
partially inserted, unable to insert) 
 
3.3 
Secondary Objectives: 
• 
To explore participants' preference for vaginal film formulation 
• 
To explore participants’ challenges with self-insertion 
 
3.4 
Secondary Endpoints 
• 
Percentage of participants who prefer the low level Eudragit® film to the high level 
Eudragit® formulation film with respect to insertion 

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• 
Participants’ description of identified challenges 
 
4 
Study Population 
 
4.1 
Selection of the Study Population 
 
The inclusion and exclusion criteria in this section will be utilized to ensure the appropriate 
selection of study participants.  
 
4.2 
Recruitment 
 
For this study, 30 pre-menopausal women, 18 – 45 years of age, will be enrolled over 
approximately a 3-month period.  Participants may be recruited from medical clinics, local 
colleges, a list of previous study participants and the community by members of the 
Reproductive Infectious Disease Research staff.  This recruitment strategy is likely to capture a 
diverse population as this community is comprised of approximately 48% White, 48% African-
American and 4% other ethnicities including Hispanic, Asian, Indian and Native American. An 
IRB approved screening script may be used to provide study information and assess minimum 
eligibility during the recruitment process.  After the study has been presented and questions 
have been answered, participants will be scheduled for an enrollment visit at UPMC Magee-
Womens Hospital.   
 
4.3 
Study Design Summary 
 
After providing written informed consent, the participant will provide answers to a brief 
questionnaire, have urine collected for pregnancy testing, and have saliva collected for rapid 
HIV testing (unless a result from previous 6 months is available).  Once deemed eligible, vaginal 
swabs will be collected (without a speculum) for sexually transmitted infection testing 
(gonorrhea, chlamydia and trichomonas).    
 
The participant will then be randomized to insertion order for the two formulations of a placebo 
vaginal film [high and low ammonio-methacrylate copolymer type B (Eudragit®)].  Once a 
participant is randomized to the film, she is considered enrolled.  
 
Clinic staff will obtain the films from the pharmacy and will provide instruction to the participant 
on the proper technique of self-insertion. The clinician and the participant will be in the same 
room during self-insertion of the films but will be separated by a privacy curtain.  The clinician 
will be available to answer questions and document concerns/comments.  The participant will 
attempt self-insertion of the first film  and immediately afterward (within 10 minutes) the clinic 
staff will perform a speculum exam to determine the location of the film. The clinical staff will 
remove all visible film and ask the participant to complete a brief questionnaire regarding her 
experience with that specific film.   The participant will then be asked to self-insert the second 
film. After the second film insertion, the clinical staff will perform another speculum exam to 
determine the film’s location and remove any visible film.  The participant will then answer 
another brief questionnaire regarding her experience with the second film as well as additional 
questions regarding her preference of film and questions surrounding challenges with self-
insertion.  It is anticipated that gonorrhea, chlamydia and trichomonas testing will be resulted 
within the week. Participants will be notified of any positive STI test reported by telephone, and 
necessary treatment and referrals will be provided. It should be noted that STI testing is 
provided in this study as a courtesy to the participants and not for eligibility purposes.  

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4.4 
Inclusion Criteria 
 
1. Ages 18-45 
 
2. Intact uterus by participant report 
 
3. Agrees to abstain from inserting anything into the vagina for 24 hours prior to the 
study visit 
 
4.5 
Exclusion Criteria 
 
Women who meet any of the following criteria by participant report will be excluded from the 
study. Of note, the study is limited to premenopausal women with an intact uterus because the 
mucosal environment differs substantially between pre- and post- menopausal women. 
Therefore, inclusion of post-menopausal women would introduce heterogeneity into the 
population. 
 
1. Menopausal (as defined as amenorrhea for one year or more without an alternative 
etiology) 
 
2. Hysterectomy (including total and supracervical)  
 
3. Currently pregnant or pregnancy within 90 days of enrollment 
 
4. Lactating 
 
5. Symptoms of a urogenital infection including vaginal discharge, pain, odor, or itching 
 
6. Menses at the time of enrollment 
 
7. Known allergy or hypersensitivity to any of the components of the placebo film 
 
8. 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.   
5 
Study Procedures 
 
This section describes visit-specific study procedures.  
    
5.1 
Pre-screening  
 
As part of participant outreach and recruitment strategies, study staff may pre-screen potential 
study participants (e.g. via telephone). During these interactions, study staff may use an IRB 
approved telephone script to explain the study to participants and ascertain elements of 
presumptive eligibility, to be confirmed at the time of enrollment. If the participant is eligible 
based on a screening script her name and appointment time will be placed on the script.  If she 

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signs consent, the telephone script will then become part of her research record. If she does not 
sign consent, the form will be de-identified. 
 
 
5.2 
Study visit 
 
The participant will present to the study clinic. Written informed consent will be obtained. A brief 
medical history will be taken to ensure eligibility. Height and weight will be obtained and 
participants will be asked a brief baseline questionnaire, which will include questions related to 
previous film use.  Saliva for HIV antibody testing (unless a negative result is available from the 
past 6 months), urine for pregnancy testing and vaginal swabs for Neisseria gonorrhoeae, 
Chlamydia trachomatis, and Trichomonas vaginalis nucleic acid amplification testing will be 
collected. The urine pregnancy test result will be available before the participant is randomized. 
Counseling and referral will take place as necessary.  HIV test results will be available before 
the end of the visit and will be provided to the participant.  Given the very low risk of the women 
being enrolled in this study, HIV test result will not be needed prior to randomizing.  In the very 
unlikely event of a positive rapid HIV test, a blood sample will be drawn to send to the main 
UPMC laboratory for confirmatory testing.  The vaginal STI testing results will not be available in 
real time and will not impact eligibility.   
 
Clinic staff will obtain study product from the pharmacy and will instruction the participant on the 
proper technique of self-insertion. The participant will attempt self-insertion of the first film and 
immediately afterward the clinic staff will perform a speculum exam to determine the location of 
the film. The clinical staff will remove all visible film.after the clinician verifies placement.  The 
clinician will use an instrument as needed (e.g. forceps) to grab and remove the film.  This 
method was successful in removing the entire piece of film from previous studies. The study 
staff will then ask the participant to complete a brief questionnaire regarding her experience with 
that specific film.  The participant will then be asked to self-insert the second film. After the 
second film insertion, the clinical staff will perform another speculum exam to determine the 
film’s location and remove any visible film.  The participant will then answer another brief 
questionnaire regarding her experience with the second film as well as additional questions 
regarding her preference of film and questions surrounding challenges with self-insertion.   
 
It is anticipated that gonorrhea, chlamydia and trichomonas testing results will be reported within 
the week. Participants will be notified of any positive STI test result by telephone, and necessary 
treatment and referrals will be provided. It should be noted that STI testing is provided in this 
study as a courtesy to the participants and not for eligibility purposes  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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The table below outlines procedure to take place at the Study Visit.  
 
Table 1: Study Visit Procedures 
Study Visit  
Component 
Procedures 
Administrative/ 
Interview 
Informed consent document 
Collect contact information 
Eligibility questionnaire 
Demographics 
Visit Questionnaire (including experience using films) 
Height and Weight 
HIV pre- and post-test counseling 
Randomization 
Verbal self-insertion instructions 
Product questionnaire 
Insertion challenges discussion 
Reimbursement 
Saliva* 
Rapid HIV test if no confirmed negative HIV test is available 
from the previous 6 months 
Urine 
Pregnancy test 
Vaginal Swab 
(w/o speculum) 
Neisseria gonorrhoeae, Chlamydia trachomatis, and 
Trichomonas vaginalis nucleic acid amplification testing 
Study Product 
Self-insertion of two formulations of a placebo vaginal film [high 
and low ammonio-methacrylate copolymer type B (Eudragit®)] 
Pelvic Exam 
Visual Inspection of vaginal film placement and removal of 
residual film following each film insertion 
*If rapid HIV testing using saliva is positive, confirmatory testing will be performed by collecting a small blood sample to be sent to 
the UPMC Central Laboratory 
 
5.3 
Telephone follow-up 
 
Clinic staff will call participants with the results of the Neisseria gonorrhoeae, Chlamydia 
trachomatis, and Trichomonas vaginalis nucleic acid amplification testing when available if 
resulted positive. This is consistent with standard clinical care.  Treatment will be provided per 
CDC recommended guidelines, as necessary. 
6 
Study Product 
 
6.1 
Regimen 
 
Each participant will receive one vaginal film containing high level Eudragit® and one vaginal 
film containing low level Eudragit®.  
 
6.2 
Administration 
 

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After eligibility is confirmed, site staff will randomize the participant to sequence of film insertion. 
The site staff will retrieve two films from the pharmacy. The site staff will provide insertion 
instructions to the participant and the participant will self-insert the vaginal films in the order 
assigned by randomization.    Neither the participant nor the study staff will know which film is 
the higher level or lower level film.  The order of use will be documented in the participant’s 
record.   
 
6.3 
Study Product Formulation   
 
Participants will receive two placebo films that differ in the content of Eudragit.  The films are 2” 
x 2.”  
 
6.4 
Study Product Supply and Accountability 
 
Study product was manufactured and package by Benefit Coatings, Stratford, CT, in compliance 
with cGMP. The packaged study product will be provided to the UPMC Magee-Womens 
Hospital Pharmacy and will be labeled to maintain the blind of the films (e.g. film A and film B).  
All study product will be available to the study staff through the Magee Investigational Drug 
Service Pharmacy. 
 
The Magee research pharmacist will maintain complete accountability records of all study 
products received for this protocol and dispensed to participants.      
 
The film is packaged into a foil-lined pouch and stored at room temperature. 
 
In the event that a participant is unable to insert the film (e.g. sticks to her finger), insertion will 
be deemed unsuccessful and the participant will not be dispensed another replacement film.   
 
However, if a film is dropped or damaged, the film will be discarded and accounted for by the 
clinical staff in the participant record and a new replacement film will be obtained from the 
pharmacy.   
 
6.5 
Study Product Dispensing  
 
Study products will be dispensed only to enrolled participants upon receipt of a written study 
product order form signed by an authorized prescriber.   
7 
Laboratory Evaluations 
 
7.1 
Laboratories 
 
UPMC Magee-Womens Hospital Clinical and Translational Research Center 
 
• 
Rapid HIV test (saliva) 
• 
Pregnancy Test (urine) 
Presbyterian/Shadyside Laboratory- UPMC Central Laboratory 
• 
Confirmatory HIV test (blood) 

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Magee-Womens Research Institute- Hillier Laboratory 
 
• 
Chlamydia trachomatis (vaginal) 
• 
Neisseria gonorrhoeae (vaginal) 
• 
Trichomonas vaginalis (vaginal) 
7.2 
Specimen Collection and Processing 
 
The site will adhere to the standards of good clinical laboratory practice and site standard 
operating procedures for proper collection, processing, labeling, handling, and transport of 
specimens. In cases where laboratory results are not available due to administrative or 
laboratory error, sites are permitted to recollect specimens. 
 
7.3 
Biohazard Containment 
 
As the transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated fluid, appropriate secretion precautions will be employed by all personnel in the 
handling of all specimens for this study as recommended by the CDC and NIH. 
8 
Assessment of Safety and Clinical Management 
 
8.1 
Safety Monitoring 
 
The study site investigators are responsible for continuous close safety monitoring of all study 
participants and for alerting the Protocol Chairs if unexpected concerns arise.  Appropriate 
safety monitoring will be contingent upon excellent communication between study participants 
and study staff, and upon cooperation among study staff, and the physician investigator. 
 
Given this study involves a single study visit, use of placebo films which are immediately 
removed after insertion, and poses minimal risk to the participant, adverse events are not 
expected.  In the very unlikely event that an unanticipated event occurs, the protocol chair and 
the DAIDS medical officers will be made aware of the event, and the event will be reported as 
applicable to the policies outlined on the IRB website:  www.irb.pitt.edu. 
 
8.2 
Adverse Events Definitions   
 
An AE is defined as any untoward medical occurrence in a clinical research participant 
administered an investigational product and which does not necessarily have a causal 
relationship with the investigational product. As such, an AE can be an unfavorable or 
unintended sign (including an abnormal laboratory finding, for example), symptom or disease 
temporally associated with the use of an investigational product, whether or not considered 
related to the product. The term “investigational product” for this study refers to the two placebo 
films. 
  
Given that the study product is a placebo product and the product will be removed immediately 
after insertion, it is exceptionally unlikely that any adverse events will be noted during the single 
visit. Nonetheless, should one occur study site staff will document any AEs in source documents 
regardless of severity and presumed relationship to study product.   

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The PI/designee will grade the severity of each AE and the relationship of the AE to study 
product:   
 
AE severity will be graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, 
Version2.0, November 2014 and the Female Genital Grading Table for Use in Microbicide 
Studies (Appendix 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, 
Version 2.0, December 2014). AEs not included in the Female Genital Grading Table will be 
graded by the DAIDS AE Grading Table Version 1.0, December 2004.  In cases where a genital 
AE is covered in both tables, the Female Genital Grading Table for Use in Microbicide Studies 
will be the grading scale utilized.   
 
The relationship of all AEs reported on CRFs will be assessed based on the Manual for 
Expedited Reporting of Adverse Events to DAIDS (Version 1.0, dated January 2010), the 
product Package Inserts and Investigators Brochures, and the clinical judgment of the 
PI/designee.  Per the Manual for Expedited Reporting of Adverse Events to DAIDS, the 
relationship categories that will be used for this study are:  
 
• 
Related: There is a reasonable possibility that the AE may be related to the 
study agent(s)  
• 
Not related: There is not a reasonable possibility that the AE is related to the 
study agent(s)  
 
The DAIDS Table for Grading Adult and Pediatric Adverse Events, the Female Genital Grading 
Table for Use in Microbicide Studies, and Version 2.0 of the Manual for Expedited Reporting of 
Adverse Events to DAIDS are available on the DAIDS Regulatory Support Center (RSC) web 
site:   http://rsc.tech-res.com/ 
All AEs will be captured on an AE log form.  
 
8.3 
Criteria for Early Termination of Study Participation 
 
Participants may voluntarily withdraw from the study for any reason at any time. The Site 
PI/designee also may withdraw participants from the study to protect their safety and/or if they 
are unwilling or unable to comply with required study procedures.   
9 
Statistical Considerations 
 
9.1 
Sample Size and Accrual 
 
The primary aim of the study is to assess proper placement of two vaginal placebo films 
containing two levels of polymer. Secondary aims are to gather women’s preference and 
experiences through questionnaire and discussion.    
 
In a previous cross-over study of placebo film products, the proportion of 32 women that 
misplaced a 2” x 2” cellulose film was 41% and 78% misplaced a 1” x 2” film product, with 50% 
placement concordance between the two films. Twenty-five women will have 80% power to 
determine whether there is a difference between polymer types of vaginal placebo films based 
on a McNemar’s test evaluated at the .05 significance level. The sample size of 30 women will 
allow for additional input regarding challenges. 
 

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9.2 
Statistical analyses 
 
McNemar’s test will be used to assess differences in the proportion of misplaced films, defined 
as partial or unable to insert the vaginal film product based on visual assessment. McNemar’s 
test will also be used to assess differences in preference for the two film products. Conditional 
logistic regression will be used to assess whether demographic characteristics such as age, 
race, and BMI are associated with product placement or product preference.  Descriptive 
statistics will be used to summarize participants’ challenges with self-insertion of the film 
products. 
 
9.3 
Blinding 
 
All participants will receive a single vaginal film containing high level and low level Eudragit® 
content placebo films. They will be blinded to the formulation with respect to Eudragit® content 
and the sequence of insertion. Evaluators of the study endpoints will also be blinded to the film 
formulation and sequence of insertion.  
 
9.4 
Random assignment 
 
The randomization scheme will be generated and maintained by a member of the Data 
Management Center at the study site and supplied to the Pharmacy.  Women will be 
randomized to the sequence of insertion of the two films, low followed by high Eudragit® content 
or high followed by low Eudragit® content in a 1:1 ratio using a permuted block design with 
random block sizes of 2 and 4.  In order to minimize bias in group assignment, participants will 
be given study identification numbers.  A study staff member will allot the identification numbers 
in sequential order as participants become eligible to enroll in the study. Participants will be 
randomized using REDCap’s randomization module to obtain the sequence of product insertion. 
The film product will be labeled in order to mask the Eudragit® content to the participants and 
study staff. The randomization scheme will be created for a total of 34 participants; the overage 
will be created to compensate for participant withdrawals or unusable products. 
 
 
 
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4 Nel AM, Mitchnick LB, Risha P, Muungo LT, Norick PM. Acceptability of vaginal film, soft-gel capsule, 
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2011;20:1207-14. 
5Raymond E, Alvarado G, Ledesma L, et al. Acceptability of two spermicides in five countries. 
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