A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial to Assess the Safety and Efficacy of 5% Monolaurin Vaginal Gel Administered Intravaginally for the Treatment of Bacterial Vaginosis
Phase: PHASE2
Conditions: Bacterial Vaginosis
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

1 
A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial to 
Assess the Safety and Efficacy of 5% Monolaurin Vaginal Gel Administered 
Intravaginally for the Treatment of Bacterial Vaginosis 
DMID Protocol Number: 12-0021 
DMID Funding Mechanism: VTEU Contract Support  
Pharmaceutical Support Provided by: Hennepin Life Sciences 
Other Identifying Numbers: None 
IND Sponsor: Division of Microbiology and Infectious Diseases 
The National Institute of Allergy and Infectious Diseases 
The National Institutes of Health 
Principal Investigator:  Patricia Winokur, MD 
DMID Clinical Project Manager: Barbara Hahn, RN, BSN 
DMID Medical Monitor:  Soju Chang, MD 
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STATEMENT OF COMPLIANCE 
 
This trial will be conducted in compliance with the protocol, International Conference on 
Harmonisation guideline E6:  Good Clinical Practice: Consolidated Guideline, the applicable 
regulatory requirements from US Code of Federal Regulations (CFR) (Title 45 CFR Part 46 and 
Title 21 CFR including Parts 50 and 56) concerning informed consent and Institutional Review 
Board regulations, and the NIAID Clinical Terms of Award. 
All individuals responsible for the design and conduct of this study have completed Human 
Subjects Protection Training and are qualified to be conducting this research prior to the 
enrollment of any subjects.  Curricula vitae for all investigators and sub-investigators participating 
in this trial are on file in a central facility (21 CFR 312.23 [a] [6] [iii] [b] edition). 

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SIGNATURE PAGE 
 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable US federal regulations and ICH guidelines. 
 
 
Site Investigator: 
Signed: 
Date: 
Name 
Title 
 
 

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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ............................................................................................. 2 
SIGNATURE PAGE................................................................................................................... 3 
TABLE OF CONTENTS ............................................................................................................ 4 
LIST OF TABLES ...................................................................................................................... 7 
LIST OF FIGURES .................................................................................................................... 8 
LIST OF ABBREVIATIONS ..................................................................................................... 9 
PROTOCOL SUMMARY ........................................................................................................ 12 
1. 
KEY ROLES .......................................................................................................... 15 
2. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ................... 17 
2.1. 
Background Information ......................................................................................... 17 
2.1.1. 
Monolaurin (GML) ................................................................................................. 19 
2.2. 
Rationale ................................................................................................................ 23 
2.3. 
Potential Risks and Benefits.................................................................................... 23 
2.3.1. 
Potential Risks ........................................................................................................ 23 
2.3.2. 
Known Potential Benefits ....................................................................................... 24 
3. 
OBJECTIVES ........................................................................................................ 25 
3.1. 
Study Objectives ..................................................................................................... 25 
3.2. 
Study Outcome Measures ....................................................................................... 25 
3.2.1. 
Safety Outcomes ..................................................................................................... 25 
3.2.2. 
Efficacy Outcomes.................................................................................................. 26 
3.2.2.1. 
Primary and Secondary Efficacy Outcomes ............................................................ 26 
3.2.2.2. 
Exploratory Efficacy Outcomes .............................................................................. 26 
4. 
STUDY DESIGN ................................................................................................... 27 
4.1. 
Substudies (if applicable) ........................................................................................ 28 
5. 
STUDY ENROLLMENT AND WITHDRAWAL ................................................... 29 
5.1. 
Subject Inclusion Criteria ....................................................................................... 29 
5.2. 
Subject Exclusion Criteria ....................................................................................... 29 
5.3. 
Treatment Assignment Procedures .......................................................................... 31 
5.3.1. 
Randomization Procedures ..................................................................................... 31 
5.3.2. 
Masking Procedures ............................................................................................... 31 
5.3.3. 
Reasons for Withdrawal.......................................................................................... 32 
5.3.4. 
Handling of Withdrawals ........................................................................................ 32 

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5.3.5. 
Termination of Study .............................................................................................. 33 
6. 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT ............................... 34 
6.1. 
Study Product Description ...................................................................................... 34 
6.1.1. 
Acquisition ............................................................................................................. 34 
6.1.2. 
Formulation, Packaging, and Labeling .................................................................... 34 
6.1.2.1. 
5% Monolaurin Vaginal Gel ................................................................................... 35 
6.1.2.2. 
Vehicle Placebo Gel ............................................................................................... 35 
6.1.3. 
Product Storage and Stability .................................................................................. 35 
6.2. 
Dosage, Preparation and Administration of Study Intervention/Investigational 
Product ................................................................................................................... 35 
6.3. 
Modification of Study Intervention/Investigational Product for a Participant .......... 36 
6.4. 
Accountability Procedures for the Study Intervention/Investigational 
Product(s) ............................................................................................................... 36 
6.5. 
Assessment of Subject Compliance with Study Intervention/Investigational 
Product ................................................................................................................... 36 
6.6. 
Concomitant Medications/Treatments ..................................................................... 37 
7. 
STUDY SCHEDULE .............................................................................................. 38 
7.1. 
Screening and Enrollment (Visit 1, Day 1) .............................................................. 38 
7.2. 
Visit 2 (Day 8 [Window: Days 8-15]) ..................................................................... 41 
7.3. 
Visit 3, Final Study Visit (Day 28 [Window: Days 22-31]) ...................................... 42 
7.4. 
Early Termination Visit .......................................................................................... 43 
7.5. 
Unscheduled Visit .................................................................................................. 43 
8. 
STUDY PROCEDURES/EVALUATIONS ............................................................. 45 
8.1. 
Clinical Evaluations ................................................................................................ 45 
8.2. 
Laboratory Evaluations ........................................................................................... 45 
8.2.1. 
Clinical Laboratory Evaluations .............................................................................. 45 
8.2.2. 
Special Assays or Procedures .................................................................................. 46 
8.2.3. 
Specimen Preparation, Handling, and Shipping....................................................... 47 
8.2.3.1. 
Instructions for Specimen Preparation, Handling, and Storage ................................ 47 
8.2.3.2. 
Specimen Shipment ................................................................................................ 47 
9. 
ASSESSMENT OF SAFETY .................................................................................. 49 
9.1. 
Specification of Safety Parameters .......................................................................... 49 
9.2. 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters .............................................................................................................. 49 

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9.2.1. 
Adverse Events ....................................................................................................... 49 
9.2.2. 
Solicited Events ...................................................................................................... 50 
9.2.3. 
Serious Adverse Events .......................................................................................... 52 
9.2.4. 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values 
or Abnormal Clinical Findings ................................................................................ 52 
9.3. 
Reporting Procedures ............................................................................................. 53 
9.3.1. 
Adverse Events ....................................................................................................... 53 
9.3.1.1. 
Serious Adverse Events .......................................................................................... 53 
9.3.2. 
Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND .......... 54 
9.3.3. 
Reporting of Pregnancy .......................................................................................... 54 
9.4. 
Type and Duration of Follow-up of Subjects after Adverse Events ......................... 54 
9.5. 
Halting Rules .......................................................................................................... 54 
9.6. 
Safety Oversight (ISM plus DSMB) ........................................................................ 55 
9.6.1. 
Data and Safety Monitoring Board .......................................................................... 55 
9.6.2. 
Independent Safety Monitor (ISM) ......................................................................... 56 
10. 
CLINICAL MONITORING .................................................................................... 57 
10.1. 
Site Monitoring Plan ............................................................................................... 57 
11. 
STATISTICAL CONSIDERATIONS ..................................................................... 58 
11.1. 
Introduction ............................................................................................................ 58 
11.2. 
Data Analysis Populations ...................................................................................... 58 
11.3. 
Study Objectives and Endpoints .............................................................................. 58 
11.4. 
Study Hypotheses ................................................................................................... 59 
11.5. 
Sample Size Considerations .................................................................................... 60 
11.6. 
Planned Interim Analyses ....................................................................................... 61 
11.7. 
Final Analysis Plan ................................................................................................. 62 
11.7.1. 
Safety Analyses ...................................................................................................... 62 
11.7.1.1. 
Overview of Safety Analyses .................................................................................. 62 
11.7.1.2. 
Analyses of Primary and Secondary Safety Outcomes ............................................ 63 
11.7.2. 
Efficacy Analyses ................................................................................................... 63 
11.7.2.1. 
Overview of Efficacy Analyses ............................................................................... 63 
12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ........................................................................................... 65 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE......................................... 66 
14. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................. 67 

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14.1. 
Ethical Standard ..................................................................................................... 67 
14.2. 
Institutional Review Board ..................................................................................... 67 
14.3. 
Informed Consent Process....................................................................................... 67 
14.4. 
Exclusion of Women, Minorities, and Children (Special Populations) .................... 67 
14.5. 
Subject Confidentiality ........................................................................................... 68 
14.6. 
Study Discontinuation............................................................................................. 68 
14.7. 
Future Use of Stored Specimens ............................................................................. 69 
14.8. 
Information Provided to Subjects at Study Completion ........................................... 69 
15. 
DATA HANDLING AND RECORD KEEPING ..................................................... 70 
15.1. 
Data Management Responsibilities ......................................................................... 70 
15.2. 
Data Capture Methods ............................................................................................ 70 
15.3. 
Types of Data ......................................................................................................... 70 
15.4. 
Timing/Reports....................................................................................................... 70 
15.5. 
Study Records Retention......................................................................................... 71 
15.6. 
Protocol Deviations ................................................................................................ 71 
16. 
PUBLICATION POLICY ....................................................................................... 72 
17. 
LITERATURE REFERENCES ............................................................................... 73 
SUPPLEMENTS/APPENDICES .............................................................................................. 76 
APPENDIX A: SCHEDULE OF EVENTS ............................................................................... 76 
APPENDIX B: Toxicity Table .................................................................................................. 78 
APPENDIX C: Female Genital Grading Table for Physical Exam Findings ............................... 79 
LIST OF TABLES 
Table 1: 
Laboratory examination of vaginal smears and the determination of the Nugent 
Score ...................................................................................................................... 18 
Table 2: 
Solicited events & grading ...................................................................................... 51 
Table 3: 
Bacterial Vaginosis:  Determination of Therapeutic Cure........................................ 59 
Table 4: 
Power to compare binomial proportions using a two-sided level 0.05 Fisher’s 
Exact Test with a sample size of N = 90 (60 subjects in the 5% Monolaurin 
Vaginal Gel arm, 30 subjects in the Vehicle Placebo Gel arm) Conditions in 
which Power is ≥.80 are highlighted ....................................................................... 61 
Table 5: 
Schedule of Events ................................................................................................. 76 
Table 6: 
Toxicity Table ........................................................................................................ 78 
Table 7: 
Female Genital Grading Table for Physical Exam Findings .................................... 79 

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LIST OF FIGURES 
Figure 1: 
Schematic of Study Design ..................................................................................... 14 
Figure 2: 
Light Microscopy of unstained vaginal smear showing clue cell ............................. 18 
 

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LIST OF ABBREVIATIONS 
 
ACOG 
American College of Obstetricians and Gynecologists 
AGUS 
Atypical Glandular Cells of Uncertain Significance 
AE 
Adverse Event/Adverse Experience 
ALT 
Alanine Aminotransferase 
ASCUS 
Atypical Squamous Cells of Uncertain Significance 
AST 
Aspartate Aminotransferase 
BV 
Bacterial Vaginosis 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CFU 
Colony Forming Unit 
cGMP 
Current Good Manufacturing Practices 
CIN 
Cervical Intraepithelial Neoplasia 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases, NIAID, 
NIH, DHHS 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
ELISA 
Enzyme-Linked Immunosorbent Assay 
FDA 
Food and Drug Administration 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
GML 
Glycerol Monolaurate 
GRAS 
generally recognized as safe 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HSIL 
High Grade Squamous Intraepithelial Dysplasia 
 
 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IDES 
Internet Data Entry System 
IEC 
Independent or Institutional Ethics Committee 
IL 
Interleukin 
IND 
Investigational New Drug Application 
ISM 
Independent Safety Monitor 
IRB 
Institutional Review Board 

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JAMA 
Journal of the American Medical Association 
KOH 
Potassium Hydroxide 
LSIL 
Low grade Squamous Intraepithelial Neoplasia 
LOCF 
Last Observation Carried Forward 

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MedDRA  
Medical Dictionary for Regulatory Activities 
MIP 
Macrophage Inflammatory Protein 
mITT 
Modified Intent-To-Treat 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 
NDA 
New Drug Application 
NF 
The National Formulary 
NIAID 
National Institute of Allergy and Infectious Diseases, NIH, DHHS 
NIH 
National Institutes of Health 
OCRA 
Office of Clinical Research Affairs, DMID, NIAID, NIH, DHHS 
OHRP 
Office for Human Research Protections 
OHSR 
Office for Human Subjects Research 
ORA 
Office of Regulatory Affairs, DMID, NIAID, NIH, DHHS 
PCR 
Polymerase Chain Reaction 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PP 
Per-Protocol 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SDCC 
Statistical and Data Coordinating Center 
SIV 
Simian Immunodeficiency Virus 
SOP 
Standard Operating Procedure 
TSST 
Toxic Shock Syndrome Toxin 
US 
United States 
USP 
United States Pharmacopeia 

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PROTOCOL SUMMARY 
 
Title: 
A Phase II, Double-Blind, Randomized, Placebo-Controlled, 
Multicenter Trial to Assess the Safety and Efficacy of 
5% Monolaurin Vaginal Gel Administered 
Intravaginally for the Treatment of Bacterial Vaginosis 
Phase: 
II 
Population: 
120 women, 18-50 years old, with clinical evidence of bacterial 
vaginosis, recruited from the community around the University of 
Iowa Hospitals and Clinics, Cincinnati Children’s Hospital 
Medical Center and Duke University School of Medicine. 
Number of Sites: 
2 
Study Duration: 
13 months 
Subject Participation 
Duration: 
4 weeks 
Estimated Time to 
Complete Enrollment: 
12 months 
Description of Agent or 
Intervention: 
5% Monolaurin Vaginal Gel administered intravaginally 
or placebo gel 
Objectives: 
Primary Objectives: 
 
To assess the safety and tolerability of 5% Monolaurin 
Vaginal Gel compared to Vehicle Placebo Gel (excipients 
only). 
 
To assess the efficacy by clinical cure rate of 5% 
Monolaurin Vaginal Gel compared to Vehicle Placebo Gel 
at Visit 2. 
Secondary Objectives: 
 
To evaluate the therapeutic cure rate of 5% Monolaurin 
Vaginal Gel compared to Vehicle Placebo Gel at Visits 2 
and 3. 
 
To evaluate the clinical cure rate of 5% Monolaurin Vaginal 
Gel compared to Vehicle Placebo Gel at Visit 3. 
 To evaluate the changes in Nugent’s criteria of vaginal 
bacterial flora at Visits 2 and 3. 

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Exploratory Objectives: 
 To evaluate the clinical and therapeutic cure rates of 5% 
Monolaurin Vaginal Gel compared to Vehicle Placebo Gel 
for each subgroup (first episode BV and recurrent BV) at 
Visits 2 and 3. 
 To evaluate quantitative changes in selected bacterial 
species at Visits 2 and 3. 
 
 To evaluate the quantitative changes of Candida spp ( in 
subjects with Candida spp. identified at screening) at Visits 
2 and 3 
 
Description of Study 
Design: 
This is a Phase 2, double-blind, randomized, placebo-controlled, 
multi-center trial of 120 BV subjects randomized at a ratio of 2:1 
to receive active test article (5% Monolaurin Vaginal Gel) or 
placebo (Vehicle Placebo Gel) as outpatient therapy.  Each 
subject will self-administer intravaginal gel twice daily for 3 
successive days for a total of six doses. There will be three 
clinic visits over 31 days. 

 
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Schematic of Study Design: 
Figure 1: 
Schematic of Study Design 
 
 
 
Screened and + Amsel criteria N=120 
 
 
 
 
Receive 5% 
monolaurin gel N=80 
 
 
 
 
rrhea or chlamydia positive 
or Safety Laboratory = 
Grade 3 
 
 
 
 
 
 
 
HIV, gonorrhea or 
chlamydia positive or 
Safety Laboratory = 
Grade 3 
 
 
HIV, gonorrhea and 
chlamydia negative and 
Safety Laboratories < 
Grade 3 
 
Follow for safety and 
efficacy 
 
Stop study drug and follow 
for safety and efficacy 
Stop study drug and follow 
for safety and efficacy 
Follow for safety and 
efficacy 
 
Receive vehicle 
placebo gel N=40 
HIV, gonorrhea or 
chlamydia positive or 
Safety Laboratory = 
Grade 3 
HIV, gonorrhea and 
chlamydia negative 
and Safety 
Laboratories < Grade 3 
Receive 5% 
monolaurin gel 
N=80 

 
 
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1. 
KEY ROLES 
 
 
Lead Principal Investigator: 
Patricia Winokur, MD University 
ofIowa 
University of Iowa Hospitals and Clinics  
200 Hawkins Drive 
Iowa City, IA 52242  
Phone: 319-384-1735 
Fax: 319-335-8318 
E-mail: patricia-winokur@uiowa.edu 
Site Investigator: 
Lea Widdice, MD 
Cincinnati Children's Hospital 
Medical Center 
333 Burnet Ave 
Cincinnati, OH 45229 
Phone: 513-636-7413 
FAX: 513-636-1129 
E-mail: lea.widdice@cchmc.org 
Site Investigator: 
Brenna L. Hughes, MD, MSCR 
Duke University School of Medicine 
2608 Erwin Road Suite 210 
Durham, NC 27705 
Phone: 919-668-0843 
FAX: 919-613-1550 
E-mail:Brenna.hughes@duke.edu 
 
DMID Scientific Lead: 
Carolyn Deal, PhD 
Sexually Transmitted Diseases Branch 
DMID/NIAID/NIH 
5601 Fishers Lane, Room 8E40 
Bethesda, MD 20892 
Phone: 301-402-0443 
E-mail: cdeal@niaid.nih.gov 
     

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DMID Medical Monitor: 
Soju Chang, MD 
Office of Clinical Research Affairs (OCRA) 
DMID/NIAID/NIH 
5601 Fishers Lane, Room 7E59 
Bethesda, MD 20892-6603 
Phone: 240-291-4178 
E-mail: Soju.chang@nih.gov 
 
 
DMID Clinical Project Manager: 
Barbara Hahn, RN, BSN 
Sexually Transmitted Diseases Branch 
DMID/NIAID/NIH 
5601 Fishers Lane, Room 8E49 
Bethesda, MD 20892-6603 
Phone: 240-627-3267 
E-mail: bhahn@niaid.nih.gov 
DMID VTEU Project Officer 
Suzanne Murray, RN, BSN 
Office of the Associate Director of Clinical 
Research 
DMID/NIAID/NIH 
5601 Fishers Lane,Room 7G25 
Bethesda, MD 20892 
Phone: 240-627-3324 
E-mail: smurray@niaid.nih.gov 
Statistical and Data Management Center 
The Emmes Corporation Point of 
Contact: Amy Price 
401 N. Washington St., Suite 700 
Rockville, MD 20850 
Phone: 301-251-1161 
Fax: 301-251-1355 
E-mail: aprice@emmes.com 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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2. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
2.1. 
Background Information 
Bacterial Vaginosis 
Bacterial Vaginosis (BV) is a disease of the vagina caused by bacteria.  Current studies suggest 
that BV is caused by an imbalance of naturally occurring bacterial flora that is characterized by a 
paucity of hydrogen peroxide-producing lactobacilli and high concentrations of facultative 
anaerobic organisms such as Gardnerella vaginalis, Mycoplasma hominis, Bacteroides species, 
and others [1]. In women of childbearing age, BV is the most common cause of vaginitis 
accounting for 22-50% of women who have symptoms of vaginitis [2]. In a cohort of young 
healthy women, nearly 30% had been treated for BV [3].  In American and European studies, the 
prevalence often ranges from 5-36% with higher prevalence reported in women attending sexually 
transmitted disease clinics [4]. 
BV has been associated with preterm delivery, chorioamnionitis, post-abortion infection, and 
pelvic inflammatory disease [5-7]. 
Signs and Symptoms 
The most common symptom of BV is an abnormal homogeneous off-white vaginal discharge 
(especially after sex) with an unpleasant smell. On physical exam, the discharge often coats the 
walls of the vagina, though there is relatively little erythema, edema or inflammation noted on the 
vulva, labia, or the vaginal walls [8].  Up to 50% of women with BV are asymptomatic [8]. 
Etiology 
A healthy vagina normally contains many microorganisms; some of the common ones are 
Lactobacillus crispatus and Lactobacillus jensenii.  Lactobacilli, particularly hydrogen peroxide- 
producing species, appear to help prevent other vaginal microorganisms from multiplying to a level 
where they cause symptoms. The microorganisms involved in BV are very diverse, but include 
Gardnerella vaginalis, Mobiluncus, Bacteroides, and Mycoplasma. A change in normal bacterial 
flora including the reduction of lactobacillus, which may be due to the use of antibiotics or pH 
imbalance, allows more resistant bacteria to gain a foothold and multiply. 
Although BV can be associated with sexual activity, there is no clear evidence of sexual 
transmission and it is possible for sexually inactive persons to develop BV [9].  Rather, BV is a 
disordering of the chemical and biological balance of the normal flora.  A variety of risk factors 
associated with BV have been identified including a history of smoking, ethnicity, intrauterine 
device use, and douching [4,9]. 
Diagnosis 
The diagnosis of BV has been based clinically on Amsel and more recently Nugent scoring criteria 
using direct Gram stain of vaginal secretions. 
Amsel criteria 
In 1983, Amsel et al. established clinical criteria for diagnosing BV [10]. To make a diagnosis of 
BV, a speculum exam is performed and a swab from inside the vagina is obtained. The American 
College of Obstetricians and Gynecologists (ACOG) clinical guidelines state that three of the four 
Amsel’s criteria must be positive to warrant a diagnosis of BV [2].  However, the Food and Drug 

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Administration (FDA) guidance to industry recommends that subjects in BV studies should meet 
all four Amsel criteria. 
o An abnormal gray discharge. 
o Vaginal pH greater than 4.5. 
o A positive amine test (often called a Whiff test where a characteristic "fishy" odor 
develops after adding a small amount of potassium hydroxide [10% KOH] to a 
microscopic slide containing the vaginal discharge). 
o ≥ 20% of the epithelial cells seen on microscopic examination are coated with bacteria 
(Clue cells). 
Figure 2: 
Light Microscopy of unstained vaginal smear showing clue cell 
   
 
Nugent criteria 
In 1991, Nugent et al. described a Gram stain scoring system of vaginal smears to diagnose BV 
[11]. The Nugent score is calculated by assessing for the presence of large Gram-positive rods 
(Lactobacillus morphotypes), small Gram-variable rods (G. vaginalis morphotypes), and curved 
Gram-variable rods (Mobiluncus spp. morphotypes). The Nugent score can range from 0 to 10. A 
score of 7 to 10 is consistent with BV while 4-6 is considered intermediate and 0-3 is negative for 
BV.  Compared to the Amsel criteria, the Nugent score allows for assessment of alteration in 
vaginal flora as a continuum rather than a dichotomy. 
In the research setting, the Nugent Score is considered the gold standard method for diagnosis of 
BV [12]).  Scoring is as follows: 
Table 1: 
Laboratory examination of vaginal smears and the determination of the Nugent 
Score 
N Score = The sum of the scores for each bacterial morphotype listed below. (Note: Number of Organisms 
seen/high power field as determined by averaging a representative field by two independent evaluators) 
Lactobacilli 
SCORE 
Gardnerella,
Bacteroides 
SCORE 
Curved gram-negative 
bacilli 
SCORE Sum= 
*N SCORE 
≥30 
0 
0 
0 
0 
0 
0 
<30-5 
1 
<1 
1 
<1 
1 
3 
<5-1 
2 
1 to <5 
2 
1 to <5 
1 
5 
<1 
3 
5 to <30 
3 
5 to <30 
2 
8 
0 
4 
≥30 
4 
≥30 
2 
10 
 
 

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Current Treatments 
The Centers for Disease Control and Prevention (CDC) recommends metronidazole 500 mg orally 
twice daily for 7 days, intravaginal metronidazole gel 0.75% once daily for 5 days or clindamycin 
cream 2% intravaginally once daily for 7 days as first line therapy for BV [9]. 
Alternative regimens using oral tinidazole, oral clindamycin or clindamycin ovules are also 
provided.  However, up to 30% of women will have recurrent BV within 3 months of therapy [13]. 
Frequent emergence of vaginal candidiasis results from antibiotic suppression of vaginal flora, and 
Candida species are frequent commensal organisms in vaginal flora. Given BV’s high recurrence 
rates and the risks for antimicrobial resistance, additional treatment options are desirable. 
2.1.1. 
Monolaurin (GML)  
Monolaurin (GML) 
Monolaurin, also commonly referred to as glycerol monolaurate (GML), is a monoglyceride 
surfactant. It is an ester formed from glycerol and lauric acid.  Laboratory studies have shown that 
GML has antibacterial, antifungal and antiviral properties. 
GML Mechanism of Action 
Several published studies indicate that monolaurin’s primary mechanism of action is the insertion 
of its fatty acid 12-carbon chain into the microorganism’s plasma membrane thus interfering with 
plasma membrane signal transduction and transcription [14-19]. 
In addition to its direct effects on pathogens, monolaurin stabilizes animal and human cell 
membranes to interfere with the damaging effects of bacterial exotoxins, endotoxins, and hypotonic 
solutions, including reduction of chemokines (interleukin [IL]-8, macrophage inflammatory protein 
[MIP]-3α) that cause vaginal inflammation [15,19,20]. This property is advantageous in the 
prevention of infection transmission [20]. Typically, agents that cause vaginal inflammation 
promote transmission of sexually transmitted infections such as human immunodeficiency virus 
(HIV) [21-24]. 
A study at the University of Minnesota demonstrated that GML’s action occurs at the 
 
 
(Schlievert unpublished data). 
Monolaurin’s mechanism of action of blocking signals at the pathogen’s plasma membrane 
provides an advantage over other antibiotics with regard to the development of resistance. The cell 
walls of bacteria have 10-20 two-component membrane signaling systems that can all be targeted 
by GML [14, 25]. This high number of targets suggests that it may be more difficult for bacteria to 
develop resistance to monolaurin. Two published studies demonstrate that bacteria with long-term 
exposure to sub-inhibitory concentrations of GML remain sensitive to its bactericidal properties. 
Petschow et al. investigated the susceptibility to metronidazole, tetracycline, and monoglycerides 
(including monolaurin) to three test strains of Helicobacter pylori.  The frequency of resistance of 
variants to either metronidazole or tetracycline when tested at five times the minimum inhibitory 
concentration was 10-5 to 10-7, whereas no resistant variants of Helicobacter pylori were found for 
any of the monoglycerides tested [26].  Schlievert et al. did not observe any increase in resistance 
to GML’s antimicrobial and anti-exotoxin effects with yearlong passage of Staphylococcus aureus 
MN8 on sub-growth-inhibitory concentrations of GML [25]. 

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The antimicrobial activity of monolaurin was examined in vitro against ~40 pathogenic vaginal 
organisms, including bacteria, yeasts, protozoa, and viruses [25].  Bacterial organisms studied 
included Gardnerella vaginalis, Bacteroides fragilis, Mycoplasma hominis, various Streptococcus 
spp., Neisseria gonorrhoeae, Escherichia coli, and others. GML was effective in inhibiting the 
growth of all potentially pathogenic Candida species (11 strains of Candida albicans were tested in 
vitro as well as one strain of each of four other major Candida species) providing for the potential 
to treat pathogenic fungal infections in the vagina. Since Candida is also controlled by monolaurin, 
fungal overgrowth secondary to antibiotic therapy should not occur.  Additionally, lactobacilli, as 
normal vaginal microflora, are not significantly affected by monolaurin suggesting GML may 
preserve normal bacterial species during treatment while inhibiting overgrowth of other pathogens 
such as yeast species.  For the microorganisms relevant to the proposed indication, the highest 
minimum microbicidal concentration of monolaurin was 500 µg/mL, which is 100-fold lower than 
the concentration of monolaurin in the proposed drug product (50 mg/mL). 
Additionally, Li et al. demonstrated that 5% Monolaurin Vaginal Gel prevents transmission and 
infection of simian immunodeficiency virus (SIV) in 12 rhesus macaque monkeys [20].  Peterson 
et al. showed that GML (250 µg/0.25 mL), when co-administered vaginally to rabbits with toxic 
shock syndrome toxin-1 (TSST-1), completely prevented TSST-1-induced Toxic Shock Syndrome 
after 24 hours [15]. 
In addition to its broad and appropriate antimicrobial activity, monolaurin has been shown in vitro 
to reduce the production of inflammatory cytokines by human vaginal epithelial cells and human T 
and B cells in response to superantigen and antigen stimulation, and to protect mammalian cells 
from exotoxin.  In vivo studies in rhesus monkeys and humans have shown that monolaurin, but not 
vehicle control, significantly reduces cytokine production. 
In summary, monolaurin has been shown to have important antimicrobial effects on pathogens 
found vaginally in women.  In addition, monolaurin also inhibits the production of exotoxins by 
susceptible microorganisms and stabilizes eukaryotic cells to inhibit microbe-induced 
inflammation. The compound does not affect lactobacilli, the normal flora of the human vagina. 
Finally, the breadth of antimicrobial activity suggests that the adverse event (AE) of vaginal 
microbial overgrowth of other microorganisms is highly unlikely. 
Pharmacokinetics (PK) 
There have been no formal PK studies of Monolaurin Vaginal Gel in animals or humans to date. 
However it is believed that monolaurin systemic absorption will be minimal, and any monolaurin 
absorbed across the vaginal wall would be quickly metabolized by plasma lipases to lauric acid and 
glycerol, or re-esterified to a triglyceride, all common compounds found in dietary fats and lipids 
[27]. There is no evidence that the presence of monoglycerides of food fats has any deleterious 
effect on cells or tissues [28].  Additionally, glyceryl monostearate, a 21 carbon monoglyceride, is 
approved for use as an excipient in vaginal cream at concentrations up to 17% (e.g., PREMARIN® 
Vaginal Cream). 
Phase 2 Clinical Studies using Monolaurin Vaginal Gel 
The following two clinical studies were performed at the University of Minnesota, and were 
designed as single-center, double-blind device clinical studies using Monolaurin Vaginal Gels 
containing up to 5% monolaurin. 
 

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 Device Clinical Pilot Study (Protocol 2005-024) – Status: Completed 
A single-center, randomized, double-blinded, device clinical pilot study of Monolaurin Vaginal 
Gel enrolled 36 women [29]. The objective was to determine the effects of an intravaginal gel 
containing GML on vaginal Candida albicans, Gardnerella vaginalis, and Lactobacillus spp. and 
to determine GML persistence vaginally. 
The key endpoints in the study were differences in colony counts of Candida albicans, 
Gardnerella vaginalis, and Lactobacillus spp. between vaginal swabs taken before (at Visit 1) and 
after use of the intravaginal gel at Visit 2, approximately 12 hours after the last administration; and 
differences in GML amounts vaginally between swabs taken before and after use of GML-
containing gel. 
The study included non-pregnant women, 18-50 years of age who suspected they might have a 
vaginal infection. Women were administered 5 mL of gel containing 0%, 0.5% or 5% of GML 
every 12 hours for 2 consecutive days for a total of four doses.  Vaginal swabs were collected 
before and immediately after the first gel administration and 12 hours after the final gel 
administration for the following tests:  vaginal pH, wet mount and KOH test, Gram staining,  yeast 
and bacterial cultures (Candida albicans, Gardnerella vaginalis, and Lactobacillus spp.) and GML 
measurement (Gas Chromatograph-Mass Spectroscopy assay). Subjects were randomly assigned 
to receive one of the three study products (control, low or high concentration of GML) and were 
provided three more applications/doses of the appropriate study product formulation for self-
administration.  At about 12 hours after the final gel administration, vaginal swabs were again 
collected and the same tests performed. 
A total of 36 women were analyzed in this study. The numbers of subjects receiving gels were as 
follows: control, N=14; 0.5% monolaurin, N=13; and 5% monolaurin, N=9. 
Results compared the prevalence of the three study microorganisms, comparing Visit 1 to Visit 
Because of the small numbers of study participants, data for GML (0.5% and 5%) were evaluated 
individually but also pooled because of sample size for determination of significant differences 
between visits. 
The prevalence of Lactobacillus between Visits 1 and 2 for all treatment groups was not 
significantly different, providing evidence that the gels with or without GML have no effect on 
lactobacilli. 
Women who received the 0.5% GML gels showed significant reductions in Candida colony- 
forming units (CFU) between Visits 1 and 2 (P=0.001) but not for the 5% GML (P=0.15) due to 
sample size (6 at Visit 1, 2 at Visit 2). When GML treatment groups (0.5% and 5% GML) were 
combined in the analysis, significant reductions of both Candida counts between Visits 1 and 2 
were found (P=0.015). The reduction of Candida in the GML gel-treated women who showed 
reductions between Visits 1 and 2 was nearly to the minimum level of detection in the analyses (102 
CFU). 
A control gel effect was found for women with Gardnerella vaginalis.  Significant reductions were 
seen in Gardnerella vaginalis counts between Visits 1 and 2 for women who received the control 
(P=0.006). Women who received the 0.5% and 5% gels did not individually show significant 
reductions between Visits 1 and 2, but when GML treatment groups (0.5% and 5% GML) were 

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combined in the analysis, the counts of Gardnerella vaginalis were found to be significantly lower 
between Visits 1 and 2 (P=0.015). 
GML was detected vaginally in the women immediately after initial application of the GML gels 
(data not shown); GML was not detected (<0.7 µg/mL) in women who received control gels. 
GML was undetectable in women during the second visit, regardless of gel treatment, indicating 
that GML did not persist in vaginal secretions for the 12 hours between treatments.  No AEs were 
reported by any of the women. 
 Device Clinical Safety Study of 5% GML Applied Vaginally – Status: Analysis and 
Final Report in Preparation 
In this single-center, double-blind, parallel design, randomized study subjects (HIV negative, 
healthy, non-pregnant women) receive once 
 vaginal 5% GML or vehicle 
placebo gel for 
 
The primary objective of the study is to determine the safety of 
 of vaginal 
GML 
 by HIV negative, healthy women for 
 
  A secondary objective is to determine the tolerability and acceptability of a 5% GML 
vaginal gel. 
The primary endpoint of the study is to assess the effect of vaginal GML on 
 
 
 
The secondary endpoints are as follows: 
1) To assess the effect of GML on 
 
 
2) To determine the effect of vaginal GML on the 
as 
determined by 
 
 
3) To determine the acceptability and tolerability of vaginal GML based on
 
 
 
The protocol specifies enrollment of 
 women ages 18-45, 
 
  At the time of enrollment, women are randomized to either the treatment or placebo 
group. The treatment group receive a 
 vaginal applicator containing either 
 
 or 
 
 
For both groups, vaginal gels are administered 
 
 
Subjects return to clinic every 
 
  At Visits 
 
 
 
The primary endpoint is based on 
  A subject is declared 
 
 

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  A subject is required to 
 
 The secondary endpoints are based on 
 
 
 by the subjects. 
This study is currently in the process of being reported and results may be used to power definitive 
pivotal studies to contribute to a New Drug Application (NDA) filing. 
Initially, 7 women were enrolled and completed the study. These women consistently reported that 
 
 This 
was deemed 
 by study participants, and thus 
 
 
 
 
 The use of these 
 
 The 
study has recently been completed, and the data are presently being analyzed. 
 
 by any of the women. 
Hereafter, the gels referred to in this protocol will be identified as 5% Monolaurin Vaginal Gel, 
and Vehicle Placebo Gel, which has the same formulation except not containing 5% GML. 
2.2. 
Rationale 
Extensive in vitro data demonstrates the antimicrobial activity of monolaurin on the spectrum of 
microorganisms associated with BV, while having a favorable effect on eukaryotic membrane 
stability by modification of inflammatory response. 
New therapies for BV are needed and 5% Monolaurin Vaginal Gel has the potential to eradicate 
flora associated with BV while maintaining some of the normal flora that is considered protective 
for vaginal health, and with the added potential of preventing the emergence of vaginal candidiasis. 
This study is designed to evaluate the safety and provide early efficacy in treatment of women with 
BV. 
2.3. 
Potential Risks and Benefits 
2.3.1. 
Potential Risks 
There are no known safety pharmacology studies of GML’s effects on the cardiovascular and 
respiratory systems. However, GML has low systemic absorption making these toxicities less 
likely.[27] 
The initial nonhuman primate study exposing rhesus macaque monkeys to 5% GML gel (N=9), or 
vehicle (N=3) for 6 months provided evidence that prolonged gel exposure does not induce 
inflammation, supported by colposcopic biopsy data that showed that normal mucosal integrity 
was  maintained. GML reduced the early inflammatory production of interleukin 8 by vaginal 
epithelial cells, but the quantitative aerobic microflora did not differ between the 5% gel and the 
control gel, with no suppression of lactobacilli even with such prolonged daily exposure [30]. 

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An initial study in 36 women exposed to gels containing 0.5% (N=13), 5% (N=9), or 0% (N=14) 
GML every 12 hours for 2 days reported no AEs, and no negative effects on lactobacilli, while 
reducing Candida and Gardnerella vaginalis [29]. 
The only minor side effect noted was vaginal leakage. 
There may be other side effects from GML, even serious ones that are not yet known. There are no 
known risks of GML to pregnant women, fetuses, or infants of breastfeeding women. The risks are 
thought to be minimal due to GML’s low systemic absorption. However, the use of GML in 
pregnancy or breastfeeding may involve risks to the subject, fetus, or nursing infant that are 
currently unforeseeable. This study will exclude pregnant and breastfeeding women and ensure that 
women of childbearing potential take precautions to avoid pregnancy during the study. 
2.3.2. 
Known Potential Benefits 
Participation will contribute to the knowledge about the safety and early effects of the treatment on 
symptoms of BV and the changes in vaginal flora.  Subjects will receive a gynecological physical 
exam and routine laboratory tests to assess their health status. 
Society may benefit from the potential development of a new treatment for BV. 

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3. 
OBJECTIVES 
3.1. 
Study Objectives 
Primary Objectives: 
 
To assess the safety and tolerability of 5% Monolaurin Vaginal Gel compared to Vehicle 
Placebo Gel (excipients only). 
 
To assess the efficacy by clinical cure rate of 5% Monolaurin Vaginal Gel compared to 
Vehicle Placebo Gel at Visit 2. 
Secondary Objectives: 
 
To evaluate the therapeutic cure rate of 5% Monolaurin Vaginal Gel compared to Vehicle 
Placebo Gel at Visits 2 and 3. 
 
To evaluate the clinical cure rate of 5% Monolaurin Vaginal Gel compared to 
Vehicle Placebo Gel at Visit 3. 
 To evaluate the changes in Nugent’s criteria of vaginal bacterial flora at Visits 2 and 3. 
Exploratory Objectives: 
 To evaluate the clinical and therapeutic cure rates of 5% Monolaurin Vaginal Gel compared 
to Vehicle Placebo Gel for each subgroup (first episode BV and recurrent BV) at Visits 2 
and 3. 
 To evaluate quantitative changes in selected bacterial species at Visits 2 and 3. 
 To evaluate the quantitative changes of Candida spp (in subjects with Candida spp. 
identified at screening) at Visits 2 and 3. 
 
3.2. 
Study Outcome Measures 
3.2.1. 
Safety Outcomes 
All safety outcomes will be assessed in the safety analysis population of all subjects who received 
one or more doses of study product. Outcomes will be reported by treatment arm. 
 
 Primary Safety Outcome – 
 
Number of subjects reporting solicited urogenital AEs following the first dose 
of the study product through Visit 2 (Day 8-15). 
 
Number of subjects reporting serious adverse events (SAEs) considered product- 
related following the first dose of the study product through Visit 3 (Day 22-31) 
 
Secondary Safety Outcomes – 
 
Number of subjects experiencing non-laboratory non-solicited AEs following the 
first dose of the study product through Visit 3 (Day 22-31). 

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 
Number of subjects experiencing laboratory AEs following the first dose of the 
study product through Visit 2 (Day 8-15). 
3.2.2. 
Efficacy Outcomes 
3.2.2.1. 
Primary and Secondary Efficacy Outcomes 
 
 
Primary Efficacy Outcome – Proportion of subjects with clinical cure in each study arm at 
Visit 2 (Day 8-15). 
 
Secondary Efficacy Outcomes – 
 
Proportion of subjects with therapeutic cure in each study arm at Visit 2 (Day 8- 
15) and at Visit 3 (Day 22-31). 
 
Proportion of subjects with Nugent score of 3 or less (negative for BV) and 4-6 
(intermediate) in each study arm at Visit 2 (Day 8-15) and at Visit 3 (Day 22-31). 
 
Proportion of subjects with clinical cure in each study arm at Visit 3 (Day 22-31). 
3.2.2.2. 
Exploratory Efficacy Outcomes 
 
 
Proportion of subjects with clinical cure in each study arm by subgroup (first time or 
recurrent infection) by Visit 2 (Day 8-15) and by Visit 3 (Day 22-31). 
 
Proportion of subjects with therapeutic cure in each study arm by subgroup (first time or 
recurrent infection) by Visit 2 (Day 8-15) and by Visit 3 (Day 22-31). 
 
Mean count of Lactobacillus spp., Gardnerella spp., and Mobiluncus spp., respectively, 
in each study arm at baseline, Visit 2 (Day 8-15) and at Visit 3 (Day 22-31). 
 
Mean fungal colony count in vaginal secretions in each study arm at baseline, at Visit 2 
(Day 8-15) and at Visit 3 (Day 22-31). 

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4. 
STUDY DESIGN 
This is a Phase 2, double-blind, randomized, placebo-controlled, multi-center trial enrolling 120 
subjects with BV who will be randomized at a ratio of 2:1 to receive active test article (5% 
Monolaurin Vaginal Gel) or placebo (Vehicle Placebo Gel). There will be three clinic visits over 
31 days. 
The study will seek women 18-50 years old with signs and symptoms of BV.  Subjects may be 
identified during a routine clinic visit, referred by their care provider, or may be recruited directly 
to the research clinic.  For women recruited following a clinic visit, the study team may review the 
Amsel criteria with the nonstudy clinician, but the expectation is that these tests will be repeated by 
study personnel to document each component of the Amsel testing after the subject has signed an 
informed consent. 
Subjects will be educated about the study and will be asked to sign an informed consent prior to 
any evaluation. 
Eligibility will be reviewed and if subjects qualify for participation, demographics, a medical 
history, including number of episodes of BV in the past year, concomitant medications review, and 
a physical exam including a gynecological exam will be performed. Women of childbearing 
potential will undergo a urine pregnancy test. Vaginal swabs will be taken to perform a KOH test, 
vaginal pH, and to review a wet prep.  Subjects must have evidence of BV using the Amsel criteria 
(subjects must have any three of the four Amsel criteria:  presence of discharge, greater than or 
equal to 20% clue cells on wet prep, positive “whiff test” on KOH prep, vaginal pH of greater than 
4.5).  Vaginal swabs for Gram stain of vaginal smear, and assessment for Candida spp., selected 
bacterial species, Trichomonas vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae will 
be collected. Those with clinical evidence of active genital ulcer disease or evidence of 
trichomonas on wet prep or OSOM® test will be excluded from the study.  Blood samples will be 
collected for safety assessments (HIV, WBC count, hemoglobin, platelets, neutrophil count, 
creatinine, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, 
random glucose).  Subjects who continue to qualify for participation will be randomized at a ratio 
of 2:1 to receive 5% Monolaurin Vaginal Gel or Vehicle Placebo Gel administered vaginally 
morning and night for 6 consecutive doses (3 days).  All subjects will be provided a 5-day memory 
aid to assess for local solicited events with instruction on use prior to discharge. The 
investigational drug (active test article or placebo) will be supplied in a kit containing sufficient 
prefilled vaginal applicators for six consecutive doses over 3 days.  Subjects will be instructed on 
the proper use of the applicators and the first dose will be self-administered with observation by 
study personnel in the clinic.  Subjects will be instructed to refrain from sexual intercourse 
including receptive oral sex or insertion of substances or objects intravaginally between Visit 1 and 
Visit 2 and 48 hours prior to Visit 3.  Subjects who experience a new or worsening solicited 
reactogenicity symptom that is grade 2 or higher will be asked to contact the study site to confirm 
the severity.  A determination will be made whether to continue or discontinue the study product by 
a licensed study clinician.   No investigational or commercial agents or therapies other than test 
article may be administered with the intent to treat the subject for BV.  For all treatment groups, 
each subject will be evaluated in the clinic at screening and at Visit 2 (Day 8 [Window Days 8-15]) 
and Visit 3 (Day 28 [Window Days 22-31]) following study drug administration. 

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Visit 2 (Day 8 [Window Days 8-15]):  At this visit, the study team will review the memory aid, the 
intercurrent medical history with assessment of AEs and SAEs, changes to the concomitant 
medications, a gynecological exam and a targeted physical exam based on symptoms will be 
performed, and vaginal pH and vaginal swabs for Gram stain, saline wet mount, KOH 10% wet 
mount and culture will be obtained. If signs and symptoms of vaginitis fail to resolve, the study 
clinician will refer the subjects to their clinician for standard treatment for BV or other etiologies 
of vaginitis at the clinician’s discretion and the subject will be classified as a clinical failure at 
Visit 2 and/or 3.  Follow-up hematology and chemistry labs (WBC count, hemoglobin, platelets, 
neutrophil count, creatinine, AST, ALT, total bilirubin, random glucose) for safety evaluation will 
be performed. 
Visit 3 (Day 28 [Window Days 22-31]) will include a review of the intercurrent medical history, 
concomitant medications, AEs and SAEs, and a gynecological exam and a targeted physical exam 
based on symptoms. Vaginal pH and vaginal swabs for Gram stain, saline wet mount, KOH 10% 
wet mount and culture will be performed. 
Subjects who have positive HIV, Chlamydia, or Neisseria gonorrhoeae, or a grade 3 laboratory 
results from Visit 1 will be contacted within 24 hours of receipt of laboratory results and will be 
asked to follow up with their provider. These subjects will be asked to discontinue the study 
therapy if the test result returns during the study product administration period of the study. 
These subjects will continue in efficacy and safety follow up. 
At visits 1, 2 and 3, an extra vaginal swab will be collected for future use, if subject consents to 
future use of specimens. 
4.1. 
Substudies (if applicable) 
None 

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5. 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1. 
Subject Inclusion Criteria 
It is the intent of this study to enroll women who are generally healthy with evidence of BV on 
gynecological evaluation.  Subjects may have asymptomatic BV, but must meet any three of the 
four Amsel criteria for BV as defined in section 7.1.  Inclusion criteria must be assessed by a 
clinician licensed to make medical diagnoses.  Subjects must meet all of the following inclusion 
criteria to participate in this study: 
1. Non-pregnant, non-breastfeeding females between the ages of 18 and 50 years, 
inclusive. 
2. Women of childbearing potential* must agree to practice reliable contraception** 
for the 28-day period before enrollment through 30 days following treatment. 
*(not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy, or 
who have not been postmenopausal for ≥1 year) 
** Acceptable birth control methods for the purposes of this study may include, but are 
not limited to, abstinence from intercourse with a male partner, monogamous 
relationship with vasectomized partner, barrier methods to include condoms and 
diaphragms, intrauterine devices, and licensed hormonal methods.  NuvaRing® 
contraceptive use will be prohibited from this study since the device can alter vaginal 
secretions. 
3. Presenting with signs of BV (as per Amsel Criteria).  Subjects must meet any 
three of the four criteria for enrollment* 
*Presence of discharge, greater than or equal to 20% clue cells on wet prep, positive 
“whiff test” on KOH prep, vaginal pH of greater than 4.5. 
4. Not currently menstruating or expected to in the next 4 days. 
5. Able to understand and comply with planned study procedures. 
6. Willing to abstain from sexual intercourse, insertion of tampons, douches, or other 
intravaginal medications or objects between Visit 1 and Visit 2 and 48 hours prior to 
Visit 3. 
7. Provide written informed consent before initiation of any study procedures and be 
available for all study visits. 
8. No known history of HIV. 
5.2. 
Subject Exclusion Criteria 
Subjects who meet any of the exclusion criteria at Visit 1 will be excluded from study 
participation.  Exclusion criteria must be assessed by a clinician licensed to make medical 
diagnoses.  Subjects will not be able to participate if they have any of the following: 
 

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1. Signs or symptoms of vaginal/cervical/pelvic infection on screening or clinical 
diagnosis of vaginal/cervical/pelvic infection in the past 14 days.  
*(including but not limited to yeast vulvovaginitis, chlamydia, gonorrhea, trichomonas, 
genital ulcer disease, pelvic inflammatory disease).  Self-treatment for presumed yeast 
vaginitis is not an exclusion if treatment was discontinued 7 days or greater prior to 
enrollment. 
2. Treatment for BV within the past 14 days. 
3. Cervical or vaginal high grade squamous intraepithelial dysplasia (HSIL), atypical 
glandular cells of uncertain significance (AGUS) or cervical intraepithelial neoplasia 
grade 2 (CIN2) or higher* 
*Atypical squamous cells of undetermined significance (ASCUS), low grade squamous 
intraepithelial lesion (LSIL) or cervical intraepithelial neoplasia grade 1 (CIN1) are 
acceptable. Individuals with a history of atypical glandular cells of uncertain significance 
(AGUS), HSIL or CIN2 and who have received subsequent evaluation and/or treatment 
with follow up normal PAP smear are eligible. Patient report will be accepted. 
4. History of undiagnosed vaginal bleeding. 
5. Use of a systemic, vaginal, or perineal antibiotic within 7 days prior to enrollment in 
this study. 
6. Use of an immunosuppressive or immunomodulatory drug* for two or more 
consecutive weeks within 6 months prior to enrollment 
*such as >0.5 mg/kg/day or ≥20 mg total dose/day of prednisone orally or >800 μg of 
inhaled beclomethasone (nasal and non-genital topical steroids are allowed). 
7. History of allergic reactions attributed to compounds of similar chemical or 
biologic composition to Monolaurin Vaginal Gel. 
8. Uncontrolled concurrent illness*.  Subjects with  a history of organ or marrow 
transplant are excluded. 
*Including, but not limited to, ongoing or active infection, active liver, kidney or 
autoimmune diseases (a history of thyroid disease will be permitted as long as the 
thyroid disease is now stable), symptomatic congestive heart failure, unstable angina 
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit 
compliance with study requirements. 
9. Acute illness within 3 days before receipt of study product (per investigator’s 
discretion). 
10. Pregnant women and women who are planning to become pregnant within 30 days 
after the final study dose, or women who are breastfeeding. 
11. Immunosuppression as a result of an underlying illness or treatment or use of 
anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 
months. 
12. Active neoplastic disease* or a history of any hematologic malignancy.  Active 
neoplastic disease is defined as neoplastic disease or treatment for neoplastic disease 
within the past 5 years. 

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*(excluding non-melanoma skin cancer) 
13. Received an experimental agent* within 30 days before receipt of study product or 
expect to receive an experimental agent during the 1 month study period. 
*(vaccine, drug, biologic, device, blood product, or medication) 
14. Any condition that would place the subject at an unacceptable risk of injury, render her 
unable to meet the requirements of the protocol, or that may interfere with successful 
completion of the study. 
15. A history of alcohol or drug abuse* during the previous 1 year that in the opinion of 
the site investigator would interfere with study procedures 
*For example, daily excessive alcohol use or frequent binge drinking as determined by 
the investigator, or daily marijuana use. 
5.3. 
Treatment Assignment Procedures 
Subjects, study site and laboratory personnel will be masked to the treatment assignments of study 
subjects. 
5.3.1. 
Randomization Procedures 
Subjects will be randomly assigned to active drug or placebo in a 2:1 ratio.  Subjects will be 
stratified by clinical site. 
The list of randomized treatment assignments will be prepared by statisticians at the Emmes 
Corporation and included in the enrollment module of the Emmes Corporation’s Internet Data 
Entry System (IDES). IDES will assign each volunteer a treatment code from the list after 
demographic and eligibility data have been entered into the system.  A designated individual at 
each site will be provided with a treatment key, which links the treatment code to the actual 
treatment assignment, which will be kept in a secure place. 
Instructions for use of the enrollment module are included in the IDES User’s Guide.  Manual 
back-up randomization procedures are provided in the Manual of Procedures (MOP) for use in the 
event that the site temporarily loses access to the Internet or the online enrollment system is 
unavailable. 
5.3.2. 
Masking Procedures 
The applicators of vaginal gels will be selected by the unmasked Site Research Pharmacist or 
designated unmasked study personnel and will be distributed to masked study personnel with no 
labels that identify the product or applicators to the site as Monolaurin Vaginal Gel or Vehicle 
Placebo Gel. 
The volunteers, the study personnel who perform study assessments after administration, data 
entry personnel at the sites, and laboratory personnel will be masked to treatment assignment. The 
Data and Safety Monitoring Board (DSMB) may receive data in aggregate and presented by 
treatment group. The DSMB may be unmasked to individual study treatment assignments,  as 
needed, to adequately assess safety issues. Refer to the MOP for unmasking procedures. 

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5.3.3. 
Reasons for Withdrawal 
Any enrolled subject may withdraw or be withdrawn from the study for the following reasons: 
 
The subject withdraws consent 
 
The study is terminated 
 
For any reason that, in the opinion of the investigator, precludes the subject's participation in 
the study 
 
The subject no longer meets inclusion/exclusion criteria 
 
The subject develops an SAE that warrants withdrawal 
 
Other safety-related reasons at the discretion of the Principal Investigator (PI), DMID 
Medical Monitor, DSMB, or the subject 
Any subject who has received at least one dose of study drug will be continued in efficacy and 
safety follow-up, if the subject agrees. 
Subjects who test positive for chlamydia, gonorrhea, HIV, or are incidentally found to have a PAP 
result consistent with AGUS or HSIL, or have a Grade 3 laboratory abnormality will be 
discontinued from receiving study product if the result is available within the 3 days of study drug 
administration. They will be continued in follow up for safety and efficacy if they have received 
one dose of study drug. (PAP smears are not part of the study protocol, but may have been done 
outside of the study protocol by the subject’s provider. Patient report of PAP smear abnormalities 
may be accepted as a criterion for discontinuation of study product).  
If a subject develops a grade 3 laboratory abnormality while still receiving study product, they will 
be contacted and asked to discontinue study product and will be continued in safety and efficacy 
follow up. If any subject experiences a severe AE related to the study product, further doses will be 
discontinued.  Additionally, subjects who experience a new or worsening solicited reactogenicity 
symptom that is grade 2 or higher will be asked to contact the study site to confirm the severity.  A 
determination will be made whether to continue or discontinue the study product by a licensed 
study clinician.  A subject who withdraws voluntarily from or has been discontinued from 
receiving further treatment will be encouraged to permit continued follow-up of AEs and to follow 
scheduled visits.  If the subject agrees, study procedures (e.g., blood sampling for safety and 
vaginal sampling) may be continued. 
Subjects may withdraw from participation in the study at any time.  If a subject withdraws or is 
withdrawn prior to completion of the study, the reason for this decision must be recorded in the 
case report forms (CRFs).  Refer to Section 7.4 for procedures to be followed if a subject 
withdraws from the study. 
5.3.4. 
Handling of Withdrawals 
In the case of subjects who fail to appear for a follow-up assessment, extensive efforts (i.e., 
documented phone calls and certified mail) should be made to locate or recall them, or at least to 
determine their health status. These efforts should be documented in the subjects' records and their 
health status documented in the appropriate CRF. If a subject is withdrawn prior to completion of 
the study, the subject will not be replaced. 
 

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5.3.5. 
Termination of Study 
The NIAID/DMID has the right to terminate this study at any time.  Reasons for terminating the 
study may include, but are not limited to, the following: 
 
Incidence or severity of AEs indicating a potential health hazard 
 
Data recording is inaccurate or incomplete 
 
The Investigator has not been adhering to the protocol or applicable regulatory guidelines in 
conducting the study 

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6. 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
6.1. 
Study Product Description 
Monolaurin (GML) 
Monolaurin, also commonly referred to as GML, is a monoglyceride surfactant.  It is an ester 
formed from glycerol and lauric acid.  Monolaurin Vaginal Gel is a clear, colorless, non-sterile 
glycol-based gel for vaginal administration. 
FDA recognizes monoglycerides, such as monolaurin, as direct food substances that are generally 
recognized as safe (GRAS) (21 CFR 184.1505).  Monolaurin is also considered safe as an 
ingredient in cosmetics and tampons (e.g., o.b.® optiBalance).  As stated, monolaurin is 
commercially available as a food grade substance from several suppliers.  HLS will use 
 
 
 for the initial Investigational New Drug Application (IND) phase 2 clinical 
trials. 
This formulation promotes rapid drug distribution, as well as adequate coverage, throughout the 
vaginal cavity.  The acidic pH keeps monolaurin in its non-ionized form in the vagina. 
Monolaurin, which is practically insoluble in water, is highly soluble in this formulation. 
Vehicle Placebo Gel 
The Vehicle Placebo Gel utilizes the same vehicle formulation as used in the Monolaurin Vaginal 
Gel. 
6.1.1. 
Acquisition 
5% Monolaurin Vaginal Gel and Vehicle Placebo Gel will be provided by Hennepin Life Sciences. 
Upon request by DMID, the investigational product will be transferred to the following address: 
DMID-Clinical Agents Repository 
Contract Fisher BioServices 
20439 Seneca Meadows Parkway 
Germantown, MD, 20876 
Tel: (240) 477-1350 
Fax: (240) 477-1360 
Email: DMID.Car@ThermoFisher.com 
 
Study product will be shipped to the investigational sites upon request and approval by DMID. 
6.1.2. 
Formulation, Packaging, and Labeling 
The vaginal gel applicators will be packaged as a kit sufficient for twice daily administration for 3 
consecutive days (six applicators).  Each vaginal gel dispensing kit will be individually labeled 
with the protocol number, dosing instructions, recommended storage conditions, the name and 
address of the manufacturer, the kit number, Investigational Use Statement (“Caution: New Drug – 

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Limited by Federal [USA] Law to Investigational Use”) and that the agent should be kept out of 
reach of children. 
6.1.2.1. 
5% Monolaurin Vaginal Gel 
 
Monolaurin Vaginal Gel is a clear and colorless non-sterile glycol-based gel for vaginal 
administration.  Monolaurin Vaginal Gel is comprised of 5% monolaurin and the following 
excipients: 
 
 
Active test article will be comprised of 5% monolaurin prepared as pre-filled vaginal gel 
applicators of identical likeness to placebo. The components of the applicator are biocompatible 
and latex-free. 
6.1.2.2. 
Vehicle Placebo Gel 
The Vehicle Placebo Gel is a clear to opaque, colorless to light gray, non-sterile glycol-based gel 
for vaginal administration and contains the following: 
 
 
 The Vehicle Placebo Gel contains the same excipients as the active product. 
The Vehicle Placebo Gel will be comprised of the identical vehicle contained in the active test 
article prepared as pre-filled vaginal gel applicators of identical likeness to active test article. The 
components of the applicator are biocompatible and latex-free. 
6.1.3. 
Product Storage and Stability 
Vaginal applicators containing active test article or placebo will be stored at room temperature (15-
30°C.) with transient spikes up to 40°C permitted if they last less than 24 hours. 
6.2. 
Dosage, Preparation and Administration of Study 
Intervention/Investigational Product 
Preparation 
No formal preparation is required for the study product. The unmasked Research Pharmacist or 
designated unmasked study personnel maintaining the study product accountability will select the 
appropriate kit based on the randomization scheme and will label the kit with the subject’s name, 
subject ID number, treatment number, and any other hospital required identifying information. 
Administration 
Study personnel will provide both verbal and written instructions for proper storage and 
administration. The first dose will be administered by the subject while the subject is still in  
clinic.  The remaining 5 doses will be administered twice daily (morning and evening) with at least 
8 hours between doses by the subject at home. If the subject received her first dose after 3 pm, she 
will be instructed to administer the next dose the following morning. 

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Dose of Study Agents/Interventions 
Active test article will be composed of 5 mL of 5% Monolaurin Vaginal Gel prepared as pre-filled 
vaginal gel applicators of identical likeness to placebo. Vehicle Placebo Gel will contain 5 mL of 
the vehicle used in the active test article. 
6.3. 
Modification of Study Intervention/Investigational Product for a 
Participant 
If a subject is found to have a positive test for HIV, chlamydia or gonorrhea or Grade 3 laboratory 
abnormality from Visit 1, she will be notified of the results, withdrawn from receiving further 
study product, but will be followed for safety and efficacy.  All subjects who have received even a 
single dose of study drug will be followed for safety and efficacy. 
If any subject experiences a severe AE related to the study product, further doses will be 
discontinued. 
If the subject misses a dose, she should note the missed dose on the memory aid, save the unused 
applicator, and resume dosing at the next recommended scheduled dose. 
6.4. 
Accountability Procedures for the Study Intervention/Investigational 
Product(s) 
The unmasked Research Pharmacist will be responsible for maintaining complete records and 
documentation of study product receipt, accountability, dispensation, storage conditions, and final 
disposition of the study product. All study products, whether administered or not, must be 
documented on the appropriate study product accountability record or dispensing log. 
Study personnel will document on the CRF the time of the application of the first study dose. The 
first dose applicator may be discarded.  Subjects will be instructed to return the kit (containing 
used and/or unused vaginal applicators) to study personnel at the clinic for Visit 2. The used kit 
and applicators will be placed in a sealed plastic bag for transport to the study site. Once the study 
personnel have verified the test article accountability, the kits and used applicators may be 
discarded in an appropriate medical waste container. 
Upon completion or termination of the study and after the final monitoring visit, any remaining 
unused study product will either be returned or destroyed appropriately at the clinical site as per 
Sponsor requirements and instructions. 
6.5. 
Assessment of Subject Compliance with Study 
Intervention/Investigational Product 
Study personnel will count the number of used/unused applicators contained in each returned 
subject kit and record this information in the test article accountability section of the subject’s 
CRF. 

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6.6. 
Concomitant Medications/Treatments 
Administration of any medications, therapies, or vaccines will be documented in the subject’s 
source documentation and reported on the subject’s data acquisition screen.  Concomitant 
medications will include all medications, vitamins, and supplements taken within the 30 days 
before enrollment and through Visit 3 (Day 28) or early termination, whichever occurs first. 
Each subject will be instructed to not use any systemic, vaginal, or perineal antibiotic, antifungal, 
immunosuppressant, or anti-inflammatory medication except oral nonsteroidal anti-inflammatory 
medication during study participation from study Day 1 through Visit 3 unless absolutely 
necessary. 
Treatment with any prescription medication(s), over-the-counter preparations and non- prescription 
medication(s) intended to treat the subject for vaginosis will be used only if subject is considered a 
clinical failure.  In this case, she will be referred to her provider for standard of care treatment.  All 
treatment medications must be documented on the concomitant medications CRF. 

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7. 
STUDY SCHEDULE 
7.1. 
Screening and Enrollment (Visit 1, Day 1) 
Subjects should be scheduled for visits when they are not menstruating and instructed to avoid 
inserting any substance into the genital tract for 48 hours before examination at Visit 1, when 
possible.  Subjects may present after having clinical evaluation by a non-study clinician or may 
present to the research clinic directly. 
The following procedures will be performed: 
 
Obtain signed informed consent. This should be performed prior to conducting any of 
the assessments listed below. 
 
Review inclusion/exclusion criteria and collect demographic information. 
 
Obtain medical history and concomitant medications (prescription and over-the-counter 
drugs, supplements, and vitamins taken 30 days prior to enrollment will be reviewed and 
documented). 
 
Review of contraceptive methods and recent menstrual history. 
 
Review sexual history. 
 
Review subject report of history of previous episodes of BV and if noted, the number of 
episodes of BV in the previous 12 months and treatments given. 
 
Assessment of current symptoms of BV 
 
Perform physical exam. 
 
Perform urine pregnancy test for female subject of childbearing potential prior to pelvic 
exam.  Must be negative prior to receipt of study drug. 
 
Gynecologic exam for evaluation of the cervix, vagina, and vulva: 
 
Assessment for genital tract infections and lesions.  If evidence of active lesions 
consistent with herpes simplex virus infection or other sexually transmitted 
infection (e.g., syphilis), subject will be excluded and may be referred to her 
provider for further management. 
 
Document vaginal discharge (quantity, color, odor, and consistency). 
 
Document objective signs of inflammation (edema, erythema, excoriation). 
Inspection and appearance of the cervix, vagina, and vulva, and document 
presence or absence of objective signs of inflammation (edema, erythema, 
excoriation). 
 
Document vaginal secretion pH testing using pH paper 4-6. 
 
Saline “wet mount” for microscopic examination (performed by licensed 
clinician or laboratory staff certified or trained to read vaginal wet mounts): 
 Document the presence of and percentage of cells that are “clue cells.” 

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 
If motile flagellated protozoa are seen, the subject will be excluded from 
participating in the trial and referred to her provider to be treated using 
established standards. 
 
KOH 10% “wet mount” for microscopic examination (performed by licensed 
clinician or laboratory staff certified or trained to read vaginal KOH 
preparations): 
 
Document presence or absence of fishy odor on “whiff test”: fishy 
(amine) odor released by the addition of a drop of 10% KOH to the 
vaginal discharge. 
 
Document presence of pseudohyphae or budding spores. 
The subject will be enrolled based on demonstration of any three of the four following Amsel 
criteria: 
 
Off-white (milky or gray), thin, homogenous discharge with minimal or 
absent pruritus or inflammation of the vulva or vagina. 
 
≥20% “Clue” cells of total epithelial cells on microscopic examination of 
saline wet mount. 
 
Vaginal secretion pH >4.5. 
 
Positive “whiff test”. 
***If the subject does not meet clinical criteria (based on Amsel criteria) for BV, she will not 
have further vaginal sampling performed and will not proceed to randomization and will not 
receive study drug. 
If subject demonstrates evidence of BV: 
For those subjects who have evidence of BV based on the above criteria and continue to meet 
inclusion/exclusion criteria, samples will be collected in the following order: 
 
Vaginal swabs for the following: 
 
Gram stain of vaginal smear (local laboratory preparation and shipment to the 
University of Iowa Clinical Pathology Laboratory). 
 
Culture or molecular testing for the following will be taken: 
 
OSOM® rapid Trichomonas testing. OSOM testing is required if the 
wet prep shows no evidence of motile flagellated protozoa.  If the wet 
prep was positive for motile protozoa, then the diagnosis of trichomonas 
has already been confirmed and OSOM testing is not required.  If 
positive for Trichomonas, the subject will be excluded from 
participating in the trial and referred to her provider to be treated using 
established standards. 
 
Bacteria and Candida species (to be sent to the Central Laboratory). 
 
Chlamydia trachomatis - testing should be performed as per local standards 
(to be sent to the Local Clinical Pathology Laboratory). If study subject 
has had Chlamydia trachomatis testing performed within the past 5 days 

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and it was negative or is still pending, this data may be used for screening.  
Vaginal swab testing is the preferred method for testing in this study, but if 
urine testing has been done within the past 5 days, this is acceptable. If 
Chlamydia testing is positive, the subject will be contacted by telephone 
and letter and referred to her provider for further management. 
 
Neisseria gonorrhoeae - testing should be performed as per local 
standards (to be sent to the Local Clinical Pathology Laboratory). If 
study subject has had Neisseria gonorrhoeae testing performed within 
the past 5 days and it was negative or is still pending, this data may be 
used for screening.  Vaginal swab testing is the preferred method for 
testing in this study, but if urine testing has been done within the past 5 
days, this is acceptable.   If gonorrhea testing is positive, the subject will 
be contacted by telephone and letter and referred to her provider for 
further management. 
 
Future Use: If the subject consents to future use, one Copan ESwab in liquid 
amies will be collected for future use (to be transported on cold packs or ice to 
the research laboratory). 
 
Obtain approximately 15 cc of blood to be sent to the local Clinical Pathology Laboratory 
for WBC count, hemoglobin, platelet, neutrophil count, creatinine, AST, ALT, total 
bilirubin, random glucose, and HIV testing.  If HIV testing has been performed within the 
past 5 days and was negative or is still pending, this test can be used for screening. 
 
Once all samples have been obtained, the subject will be enrolled in IDES and randomly 
assigned to a treatment group. 
 
Subjects will be counseled on proper administration and storage of the vaginal gel. 
 
Subjects will self-administer the first dose of the investigational vaginal gel or 
vehicle placebo gel with observation by study personnel while in the clinic using the 
first applicator in the assigned study kit. 
 
Subjects will receive 5 further doses (vaginal applicators with instructions) for self- 
administration twice-daily (morning and evening) with at least 8 hours between doses. 
 
Subjects will be instructed to return used applicators to the disposal bag provided in the 
kit to return to the clinic at Visit 2 (between Study Days 8-15). 
 
Review for AEs/SAEs 
 
Provide counseling to refrain from penile-vaginal or receptive oral sexual intercourse or 
insertion of any substance (other than study product), products, or objects between Visit 
1 and Visit 2 and 48 hours prior to Visit 3. 
 
Provide memory aid and instruct subject on how to complete the memory aid for 5 
days from the first day of therapy. 
 
Counsel subjects on avoidance of pregnancy (for all female subjects of childbearing 
potential). 
*If a subject’s laboratory results show a positive gonorrhea, chlamydia, HIV test or grade 3 
abnormality, study personnel will contact the subject to inform her of the results and instruct 

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her to discontinue study treatment. Telephone contact is the preferred method of contact, 
though initial contacts may include other forms of communication with follow-up discussions 
provided by telephone or in person. 
7.2. 
Visit 2 (Day 8 [Window: Days 8-15]) 
All subjects will return for Visit 2 on Day 8 (Window: Days 8-15) at which time the following 
assessments will be performed. 
 
Review changes in medical history: 
 
Review symptoms of BV since Visit 1 and treatments for BV other than 
investigational drug. 
 
Review all concomitant medications since Visit 1. 
 
Review for sexual intercourse, insertion of intravaginal substances, or objects since Visit 
1. 
 
Review for AEs and SAEs. 
 
Review Memory Aid and collect applicator kit. 
 
Perform targeted general physical exam based on symptoms. 
 
Perform gynecologic exam of cervix, vagina, and vulva: 
 
Assessment of vaginal discharge (quantity, color, odor, and consistency). 
 
Record presence or absence of objective signs of inflammation of cervix, vagina and 
vulva (edema, erythema, excoriation) and presence or absence of lesions. 
 
Collect vaginal secretions for pH testing using pH paper 4-6. 
 
Perform KOH 10% wet mount on vaginal (must be performed by a licensed clinician or 
trained laboratory personnel) and record “whiff test”: fishy (amine) odor released by the 
addition of a drop of 10% KOH to the vaginal discharge. 
 
Evaluate for pseudohyphae or budding spores (must be performed by a licensed 
clinician or trained laboratory personnel). 
 
Perform saline wet mount (must be performed by a licensed clinician or trained 
laboratory personnel). 
 
Evaluate and record presence and percent of ‘Clue’ cells in vaginal secretions. 
 
Record for presence of flagellated protozoa (if positive, refer to provider for 
further therapy). 
 
Collect vaginal swabs for: 
 
Gram stain of vaginal smear. 
 
Swabs for culture of Gardnerella spp., Mobilluncus spp., Lactobacilli 
spp., Candida spp. 
 
Future Use: If the subject consents to future use, one Copan ESwab in liquid 
amies will be collected for future use (to be transported on cold packs or ice to 
the research laboratory). 

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 
Obtain approximately 10 cc of blood for: 
 
WBC count, hemoglobin, platelet, neutrophil count. 
 Creatinine, ALT, AST, total bilirubin, random glucose. 
 
Counsel subjects to refrain from penile-vaginal or receptive oral sexual intercourse or 
insertion of any substance, products, or objects into vagina for 48 hours prior to Visit 3. 
 
Counsel subjects on avoidance of pregnancy (for all female subjects of childbearing 
potential). 
 
Subjects will be counseled to come in for an unscheduled visit if their vaginitis symptoms 
recur/worsen between Visit 2 and 3. 
 
Document Investigator assessment of clinical cure. 
If the signs and symptoms of BV fail to resolve and further treatment is required (in the 
Investigator’s opinion), the subject will be referred to her provider for standard treatment. Therapy 
will be recorded on the appropriate source document and electronic CRF (eCRF) pages and the 
subject will be followed through Visit 3 for safety.  At Visit 3, these subjects will be classified as a 
clinical failure. 
7.3. 
Visit 3, Final Study Visit (Day 28 [Window: Days 22-31]) 
All subjects will return for Visit 3 on Day 28 (Window: Days 22-31) at which time the following 
assessments will be performed: 
 
Review changes in medical history. 
 
Review all concomitant medications since Visit 2. 
 
Review of BV symptoms and treatments for BV other than investigational drug. 
 
Review history of sexual intercourse, insertion of intravaginal substances or objects 
within the past 48 hours. 
 
Review Memory aid if solicited events continued at last visit and collect applicator kit, 
if not done at Visit 2. 
 
Review AEs/SAEs:  If AEs or SAEs continue at Visit 3, the study team will follow until 
resolution or stabilization of the event.  Laboratory abnormalities that were stable at Visit 
2 (i.e., were abnormal at Visit 1 prior to receipt of study drug and continued to be 
abnormal but no worse at Visit 2) do not need to be repeated and are considered 
stabilized.  Laboratory abnormalities that occurred between Visit 1 and Visit 2 or 
worsened at Visit 2 should be repeated until the test has stabilized or resolved. 
 
Perform targeted general physical exam based on symptoms. 
 
Gynecologic exam of cervix, vagina, and vulva: 
 
Assessment of vaginal discharge (quantity, color, odor, and consistency) 
 
Assess cervix, vagina, and vulva for presence or absence of objective signs of 
inflammation (edema, erythema, excoriation) and/or genital lesions. 
 
Collect vaginal secretions for pH testing using pH paper 4-6. 

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 
Perform KOH 10% wet mount on vaginal secretions (performed by licensed clinician 
or trained laboratory personnel) 
 
Record “whiff test”: fishy (amine) odor released by the addition of a drop of 10% 
KOH to the vaginal discharge. 
 
Evaluate for pseudohyphae or budding spores (performed by a licensed clinician or 
trained laboratory personnel). 
 
Perform saline wet mount (performed by a licensed clinician or trained laboratory 
personnel). 
 
Evaluate and record presence and percent of “clue cells” in vaginal secretions. 
 
Record for presence of flagellated protozoa (if positive, refer to provider for further 
therapy). 
 
Collect vaginal swabs for: 
 
Gram stain of vaginal smear 
 
Swabs for culture of Gardnerella spp., Mobilluncus spp., Lactobacilli spp., and 
Candida spp. 
 
Future Use: If the subject consents to future use, one Copan ESwab in liquid amies will 
be collected for future use (to be transported on cold packs or ice to the research 
laboratory).  Document Investigator assessment of clinical cure. 
7.4. 
Early Termination Visit 
For subjects who are withdrawn from the study early, follow-up assessments will be completed 
according to the protocol schedule, if possible, including review of concomitant medications, 
history of sexual intercourse, insertion of intravaginal substances or objects and BV symptoms, 
gynecological exam, targeted physical exam if indicated based on symptoms, review of clinical 
cure, blood for WBC count, hemoglobin, platelet, neutrophil count, creatinine, AST, ALT, total 
bilirubin, random glucose), vaginal sampling (wet mount, KOH preparation, and vaginal swabs for 
Gram stain, culture of Gardnerella, Mobiluncus, Lactobacillus and Candida spp.), return of 
applicator kit (if applicable) and reason for termination or withdrawal.  If subject declines to return 
for an in-person visit, the study personnel will seek permission to contact the subject by telephone 
22-31 days from introduction of treatment to assess for AEs and SAEs.  If subject continues to 
have signs and symptoms of BV or other genital infections, she will be referred to her provider for 
further management. 
7.5. 
Unscheduled Visit 
Unscheduled visits may occur at any time during the study. The procedures below are to be 
performed at any unscheduled visit.  See the MOP for instructions for documentation and data 
reporting. 
 
Obtain interim medical history and solicit information on vaginal symptoms. 
 
Perform a targeted physical exam if indicated based on symptoms. 
 
Perform gynecological exam and collect appropriate samples (e.g., appropriate clinical 
samples for genital infectious pathogens). 

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 
Review concomitant medications. 
 
Review of memory aid, if applicable. 
 
Review of AEs/SAEs, if applicable. 

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8. 
STUDY PROCEDURES/EVALUATIONS 
8.1. 
Clinical Evaluations 
Medical History: Will be obtained by interview of the subjects prior to randomization.  Subjects 
will be queried regarding a history of significant medical disorders of the head, eyes, ears, nose, 
throat, mouth, cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney, nervous 
system, blood, lymph glands, endocrine system, musculoskeletal system, skin, and 
genital/reproductive tract.  A history of any allergies, cancer, immunodeficiency, psychiatric 
illness, substance abuse, and autoimmune disease will be solicited. 
Concomitant Medications:  All current medications and medications taken in the 30 days before 
enrollment (prescription and over-the-counter drugs, supplements and vitamins) will be included 
through Visit 3 (Day 28) after enrollment.  Assessment of eligibility also will include a review of 
prohibited medications (per the exclusion criteria). 
Physical Examination:  This examination will be conducted at Visit 1 and will assess general 
appearance the following areas/symptoms: skin, inguinal lymph nodes, head, eyes, ears, nose, 
throat, neck, respiratory, cardiovascular, abdomen, extremities, musculoskeletal, and neurological. 
Gynecological Examination: This examination will be conducted at each visit and will assess for 
presence of discharge, appearance of the cervix, vulva, and vaginal mucosa, and presence of 
specific lesions.  Bimanual exam is not required, but may be performed at the discretion of the 
licensed clinician. 
Targeted Physical Examination: This may be conducted at any study visit based on interim 
medical history. 
Solicited Events Assessments:  Study personnel will take a brief history of subjects for assessment 
of AEs. This will include genital signs and symptoms of odor, pain, tenderness, discharge, 
swelling, itching, and dryness. 
8.2. 
Laboratory Evaluations 
8.2.1. 
Clinical Laboratory Evaluations 
Clinical laboratory evaluations will be performed by the local Clinical Pathology Laboratory. 
Specific tests to be performed are described below: 
 
HIV testing will be performed as per local standards (performed at Visit 1 only).  It 
is recommended that an antibody or antibody/antigen test be used for screening. If 
antibody or antibody/antigen testing results in an indeterminate test, HIV PCR may 
be used to further evaluate the HIV status of the subject. 
 
Hematology includes: WBC count, hemoglobin, platelet, neutrophil count. 
 
Clinical chemistry includes:  creatinine, AST (SGOT), ALT (SGPT), and total 
bilirubin, and glucose (random). 
 
Urine Pregnancy test: Urine pregnancy test in females of childbearing potential will 

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be performed in the research clinic, local clinical care clinic or Local Pathology 
Laboratory.  Result must be negative within 8 hours before first administration of 
study product. 
 
Sexually transmitted infection testing: Testing for Chlamydia trachomatis and 
Neisseria gonorrhoeae. Samples will be obtained and processed as per local clinic 
guidelines and will be sent to the site Clinical Pathology Laboratory.  Either culture or 
molecular testing for Neisseria gonorrhoeae and chlamydia is acceptable. 
Trichomonas testing using wet preps may be performed in the clinic as per local 
clinic guidelines. The OSOM® rapid Trichomonas testing will be performed on all 
subjects who do not have Trichomonas identified on wet prep at screening. 
One or more of the laboratory parameters may be repeated at any time during the study as 
determined by the Investigator, if indicated by an AE. Grade 3 abnormal laboratory values should 
be repeated within 10 days if possible and followed up as clinically relevant. 
8.2.2. 
Special Assays or Procedures 
Vaginal Swabs (Please refer to MOP for details on vaginal swab collection) 
The study coordinator or investigator will label the tubes with a unique identification number and 
store the vaginal swabs inside the supplied transport tubes in an insulated cooler with cold packs or 
placed in the refrigerator (2-8°C) within 1 hour of collection. The swabs will be packaged in 
accordance with the federal shipping guidelines for diagnostic biological material. A reconciliation 
system will be used to facilitate tracking of vaginal swab specimens. For    subjects enrolled at the 
Cincinnati Children’s Hospital Medical Center and Duke University School of Medicine vaginal 
swabs will be shipped within 24 hours of collection by overnight delivery on Monday through 
Thursday using cold packs in a Styrofoam container to the designated central laboratory.  For 
subjects enrolled at the University of Iowa, specimens will be transported by hand to the central 
laboratory Monday through Friday. If transported within 1 hour of collection, the samples may be 
transported at room temperature. If the time exceeds 1 hour after collection, the samples should be 
transported in an insulated cooler with cold packs. 
If the subject consents to future use, a vaginal swab will be collected for future use.  A Copan 
ESwab in liquid amies will be used to swab the vaginal walls.  The study coordinator or 
investigator will label the tubes with a unique identification number. Once collected the swab will 
be broken off in the transport tube that contains the liquid amies solution and will be transported 
on cold packs or ice to the research lab within 1 hour of collection.  In the research laboratory, the 
tube should be vortexed for 5 minutes and then using sterile procedures with sterile pipets, aliquot 
the liquid amies solution into three cryovials that have been labeled with global trace bar codes. 
Gram stain Assay (University of Iowa) 
Slides will be fixed using the SOP for using CytoPrep fixation (see the MOP) at the local site from 
vaginal swabs collected from every subject at Visits 1, 2 and 3 for central scoring. The fixed slide 
will be sent to the University of Iowa VTEU team where they will be transported to the University 
of Iowa Clinical Pathology Laboratory for staining and analysis. The smear will be evaluated for 
bacterial morphotypes and interpreted in accordance with Nugent's criteria 

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(relative populations of the morphotypes Lactobacillus, Gardnerella, Bacteroides, 
Peptostreptococcus, and Mobiluncus spp. [11]) using the standardized 0-10 point scoring system to 
interpret the Gram stain results as follows: 
 
0-3 classified as normal/no BV detected 
 
4-6 classified as intermediate 
 
7-10 indicative of BV 
 
Each stained slide will be read by two independent observers who will be masked to the other’s 
results.  Discordant results (results that differ in the absolute Nugent score) will be re-reviewed by 
the initial two readers to reach a consensus.  If a consensus cannot be reached, the slide will be 
reviewed by a third observer to resolve the discrepancy.  A single Nugent score value will be 
recorded. 
The same Gram stained slides used to assess the presence of bacterial morphotypes will also be 
evaluated for the presence of yeast by using the 100x objective.  A categorical score will be 
assigned to each specimen slide, after the reader viewed and examined the entire area of each 
stained slide to determine the presence or absence of yeast cells showing blastoconidia (cell buds). 
8.2.3. 
Specimen Preparation, Handling, and Shipping 
Instructions for specimen preparation, handling, storage, and shipping are included in the MOP. 
8.2.3.1. 
Instructions for Specimen Preparation, Handling, and Storage 
After collection, study required vaginal swab tubes will be placed at 2-8°C within 1 hour of 
collection and stored at 2-8°C until shipped. If subjects have consented to future use, the future 
use vaginal swabs will be transported on cold packs or ice to the research laboratory where they 
will be vortexed for five minutes and then aliquoted into three cryovials that will then be frozen at 
-70 C or colder. 
8.2.3.2. 
Specimen Shipment 
Prior to transport, vaginal swab tubes containing specimens (which have been stored at 2-8°C) will 
be placed in a small plastic bag with a handful of cotton balls, and then placed in a Styrofoam™ 
container and cardboard box with a disposable ice pack. They will be shipped to the University of 
Iowa by overnight delivery, by placing the package in a drop box or calling for pickup by FedEx.  
Specimens will be shipped daily Monday through Thursday. 
For those who have consented to future use, the future use specimens (cryovials containing aliquots 
of the liquid amies solution obtained from the vaginal swabs), will be sent on dry ice to the Fisher 
repository. 
“All infectious specimens will be transported using packaging mandated in the Code of Federal 
Regulations (49 CFR Part 173: Shippers, General Requirements for Shipments and Packaging 

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and under the US Department of Transportation- Pipeline and Hazardous Materials Safety 
Administration (PHMSA)  and according to individual carrier guidelines, as applicable.” 
. 

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9. 
ASSESSMENT OF SAFETY 
9.1. 
Specification of Safety Parameters 
Investigators are required to report promptly to the sponsor any AE that may reasonably be 
regarded as caused by or probably caused by the drug.  If the AE is alarming, the investigator shall 
report the adverse effect immediately (§ 312.64(b)). Safety will be assessed by incidence and 
severity of solicited and non-solicited AEs and SAEs. A DSMB will be convened by DMID to 
review safety information from study participants. 
Sponsors are specifically required to notify all participating investigators and FDA in a written 
IND safety report of any AE associated with the use of the drug that is both serious and 
unexpected, and any finding from tests in laboratory animals that suggests a significant risk for 
human subjects (§ 312.32(c)(1)(i)(A),(B)).  More generally, sponsors are required to keep each 
participating investigator informed of new observations discovered by or reported to the sponsor 
on the drug particularly with respect to AEs and safe use (§ 312.55(b)). 
Also, Investigators are required to report promptly to the IRB all unanticipated problems involving 
risks to human subjects or others including AEs that should be considered unanticipated problems 
(§§ 56.108(b)(1), 312.53(c)(1)(vii), and 312.66). 
9.2. 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
9.2.1. 
Adverse Events 
AE monitoring and reporting is a routine part of every clinical trial.  All clinical site staff and the 
Sponsor’s employees share in the responsibility for reporting AEs.  All clinical site staff and the 
Sponsor’s employees who learn about or are notified of a SAE must collect and promptly report 
(24 hours) data according to the regulations.  Failure to report AEs according to the timeframes and 
definitions as outlined in the regulations can result in regulatory actions. 
Adverse Event:  ICH E6 defines an AE as any untoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product regardless of its causal 
relationship to the study treatment.  An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the use 
of medicinal (investigational) product. The occurrence of an AE may come to the attention of 
study personnel during study visits and interviews of a study recipient presenting for medical care, 
or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for “serious adverse events” 
should be captured on the appropriate CRF. Information to be collected includes event description, 
time of onset, clinician’s assessment of severity, relationship to study product (assessed only by 
those with the training and authority to make a diagnosis, which would include MD, PA, Nurse 
Practitioner, DO), and time of resolution/stabilization of the event.  All AEs occurring while on 
study must be documented appropriately regardless of relationship.  All AEs will be followed to 
adequate resolution or are considered stable. 

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Any medical condition that is present at the time that the subject is screened should be considered 
as baseline and not reported as an AE.  However, if it deteriorates at any time during the study, it 
should be recorded as an AE. 
All AEs must be graded for severity and relationship to study product. 
Severity of Event:  All AEs will be assessed by the clinician using a protocol defined grading 
system.  For events not included in the protocol defined grading system, the following guidelines 
will be used to quantify intensity. 
 
Mild:  events require minimal or no treatment and do not interfere with the subject’s 
daily activities. 
 
Moderate: events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
 
Severe:  events interrupt a subject’s usual daily activity and may require systemic 
drug therapy or other treatment.  Severe events are usually incapacitating. 
Changes in the severity of an AE should be documented to allow an assessment of the duration of 
the event at each level of intensity.  AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
Relationship to Study Products: The clinician’s assessment of an AE's relationship to test article 
(study drug) is part of the documentation process, but it is not a factor in determining what is or is 
not reported in the study. If there is any doubt as to whether a clinical observation is an AE, the 
event should be reported.  All AEs must have their relationship to study product assessed using the 
terms: related or not related. In a clinical trial, the study product must always be suspect. To help 
assess, the following guidelines are used. 
 
Related – There is a reasonable possibility that the study product caused the AE. 
Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study product and the AE. 
 
Not Related – There is not a reasonable possibility that the administration of the 
study product caused the event. 
9.2.2. 
Solicited Events 
Solicited events assessments will be captured on a memory aid starting on Day 1, the first day of 
therapy and continuing for 5 days. 
The subject will record the presence and intensity of vulvo-vaginal solicited events on the memory 
aid. 

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Table 2: 
Solicited events & grading 
 
Grade 1 Mild 
Grade 2 Moderate 
Grade 3 Severe 
Vaginal odor 
Mild unpleasant odor 
Moderate unpleasant odor 
Severe, unpleasant odor 
Vaginal pain 
Pain causing no or minimal 
interference with usual social 
and functional activities 
Pain causing greater than 
minimal interference with 
usual social and functional 
activities or the need for non- 
narcotic medication 
Pain causing inability to 
perform usual social and 
functional activities or the 
need for narcotic medication 
Vaginal tenderness 
Mild tenderness 
Moderate tenderness 
Severe tenderness 
Vulvar/vaginal itching 
Itching causing no 
interference with usual social 
and functional activities 
Itching causing interference 
with usual social and 
functional activities 
Itching causing inability to 
perform usual social and 
functional activities 
Vaginal dryness 
Dryness not interfering with 
sexual function, social, and 
functional activities 
Dryness causing greater than 
minimal interference with 
usual sexual, social and 
functional activities 
NA 
Vaginal discharge by participant’s 
report 
Mild increase in participant’s 
usual amount of discharge, 
regardless of color or 
quantity; no sanitary 
protection required 
Moderate to profuse increase in 
discharge requiring pad use or 
other hygienic intervention 
NA 
Vulvar inflammation 
(Redness/Swelling) 
Mild swelling, or redness; no 
interference with usual, 
social and functional 
activities 
Moderate swelling, or redness; 
interference with usual, social 
and functional activities 
Severe swelling or redness, or 
presence of mucosal 
ulceration; inability to 
perform usual, social and 
functional activities 
 
Any symptoms still present on Day 5 will continue to be followed by subject memory aid notations 
until symptom resolution.  Subjects will also be asked to record any medications taken and any 
emergency room or physician visits (other than routine check-ups). 
Severity of solicited events symptoms are graded according to the table above.  For symptoms not 
specifically mentioned will be graded using the following scale: 
 
Grade 1:  Mild (does not interfere with activity) 
 
Grade 2:  Moderate (interferes with activity) 
 
Grade 3:  Severe (prevents daily activity) 

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9.2.3. 
Serious Adverse Events 
An adverse event or suspected adverse reaction is considered “serious” if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: 
 Death, 
 A life-threatening AE*, 
 Inpatient hospitalization or prolongation of existing hospitalization, 
 A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
 A congenital anomaly/birth defect. 
 Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.  Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
*Life-threatening AE.  An AE is considered “life-threatening” if, in the view of either the 
investigator or sponsor, its occurrence places the subject at immediate risk of death.  It does not 
include an AE, had it occurred in a more severe form, might have caused death. 
All SAEs will be: 
 Reviewed and evaluated by a study clinician 
 Recorded on the appropriate Adverse Event CRF 
 Followed through resolution by a study clinician 
 A study clinician will determine whether the SAE is considered related to study 
treatment. 
9.2.4. 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values or 
Abnormal Clinical Findings 
Collection of specific safety laboratory data is outlined in the study visit schedule.  Toxicity tables 
are based on the FDA toxicity tables developed for normal healthy adult volunteers. 
Laboratory values that are abnormal based on the toxicity tables will be reported on the appropriate 
CRF. 
In the event a subject experiences an AE or vulvar or vaginal reaction that is still present at the end 
of the subject’s participation in the study, the subject must be followed until resolution of the event 
or until the event or abnormality stabilizes to the investigator's and/or sponsor's satisfaction.  
Follow-up procedures, evaluations, and outcomes will be recorded on the subject's CRFs. 

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9.3. 
Reporting Procedures 
9.3.1. 
Adverse Events 
AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on 
the appropriate CRF. Solicited AEs will be collected from the time of the first product 
administration through Day 5. Non-solicited AEs and SAEs will be collected from the time of first 
product administration throughout the entire study period. Information to be collected includes 
event description, date of onset, investigator assessment of severity, investigator assessment of 
relationship to study product, date of resolution of the event, seriousness, and outcome. The 
intensity of non-serious AEs will be assessed by a licensed study clinician (i.e., medical doctor, 
nurse, nurse practitioner, physician’s assistant). The causality of non-serious AEs will be assessed 
by a licensed clinician able to make diagnoses listed on the Form FDA 1572.  All AEs occurring 
during the AE reporting period of the study will be documented appropriately regardless of 
relationship.  All AEs will be followed to adequate resolution or until considered stable. 
Any medical condition that is present at the time of enrollment will be considered as pre-existing at 
Baseline and will not be reported as an AE. If the severity or frequency of any pre-existing 
medical condition increases during the study period, then it will be recorded as an AE. 
AEs will be followed until resolution even if this extends beyond the study-reporting period. 
Resolution of an AE is defined as the return to pretreatment status or stabilization of the condition 
with the expectation that it will remain chronic. 
9.3.1.1. 
Serious Adverse Events 
Information to be collected includes event description, date of onset, investigator assessment of 
severity, investigator assessment of relationship to study product, date of resolution of the event, 
seriousness, and outcome. The intensity of SAEs will be assessed by a licensed study physician.  
The causality of SAEs will be assessed by a licensed physician able to make diagnoses listed on the 
Form FDA 1572. 
Serious adverse events will be recorded on the appropriate Adverse Event CRF and will be 
reported to the site’s Independent Safety Monitor.  Events will be reviewed and followed to 
resolution by a study physician.  SAEs will be collected on each subject until her last study visit. 
Any AE that meets a protocol-defined serious criterion must be submitted immediately 
(within 24 hours of site awareness) on an SAE form to the DMID Pharmacovigilance Group, 
at the following address: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Dr. Suite 650 
Bethesda, MD 20817, USA 
SAE Hot Line: 1-800-537-9979 (US) or 1-301-897-1709 (outside US) 
SAE FAX Phone Number: 1-800-275-7619 (US) or 1-301-897-1710 (outside US) 
SAE Email Address: PVG@dmidcroms.com 
 
 

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Additionally, materials must be submitted to the Statistical and Data Coordinating Center (SDCC), 
Emmes Corporation, through the IDES system. Other supporting documentation of the event may 
be requested by the DMID Pharmacovigilance Group and should be provided as soon as possible. 
The DMID Medical Monitor and Clinical Protocol Manager will be notified of the SAE by the 
DMID Pharmacovigilance Group. The DMID Medical Monitor will review and assess the SAE for 
regulatory reporting and potential impact on study subject safety and protocol conduct. 
At any time after completion of the study, if the investigator becomes aware of an SAE that is 
suspected to be related to study product, the investigator will report the event to the DMID 
Pharmacovigilance Group. 
9.3.2. 
Regulatory Reporting for Studies Conducted Under DMID-Sponsored IND 
Following notification from the investigator, DMID, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected.  DMID will report an AE as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between the drug and the 
AE.  DMID will notify FDA and all participating investigators (i.e., all investigators to whom the 
sponsor is providing drug under its INDs or under any investigator’s IND) in an IND safety report 
of potential serious risks from clinical trials or any other source, as soon as possible, but in no case 
later than 15 calendar days after the sponsor determines that the information qualifies for reporting 
as specified in 21 CFR Part 312.32.  DMID will also notify FDA of any unexpected fatal or life-
threatening suspected adverse reaction as soon as possible but in no case later than 7 calendar days 
after the sponsor’s initial receipt of the information.  Relevant follow-up information to an IND 
safety report will be submitted as soon as the information is available.  Upon request from FDA, 
DMID will submit to FDA any additional data or information that the agency deems necessary, as 
soon as possible, but in no case later than 15 calendar days after receiving the request. 
All serious events designated as “not related” to study product(s), will be reported to the FDA at 
least annually in a summary format. 
9.3.3. 
Reporting of Pregnancy 
Pregnancies occurring in study subjects will be reported in IDES. No further treatment will be 
administered to pregnant subjects, but all study-mandated blood samples will be obtained and the 
subject will continue in follow-up for safety events (see Section 7.6).  In addition, pregnant subjects 
will no longer undergo pelvic exams or swabs collection.  Pregnancies will be followed to 
pregnancy outcome pending the subject’s permission. 
9.4. 
Type and Duration of Follow-up of Subjects after Adverse Events 
AEs will be followed until resolved or subject is considered stable. 
9.5. 
Halting Rules 
Study enrollment and dosing will be halted and an ad hoc DSMB review will be performed if any 
of the following occur at any time during the study: 
Study Halting Events: 
1. One or more subject experiences a treatment-related SAE. 

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2. One or more subject experiences vulvar and/or vaginal ulceration, abscess, or necrosis 
associated with study product administration. 
3. Two or more subjects experience a treatment-related severe (Grade 3) unsolicited adverse 
event. 
4. Three or more subjects who received at least one treatment dose experience the same severe 
(Grade 3) solicited AE as evaluated by a licensed clinician. 
5. Three or more subjects who received at least one treatment dose experience a severe (Grade 
3) study related laboratory abnormality in the same laboratory parameter. 
6. An overall pattern of symptomatic, clinical, or laboratory events that the DMID, Medical 
Monitor, or DSMB consider associated with study product and that may collectively 
represent a serious potential concern for safety. 
9.6. 
Safety Oversight (ISM plus DSMB) 
9.6.1. 
Data and Safety Monitoring Board 
Because this is a large Phase II Randomized Clinical Trial, a DSMB will be created to review this 
study.  The DSMB will be composed of three to four members and may include at least one 
physician involved in research, one biostatistician and potentially an expert in the field of 
microbiology. This committee will be charged with reviewing the protocols with respect to ethical 
and safety standards and making recommendations if necessary.  During the studies, the 
Committee will meet (either in person, via teleconference or web-based meetings) at least annually 
to review safety issues and to monitor center performance in execution of the protocol. 
Prior to each meeting, a formal, detailed report will be generated with emphasis placed on safety 
issues. 
A formal DSMB review will occur after 30 subjects have received at least one dose of study drug 
and have completed Visit 2. The DSMB will either recommend continued enrollment of the 
remaining subjects or discontinuation of enrollment. Though the timing of the DSMB review will 
be expedited, enrollment may continue while awaiting the DSMB review.  In addition, a 
computerized system will be used to acquire any data regarding halting criteria throughout the 
study. 
Additionally, a single fully blinded interim analysis is planned to reassess the adequacy of the 
sample size based on subjects meeting eligibility for the Modified Intent-to-Treat (mITT) cohort 
(see also Section 11).  After eighty subjects have been enrolled and have available test results for 
Nugent score, HIV, chlamydia and gonorrhea, the fraction of subjects who are enrolled to date who 
are eligible for the mITT cohort will be estimated.  Based on this calculation, the enrollment target 
may be increased from 120 subjects to a maximum of 150 as required to achieve the target of 90 
subjects eligible for the mITT cohort. The study sponsor and investigators will have access to the 
data shared in fully blinded reports issued to the DSMB. 
If any of the halting rules are met, the study will not proceed with the remaining enrollment 
without a review by and recommendation from the DSMB to proceed.  Upon completion of this 
review and receipt of the advice of the DSMB, DMID will determine if study entry or study dosing 
should be interrupted or if study entry and study dosing may continue according to the protocol. 

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The study is masked. The DSMB has the option to request unmasking to make determinations 
regarding study outcome. 
9.6.2. 
Independent Safety Monitor (ISM) 
Safety oversight for this study will include an ISM in close proximity to each of the clinical 
research sites. The ISM will receive and evaluate SAEs blinded and provide an independent written 
summary to the DMID Clinical Project Manager and DMID Medical Monitor. The ISM may be 
asked by the DMID Medical Monitor to review additional safety events (i.e. significantly increased 
frequency of non-serious adverse events). 

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10. 
CLINICAL MONITORING 
10.1. 
Site Monitoring Plan 
Site monitoring will be conducted to ensure that human subject protection, study procedures, 
laboratory procedures, study intervention administration, and data collection processes are of high 
quality and meet sponsor, International Conference on Harmonisation (ICH)/Good Clinical 
Practice (GCP) guidelines and applicable regulatory requirements, and that the study is conducted 
in accordance with the protocol and sponsor’s standard operating procedures. The DMID or its 
designee will conduct site-monitoring visits as specified in the monitoring plan. 
Monitoring visits will include, but are not limited to, review of regulatory files, accountability 
records, CRFs, informed consent forms (ICFs), medical and laboratory reports, and protocol 
compliance.  Study monitors will meet with investigators to discuss any problems and actions to 
be taken and document visit findings and discussions. 

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11. 
STATISTICAL CONSIDERATIONS 
11.1. 
Introduction 
This is a Phase 2, double-blind, randomized, placebo-controlled, multi-center trial comparing 5% 
Monolaurin Vaginal Gel to Vehicle Placebo Gel as outpatient therapy.  A total of 120 eligible 
subjects with BV will be enrolled.  Treatment assignments will be randomly allocated in a 2:1 ratio 
of test article to placebo, with the randomization stratified by clinical site.  Each subject will 
receive intravaginal gel twice daily for three successive days for a total of 6 doses. There will be 3 
clinic visits over 31 days. 
11.2. 
Data Analysis Populations 
The Per-Protocol (PP) efficacy analysis population includes all randomized subjects who met all 
inclusion/exclusion criteria, did not have any significant protocol deviations, complied with the 
assigned study treatment, returned to the study site for the Test of Cure visit within the specified 
window (Visit 2 Study Day 8 relative to the first day of treatment [Window: Days 8-15]), or 
discontinued study product early due to lack of treatment effect or received vaginosis or systemic 
antimicrobial therapy other than study drug during the study.  Subjects with Visit 1 test results 
including a grade 3 laboratory abnormality, a positive Visit 1 HIV, Chlamydia, or Neisseria 
gonorrhoeae test, a PAP result consistent with HSIL, AGUS, or CIN2 or greater, or a Visit 1 
Nugent score < 4 will excluded from the PP population. 
A subject is compliant with study treatment if she uses at least 5 of 6 doses of study product, as 
assessed by the study coordinator’s count of used / unused applicators in each returned subject kit. 
If a kit is not returned, compliance will be assessed by the subject’s self-report on the memory aid.   
Significant protocol deviations include sexual intercourse including receptive oral sex or insertion 
of substances or objects intravaginally between Visit 1 and Visit 2. 
The Modified Intent-to-Treat (mITT) efficacy analysis population includes all randomized subjects 
who met all inclusion/exclusion criteria excluding those who have a Nugent score <4 at Visit 1 or 
are positive for other concomitant vulvovaginal infections at baseline which may interfere with the 
efficacy assessment. The mITT population will be used as the primary analysis population for the 
test of 5% Monolaurin Vaginal Gel to Vehicle Placebo Gel. 
The Evaluable efficacy analysis population includes all subjects in the mITT population who 
received study treatment and returned for at least one post-baseline visit. 
The Intent-to-Treat (ITT) efficacy analysis population includes all randomized subjects. 
The safety population includes all randomized subjects who received at least one dose of study 
product. 
11.3. 
Study Objectives and Endpoints 
The primary study objectives are to compare 5% Monolaurin Vaginal Gel with vehicle placebo gel 
(excipients only) with respect to 1) safety and tolerability, and 2) efficacy by clinical cure at Visit 
2. The primary safety outcome measures are the number of subjects reporting solicited urogenital 
AEs following the first dose of the study product through Visit 2 (Days 8-15) and the number of 

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subjects reporting SAEs considered product related following the first dose of study product 
through Visit 3 (Day 22-31). The primary efficacy outcome measure is the proportion of subjects 
with clinical cure in each study arm at Visit 2 (Days 8-15). 
A clinical cure is defined by normal Amsel criteria. Normal Amsel criteria are defined as: normal 
physiological vaginal discharge, whiff test negative for any amine “fishy” odor, saline wet mount 
less than 20% for clue cells, and vaginal pH is <=4.5. 
A clinical failure is defined by a) one or more abnormal Amsel criteria, b) early discontinuation of 
study therapy due to lack of treatment effect, c) use of any vaginosis therapy other than study 
product during the study, or d) in the investigators opinion, requires additional treatment for 
vaginosis. 
Subjects who do not meet the criteria for either the clinical cure or clinical failure definitions are 
not evaluable for clinical cure. 
A secondary efficacy outcome measure is the proportion of subjects with therapeutic cure in each 
study arm at Visit 2 (Day 8-15) and at Visit 3 (Day 22-31). Therapeutic cure is defined as both a 
clinical cure AND a bacteriological cure (Nugent score 0-3).  Subjects who were clinical failures, 
or have a Nugent score >3 are therapeutic failures.  Subjects who are not evaluable for clinical 
cure, or do not have a Nugent score result are not evaluable for therapeutic cure. 
Table 3: 
Bacterial Vaginosis:  Determination of Therapeutic Cure 
If the clinical cure outcome is… 
and the Nugent (bacteriological) 
score result is… 
then the overall therapeutic cure 
outcome is… 
Cure 
0-3 
Cure 
Cure 
>3 
Failure 
Cure 
Not Evaluable 
Not Evaluable 
Failure 
0-3 
Failure 
Failure 
>3 
Failure 
Failure 
Not Evaluable 
Failure 
Not Evaluable 
0-3 
Not Evaluable 
Not Evaluable 
>3 
Failure 
Not Evaluable 
Not Evaluable 
Not Evaluable 
 
Subjects who are non-evaluable for clinical cure at the Test of Cure visit are excluded from the PP 
population, but included in the mITT, ITT, and Evaluable populations as treatment failures. Last 
Observation Carried Forward will be used as a sensitivity analysis.  Non-evaluable therapeutic 
cures will be handled similarly. 
11.4. 
Study Hypotheses 
There are three planned formal tests of hypotheses which compare 5% Monolaurin Vaginal gel 
with Vehicle Placebo Gel (excipients only), with respect to the primary safety and efficacy 
outcomes. The first hypothesis test compares the proportion of subjects in each study arm who 
experience solicited urogenital AEs through Visit 2 (Day 8-15 study window). The second 

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hypothesis test compares the proportion of subjects in each study arm who experience product 
related SAEs following the first dose of the study product through Visit 3 (Day 22-31). The third 
hypothesis test compares the proportion of subjects who achieve clinical cure at Visit 2 (Day 8- 
15). The null hypothesis for each comparison is that there is no difference in proportions between 
study arms, with a two-sided alternative which considers the possibility of a difference in either 
direction.  Each test will be conducted using a Fisher’s exact test at the 5% two-sided level of 
significance level without adjustment for multiplicity. The two safety hypotheses will be tested in 
the safety data analysis population. The primary efficacy analysis will be conducted in the mITT 
efficacy analysis population, and repeated as a secondary analysis in the PP efficacy analysis 
population, Evaluable efficacy analysis population and Intent-to-Treat efficacy analysis 
population. 
11.5. 
Sample Size Considerations 
The statistical information goal for the study is 90 subjects eligible for the primary efficacy 
analysis of clinical cure in the mITT efficacy population.  This is an ad-hoc sample size determined 
by logistical and feasibility considerations, as there is insufficient pilot data upon which to base 
more formal sample size calculations. 
Subjects who have a Nugent score <4 at Visit 1 or are positive for other concomitant vulvovaginal 
infections at baseline which may interfere with the efficacy assessment will be excluded from the 
mITT population. 
Based on observed rates of these outcomes at the participating clinics, it is anticipated that a total 
of 120 subjects will be enrolled to reach this target.  However, enrollment will be continued past 
120 subjects to a maximum of 150, if necessary to reach the informational goal of 90 eligible 
subjects. 
The table below shows the statistical power conferred by this sample size for a two-sided level 5% 
Fisher’s exact test comparing binomial proportions, under different assumed proportions. 
 
 

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Table 4: 
Power to compare binomial proportions using a two-sided level 0.05 Fisher’s 
Exact Test with a sample size of N = 90 (60 subjects in the 5% Monolaurin 
Vaginal Gel arm, 30 subjects in the Vehicle Placebo Gel arm) Conditions in 
which Power is ≥.80 are highlighted 
Vehicle Placebo Gel (N=30) 
5% Monolaurin Vaginal Gel (N=60) 
.05 
.10 
.20 
.30 
.40 
.50 
.60 
.70 
.80 
.90 
.95 
.05 
.02 
.04 
.38 
.82 
.97 
>.99 
>.99 
>.99 
>.99 
>.99 
>.99 
.10 
.13 
.03 
.15 
.52 
.85 
.98 
>.99 
>.99 
>.99 
>.99 
>.99 
.20 
.53 
.22 
.03 
.12 
.42 
.78 
.96 
>.99 
>.99 
>.99 
>.99 
.30 
.86 
.61 
.15 
.03 
.12 
.41 
.76 
.95 
>.99 
>.99 
>.99 
.40 
.98 
.89 
.47 
.13 
.04 
.13 
.41 
.76 
.96 
>.99 
>.99 
.50 
>.99 
.98 
.79 
.42 
.13 
.04 
.13 
.42 
.79 
.98 
>.99 
.60 
>.99 
>.99 
.96 
.76 
.41 
.13 
.04 
.13 
.47 
.89 
.98 
.70 
>.99 
>.99 
>.99 
.95 
.76 
.41 
.12 
.03 
.15 
.61 
.86 
.80 
>.99 
>.99 
>.99 
>.99 
.96 
.78 
.42 
.12 
.03 
.22 
.53 
.90 
>.99 
>.99 
>.99 
>.99 
>.99 
.98 
.85 
.52 
.15 
.03 
.13 
.95 
>.99 
>.99 
>.99 
>.99 
>.99 
>.99 
.97 
.82 
.38 
.04 
.02 
 
With respect to the safety objectives, for a sample size of 60 subjects in the treatment arm with no 
observed serious adverse events related to study product, the 95% confidence interval for the 
estimated proportion is (.00,.06) (Clopper-Pearson interval). 
In actuality, the safety analysis cohort will be larger than the mITT cohort, and the confidence 
interval will be more precise than this. 
11.6. 
Planned Interim Analyses 
The DSMB will meet and review safety data and enrollment data when 30 subjects have completed 
Visit 2 and at least annually as outlined in the DSMB charter. The study will be monitored to 
determine if any of the safety halting rules described in Section 9.5 are met. Additionally, a single 
fully blinded interim analysis is planned to reassess the adequacy of the sample size based on 
subjects meeting eligibility for the mITT cohort.  After eighty subjects have been enrolled and have 
available test results for Nugent score, HIV, chlamydia and 

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gonorrhea, the fraction of subjects who are enrolled to date who are eligible for the mITT cohort 
will be estimated.  Based on this calculation, the enrollment target may be increased from 120 
subjects to a maximum of 150 as required to achieve the target of 90 subjects eligible for the mITT 
population. The study sponsor and investigators will have access to the data shared in fully 
blinded reports issued to the DSMB. 
11.7. 
Final Analysis Plan 
The primary and secondary analyses are briefly described in this section. Further details of the 
analyses as well as the analysis plan for the exploratory analyses will be described in a separate 
statistical analysis plan document. 
11.7.1. 
Safety Analyses 
11.7.1.1. Overview of Safety Analyses 
 
Solicited Adverse Event Data 
Descriptive techniques will be used to summarize the solicited adverse events data.  Local and 
systemic solicited events will be tabulated, with symptom type crossed by severity grade. 
Tables will be prepared for each treatment arm, and for the combined safety analysis cohort. The 
data in each table will also be depicted graphically, as a bar-chart of symptom incidence, and 
provided as listings of events.  In the tables, figures and listings, color-coding using a heat chart 
(yellow, orange, red) will be used to highlight severity (mild, moderate, severe). 
The solicited AE outcome data consist of multiple symptoms types, with ordinal severity grades, 
taken repeatedly over a 5-day reporting period following first administration of study product. To 
facilitate analysis and interpretation, the data will be simplified in different ways in different 
analyses.  For example, individual symptoms will be used to form the composite endpoint “any 
local symptom”. The ordinal severity grades will be dichotomized, e.g., none or mild versus 
moderate or severe. The grade will be summarized by the maximum severity over the five day 
reporting period so as to obtain a single observation per subject. 
Unsolicited Adverse Event Data 
Unsolicited AEs will be coded by MedDRA® for preferred term and system organ class. The 
proportion of subjects and exact 95% confidence intervals of AEs in aggregate, as well as by 
MedDRA® categories, will be computed. The number of SAEs is likely to be small in this study 
and will be reported by a detailed listing showing the type, MedDRA® coding, relevant dates 
(treatment dosing dates and AE onset and resolution dates), severity, relatedness, and outcome for 
each event. 
Clinical Safety Laboratories 
Results of safety laboratories assessed prior to and after administration of study product will be 
summarized by treatment group and grade. Changes in laboratory parameters pre- and post- 

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treatment will also be examined.  Standard summary statistics, including means, standard 
deviations and 95% confidence intervals, will be computed.  Additionally, graded results will 
either be analyzed as a binary variable (normal, abnormal), or a multinomial variable (Grade 0, 
Grade 1, Grade 2, Grade 3) using either logistic regression or ordinal logistic regression 
respectively to make treatment group comparisons. 
11.7.1.2. Analyses of Primary and Secondary Safety Outcomes 
All safety outcomes will be assessed in the safety analysis population of all randomized subjects 
who received one or more doses of study product.  Outcomes will be reported overall and by 
treatment arm. 
 
Primary Safety Outcome – 
 
Number of subjects reporting solicited urogenital AEs following the 
first dose of the study product through Visit 2 (Day 8-15) 
 
Number of subjects reporting serious adverse events (SAEs) considered 
product-related following the first dose of the study product through Visit 
3 (Day 22-31) 
 
Secondary Safety Outcomes – 
 
Number of subjects experiencing non-laboratory non-solicited AEs following the 
first dose of the study product through Visit 3 (Day 22-31) 
 
Number of subjects experiencing laboratory AEs following the first dose of 
the study product through Visit 2 (Day 8-15). 
 
Two tests of hypotheses will be conducted in the safety analysis population.  Each test will be 
conducted using a Fisher’s exact test at the 5% two-sided level of significance level without 
adjustment for multiplicity.  The point estimate for the arm-specific proportions and difference in 
proportions as well as corresponding two-sided level 95% confidence intervals will be reported. As 
described in Section 11.7.1.1, additional descriptive analyses of solicited adverse event data, 
unsolicited adverse event data, and clinical safety laboratory values will be performed. 
11.7.2. 
Efficacy Analyses 
11.7.2.1. Overview of Efficacy Analyses 
11.7.2.1.1. Analyses of Primary and Secondary Efficacy Outcomes 
 Primary Efficacy Outcome – the proportion of subjects with clinical cure in each study 
arm at Visit 2 (Day 8-15). 
A test of hypothesis for the primary efficacy outcome will be conducted in the mITT efficacy 
analysis population, and repeated as a secondary analysis in the PP efficacy analysis population, 
Evaluable efficacy analysis population, and Intent-to-Treat efficacy analysis population.  Fisher’s 
exact test at the 5% two-sided level of significance level will be used without adjustment for 
multiplicity.  The point estimates for the arm-specific proportions and difference in proportions as 
well as corresponding 95% confidence intervals will be reported. 

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 Secondary Efficacy Outcomes – 
 
Proportion of subjects with therapeutic cure in each study arm at Visit 2 (Day 8- 
15) and at Visit 3 (Day 22-31). 
 
Proportion of subjects with clinical cure in each study arm by Visit 3 (Day 22-31) 
 
Proportion of subjects with Nugent score of 3 or less (negative for BV) and 4-6 
(intermediate) in each study arm at Visit 2 (Day 8-15) and at Visit 3 (Day 22-31) 
The analyses of the secondary efficacy outcomes will be conducted in the mITT efficacy analysis 
population and repeated in the PP efficacy analysis population, Evaluable efficacy analysis 
population and Intent-to-Treat efficacy analysis population.  The point estimates for the arm-
specific proportions and difference in proportions as well as corresponding 95% confidence 
intervals will be reported. 
Additional descriptive analyses of the primary and secondary efficacy outcomes will be performed 
including tabular and graphical displays of the data, reporting outcomes overall and separately by 
treatment arm. 
11.7.2.1.2. Analyses of Exploratory Efficacy Outcomes 
 Proportion of subjects with clinical cure in each study arm by subgroup (first time or 
recurrent infection) by Visit 2 (Day 8-15) and by Visit 3 (Day 22-31). 
 Proportion of subjects with therapeutic cure in each study arm by subgroup (first time 
or recurrent infection) by Visit 2 (Day 8-15) and by Visit 3 (Day 22-31). 
 Mean count of Lactobacillus spp., Gardnerella spp., and Mobiluncus spp., respectively, 
in each study arm at baseline, at Visit 2 (Day 8-15) and at Visit 3 (Day 22-31). 
 Mean fungal colony count in vaginal secretions in each study arm at baseline, at Visit 2 
(Day 8-15) and at Visit 3 (Day 22-31). 
Analyses of the exploratory efficacy outcome measures will be detailed in the separate statistical 
analysis plan document. 

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12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6, Section 4.9, and regulatory and institutional requirements for the 
protection of confidentiality of subjects.  Each site will permit authorized representatives of the 
DMID, its designees, and appropriate regulatory agencies to examine (and when required by 
applicable law, to copy) clinical records for the purposes of quality assurance (QA) reviews, 
audits, and evaluation of the study safety and progress. These representatives will be permitted 
access to all source data, which include, but are not limited to, hospital records, clinical and office 
charts, laboratory notes, memoranda, subjects’ memory aid or evaluation checklists, pharmacy 
dispensing records, recorded data from automated instruments, copies or transcriptions certified 
after verification as being accurate and complete, microfiches, photographic negatives, microfilm 
or magnetic media, X-rays, Gram stain slides, and subject files and records kept at the pharmacy, 
at the laboratories, and medico-technical departments involved in the clinical trial.  Data collection 
forms will be derived from the eCRFs and be provided by the SDCC. The authority to collect this 
information is under 42 U.S. Code 285f. 
The site may provide certified copies of the medical record or other source documents for 
monitoring.  Medical history and inclusion/exclusion evaluations are by patient report and do not 
require review of the medical records prior to enrollment. 

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13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written DMID-accepted site quality management plan, the investigational site is 
responsible for conducting routine QA and quality control (QC) activities to internally monitor 
study progress and protocol compliance. The site PI will provide direct access to all trial-related 
sites, source data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor, and inspection by local and regulatory authorities. The site PI will ensure all study 
personnel are appropriately trained and applicable documentation is maintained on site. 
DMID-designated clinical monitors will verify that the clinical trial is conducted and data are 
generated, documented (recorded), and reported in compliance with the protocol, ICH/GCP 
guidelines, and the applicable regulatory requirements.  Clinical monitoring reports will be 
submitted to DMID. 
The SDCC will implement QC procedures beginning with the data entry system and generate data 
QC checks that will be run on the database. Any missing data or data anomalies will be 
communicated to the site(s) for clarification and resolution. 

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14. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1. 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the principles set 
forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research of the US National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research (April 18, 1979) and codified in 45 CFR Part 46 and/or the 
ICH E6; 62 Federal Regulations 25691 (1997). The investigator’s Institution will hold a current 
Federalwide Assurance (FWA) issued by Office for Human Research Protections (OHRP) for 
federally funded research. 
14.2. 
Institutional Review Board 
Prior to enrollment of subjects into this trial, the approved protocol and the ICF will be reviewed 
and approved by the appropriate IRB. The responsible official for the IRB will sign the IRB letter 
of approval of the protocol prior to the start of this trial and a copy will be provided to DMID. 
Notification of the IRB's composition, or the IRB’s FWA number, will be provided to DMID. 
Should amendments to the protocol be required, the amendments will be written by the sponsor 
and provided to the investigator for submission to the IRB. 
14.3. 
Informed Consent Process 
All subjects must sign an ICF that complies with the requirements of both 21 CFR 50 and 45 CFR 
46. 
Prior to participation in the trial, subjects will receive a comprehensive explanation of the proposed 
treatment, including the nature and risks of the trial, alternate therapies, any known AEs, the 
investigational status of the components, and the other elements that are part of obtaining proper 
informed consent.  Subjects will also receive a detailed explanation of the proposed use and 
disclosure of their protected health information, including specifically their vaginal swab 
specimens and serum samples.  Subjects will be allowed sufficient time to consider participation in 
the trial, after having the nature and risks of the trial explained to them. The consent form must not 
include any exculpatory statements. 
DMID will provide the investigator, in writing, any new information that significantly affects risk 
related to a subject’s receipt of the investigational product. This new information will be 
communicated by the investigator to subjects who consent to participate in the trial in accordance 
with IRB requirements. The informed consent document will be updated and subjects will be re-
consented, if necessary. 
14.4. 
Exclusion of Women, Minorities, and Children (Special Populations) 
This study will be inclusive of all healthy non-pregnant women, non-breastfeeding who meet the 
inclusion/exclusion criteria, regardless of religion, or ethnic background. Only individuals who 

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are 18 to 50 years old, inclusive, will be included at this time.  Pregnant and breastfeeding women 
and children are excluded for safety reasons.  Prisoners are excluded due to the rigorous study 
schedule that would not be feasible in an incarcerated population.  Should the outcome of this 
study be deemed acceptable, additional trials may be initiated in other populations. 
14.5. 
Subject Confidentiality 
Subjects will have code numbers and will not be identified by name.  Subject confidentiality is 
strictly held in trust by the participating investigators, their staff, the sponsor(s), and their agents. 
This confidentiality extends to genetic and biological sample tests, in addition to the clinical 
information relating to participating subjects. 
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence.  Documented evidence that shows that a potential investigator is aware of and agrees 
to the confidential nature of the information related to the study must be obtained by means of a 
confidentiality agreement. No information concerning the trial or the data will be released to any 
unauthorized third party without prior written approval of the sponsor. 
All information provided by the sponsor and all data and information generated by the site as part 
of the study (other than a subject’s medical records) will be kept confidential by the investigator 
and other site staff. This information and data will not be used by the investigator or other site 
personnel for any purpose other than conducting the study. These restrictions do not apply to: (1) 
information that becomes publicly available through no fault of the investigator or site staff; (2) 
information that it is necessary to disclose in confidence to an IRB solely for the evaluation of the 
study; (3) information that it is necessary to disclose in order to provide appropriate medical care to 
a study subject; or (4) study results that may be published as described in Section 16.  If a written 
contract for the conduct of the study that includes confidentiality provisions inconsistent with this 
statement is executed, that contract’s confidentiality provisions shall apply rather than this 
statement. 
The study monitor, applicable regulatory authorities, such as the FDA, or other authorized 
representatives of the sponsor may inspect all documents and records required to be maintained by 
the site principal investigator. This includes, but is not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the subjects in this trial. The participating sites will permit 
access to such records. 
14.6. 
Study Discontinuation 
If the study is discontinued, enrolled subjects will continue to be followed for safety assessments.   
Subjects will be instructed to discontinue use of study product. If signs or symptoms of BV or 
other genital infections persist either during the study or at the last visit, the subject will be referred 
to her provider for further management. 
If the study drug is discontinued prior to completion of the 3-day course of therapy, subjects will 
continue to be evaluated for symptoms of ongoing BV or other genital infections and will be 
referred for further therapy if signs and symptoms persist. 
Subjects will be compensated for the participation in this study.  Compensation will be in 
accordance with the local IRB’s policies and procedures, and subject to IRB approval. 

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14.7. 
Future Use of Stored Specimens 
Subjects will be asked for permission to allow the study team to obtain extra vaginal swabs and to 
keep extra swab specimen for possible use in future research studies, such as testing for viruses or 
bacteria.  Samples will be stored at a central clinical storage facility.  Samples may be shared with 
other investigators at other institutions. The samples will not be sold or used directly for 
production of any commercial product.  Each sample will be encoded (labeled) only with a barcode 
and a unique tracking number to protect subject’s confidentiality. 
There are no benefits to subjects in the collection, storage, and subsequent research use of 
specimens.  Reports about future research done with a subject’s samples will NOT be kept in their 
health records.  Subjects can decide if they want their samples to be used for future research or 
have their samples destroyed at the end of the study.  A subject’s decision can be changed at any 
time prior to the end of the study by notifying the study doctors or nurses in writing.  However, if a 
subject consents to future use and some of their blood or swab specimens have already been used 
for research purposes, the information from that research may still be used. 
14.8. 
Information Provided to Subjects at Study Completion 
There is increasing discussion in the research community in support of disclosure of individual 
research results.  Several ethical principles have been invoked, including respect for persons who 
have the right to access information about their own health regardless of the utility of those results, 
if they wish to do so.  Surveys suggest that many research participants value and desire the return 
of research results.  Arguments against disclosure include: i) individual research results are often of 
experimental nature and difficult to translate into useful clinical applications; 
ii) some results have the potential to provoke unnecessary distress and anxiety; and iii) 
expectations of disclosure may set a false inducement for participation. 
In this protocol, we intend to provide each participant with a lay summary of overall study results.  
In addition, participants may choose to receive their individual results (e.g., their treatment 
assignment or individual endpoint data, as appropriate) and will be informed about any risks and 
benefits of disclosure. Offering participants the option to decline and explaining the clinical 
significance of individual treatment is intended to minimize the negligible risks associated with 
disclosure.  Interested subjects will be asked to provide contact information for receipt of the 
information.  Results will be provided in an IRB-approved written document after the Clinical 
Study Report has been finalized. 

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15. 
DATA HANDLING AND RECORD KEEPING 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported. 
Data collection forms will be derived from the eCRFs and provided by the SDCC to the sites to 
record and maintain data for each subject enrolled in the study.  All source documents should  be 
completed in a neat, legible manner to ensure accurate interpretation of data.  Permanent ink is 
required to ensure clarity of reproduced copies. When making a change or correction, the original 
entry should be crossed out with a single line, and the change should be initialed and dated.  Do 
not erase, overwrite, or use correction fluid or tape on the original. 
Data reported in the eCRF should be consistent with the data collection form/source documents or 
the discrepancies should be documented. 
The sponsor and/or its designee will provide guidance to investigators on making corrections to  the 
data collection forms and eCRFs. 
15.1. 
Data Management Responsibilities 
All data collection forms and laboratory reports must be reviewed by the clinical team and data 
entry staff, who will ensure that they are accurate and complete.  AEs must be graded, assessed for 
severity and causality, and reviewed by the site PI or designee.  Data collection is the 
responsibility of the clinical trial staff at the site under the supervision of the site PI.  During the 
study, the investigator must maintain complete and accurate documentation for the study. 
The Emmes Corporation will serve as the SDCC for this study, and will be responsible for data 
management, quality review, analysis, and reporting of the study data. 
15.2. 
Data Capture Methods 
Clinical data (including AEs, concomitant medications, and solicited events data) will be entered 
into a 21 CFR Part 11-compliant IDES provided by The Emmes Corporation. The data system 
includes password protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate.  Clinical data will be entered 
directly from the data collection forms/source documents. 
15.3. 
Types of Data 
Data for this study will include safety, laboratory and outcome measures (e.g., solicited events, 
clinical cure, and therapeutic cure). 
15.4. 
Timing/Reports 
Safety data will be reviewed by the DSMB per the DSMB charter for this study. The DSMB will 
make a recommendation at that time as to the advisability of proceeding with further enrollment or 
use of study product. Interim statistical reports may be generated as deemed necessary and 
appropriate by DMID. 

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15.5. 
Study Records Retention 
 
Records and documents pertaining to the conduct of this study, including data collection forms, 
source documents, consent forms, laboratory test results, and medication inventory records, must 
be retained by the investigator for at least 2 years following submission of a Biologics License 
Application or until DMID authorizes transfer or destruction of study records.  No study records 
will be destroyed without prior authorization from NIAID. 
15.6. 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP 
requirements. The noncompliance may be either on the part of the subject, the investigator, or the 
study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
These practices are consistent with ICH E6: 
4.5 
Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
5.1 
Quality Assurance and Quality Control, section 5.1.1 
5.20 
Noncompliance, sections 5.20.1, and 5.20.2. 
It is the responsibility of the site to use continuous vigilance to identify and report deviations 
within 5 working days of identification of the protocol deviation, or within 5 working days of the 
scheduled protocol-required activity.  All deviations must be promptly reported via The Emmes 
Corporation’s IDES. 
All protocol deviations, as defined above, must be addressed in study subject data collection forms.  
A completed copy of the DMID Protocol Deviation Form must be maintained in the Regulatory 
File, as well as in the subject's chart. Protocol deviations must be sent to the local IRB/IEC per 
their guidelines. The site principal investigator and personnel are responsible for knowing and 
adhering to their IRB requirements. 

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16. 
PUBLICATION POLICY 
Following completion of the study, the investigator is expected to publish the results of this 
research in a scientific journal. The International Committee of Medical Journal Editors (ICMJE) 
member journals have adopted a trials-registration policy as a condition for publication. This 
policy requires that all clinical trials be registered in a public trials registry such as  
ClinicalTrials.gov, which is sponsored by the National Library of Medicine.  Other biomedical 
journals are considering adopting similar policies.  It is the responsibility of DMID to register this 
trial in an acceptable registry.  Any clinical trial starting enrollment after 01 July 2005 must be 
registered on or before subject enrollment.  For trials that began enrollment prior to this date, the 
ICMJE member journals will require registration by 13 September 2005, before considering the 
results of the trial for publication. 
The ICMJE defines a clinical trial as any research project that prospectively assigns human 
subjects to intervention or comparison groups to study the cause-and-effect relationship between a 
medical intervention and a health outcome.  Studies designed for other purposes, such as to study 
pharmacokinetics or major toxicity (e.g., Phase I trials), would be exempt from this policy. 

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17. 
LITERATURE REFERENCES 
 
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3. McCormack WM, Jr., Zinner SH, McCormack WM. The incidence of genitourinary 
infections in a cohort of healthy women. Sexually transmitted diseases 1994; 21:63-4. 
 
4. Morris M, Nicoll A, Simms I, Wilson J, Catchpole M. Bacterial vaginosis: a public 
health review. Bjog 2001; 108:439-50. 
 
5. Hauth JC, Goldenberg RL, Andrews WW, DuBard MB, Copper RL. Reduced incidence of 
preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. 
The New England journal of medicine 1995; 333:1732-6. 
 
6. Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial vaginosis and 
preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study 
Group. The New England journal of medicine 1995; 333:1737-42. 
 
7. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late 
miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and 
bacterial vaginosis: a randomised controlled trial. Lancet 2003; 361:983-8. 
 
8. Donders G. Diagnosis and management of bacterial vaginosis and other types of abnormal 
vaginal bacterial flora: a review. Obstet Gynecol Surv 2010; 65:462-73. 
 
9. Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR 
Recommendations and reports : Morbidity and mortality weekly report Recommendations and 
reports / Centers for Disease Control 2010; 59:1-110. 
 
10. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific 
vaginitis. Diagnostic criteria and microbial and epidemiologic associations. The American journal 
of medicine 1983; 74:14-22. 
 
11. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved 
by a standardized method of gram stain interpretation. Journal of clinical microbiology 1991; 
29:297-301. 
 
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13. Wilson J. Managing recurrent bacterial vaginosis. Sex Transm Infect 2004; 80:8-11. 
 
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15. Peterson ML, Schlievert PM. Glycerol monolaurate inhibits the effects of Gram-positive 
select agents on eukaryotic cells. Biochemistry 2006; 45:2387-97. 
 
16. Projan SJ, Brown-Skrobot S, Schlievert PM, Vandenesch F, Novick RP. Glycerol 
monolaurate inhibits the production of beta-lactamase, toxic shock toxin-1, and other 
staphylococcal exoproteins by interfering with signal transduction. Journal of bacteriology 1994; 
176:4204-9. 
 
17. Schlievert PM, Deringer JR, Kim MH, Projan SJ, Novick RP. Effect of glycerol monolaurate 
on bacterial growth and toxin production. Antimicrobial agents and chemotherapy 1992; 36:626- 
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18. Vetter SM, Schlievert PM. Glycerol monolaurate inhibits virulence factor production 
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glycerol monolaurate. Clinical and diagnostic laboratory immunology 1996; 3:10-3. 
 
20. Li Q, Estes JD, Schlievert PM, et al. Glycerol monolaurate prevents mucosal SIV 
transmission. Nature 2009; 458:1034-8. 
 
21. Fichorova RN, Tucker LD, Anderson DJ. The molecular basis of nonoxynol-9-induced 
vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 
transmission. The Journal of infectious diseases 2001; 184:418-28. 
 
22. Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat 
Rev Microbiol 2004; 2:33-42. 
 
23. Laga M, Manoka A, Kivuvu M, et al. Non-ulcerative sexually transmitted diseases as risk 
factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993; 7:95-102. 
 
24. Plummer FA. Heterosexual transmission of human immunodeficiency virus type 1 (HIV): 
interactions of conventional sexually transmitted diseases, hormonal contraception and HIV-1. 
AIDS Res Hum Retroviruses 1998; 14 Suppl 1:S5-10. 
 
25. Schlievert PM, Peterson ML. Glycerol monolaurate antibacterial activity in broth and 
biofilm cultures. PloS one 2012; 7:e40350. 
 
26. Petschow BW, Batema RP, Ford LL. Susceptibility of Helicobacter pylori to 
bactericidal properties of medium-chain monoglycerides and free fatty acids. Antimicrobial 
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27. Boyle E, German JB. Monoglycerides in membrane systems. Crit Rev Food Sci Nutr 1996; 
36:785-805. 
 
28. Seventeenth Report of the Joint FAO/WHO Expert Committee on Food Additives Wld 
Hlth Org Techn Rep Ser 1974, No 539. Vol. 53, 1974. 
 
29. Strandberg KL, Peterson ML, Lin YC, Pack MC, Chase DJ, Schlievert PM. Glycerol 
monolaurate inhibits Candida and Gardnerella vaginalis in vitro and in vivo but not Lactobacillus. 
Antimicrobial agents and chemotherapy 2010; 54:597-601. 
 
30. Schlievert PM, Strandberg KL, Brosnahan AJ, et al. Glycerol monolaurate does not alter 
rhesus macaque (Macaca mulatta) vaginal lactobacilli and is safe for chronic use. Antimicrobial 
agents and chemotherapy 2008; 52:4448-54. 

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SUPPLEMENTS/APPENDICES 
APPENDIX A: SCHEDULE OF EVENTS 
Table 5: 
Schedule of Events 
 
Early Termination 
Unscheduled 
 
Visit 1 
Visit 2 
Visit 3 
 
Day 1 
8 
(Window 
Days 8- 
15)
28 
(Window 
Days 22- 
31)
Informed Consent 
X 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History1 
X 
 
 
 
 
Concomitant Medication 
X 
X 
X 
X 
X 
Intercurrent Medical History2
X 
X 
X 
X 
Physical Exam 
X 
Targeted Physical Exam 
{X} 
{X} 
{X} 
Urine Pregnancy Test 
X 
Gynecological Exam3
X 
X 
X 
X 
X† 
Vaginal Swabs for Nugent Score, bacterial/fungal cultures, 
trichomonas testing and appropriate samples for 
gonorrhea, 
chlamydia testing4
 
X 
 
X 
 
X 
 
X 
 
X† 
Vaginal Swab for Future Use (if subject consents to future 
use sample collection) 
X 
X 
X 
X 
 
Randomization 
X 
Study Drug Administration 
X 
Distribute Memory Aid and Study Drug Kit 
X 
Counsel on intravaginal products, objects, sexual 
intercourse, and pregnancy avoidance 
 
X 
 
X 
 
 
 
Safety Labs 
X 
X 
X^ 
X 
Telephone Contact to Stop Study Treatment 
[X] 
Review Vaginal Symptomology 
X 
X 
X 
X 
X 
Review for insertion of intravaginal products, objects, and 
sexual intercourse 
 
X 
X 
X 
 
Review Memory Aid and Collect Study Drug Kit 
 
X 
X+ 
X 
 
Assessment of Clinical Cure 
X 
X 
X 
Assessment of Therapeutic Cure 
X 
X 
X 
AE/SAE 
X 
X 
X 
X* 
X 
 
1 Include menstrual, contraceptive, sexual history and history of previous episodes of vaginitis. 
2 Include use of intravaginal products or objects, sexual intercourse, treatment for vaginitis (other than the study product). 
3 Evaluate cervix, vagina, and vulva. Perform Vaginal pH, Saline Wet Mount, KOH Wet Mount, “Whiff Test”. 

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4 Collect vaginal swabs for study specific tests (gram stain, cultures for bacterial flora and yeast) and trichomonas OSOM testing (if saline wet 
mount is negative, Visit 1 only) and institution specific samples for culture or molecular testing for Chlamydia, Neisseria gonorrheae. (Visit 1 
only). Samples for gonorrhea and chlamydia testing will be consistent with standard of care at the institution). 
5 Provide instructions on proper use of study drug applicator and observe first dose. Remaining 5 doses will be administered by the subject at 
home on Day 2 and Day 3. 
6 Safety Laboratories Include: White blood cell count, hemoglobin, platelet count, absolute neutrophil count, creatinine, ALT, AST, total 
bilirubin, random glucose, HIV test (Visit 1 only). 
{ } Targeted physical examination if indicated based on review of symptoms. 
[ ] Subjects will be called regarding grade 3 laboratory abnormalities within 24 hours of receipt of results and told to discontinue study product. 
Subjects with positive HIV, chlamydia or gonorrhea tests will be contacted as soon as possible after results are available and referred to 
their primary care provider for appropriate treatment. 
+ Memory Aid will be reviewed only if solicited events continued at Visit 2. Study Drug Kit returned only if not returned at Visit 2. 
* If subject declines to return for an in-person visit, the study personnel will ask to contact the subject by telephone to assess for AE/SAEs on 
Day 22-31. 
† Evaluate cervix, vagina, and vulva. Collect appropriate clinical samples for genital infectious pathogens. 
# Assess for vaginal discharge (quantity, color, odor, and consistency) and record presence or absence of objective signs of 
inflammation of cervix, vagina, and vulva (edema, erythema, excoriation). 
^ Laboratory abnormalities that occurred between Visit 1 and Visit 2 or worsened at Visit 2 should be repeated until resolved or has stabilized. 
Further testing beyond Visit 3 is at the discretion of the PI or study investigator. 

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APPENDIX B: Toxicity Table 
Table 6: 
Toxicity Table 
HEMATOLOGY 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe 
(Grade 3) 
Hemoglobin (Female) - g/dL 
11.0-11.5 
9.5-10.9 
<9.5 
WBC Increase - cell/mm3 
11,001- 
15,000 
15,001-20,000 
>20,000 
WBC Decrease - cell/mm3 
2,500-3,500 
1,500-2,499 
<1500 
Platelets Decreased - cell/mm3 
120,000- 
130,000 
100,000- 
119,999 
<100,000 
Neutrophils Decrease - cell/mm3 
1,500-1,799 
1,000-1,499 
<1000 
 
 
 
 
CHEMISTRIES 
 
 
 
Glucose – Hypoglycemia mg/dL 
60-64 
55-59 
<55 
Glucose – Hyperglycemia Random – mg/dL 
140-159 
160-200 
>200 
Creatinine – mg/dL 
>ULN-1.7 
1.8-2.0 
>2.0 
AST U/L 
44-105 
106-175 
>175 
ALT U/L 
34-105 
106-175 
>175 
Bilirubin (serum total) mg/dL 
1.3-2.0 
2.1-2.5 
> 2.5 
 
 
 
 

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APPENDIX C: Female Genital Grading Table for Physical Exam Findings 
Table 7: 
Female Genital Grading Table for Physical Exam Findings 
Parameter 
Grade 1 Mild 
Grade 2 Moderate 
Grade 3 Severe 
Vulvar Edema 
Mild, non-pitting edema 
Moderate, 1-2+ pitting 
edema 
3+ pitting edema, severe 
enough to require urinary 
drainage, or weeping edema 
+/- skin breakdown 
Vulvar Erythema 
Erythema covering less than 
50% of vulvar surface 
Erythema covering 50% or 
more of vulvar surface 
NA 
Vulvar Lesions 
Blisters, ulcerations, 
pustules- no treatment 
indicated 
Blisters, ulcerations or 
pustules, with treatment 
indicated 
Severe epithelial disruption 
with hospitalization 
indicated 
Vaginal Edema 
Mild-moderate engorgement 
Loss of ruggae and friability 
NA 
Vaginal Erythema 
Erythema covering less than 
50% of vaginal surface 
Erythema covering 50% or 
more of the vaginal surface 
NA 
Vaginal Discharge 
Mild increase in amount 
Moderate - significant 
increase in amount with 
pooling in vagina on 
examination 
NA 
Vaginal Abrasions or 
lacerations 
Superficial disruptions and 
disruptions extending 
through the mucosa with 
minimal impact on life 
Large disruptions extending 
through the mucosa or large 
superficial disruptions, 
hospitalization not indicated 
Large disruptions extending 
throughout the mucosa or 
large superficial disruptions, 
hospitalization indicated 
Cervical Edema and 
Friability
Edema without friability 
Friable cervix 
NA 
Cervical Erythema 
Erythema covering less than 
50% of cervix 
Erythema covering 50% or 
more of cervix 
NA 
Cervical Lesions 
Blisters, ulcerations, or 
pustules, no treatment 
indicated 
Blisters, ulcerations or 
pustules with treatment 
indicated 
NA