Clinical trial NCT04370548
Conditions: Bacterial Vaginosis
Sponsor: Daré Bioscience, Inc.
Start date: 2020-06-16; Completion date: 2020-12-07
Enrollment: 307 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, randomized, double-blind, placebo-controlled study of DARE-BV1 (clindamycin phosphate vaginal gel, 2%) (QD x 1 day) compared to placebo vaginal gel (HEC Universal Placebo Gel) (QD × 1 day) for the treatment of bacterial vaginosis. Patients will be evaluated at three time points: a Day 1 Screening/Randomization visit, a Day 7-14 Interim Assessment visit, and a Day 21 - 30 Test of Cure \[TOC\] visit). Patients who discontinue prematurely from the study will receive a safety follow-up phone call between Day 21-30. The total study duration will be approximately one month for each individual patient.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: DARE-BV1clindamycin phosphate vaginal gel, 2%
Intervention descriptions: intervention 1: One full applicator (5 g) of clindamycin phosphate vaginal gel, 2% (100 mg clindamycin) or placebo gel will be applied intravaginally as a single dose within 1 day of randomization.

Protocol documents:
Prot_000.pdf: 
Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 1 of 56 
1 
TITLE PAGE 
Protocol Number: 
DARE-BV1-001 
Study Title: 
A Phase 3 Multi-center, Double-blind, Placebo-controlled, Randomized 
Study of DARE-BV1 in the Treatment of Bacterial Vaginosis 
Development Phase: 
Phase 3 
Sponsor: 
Daré Bioscience, Inc. 
3655 Nobel Drive, Suite 260 
San Diego, CA 92122 
Tel.: (858) 926-7655 
Sponsor Contact: 
Nadene Zack, MS 
Vice President, Clinical Operations 
Daré Bioscience, Inc. 
3655 Nobel Drive, Suite 260 
San Diego, CA 92122 
Tel.: (858) 926-7655 x 109 
Medical Monitor 
Contact: 
Judy Gendreau, MD 
Daré Bioscience, Inc. 
3655 Nobel Drive, Suite 260 
San Diego, CA 92122 
Tel.: (858) 367-7002 
Mobile.: (858) 775-3680 
Version Number: 
4.0 
Version Date: 
14 Aug 2020 
This study will be carried out in compliance with the International Council for Harmonisation 
(ICH) E6 (R2) guidance on Good Clinical Practice (GCP) and the United States (U.S.) Code of 
Federal Regulations (CFR) applicable to clinical studies (21 CFR Part 50, 21 CFR Part 56, and 
21 CFR Part 312). 
 
 
 
 
 
 
 
 
 


Clinical Study Protocol 
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2 
TABLE OF CONTENTS 
2.1 
CONTENTS 
1 
TITLE PAGE ................................................................................................................................. 1 
2 
TABLE OF CONTENTS .............................................................................................................. 2 
2.1 
Contents .......................................................................................................................................... 2 
2.2 
List of Tables .................................................................................................................................. 7 
2.3 
List of Figures ................................................................................................................................. 7 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................................... 8 
4 
PROTOCOL SUMMARY ............................................................................................................ 9 
4.1 
Synopsis ........................................................................................................................................... 9 
4.2 
Schedule of Assessments .............................................................................................................. 17 
5 
INTRODUCTION ....................................................................................................................... 24 
5.1 
Study Rationale and Background ............................................................................................... 24 
5.2 
Risk/Benefit Assessment .............................................................................................................. 25 
5.2.1 
Known Potential Risks/Benefits .......................................................................................... 25 
5.2.2 
Assessment of Potential Risks and Benefits ........................................................................ 26 
6 
OBJECTIVES AND ENDPOINTS ............................................................................................ 26 
6.1 
Primary Objective and Endpoint ............................................................................................... 26 
6.2 
Secondary Objectives and Endpoints ......................................................................................... 26 
7 
STUDY DESIGN .......................................................................................................................... 27 
7.1 
Overall Design .............................................................................................................................. 27 
7.2 
Scientific Rationale for Study Design ......................................................................................... 29 
7.3 
Justification for Dose ................................................................................................................... 29 
7.4 
End of Study Definition ............................................................................................................... 29 


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7.5 
Study Duration ............................................................................................................................. 29 
8 
STUDY POPULATION .............................................................................................................. 30 
8.1 
Inclusion Criteria ......................................................................................................................... 30 
8.2 
Exclusion Criteria ........................................................................................................................ 31 
8.3 
Screen Failures ............................................................................................................................. 31 
8.4 
Strategies for Recruitment and Retention ................................................................................. 32 
9 
STUDY INTERVENTION .......................................................................................................... 32 
9.1 
Study Intervention Administration ............................................................................................ 32 
9.1.1 
Study Intervention Description ............................................................................................ 32 
9.1.2 
Dosing and Administration .................................................................................................. 32 
9.2 
Preparation/Handling/Storage/Accountability ......................................................................... 32 
9.2.1 
Acquisition and Accountability ........................................................................................... 32 
9.2.2 
Formulation, Appearance, Packaging, and Labeling ........................................................... 32 
9.2.3 
Product Storage and Stability .............................................................................................. 33 
9.3 
Measures to Minimize Bias: Randomization and Blinding ...................................................... 33 
9.3.1 
Randomization ..................................................................................................................... 33 
9.3.2 
Blinding ............................................................................................................................... 33 
9.4 
Study Intervention Compliance .................................................................................................. 33 
9.5 
Electronic Diary ........................................................................................................................... 34 
9.6 
Concomitant Therapy .................................................................................................................. 34 
9.7 
Patient Discontinuation/Withdrawal From the Study .............................................................. 35 
9.8 
Lost to Follow-up ......................................................................................................................... 35 
10 
STUDY ASSESSMENTS AND PROCEDURES ...................................................................... 35 
10.1 
Study Visits ................................................................................................................................... 35 
10.1.1 
Visit 1: (Day 1) Screening/Randomization ......................................................................... 36 


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10.1.2 
Visits PK1-PK5 (Days 2, 3, 4, 5, and 6): Pharmacokinetic Draw Visits (for 
Pharmacokinetic Subset Only) ............................................................................................ 37 
10.1.3 
Visit 2 (Days 7-14): Interim Assessment ............................................................................ 37 
10.1.4 
Visit 3 (Days 21-30): Test of Cure (TOC) .......................................................................... 38 
10.1.5 
Early Discontinuation Visit ................................................................................................. 39 
10.1.6 
Safety Follow-up Phone Call ............................................................................................... 39 
10.1.7 
Unscheduled Visits .............................................................................................................. 39 
10.2 
Efficacy Assessments ................................................................................................................... 39 
10.3 
Safety and Other Assessments .................................................................................................... 40 
10.3.1 
Medical, Gynecological, Contraceptive, and Relevant Sexual History ............................... 40 
10.3.2 
Demographics ...................................................................................................................... 40 
10.3.3 
Vital Signs, Height, and Weight .......................................................................................... 40 
10.3.4 
Urine Pregnancy Test .......................................................................................................... 40 
10.3.5 
Urinalysis ............................................................................................................................. 40 
10.3.6 
Hematology/Chemistry ........................................................................................................ 41 
10.3.7 
Physical Examination .......................................................................................................... 41 
10.3.8 
Pelvic Examination .............................................................................................................. 41 
10.3.9 
Specimen Collection ............................................................................................................ 41 
10.3.10 
Prior and Concomitant Medications .................................................................................... 41 
10.3.11 
Adverse Events .................................................................................................................... 41 
10.3.12 
Local Site Reactions ............................................................................................................ 42 
10.3.13 
Acceptability Assessment .................................................................................................... 42 
10.3.14 
Pharmacokinetics and Vaginal Clindamycin Assessments ................................................. 42 
10.4 
Adverse Events and Serious Adverse Events ............................................................................ 42 
10.4.1 
Definition of Adverse Events .............................................................................................. 42 
10.4.2 
Definition of Serious Adverse Events ................................................................................. 42 
10.4.3 
Classification of an Adverse Event ..................................................................................... 43 


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10.4.3.1 
Severity of Event ............................................................................................................ 43 
10.4.3.2 
Relationship to Study Intervention ................................................................................. 43 
10.4.4 
Time Period and Frequency for Event Assessment and Follow-up .................................... 44 
10.4.5 
Adverse Event Reporting .................................................................................................... 44 
10.4.6 
Serious Adverse Event Reporting ....................................................................................... 44 
10.4.7 
Reporting of New Information to Patients .......................................................................... 45 
10.4.8 
Reporting of Pregnancy ....................................................................................................... 45 
11 
STATISTICAL CONSIDERATIONS ....................................................................................... 45 
11.1 
Statistical Hypotheses .................................................................................................................. 45 
11.2 
Randomization and Stratification .............................................................................................. 45 
11.3 
Sample Size Determination ......................................................................................................... 45 
11.4 
Populations for Analyses ............................................................................................................. 46 
11.5 
Statistical Analyses....................................................................................................................... 46 
11.5.1 
General Approach ................................................................................................................ 46 
11.5.2 
Analysis of the Primary Efficacy Endpoint ......................................................................... 46 
11.5.3 
Analysis of the Secondary Endpoints .................................................................................. 47 
11.5.4 
Safety Analyses ................................................................................................................... 47 
11.5.5 
Pharmacokinetic Analysis ................................................................................................... 48 
11.5.6 
Baseline Descriptive Statistics ............................................................................................ 48 
11.5.7 
Product Acceptability .......................................................................................................... 48 
11.5.8 
Planned Interim Analyses .................................................................................................... 48 
11.5.9 
Sub-group Analyses............................................................................................................. 48 
11.5.10 
Tabulation of Individual Patient Data ................................................................................. 48 
12 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......... 48 
12.1 
Regulatory, Ethical, and Study Oversight Considerations ...................................................... 48 
12.1.1 
Ethical Conduct of the Study ............................................................................................... 48 


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12.1.2 
Institutional Review Board .................................................................................................. 48 
12.1.3 
Informed Consent Process ................................................................................................... 49 
12.1.4 
Study Discontinuation and Closure ..................................................................................... 49 
12.1.5 
Potential Impact of the COVID-19 Pandemic ..................................................................... 50 
12.1.6 
Confidentiality and Privacy ................................................................................................. 50 
12.1.7 
Future Use of Stored Specimens and Data .......................................................................... 50 
12.1.8 
Key Roles and Study Governance ....................................................................................... 51 
12.1.9 
Safety Oversight .................................................................................................................. 51 
12.1.10 
Clinical Monitoring ............................................................................................................. 51 
12.1.11 
Quality Assurance and Quality Control ............................................................................... 51 
12.1.12 
Data Handling and Record Keeping .................................................................................... 51 
12.1.12.1 Data Collection and Management Responsibilities ........................................................ 52 
12.1.12.2 Study Records Retention ................................................................................................ 52 
12.1.13 
Protocol Deviations ............................................................................................................. 52 
12.1.14 
Publication and Data Sharing Policy ................................................................................... 52 
12.1.15 
Conflict of Interest Policy ................................................................................................... 53 
12.2 
Protocol Signature Page - Sponsor ............................................................................................. 54 
12.3 
Protocol Signature Page – Principal Investigator ..................................................................... 55 
13 
REFERENCES ............................................................................................................................. 56 
 


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2.2 
LIST OF TABLES 
Table 1: Schedule of Assessments .............................................................................................................. 17 
Table 2: Schedule of Assessments for Pharmacokinetic Subset ................................................................. 20 
 
2.3 
LIST OF FIGURES 
Figure 1: Study Flow Charts ....................................................................................................................... 23 
 
 


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3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Definition 
AE 
Adverse Event 
BV 
Bacterial Vaginosis 
CFR 
Code of Federal Regulations 
CMH 
Cochran-Mantel-Haenszel test 
eCRF 
Electronic Case Report Form 
eDiary 
Electronic Diary 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
hCG 
Human Chorionic Gonadotropin 
HEC 
Hydroxyethylcellulose 
HPV 
Human Papillomavirus 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
Intrauterine Device 
KOH 
Potassium Hydroxide 
LTFU 
Lost to Follow-Up 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
Minimum 
mITT 
Modified Intent-to-Treat 
N 
Number of Patients 
NAAT 
Nucleic Acid Amplification Test 
PK 
Pharmacokinetics 
PKS 
Pharmacokinetics Subset (population) 
PP 
Per-Protocol 
QD 
Daily (Latin: Quaque Die) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
spp. 
Species Pluralis (i.e., multiple species in a given genus) 
STI 
Sexually-transmitted Infections 
TEAE 
Treatment Emergent Adverse Events 
TOC 
Test of Cure 
U.S. 
United States 
WHO-DD 
World Health Organization Drug Dictionary 
 


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4 
PROTOCOL SUMMARY 
4.1 
SYNOPSIS 
Name of Sponsor/Company: 
Daré Bioscience, Inc.  
Name of Investigational Product: 
Clindamycin phosphate vaginal gel, 2% (DARE-BV1) 
Name of Active Ingredient: 
Clindamycin phosphate  
Title of Study:  
A Phase 3 Multi-center, Double-blind, Placebo-controlled, Randomized Study of DARE-BV1 in the 
Treatment of Bacterial Vaginosis 
Study Centers: Approximately 36 sites in the United States 
Study Period: 
The study duration for each patient will be up to approximately 1 month:  
 
Visit 1 (Day 1) screening and randomization, including treatment;  
 
Visit 2 (Day 7-14) interim assessment of efficacy parameters and safety; 
and  
 
Visit 3 (Day 21-30) assessment of clinical cure and safety or the Follow-up 
Safety Phone Visit (Day 21-30) for patients who discontinue prematurely 
from the study. 
For patients in the pharmacokinetics (PK) subset only, there will be additional 
blood draws at Visit 1 (Day 1) as well as 5 additional visits between Visit 1 and 
Visit 2 (Visits PK1-PK5 on Days 2 through 6).  
Phase of 
development: 3 
Objectives: 
Primary: 
Assess the efficacy of DARE-BV1 for the treatment of bacterial vaginosis (BV) in postmenarchal 
females. 
Secondary: 
Assess the safety and acceptability of DARE-BV1. 
Study Design:  
This is a multicenter, randomized, double-blind, placebo-controlled study of DARE-BV1 (clindamycin 
phosphate vaginal gel, 2%) (daily [QD] × 1 day) compared to placebo vaginal gel 
(hydroxyethylcellulose [HEC] Universal Placebo Gel) (QD × 1 day) for the treatment of BV. Patients 
will be evaluated at 3 time points: a Day 1 Screening/Randomization visit, a Day 7-14 Interim 


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Assessment visit, and a Day 21-30 Test of Cure [TOC] visit). Patients who discontinue prematurely 
from the study will receive a safety follow-up phone call between Day 21-30. The total study duration 
will be up to approximately 1 month for each individual patient. 
The date of the patient’s last menstrual period and expected timing of her next menses will need to be 
taken into consideration prior to scheduling the Screening/Randomization Visit to ensure the patient is 
not menstruating at the time of the visit, nor expected to start menstruating during the first 7 days after 
study drug administration. In the event that the patient is found to be menstruating at the time of the 
initial Screening/Randomization Visit, or is due to start menstruating within 1 week of the visit, then 
randomization should be delayed. Split screening visits are therefore allowed (while noting protocol 
requirements for those assessments that must be repeated or delayed until the day of randomization). 
At the Screening/Randomization Visit (Day 1), past medical and obstetrical/gynecological history, 
contraception and medically relevant sexual history, and number of episodes of BV in the preceding 
12 months (along with treatment given) will be collected/evaluated. Signs and symptoms of BV will be 
evaluated, including color, odor, and consistency of vaginal discharge, plus vulvovaginal itching and 
irritation will be assessed. Additionally, the following samples/tests will be collected and performed: 
saline wet mount to assess clue cell percentage, 10% potassium hydroxide (KOH) “whiff test” and 
KOH wet mount microscopy for yeast assessment, vaginal culture for Candida species, vaginal pH, 
preparation of slides for centralized Gram stain for Nugent scoring, urine pregnancy test, nucleic acid 
amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae, OSOM® test for 
Trichomonas vaginalis, blood sample for chemistry and hematology, and urinalysis.   
Patients will be provided with instructions for using a daily electronic diary (eDiary). The patient 
eDiary will be utilized to collect information regarding study drug administration, symptoms related to 
BV, relevant adverse events (AEs) and other pertinent information. 
Eligible patients will be randomly assigned via Interactive Response Technology (IRT) to one of the 
following treatment groups (2:1): clindamycin phosphate vaginal gel, 2% (DARE-BV1; 1 dose is 5 g 
gel = 100 mg clindamycin) QD × 1 day, or placebo vaginal gel (Universal HEC Placebo Gel, 5 g), 
QD × 1 day. Study drug will be applied intravaginally within 1 day of randomization. 
The patients will return to the clinic for Visit 2 on Day 7-14 for the Interim Assessment. A third and 
final visit will be conducted at Day 21-30 for TOC. Similar to the requirement at randomization, 
patients should not be actively menstruating on the day of the Interim or TOC Visit, although the TOC 
Visit should take priority, if scheduling around menses is challenging. At both the Visit 2 (Day 7-14) 
and Visit 3 (Day 21–30) visits, the Investigator will perform gynecological examinations and collect 
specimens for the following tests: saline wet mount to assess clue cell percentage, 10% KOH whiff test 
and wet mount microscopy for yeast assessment, vaginal pH, preparation of slides for the centralized 
Gram stain for Nugent Scoring, urinalysis, and urine pregnancy test. Additionally, the signs and 
symptoms of BV including color, odor, and consistency of vaginal discharge, plus vulvovaginal itching 
and irritation will be evaluated at each visit. Post-treatment blood chemistry and hematology 
assessments will be obtained at the TOC Visit (Visit 3, Day 21-30). Repeat testing for N. gonorrhea, 
C. trachomatis, T. vaginalis or Candida species may be obtained at any time if clinically warranted to 
determine the etiology of a change or worsening in vaginal discharge or other signs or symptoms.  
Assessment and documentation of AEs and concomitant medications will occur at each visit. A review 
of patient-reported and Investigator-assessed local site reactions will occur at each visit after 
randomization and treatment. 
Approximately 20 patients at selected sites (2-4 sites are anticipated) will participate in a PK study. The 
patients in this subset will apply the study drug during Visit 1 at the study clinic and will have blood 
draws for plasma clindamycin assessment taken at 0 hours (pre-dose) and then at 2, 4, 6, and 8 hours 
(± 15 minutes) post-dose, as well as at 24, 48, 72, 96, 120, and 144 hours (±2 hours) post-dose 


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(Days 2-7). In addition, samples for vaginal clindamycin concentrations will be collected on Days 1-7 
(with the Day 1 sampling schedule starting pre-dose). For these patients, the assessments for the 
Interim Assessment (Day 7-14) visit may be done on the same day as the Day 7 PK sample collection.  
If necessary due to persistent symptoms of BV, patients may be offered other BV treatment prior to 
completion of the study; however, whenever feasible, other therapy should not be initiated until the 
patient has completed the final TOC Visit (Visit 3, Day 21-30). If initiated prior to Visit 3, then the 
patient should remain in the study and return to the clinic for the final TOC Visit (Visit 3, Day 21-30). 
If other BV treatment is prescribed at Visit 3, then the patient should either be followed by the study 
doctor (if the patient is regularly treated at their clinic), or referred back to their local health care 
provider for further follow-up, as appropriate. The choice of other BV therapy is left up to the 
Investigator in collaboration with the patient, based on the current standard of care. Any other 
medications received for treatment of BV should be recorded as concomitant medications.  
The goal is for all patients to complete the study, regardless of whether additional BV treatment, yeast 
treatment or other anti-microbial therapy is required prior to completion of the final TOC Visit (Visit 3, 
Day 21-30). Patients who discontinue prematurely from the study for any reason will receive a Safety 
Follow-up phone call between Study Days 21-30 to assess the status of BV symptoms, AEs, and 
medication usage.  
Primary Efficacy Endpoint: 
 
The primary efficacy endpoint is the proportion of patients with Clinical Cure at the TOC visit 
(Day 21-30). Clinical Cure is defined as: 
o Resolution of abnormal vaginal discharge associated with BV; 
o Negative 10% KOH whiff test; and 
o Clue cells < 20% of the total epithelial cells in the saline wet mount. 
Secondary Efficacy Endpoints: 
 
Proportion of patients with Bacteriological Cure at the TOC visit (Day 21-30). Bacteriological 
Cure is defined as a Nugent score < 4. 
 
Proportion of patients with Therapeutic Cure at the TOC visit (Day 21-30). Therapeutic Cure 
is defined as both a Clinical Cure (defined above) and Bacteriological Cure (Nugent 
Score < 4). 
 
Proportion of patients with Clinical Cure (defined above) at the Interim Assessment visit 
(Day 7-14). 
 
Proportion of patients with Bacteriological Cure (Nugent score < 4) at the Interim Assessment 
visit (Day 7-14). 
 
Proportion of patients with Therapeutic Cure at the Interim Assessment visit (Day 7-14).  
Safety and Acceptability Assessments: 
 
Clinical laboratory tests (chemistry, hematology, and urinalysis) 
 
OSOM® test for Trichomonas vaginalis 
 
NAATs for Chlamydia trachomatis and Neisseria gonorrhoeae 
 
Clinical and microscopic assessment for vulvovaginal candidiasis 
 
Vaginal culture for Candida species 


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 
Review of treatment-emergent adverse events (TEAEs) and local site reactions 
 
Review of concomitant medications 
 
Acceptability Questionnaire 
Additional Pharmacokinetic Assessments (PK subset only): 
 
Pharmacokinetic blood draws to assess plasma clindamycin levels for Days 1-7 
 
Vaginal clindamycin concentration levels for Days 1-7 
Number and types of patients (planned): 
Approximately 282 patients will be enrolled. 
Criteria for Inclusion: 
Diagnosis and Main Eligibility Criteria: 
Patients with a clinical diagnosis of BV (see below) at the Screening/Randomization Visit who meet 
the following eligibility criteria may participate in the study: 
Inclusion Criteria: 
1. Patients must provide written informed consent prior to any study-related procedures being 
performed. Patients from 12 through 17 years old may participate where permitted by 
applicable local regulations and Institutional Review Board (IRB) approval and with 
appropriate documentation of consent from the parent(s)/guardian(s) and assent from the 
patient. 
2. Patients must have a clinical diagnosis of BV, defined as having all of the following: 
a. Off-white (milky or gray), thin, homogeneous discharge with minimal or absent 
pruritus and inflammation of the vulva and vagina 
b. The presence of clue cells > 20% of the total epithelial cells on microscopic 
examination of the saline wet mount 
c. Vaginal secretion pH of > 4.5 
d. A fishy odor of the vaginal discharge with the addition of a drop of 10% KOH (i.e., a 
positive whiff test) 
3. Patients must be females ≥ 12 years of age with no known medical conditions that, in the 
Investigator’s opinion, may interfere with study participation. 
4. Patients must agree to abstain from sexual intercourse and/or sexual activity throughout the 
first 7 days following treatment. Non-pregnant patients must also agree to use adequate birth 
control (see Inclusion Criterion #5) should they later engage in heterosexual intercourse 
through the final study visit (Visit 3, Day 21-30). 
5. This trial will enroll pregnant women; however, non-pregnant patients of childbearing potential 
should use adequate birth control after Day 7 if engaging in heterosexual intercourse, and 
should not plan on becoming pregnant for the duration of the study. Acceptable forms of birth 
control include oral contraceptives (“the pill”), intrauterine devices (IUDs), contraceptive 
implants under the skin, patches or injections, and non-polyurethane condoms (e.g., latex, 
polyisoprene) with or without spermicide. Patients in same sex relationships, or monogamous 
relationships with vasectomized males, may also participate. Abstinence may also be 
acceptable, per the Investigator’s judgment. Oral or transdermal hormonal contraceptives must 


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be in use for 1 full cycle (e.g., 4 to 8 weeks) prior to study drug application. Injectable or 
implanted contraceptives (e.g., Depo-Provera, Nexplanon, or hormonal IUD) must have been 
injected/inserted at least 7 days prior to study drug application.  
Patients who are not of childbearing potential will not need a urine pregnancy test prior to 
randomization or at subsequent visits.  The patient is considered to be of non-child bearing 
potential if one of the following is satisfied:  
a. Postmenopausal for at least 1 year prior to the Screening/Randomization Visit (Visit 1) 
(defined as amenorrheic for more than 1 continuous year), or 
b. Surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or 
hysterectomy) at least 6 months before first dose, or 
c. Non-surgical permanent sterilization procedure performed at least 3 months prior to 
study drug application. 
6. Patients must be willing to refrain from the use of all intra-vaginal products (e.g., douches, 
feminine deodorant sprays, condoms, spermicides, vaginal moisturizers or lubricants, tampons, 
vaginal birth control rings [e.g., NuvaRing®], and diaphragms) through the first 7 days at a 
minimum, and ideally through Visit 3 (Day 21-30) or Study Exit/Early Discontinuation. 
Exclusion Criteria: 
1. Patients with active vulvovaginitis or other active infectious causes of cervicitis, vaginitis, or 
vulvitis, based on the results of the thorough clinical assessments and in-clinic microscopic 
assessments performed prior to enrollment  (e.g., candidiasis, Trichomonas vaginalis, 
Chlamydia trachomatis, Neisseria gonorrhoeae, or genital lesions or ulcers consistent with 
human papillomavirus (HPV), Herpes simplex, syphilis, chancroid, etc.). Patients with a 
history of genital herpes or condylomata who have been asymptomatic for at least 6 months 
may be considered for eligibility. 
2. Potential patients who are breastfeeding or, if of child-bearing potential, unwilling to practice 
acceptable means of birth control or abstinence during the study as described above. 
3. Patients with a vaginal, vulvar, or genitourinary condition that, according to the Investigator’s 
judgment, may confound the interpretation of clinical response. 
4. Patients with a history of regional enteritis, ulcerative colitis, or a history of Clostridium 
difficile-associated diarrhea. 
5. Patients with known current drug or alcohol abuse that could impact study compliance.  
6. Patients currently receiving or who have received antifungal or antibacterial therapy (systemic 
or intravaginal) within 14 days of the Screening/Randomization Visit (Visit 1).  
7. Patients who have used any other investigational product within 30 days of the 
Screening/Randomization Visit (Visit 1). 
8. Patients who will undergo evaluation or treatment during the study for abnormal cytology 
and/or findings from high risk HPV testing and/or Pap test finding. 
9. Patients with known sensitivity to clindamycin phosphate or other lincosamides or any of the 
inactive ingredients in the study drug. 
10. Patients with a history of any severe acute or chronic medical or psychiatric condition or 
laboratory abnormality that could increase the risk associated with trial participation or study 
treatment administration or could interfere with the interpretation of trial results and, in the 
judgment of the Investigator, would make the patient inappropriate for entry into the trial. 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
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Test Product, Dose, and Mode of Administration: 
DARE-BV1 (clindamycin phosphate vaginal gel, 2%) will be supplied in tubes with accompanying 
applicators. To dispense the product, the patient will screw the applicator onto the tube and express 
product from the tube into the applicator, up to the stop line on the applicator. One full applicator (5 g) 
of clindamycin phosphate vaginal gel, 2% (100 mg clindamycin) will be applied intravaginally as a 
single dose. 
Reference Therapy, Dose, and Mode of Administration: 
Placebo vaginal gel (HEC Universal Placebo Gel) will be supplied in matching tubes with 
accompanying applicators, as above. One full applicator of placebo vaginal gel (5 g) will be applied 
intravaginally as a single dose.  
Statistical Analyses: 
All statistical processing will be performed using SAS®, Version 9.4, or later. Continuous variables 
will be summarized with number of patients (N), mean, median, standard deviation (SD), minimum 
(Min), and maximum (Max). Categorical variables will be summarized with frequency counts and 
percentages. 
All efficacy analyses will be conducted using a 2-sided test at an alpha level of 0.05. The primary 
efficacy analyses will be conducted on the modified intent-to-treat (mITT) population. Additionally, 
efficacy analyses will be performed on the per-protocol (PP) population and will be considered 
supportive. Safety analyses will be performed on the Safety population. Patients will be analyzed 
according to the treatment to which they were randomized for intent-to-treat (ITT) and mITT analyses, 
regardless of actual treatment received. For all other analysis populations, patients will be analyzed 
according to the treatment they received. 
Populations: 
Intent-to-Treat (ITT): All randomized patients 
Safety: All ITT population patients who applied study drug 
Pharmacokinetic Subset (PKS): All Safety population patients who are enrolled into the PK subset 
Modified Intent-to-Treat (mITT): All Safety population patients except those excluded due to 
demonstrating a positive test result for other concomitant vaginal or cervical infections at baseline 
(e.g., T. vaginalis, N. gonorrhoeae, C. trachomatis, Candida species) or who are determined to have a 
baseline Nugent score of < 7. If the Nugent score at baseline is missing, then the patient is excluded 
from the mITT population.  
Per-Protocol (PP): The PP population will include patients from the mITT population who either 
receive other BV therapy during the study for any reason, or meet the following criteria: 
1. Meet all 4 Amsel’s criteria at screening 
2. Apply study drug within 1 day of randomization 
3. Do not use a prohibited medication prior to the Day 21-30 visit 
4. Attend the Day 21-30 visit  
5. Have no other major protocol violations that impact the primary or secondary endpoints. 
For the mITT and PP populations, if the patient receives other BV therapy for any reason, the patient 
will be included in the analysis as a treatment failure for all visits on or after receipt of the other 
therapy. Patients will be excluded from the PP population if they receive study treatment that was not 


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Daré Bioscience, Inc. 
 
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the treatment to which they were randomized. A review of the data will be performed prior to locking 
the database and unblinding the study to determine which medications and major protocol violations 
would impact the primary and secondary endpoints and cause a patient to be excluded from the PP 
population. 
Efficacy Analyses: 
All efficacy endpoints will be summarized for each treatment group using descriptive statistics, 
including 95% confidence intervals (within treatment group), as appropriate. 
Primary Efficacy Analyses: 
The primary efficacy analysis of Clinical Cure at Day 21-30 will be analyzed for the mITT population 
with a Cochran-Mantel-Haenszel (CMH) test stratified by study center and race (African-
American/Black versus all others). The method for handling of patients in the mITT analysis without a 
Clinical Cure result at Day 21-30 will be described in the final Statistical Analysis Plan. 
Secondary Efficacy Analyses: 
Hypothesis testing for the secondary efficacy endpoints will be conducted in a sequential manner to 
control the Type 1 error rate, in the order presented below: 
 
Proportion of patients in the mITT population with Bacteriological Cure at the TOC visit 
(Day 21-30).  
 
Proportion of mITT patients with Therapeutic Cure at the TOC visit (Day 21-30).  
 
Proportion of mITT patients with Clinical Cure (defined above) at the Interim Assessment 
visit (Day 7-14). 
 
Proportion of mITT patients with Bacteriological Cure (Nugent score < 4) at the Interim 
Assessment visit (Day 7-14). 
 
Proportion of mITT patients with Therapeutic Cure at the Interim Assessment visit 
(Day 7-14).  
Analysis of the secondary endpoints will follow the same method as the analysis of the primary 
endpoint.  
The PP population will be used to perform sensitivity analyses of the above primary and secondary 
efficacy analyses. Patients in the PP population without a Clinical Cure assessment at the TOC visit 
(Day 21-30) will be excluded from the PP analyses.  
Pharmacokinetic Analysis: 
The following PK parameters will be summarized for the PKS population to assess plasma and vaginal 
clindamycin levels for Days 1-7:  
1. minimum concentration (Cmin)  
2. maximum concentration (Cmax)  
3. area under the curve (AUC0-t), where t is the last time-point with measurable 
concentration)  
4. time to maximum concentration (Tmax)  
5. elimination half-life (t1/2) 
Descriptive summaries of plasma and vaginal clindamycin levels will be presented for each timepoint. 


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Daré Bioscience, Inc. 
 
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Safety Analyses: 
Descriptions of AEs will include the date of onset, the date the AE ended, the maximum severity of the 
AE, relationship to study drug, seriousness, any action taken, and the outcome. 
All TEAEs occurring during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities (MedDRA) terminology. Treatment-emergent AEs are those AEs 
with an onset at the time of, or after the application of study drug. All reported TEAEs will be 
summarized by treatment group, system organ class and preferred term. Adverse events summaries will 
also include severity, relationship to study drug, and seriousness. When summarizing events by 
causality and severity, each patient will be counted only once within a system organ class or a preferred 
term by using the event with the greatest relationship and highest severity within each classification. In 
addition, a list of patients who had a serious adverse event (SAE) or who prematurely discontinued 
from the study due to an AE will be provided. 
Changes from baseline and shifts from baseline will be summarized for safety laboratory results. A 
listing that displays all out-of-range laboratory test results will also be provided.  
Local site reactions will be summarized at each visit. 
Interim Analysis: 
No interim analyses are planned. 
Sample Size Justification: 
The sample size calculations were performed using SAS® version 9.4 for the 2-group chi-square test. It 
is expected that this test will provide approximately the same power as the CMH test stratified by 
analysis center and race. A sample size of 188 DARE-BV1 versus 94 placebo patients will have 90% 
power to detect a statistically significant difference at a significance level of 0.05 (2-tailed) under the 
assumption that the clinical cure rates will be 55% and 30% for DARE-BV1 and placebo, respectively. 
This sample size assumes 35% of randomized patients will not be in the mITT population.  
 
 
 
 
 


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DARE-BV1-001 
Daré Bioscience, Inc. 
 
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4.2 
SCHEDULE OF ASSESSMENTS 
Table 1: Schedule of Assessments  
Visit 
Visit 1 
Visit 2 
Visit 3 
Safety Follow-up Phone 
Visit 
 
 
Early 
Discontinuation 
Visit Name 
Screening/ 
Randomization 
Interim 
Assessment 
Test of Cure 
(TOC) 
 (FU after Early 
Discontinuation)1  
+5 days 
Study Day(s) 
1 
7-14 
21-30 
21-30 
 
 
Written informed consent administration 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical, gynecological, contraceptive, & 
relevant sexual history2 
X 
 
 
 
 
Height 
X 
 
 
 
 
Weight 
X 
 
 
 
 
Vital signs 
X 
X 
X 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
Urine pregnancy test3 
X 
X 
X 
 
X 
Urinalysis4  
X 
X 
X 
 
X 
Hematology/chemistry 
X 
 
X 
 
X 
Physical examination5 
X 
 
X 
 
X 
Pelvic examination6 
X 
X 
X 
 
X 
Assessment of local site reactions7 
X 
X 
X 
 
X 
Amsel’s criteria assessments: 
 
 
 
 
 
-Vaginal discharge evaluation 
X 
X 
X 
 
X 
-KOH whiff test  
X 
X 
X 
 
X 
-Clue cells (wet mount) 
X 
X 
X 
 
X 
-Vaginal secretion pH 
X 
X 
X 
 
X 
Signs and symptoms of BV, including color, 
odor, and consistency of vaginal discharge, 
vulvovaginal itching, and irritation8 
X 
X 
X 
X 
X 
KOH wet mount for microscopic yeast 
assessment9 
X 
X 
X 
 
X 
Vaginal culture for Candida species10  
X 
 
 
 
 
Collect sample/prepare slides for Nugent 
score10 
X 
X 
X 
 
X 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 18 of 56 
Visit 
Visit 1 
Visit 2 
Visit 3 
Safety Follow-up Phone 
Visit 
 
 
Early 
Discontinuation 
Visit Name 
Screening/ 
Randomization 
Interim 
Assessment 
Test of Cure 
(TOC) 
 (FU after Early 
Discontinuation)1  
+5 days 
Study Day(s) 
1 
7-14 
21-30 
21-30 
 
 
Perform OSOM® test for Trichomonas 
vaginalis10 
X 
 
 
 
 
Collect samples for Chlamydia trachomatis and 
Neisseria gonorrhoeae NAATs10 
X 
 
 
 
 
Review eligibility criteria 
X 
 
 
 
 
Randomization 
X 
 
 
 
 
Review of eDiary 
X 
X 
X 
 
X 
Dispense study drug and instructions 
X 
 
 
 
 
Collect study drug and perform compliance 
assessment11 
 
X 
 
 
 
Record treatment application date 
 
X 
 
 
 
Acceptability Questionnaire 
 
X 
X 
 
X 
Abbreviations: BV = bacterial vaginosis; eDiary = electronic diary; FU = follow-up; KOH = potassium hydroxide; NAAT = nucleic acid amplification test; 
TOC = Test of Cure 
Notes 
If necessary due to persistent symptoms of BV, patients may be offered other BV treatment prior to completion of the study; however, whenever feasible, other BV therapy should 
not be initiated until the patient has completed the final TOC Visit (Visit 3, Day 21-30). If initiated prior to Visit 3, then the patient should remain in the study and return to the 
clinic for the final TOC Visit (Visit 3, Day 21-30). If other treatment is prescribed at Visit 3, then the patient should either be followed by the study doctor (if the patient is 
regularly treated at their clinic), or be referred back to their local health care provider for further follow-up, as appropriate. The choice of other BV therapy is left up to the 
Investigator in collaboration with the patient, based on the current standard of care.  
Any other medications received for treatment of BV should be recorded as concomitant medications. 
1 Patients who are discontinued early from the study will be contacted by phone between study Day 21-30 to assess BV symptoms, adverse events and concomitant medications.  
2 For medical, gynecological, contraceptive, and relevant sexual history, the recorded information will include: acute and chronic history of medical and gynecological conditions 
(including history of BV), smoking, illicit drug and alcohol use history, menstrual cycle history (start date of last menstrual cycle and expected timing of next menses will be 
collected), medically relevant sexual history including history of sexually-transmitted infections (STIs), current sexual activity, previous/current contraceptive use, and pregnancy 
history. 
3 Pregnancy testing via urine human chorionic gonadotropin (hCG) testing will be performed for each patient, unless patient is of non-child-bearing potential as defined within 
Inclusion Criterion #5, at each visit (serum hCG testing will be done only if deemed necessary by the Investigator). 
4 At all visits an in-clinic urine dipstick will be performed. At Visit 1, Visit 3, and the Early Discontinuation visit a central laboratory urinalysis will also be performed. 
5 A complete physical examination should be performed at Visit 1; at Visit 3 and at the Early Discontinuation visit (if applicable), a directed physical examination should be 
performed in accordance with the Investigator’s judgment. Rectal and breast examinations are not required for the complete or directed physical examinations. 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 19 of 56 
6 Pelvic examination will include a vaginal wall inspection as well as an examination of the cervix and will include assessment and appropriate reporting of any abnormalities, and 
confirmation that all findings are consistent with BV, versus Candidiasis or other causes of the patient’s vaginal signs or symptoms. 
7 A review of patient-reported and Investigator-assessed local site reactions will occur at each visit after randomization and treatment. A baseline assessment will be recorded for 
all subjects during Visit 1 Screening assessments. 
8 The color, odor, and consistency of vaginal discharge are to be assessed as part of the assessment of the Amsel Criteria, and the presence of vulvovaginal itching and irritation are 
to be assessed as part of the assessment of Local Site Reactions.   
9 The microscopic yeast assessment may be done on the same sample obtained for the 10% KOH whiff test. A swab of the vaginal pool should be utilized for both assessments.  
10 Diagnostic assessments for Candida spp, C. trachomatis, N. gonorrhoeae, or T. vaginalis may be repeated after baseline if changes in the patient’s clinical condition warrant re-
testing. Full instructions for the collection of all samples, including the slides for Nugent scoring, will be provided in the laboratory procedures manual.  
11 Perform compliance assessment by weighing both the dispensed and returned tubes and recording the weights in the eCRF. 


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DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
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Table 2: Schedule of Assessments for Pharmacokinetic Subset 
Visit 
Visit 1 
Visits 
PK1-PK5 
Visit 2 
Visit 3 
Safety Follow Up 
Phone Visit 
Early  
Discontinuation 
Visit Name 
Screening/ 
Randomization 
PK Draws (PK 
Subset Only) 
Interim 
Assessment 
Test of Cure 
(TOC) 
FU after Early  
Discontinuation)1 
+5 days 
Study Day(s) 
1 
2, 3, 4, 5, 6 
7-14 
21-30 
21-30 
 
Written informed consent administration 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical, gynecological, contraceptive, & 
relevant sexual history2 
X 
 
 
 
 
 
Height 
X 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
Vital signs 
X 
 
X 
X 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
Urine pregnancy test3 
X 
 
X 
X 
 
X 
Urinalysis4 
X 
 
X 
X 
 
X 
Hematology/chemistry 
X 
 
 
X 
 
X 
Physical examination5 
X 
 
 
X 
 
X 
Pelvic examination6 
X 
 
X 
X 
 
X 
Assessment of local site reactions7 
X 
 
X 
X 
 
X 
Amsel’s criteria assessments: 
 
 
 
 
 
 
-Vaginal discharge evaluation 
X 
 
X 
X 
 
X 
-KOH whiff test 
X 
 
X 
X 
 
X 
-Clue cells (wet mount) 
X 
 
X 
X 
 
X 
-Vaginal secretion pH 
X 
 
X 
X 
 
X 
Signs and symptoms of BV, including 
color, odor, and consistency of vaginal 
discharge, vulvovaginal itching, and 
irritation8 
X 
 
X 
X 
X 
X 
Collect sample for KOH wet mount for 
microscopic yeast assessment9 
X 
X 
X 
X 
 
X 
Vaginal culture for Candida species10 
X 
 
 
 
 
 
Collect samples/prepare slides for Nugent 
score10 
X 
 
X 
X 
 
X 
OSOM® test for Trichomonas vaginalis10 
X 
 
 
 
 
 
Collect swabs for Chlamydia trachomatis 
and Neisseria gonorrhoeae NAATs10 
X 
 
 
 
 
 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 21 of 56 
Visit 
Visit 1 
Visits 
PK1-PK5 
Visit 2 
Visit 3 
Safety Follow Up 
Phone Visit 
Early  
Discontinuation 
Visit Name 
Screening/ 
Randomization 
PK Draws (PK 
Subset Only) 
Interim 
Assessment 
Test of Cure 
(TOC) 
FU after Early  
Discontinuation)1 
+5 days 
Study Day(s) 
1 
2, 3, 4, 5, 6 
7-14 
21-30 
21-30 
 
Review eligibility criteria 
X 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
Review of eDiary 
X 
X 
X 
X 
 
X 
Dispense study drug and instructions 
X 
 
 
 
 
 
Collect study drug and perform compliance 
assessment11 
 
 
X 
 
 
 
Record treatment application date 
 
 
X 
 
 
 
Acceptability Questionnaire 
 
 
X 
X 
 
X 
Collect samples for clindamycin plasma 
level assessment  
(PK subset only) 
X 
(for PK subset 
only) 
X 
(for PK subset 
only) 
X 
(for PK subset 
only on 
Day 7) 
 
 
X 
(for PK subset 
only if within 
first 7 days) 
Collect samples for vaginal clindamycin 
concentration  
(PK subset only) 
X 
(for PK subset 
only) 
X 
(for PK subset 
only) 
X 
(for PK subset 
only on 
Day 7) 
 
 
X 
(for PK subset 
only, if 
applicable) 
Abbreviations: BV = bacterial vaginosis; eDiary = electronic diary; FU = follow-up; KOH = potassium hydroxide; NAAT = nucleic acid amplification test; 
PK = pharmacokinetic; TOC = Test of Cure 
Notes 
If necessary due to persistent symptoms of BV, patients may be offered other BV treatment prior to completion of the study; however, whenever feasible, other BV therapy should 
not be initiated until the patient has completed the final TOC Visit (Visit 3, Day 21-30). If initiated prior to Visit 3, then the patient should remain in the study and return to the 
clinic for the final TOC Visit (Visit 3, Day 21-30). If other treatment is prescribed at Visit 3, then the patient should either be followed by the study doctor (if the patient is 
regularly treated at their clinic), or be referred back to their local health care provider for further follow-up as appropriate. The choice of other BV therapy is left up to the 
Investigator in collaboration with the patient, based on the current standard of care.  
Any additional medications received for treatment of BV should be recorded as concomitant medications. 
1 Patients who are discontinued early from the study will be contacted by phone between study Day 21-30 to assess BV symptoms, adverse events and concomitant medications.  
2 For medical, gynecological, contraceptive, and relevant sexual history, the recorded information will include: acute and chronic history of medical and gynecological conditions 
(including history of BV), smoking, illicit drug and alcohol use history, menstrual cycle history (start date of last menstrual cycle and expected timing of next menses will be 
collected), medically relevant sexual history including history of sexually-transmitted infections (STIs), current sexual activity, previous/current contraceptive use, and pregnancy 
history. 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 22 of 56 
3 Pregnancy testing via urine human chorionic gonadotropin (hCG) testing will be performed for each patient, unless patient is of non-childbearing potential as defined in Inclusion 
Criterion #5, at each visit (serum hCG testing will be done only if deemed necessary by the Investigator). 
4 At all visits an in-clinic urine dipstick will be performed. At Visit 1, Visit 3, and the Early Discontinuation visit a central laboratory urinalysis will also be performed. 
5 A complete physical examination should be performed at Visit 1; at Visit 3 and at the Early Discontinuation visit (if applicable), a directed physical examination should be 
performed in accordance with the Investigator’s judgment. Rectal and breast examinations are not required for the complete or directed physical examinations. 
6 Pelvic examination will include a vaginal wall inspection as well as an examination of the cervix and will include assessment and appropriate reporting of any abnormalities, and 
confirmation that all findings are consistent with BV, versus Candidiasis or other causes of the patient’s vaginal signs or symptoms. 
7 A review of patient-reported and Investigator-assessed local site reactions will occur at each visit after randomization and treatment.  A baseline assessment will be recorded for 
all subjects during Visit 1 Screening assessments. 
8 The color, odor, and consistency of vaginal discharge are to be assessed as part of the assessment of the Amsel Criteria, and the presence of vulvovaginal itching and irritation are 
to be assessed as part of the assessment of Local Site Reactions.   
9 The microscopic yeast assessment may be done on the same sample obtained for the 10% KOH whiff test. A swab of the vaginal pool should be utilized for both assessments.  
10 Diagnostic assessments for Candida spp, C. trachomatis, N. gonorrhoeae, or T. vaginalis may be repeated after baseline if changes in the patient’s clinical condition warrant re-
testing. Full instructions regarding the collection of all samples, including the slides for Nugent scoring, will be included in the laboratory procedures manual.  
11 Perform compliance assessment by weighing both the dispensed and returned tubes and recording the weights in the eCRF. 
 
 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 23 of 56 
 
Figure 1: Study Flow Charts 
 
 
 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
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Page 24 of 56 
5 
INTRODUCTION 
5.1 
STUDY RATIONALE AND BACKGROUND 
Bacterial vaginosis (BV) is the most common vaginal infection in postmenarchal females of childbearing 
age. It is a condition in which there is excess growth of certain types of bacteria within the vagina. Recent 
descriptions have identified in particular the overgrowth of Gardnerella vaginalis and Atopobium 
vaginae. This overgrowth affects the normal balance of bacteria within the vagina and can lead to 
symptoms that include: 
 
A thin white or gray vaginal discharge 
 
Pain, itching, or burning in the vagina 
 
A strong fish-like odor, especially after sex 
 
Burning when urinating 
 
Itching around the outside of the vagina 
The causes of BV are not fully understood. It is known that BV is more common in sexually active 
women, but it is not known how sex contributes to BV (Hay, 2014; Center for Disease Control, 2017). 
In addition to its symptoms, there is some evidence that BV may contribute to pelvic inflammatory 
disease, preterm birth, and higher risk of acquisition of sexually transmitted infections (Center for Disease 
Control, 2017; Sobel & Sobel, 2015; Taylor, 2013). 
Currently, in the United States (U.S.), oral and intravaginal metronidazole, intravaginal clindamycin, oral 
tinidazole, and oral secnidazole are available for the treatment of BV. 
DARE-BV1 is a thermosetting bioadhesive intravaginal gel formulated with 2% clindamycin phosphate 
designed to release the active ingredient for an extended period of time (Mondal, 2011). The extended 
period of time is approximately 7 days, based on in vitro data, and will be better defined in this study with 
the pharmacokinetic (PK) subset. Research has shown that effective drug delivery is essential to 
optimizing drug therapy for BV. Because of its chemical composition, DARE-BV1 is designed as non-
toxic and should not compromise condoms or diaphragms. 
DARE-BV1 is a viscous solution that undergoes solution to gel (sol-to-gel) transition at body 
temperature. This property allows the product to remain at the site of vaginal infection. By the process of 
“reverse thermal gelation,” the viscosity of the base matrix increases from room temperature when 
exposed to body temperature. 
Clindamycin has been found effective against organisms usually associated with BV such as Bacteroides 
species (spp.), Peptococcus spp., Gardnerella vaginalis, Mobiluncus spp., and Mycoplasma hominis. 
Clindamycin can be classified as a time-dependent antibiotic for which maximizing the exposure time and 
the amount of drug is recommended to improve efficacy. Topical application, safety, and efficacy of 
vaginally delivered clindamycin phosphate have been widely demonstrated in published literature 
(e.g., Donders, 2014). 
DARE-BV1, formulated with clindamycin, is designed to produce a prolonged duration of exposure to 
clindamycin at the site of infection. 
DARE-BV1 has been evaluated in a fertility and early embryonic development to implantation study in 
rats (Segment 1 reproductive toxicology).  It has also been tested in embryo-fetal development toxicity 
and toxicokinetic studies in rats and rabbits (Segment 2 reproductive toxicology).  No adverse outcomes 
were noted in these studies.  Based on these findings, the administration of DARE-BV1 to pregnant 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 25 of 56 
women is justified.  Therefore, patients who are known to be pregnant at the time of screening (and who 
satisfy all entry criteria) will be allowed to enroll in the study. 
5.2 
RISK/BENEFIT ASSESSMENT 
5.2.1 
Known Potential Risks/Benefits 
DARE-BV1 clindamycin phosphate vaginal gel, 2%, is contraindicated in patients with a prior history of 
hypersensitivity to clindamycin or other lincosamides or other ingredients of the formulation. 
In currently marketed clindamycin phosphate vaginal cream 2% (Clindesse®), the most common adverse 
reactions, reported in ≥2% of patients and at a higher rate in the active treatment group than in the placebo 
group, were vaginosis fungal (14%), headache (7%), back pain (5%), constipation (2%), and urinary tract 
infection (2%) (Perrigo Specialty Pharmaceuticals, 2014). 
Many oral antibiotics, including clindamycin, may cause overgrowth of dangerous bacteria in the large 
intestine (e.g. Clostridium difficile). This may cause mild diarrhea, or it may cause a life-threatening 
condition called colitis (inflammation of the large intestine). Clindamycin is more likely to cause this type 
of infection than many other antibiotics. Patients with Crohn’s disease (regional enteritis), ulcerative 
colitis, or C. difficile-related diarrhea are not eligible for the study.  Patients with other types of chronic 
enteritis or colitis should be discussed with the Medical Monitor prior to randomization.        
Other known side effects of oral clindamycin treatment are listed below. This information is not based on 
treatment with 2% clindamycin vaginal gel, which would be expected to result in significantly lower 
systemic blood levels than those obtained with oral formulations. 
 
Nausea 
 
Vomiting 
 
Unpleasant or metallic taste in the mouth 
 
Joint pain 
 
Pain when swallowing 
 
Heartburn 
 
White patches in the mouth 
 
Thick, white vaginal discharge 
 
Burning, itching, and swelling of the vagina 
 
Peeling or blistering skin 
 
Rash 
 
Hives 
 
Itching 
 
Difficulty breathing or swallowing 
 
Hoarseness 
 
Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs 
 
Yellowing of the skin or eyes 
 
Decreased urination 
Potential benefits of DARE-BV1 in treatment of BV include its simplicity of use (a single application), its 
thermoreversible properties that should keep the product from leaking out and increase residence time, the 
well-established effectiveness of clindamycin in treating BV, and the infrequency of serious side effects 
associated with clindamycin use. 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 26 of 56 
5.2.2 
Assessment of Potential Risks and Benefits 
Potential risks that may be associated with use of DARE-BV1 have been minimized in this study by the 
following: 
 
Establishing eligibility criteria that exclude patients with clinically significant conditions that 
would preclude DARE-BV1 use; 
 
Selecting Investigators with the proper level of training and experience in assessing and treating 
BV; 
 
Ensuring adequate monitoring is performed to identify any safety issues associated with the study 
procedure and patients; and 
 
Regularly reviewing reported serious adverse event (SAEs) and adverse events (AEs) throughout 
the study and taking appropriate medical measures to resolve the AEs. 
The expected risk/benefit profile for DARE-BV1 is sufficient to perform this Phase 3 clinical study. 
6 
OBJECTIVES AND ENDPOINTS 
6.1 
PRIMARY OBJECTIVE AND ENDPOINT 
The primary objective of the study is to assess the efficacy of DARE-BV1 for the treatment of BV in 
postmenarchal females. 
The primary efficacy endpoint is the proportion of patients with Clinical Cure at the Test of Cure (TOC) 
visit (Day 21-30). Clinical Cure is defined as: 
 
Resolution of abnormal vaginal discharge associated with BV; 
 
Negative 10% potassium hydroxide (KOH) whiff test; and 
 
Clue cells < 20% of the total epithelial cells in the saline wet mount. 
6.2 
SECONDARY OBJECTIVES AND ENDPOINTS 
The secondary efficacy endpoints of the study include assessment of Bacteriological Cure and 
Therapeutic Cure of BV in postmenarchal females. Secondary efficacy endpoints are: 
 
Proportion of patients with Bacteriological Cure at the TOC visit (Day 21-30). Bacteriological 
Cure is defined as a Nugent score < 4. 
 
Proportion of patients with Therapeutic Cure at the TOC visit (Day 21-30). Therapeutic Cure is 
defined as both a Clinical Cure (defined above) and Bacteriological Cure (Nugent Score < 4). 
 
Proportion of patients with Clinical Cure (defined above) at the Interim Assessment visit (Day 7-
14). 
 
Proportion of patients with Bacteriological Cure (Nugent score <4) at the Interim Assessment 
visit (Day 7-14).  
 
Proportion of patients with Therapeutic Cure at the Interim Assessment visit (Day 7-14).  
The secondary objective of the study is to assess the safety and acceptability of DARE-BV1. Assessments 
include: 
 
Clinical laboratory tests (chemistry, hematology, and urinalysis) 
 
OSOM® test for Trichomonas vaginalis 


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 
Nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae 
 
Clinical and microscopic assessment for vulvovaginal candidiasis 
 
Vaginal culture for Candida species 
 
Review of treatment-emergent adverse events (TEAEs) 
 
Review of concomitant medications 
 
Acceptability Questionnaire 
The PK assessment (PK subset only) is as follows: 
 
Pharmacokinetic blood draws to assess plasma clindamycin levels for Days 1-7 
 
Collect samples for vaginal clindamycin concentrations for Days 1-7 
 
7 
STUDY DESIGN 
7.1 
OVERALL DESIGN 
This is a multicenter, randomized, double-blind, placebo-controlled study of DARE-BV1 clindamycin 
phosphate vaginal gel, 2% (daily [QD] × 1 day) compared to placebo vaginal gel (hydroxyethylcellulose 
[HEC] Universal Placebo Gel) (QD × 1 day) for the treatment of BV. Patients will be evaluated at 3 time 
points: a Day 1 Screening/Randomization visit, a Day 7-14 Interim Assessment visit, and a Day21-30 
TOC visit (or a Day 21-30 Safety Follow-up phone call visit for patients who are prematurely 
discontinued). The total study duration will be up to approximately 1 month for a patient. 
At the Screening/Randomization Visit (Day 1), past medical and obstetrical/gynecological/menstrual 
history, contraception and medically relevant sexual history, and lifetime BV history and number of 
episodes of BV in the preceding 12 months (along with treatment given) will be collected/evaluated. 
Signs and symptoms of BV will be evaluated, including color, odor and consistency of vaginal discharge, 
plus vulvovaginal itching and irritation will be assessed.  
Additionally, the following samples/tests will be collected and performed: saline wet mount to assess clue 
cell percentage and other pertinent findings (e.g., trichomonads, white blood cells, other cellular and 
microbial elements), 10% KOH whiff test and KOH wet mount for yeast assessment; vaginal culture for 
Candida species; vaginal pH; slide preparation for centralized Gram stain for Nugent scoring, urine 
pregnancy test, NAATs for Chlamydia trachomatis and Neisseria gonorrhoeae, OSOM® test for 
Trichomonas vaginalis, blood sample for chemistry and hematology and urinalysis. 
A major goal of the screening process is to confirm the presence of BV and to rule out the presence of 
other infectious and non-infectious causes of vulvovaginitis. Careful attention must therefore be paid to 
both the clinical assessment of the patient and to microscopic assessments (saline and KOH wet mount). 
However,  the medical literature suggests that clinical and microscopic assessments are less than optimal 
at identifying patients with candidiasis (Schwebke, 2020; Lowe, 2009); therefore, a vaginal culture for 
Candida species will be obtained at baseline on each randomized patient, and used to determine if the 
patient will be included in the modified intent-to-treat (mITT) population. The NAAT testing for 
N. gonorrhea and C. trachomatis will be obtained for similar reasons, and rapid testing for T. vaginalis 
will be performed onsite to rule out Trichomonas prior to randomization.  
In the event that there is any ambiguity in the patient’s signs, symptoms, or microscopic assessments 
suggesting that the patient may have a mixed infection, then randomization and treatment should be 
delayed until the results of the yeast culture and/or NAATs are available (assuming the patient is able and 
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(or if it is not feasible to delay treatment), then the patient should be screen-failed.      
If, however, the patient’s screening assessments support the diagnosis of BV only and the patient is 
randomized, but it is later learned that the Candida culture was positive at screening, the clinician should 
assess whether antifungal therapy is clinically warranted, or if the culture represents a subclinical 
condition that does not require medical treatment.  An AE should be captured in the eCRF only if the 
patient requires treatment for signs/symptoms consistent with a yeast infection, i.e., a positive culture by 
itself does not constitute an AE.   
Patients with positive NAAT results at screening for C. trachomatis or N. gonorrheae should be treated as 
indicated per the investigator’s judgment, and an AE captured in the eCRF.  In such cases, the AE eCRF 
question “Did this adverse event begin prior to using the study medication?” should be answered “Yes” to 
indicate that the AE onset was prior to dosing.    
Patients should not be menstruating at the Screening/Randomization Visit, nor expected to begin 
menstruating during the 7 days after study drug administration; therefore, the optimal timing for the 
Day 1 visit should be carefully evaluated during pre-screening. If the patient is found to be menstruating 
at the time of the initial Screening/Randomization visit or is due to start menstruating within 1 week of 
the visit, then randomization should be delayed. For this reason (and others), split screening visits are 
allowed. Ideally the patient will return to the clinic as soon as possible after the end of her menses for 
completion of all assessments and randomization; however, a 14-day window is provided to 
accommodate this and other circumstances that could require a delay in randomization. Section 10.1.1 
provides additional information regarding the assessments that must be completed on the day of 
randomization (Day 1), regardless of the reason for the delay.  
At Visit 1 patients will also be provided with instructions for using a daily electronic diary (eDiary). The 
patient eDiary will be utilized to collect information regarding study drug administration, symptoms 
related to BV, relevant AEs and other pertinent information. Site staff will review the patient’s eDiary 
responses with the patient at each study visit to ensure that all relevant information is documented in the 
electronic case report form (eCRF) (such as medication use and AEs since the previous visit). 
Eligible patients will be randomly assigned via Interactive Response Technology (IRT) to one of the 
following treatment groups (2:1): clindamycin phosphate vaginal gel, 2% (DARE-BV1; 1 dose is 5 g 
gel = 100 mg clindamycin) QD × 1 day, or placebo vaginal gel (Universal HEC Placebo Gel), 5 g, 
QD × 1 day. Study drug will be applied intravaginally within 1 day of randomization.  
The patients will return to clinic for Visit 2 on Day 7-14 for the Interim Assessment visit. A third and 
final visit will be conducted at Day 21-30 for Test of Cure (TOC). Similar to the requirement at 
randomization, patients should not be actively menstruating on the day of the Interim or TOC Visit, 
although the TOC Visit should take priority, if scheduling around menses is challenging. At both the 
Visit 2 (Day 7-14) and Visit 3 (Day 21-30) visits, the Investigator will perform gynecological 
examinations and collect specimens for the following tests: saline wet mount to assess clue cell 
percentage, 10% KOH whiff test and wet mount microscopic yeast assessment, vaginal pH, preparation of 
slides for the centralized Gram stain for Nugent Scoring, urinalysis, and urine pregnancy test. 
Additionally, the signs and symptoms of BV including color, odor, and consistency of vaginal discharge, 
plus vulvovaginal itching and irritation will be evaluated at each visit. Post-treatment blood chemistry and 
hematology assessments will be obtained at the TOC Visit (Visit 3, Day 21-30). If clinical symptoms 
(supported by microscopic findings) indicate active vulvovaginal candidiasis at Visit 2 or Visit 3, a 
vaginal yeast culture should be obtained. Repeat diagnostic testing for N. gonorrhoeae, C. trachomatis or 
T. vaginalis may also be obtained at any time if clinically warranted to determine the etiology of a change 
or worsening in vaginal discharge or other signs or symptoms. Any clinically significant conditions 
arising after randomization should be recorded as AEs.  


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Approximately 20 patients at selected sites (2-4 sites are anticipated) will participate in a PK study. The 
patients in this subset will apply the study drug at the study clinic during Visit 1 and will have blood 
draws for plasma clindamycin assessment taken at 0 hours (pre-dose) and then at 2, 4, 6, and 8 hours 
(±15 minutes) post-dose, as well as at 24, 48, 72, 96, 120, and 144 hours (±2 hours) post-dose (Days 2-7). 
In addition, samples for vaginal clindamycin concentrations will be collected on Days 1--7 (with the 
Day 1 sampling schedule starting pre-dose; no post-dose vaginal clindamycin samples will be collected 
on Day 1). For these patients, the assessments for the Interim Assessment (Day 7-14) visit may be done 
on the same day as the Day 7 PK draw. 
Assessment and documentation of AEs and concomitant medications will occur at each visit. A review of 
patient-reported and Investigator-assessed local site reactions will occur at each visit after randomization 
and treatment. Patients’ daily eDiary entries will be reviewed at each visit. 
If necessary due to persistent symptoms of BV, patients may be offered other BV treatment prior to 
completion of the study; however, whenever feasible, other therapy should not be initiated until the 
patient has completed the final TOC Visit (Visit 3, Day 21-30). If initiated prior to Visit 3, then the 
patient should remain in the study and return to the clinic for the final TOC Visit (Visit 3, Day 21-30). If 
other BV treatment is prescribed at Visit 3, then the patient should either be followed by the study doctor 
(if the patient is regularly treated at their clinic), or referred back to their local health care provider for 
further follow-up, as appropriate. The choice of other BV therapy is left up to the Investigator in 
collaboration with the patient, based on the current standard of care. Any other medications received for 
treatment of BV should be recorded as concomitant medications. 
The goal is for all patients to complete the study, regardless of whether additional BV treatment (or other 
antibacterial/antifungal therapy) is provided prior to completion of the final TOC visit/Visit 3. Patients 
who discontinue prematurely from the study for any reason will receive a Safety Follow-up phone 
call between Study Days 21-30 to assess the status of BV symptoms, AEs, and medication usage. 
7.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
A double-bind, placebo-controlled, randomized design is appropriate for investigating the efficacy, safety 
and acceptability of a vaginal antibiotic treatment for BV because this study design has been well-
established in the published literature for evaluating BV treatment in a Phase 3 study. The study design is 
also consistent with the current U.S. Food and Drug Administration (FDA) draft guidance entitled 
“Bacterial Vaginosis: Developing Drugs for Treatment,” dated August 2019. 
7.3 
JUSTIFICATION FOR DOSE 
Use of one full applicator (5 g) of clindamycin phosphate vaginal gel, 2% (100 mg clindamycin) is 
justified based on published data for existing marketed vaginal clindamycin treatments for BV.  
7.4 
END OF STUDY DEFINITION 
The end of the study is defined as completion of the last visit or procedure shown in the Schedule of 
Assessments in the trial globally. 
7.5 
STUDY DURATION 
The study duration for each patient will be up to approximately 1 month: Visit 1 (Day 1) 
Screening/Randomization Visit including treatment; Visit 2 (Day 7-14) for interim assessment of efficacy 


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parameters and safety; and either the final Visit 3 (Day 21-30) assessment of efficacy and safety, or the 
Follow-up Safety Phone Visit (Day 21-30) for patients who discontinue prematurely from the study.  
8 
STUDY POPULATION 
Patients with a clinical diagnosis of BV at the Screening/Randomization Visit who meet the following 
eligibility criteria may participate in the study. 
8.1 
INCLUSION CRITERIA 
1. Patients must provide written informed consent prior to any study-related procedures being 
performed. Patients from 12 through 17 years old may participate where permitted by applicable 
local regulations and Institutional Review Board (IRB) approval and with appropriate 
documentation of consent from the parent(s)/guardian(s) and assent from the patient. 
2. Patients must have a clinical diagnosis of BV, defined as having all of the following: 
a. Off-white (milky or gray), thin, homogeneous discharge with minimal or absent pruritus 
and inflammation of the vulva and vagina 
b. The presence of clue cells > 20% of the total epithelial cells on microscopic examination 
of the saline wet mount 
c. Vaginal secretion pH of > 4.5 
d. A fishy odor of the vaginal discharge with the addition of a drop of 10% KOH (i.e., a 
positive whiff test) 
3. Patients must be females ≥ 12 years of age with no known medical conditions that, in the 
Investigator’s opinion, may interfere with study participation. 
4. Patients must agree to abstain from sexual intercourse and/or sexual activity throughout the first 
7 days following treatment. Non-pregnant patients must also agree to use adequate birth control 
(see Inclusion Criterion #5) should they later engage in heterosexual intercourse through the 
final study visit (Visit 3, Day 21-30).  
5. This trial will enroll pregnant women; however, non-pregnant patients of childbearing potential 
should use adequate birth control after Day 7 if engaging in heterosexual intercourse, and should 
not plan on becoming pregnant for the duration of the study. Acceptable forms of birth control 
include oral contraceptives (“the pill”), intrauterine devices (IUDs), contraceptive implants under 
the skin, patches or injections, non-polyurethane condoms (e.g., latex, polyisoprene) with or 
without spermicide. Patients in same sex relationships, or monogamous relationships with 
vasectomized males, may also participate. Abstinence may also be acceptable, per the 
Investigator’s judgment. Oral or transdermal hormonal contraceptives must be in use for 1 full 
cycle (e.g., 4 to 8 weeks) prior to study drug application. Injectable or implanted contraceptives 
(e.g., Depo-Provera, Nexplanon, or hormonal IUD) must have been injected/inserted at least 
7 days prior to study drug application.  
Patients who are not of childbearing potential will not need a urine pregnancy test prior to 
randomization or at subsequent visits.  The patient is considered to be of non-child bearing 
potential if one of the following is satisfied:  
a. Postmenopausal for at least 1 year prior to the Screening/Randomization Visit (Visit 1) 
(defined as amenorrheic for more than 1 continuous year), or 
b. Surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or 


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hysterectomy) at least 6 months before first dose, or 
c. Non-surgical permanent sterilization procedure performed at least 3 months prior to study 
drug application. 
Patients must be willing to refrain from the use of all intra-vaginal products (e.g., douches, 
feminine deodorant sprays, condoms, spermicides, vaginal moisturizers or lubricants, tampons, 
vaginal birth control rings [e.g., NuvaRing®], and diaphragms) through the first 7 days at a 
minimum, and ideally through Visit 3 (Day 21-30) or Study Exit/Early Discontinuation. 
8.2 
EXCLUSION CRITERIA 
1. Patients with active vulvovaginitis or other active infectious causes of cervicitis, vaginitis, or 
vulvitis, based on the results of the thorough clinical assessments and in-clinic microscopic 
assessments performed prior to enrollment  (e.g., candidiasis, Trichomonas vaginalis, Chlamydia 
trachomatis, Neisseria gonorrhoeae, or genital lesions or ulcers consistent with human 
papillomavirus (HPV), Herpes simplex, syphilis, chancroid, etc.). Patients with a history of 
genital herpes or condylomata who have been asymptomatic for at least 6 months may be 
considered for eligibility. 
2. Potential patients who are breastfeeding or, if of child-bearing potential, unwilling to practice 
acceptable means of birth control or abstinence during the study as described above. 
3. Patients with a vaginal, vulvar, or genitourinary condition that, according to the Investigator’s 
judgment, may confound the interpretation of clinical response. 
4. Patients with a history of regional enteritis, ulcerative colitis, or a history of C. difficile-associated 
diarrhea. 
5. Patients with known current drug or alcohol abuse that could impact study compliance.  
6. Patients currently receiving or who have received antifungal or antibacterial therapy (systemic or 
intravaginal) within 14 days of the Screening/Randomization Visit (Visit 1). 
7. Patients who have used any other investigational product within 30 days of the 
Screening/Randomization Visit (Visit 1). 
8. Patients who will undergo evaluation or treatment during the study for abnormal cytology and/or 
findings from high risk HPV testing and/or Pap test finding. 
9. Patients with known sensitivity to clindamycin phosphate or other lincosamides or any of the 
inactive ingredients in the study drug. 
10. Patients with a history of any severe acute or chronic medical or psychiatric condition or 
laboratory abnormality that could increase the risk associated with trial participation or study 
treatment administration or could interfere with the interpretation of trial results and, in the 
judgment of the Investigator, would make the patient inappropriate for entry into the trial. 
8.3 
SCREEN FAILURES 
Screen failures are defined as patients who consent to participate in the clinical trial but are not 
randomized to receive treatment. Screen failures may be re-screened in cases where the unmet selection 
criteria have been resolved after previous screen failure. A new Informed Consent Form (ICF) will be 
needed for re-screened patients if more than 30 days have passed since informed consent was obtained. 
Re-screened patients who are re-screened past the 30-day window and are re-consented will be assigned a 
new patient number. Randomized patients prematurely withdrawn from the study will not be replaced. 


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8.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Patients will be recruited to this study by the participating study physicians. Advertising will be allowed 
in accordance with applicable regulations and as approved by the Sponsor or designee and the IRB. 
9 
STUDY INTERVENTION 
9.1 
STUDY INTERVENTION ADMINISTRATION 
9.1.1 
Study Intervention Description 
Test Product, Dose, and Mode of Administration: DARE-BV1 (clindamycin phosphate vaginal gel, 
2%) will be supplied in tubes with accompanying applicators. To dispense the product, the patient will 
screw the applicator onto the tube and express product from the tube into the applicator, up to the stop 
line in the applicator. One full applicator (5 g) of clindamycin vaginal gel, 2% (100 mg clindamycin) will 
be applied intravaginally as a single dose. 
Reference Therapy, Dose and Mode of Administration: Placebo vaginal gel (HEC Universal Placebo 
Gel) will also be supplied in matching tubes with accompanying applicators, as above. One full applicator 
of placebo vaginal gel (5 g) will be applied intravaginally as a single dose. 
Additional details regarding clinical trial material will be provided in the pharmacy manual. 
9.1.2 
Dosing and Administration 
One full applicator (5 g) of clindamycin phosphate vaginal gel, 2% (100 mg clindamycin) or placebo gel 
will be applied intravaginally as a single dose within 1 day of randomization. 
9.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
9.2.1 
Acquisition and Accountability 
Receipt, use and return of the study drug will be documented in an accountability log in each site’s 
regulatory file. The log should specify lot/batch number and dates of supply and return. Study drug will 
not be distributed to the participating center until all agreements between the Principal Investigator and 
Sponsor are finalized and IRB approvals have been obtained. Distributed study drug will be used only for 
this study, in accordance with this protocol and instructions for use. 
At the end of the study, the monitor will review final accountability of all clinical supplies. Used study 
drug destruction/disposal will occur on-site following site-specific destruction standard operating 
procedures in accordance with instructions provided by the Sponsor or designee. If destruction services 
are not available on-site, unused study drug will be returned to the packaging and labeling vendor for 
destruction services. Guidance for remaining unused study product return or disposal will be provided by 
the Sponsor at the end of the study.  
9.2.2 
Formulation, Appearance, Packaging, and Labeling 
The study drug will be supplied with appropriate packaging and labeling in accordance with International 
Council for Harmonisation (ICH) E6 (R2) Section 5.13 and 21 Code of Federal Regulations (CFR) 312.6. 
Details regarding study drug packaging, labeling, and use instructions will be provided in the study 
reference manual. 


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9.2.3 
Product Storage and Stability 
The study drug should be stored at room temperature between 15°C (59°F) and 30°C (86°F), and in a 
secured space at each site. All clinical supplies should only be handled by authorized personnel according 
to the delegation log in the site regulatory file. 
9.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
9.3.1 
Randomization 
Randomization will occur after a patient’s eligibility has been confirmed. Patients will be assigned a 
unique patient identification number by the site at screening. Following completion of the screening 
procedures, eligible patients will be randomized in a blinded manner via the validated, access controlled, 
IRT system. Stratification factors in the randomization are: PK subset (Yes/No), site, and race (African-
American/Black versus all others). Patients will be randomized to 1 of 2 treatment groups (DARE-BV1 
[clindamycin phosphate vaginal gel, 2%] or placebo vaginal gel) in a 2:1 ratio, with approximately 
188 patients be randomized to DARE-BV1, and 94 patients randomized to placebo vaginal gel.  
Randomization will be requested by adequately trained and delegated site staff with appropriate user 
access to the IRT system. Unique patient randomization numbers and treatment allocations will be 
provided within the IRT system and will be generated from the randomization scheme. A randomization 
number will be automatically provided by the IRT system and confirmed by email, ensuring concealment 
of treatment allocation.  
9.3.2 
Blinding 
This is a double-blind study. The Principal Investigator and other site staff will be blinded to study 
treatment throughout the conduct of the study. Treatment randomization information will be kept 
confidential and will not be released to the blinded Investigator or blinded Investigator site personnel until 
the study database has been locked or the Investigator requests unblinding for safety reasons.  
At the initiation of the study, the site will be instructed on procedures for breaking the blind for safety 
reasons. The study blind should be maintained whenever possible to avoid bias. Active study drug and 
placebo reference therapy will be packaged in matching tubes with accompanying applicators. 
If the treatment assignment must be revealed for the safety of the patient or to treat an AE, the 
Investigator should contact the Medical Monitor or designee. A decision to break the blind should be 
reached by the Medical Monitor or designee and the Investigator.  
The Investigator or designee may break the blind independent of the Medical Monitor only if it is 
considered an emergency by the Investigator. If this occurs, the Medical Monitor and the Sponsor must be 
notified within 24 hours of breaking the blind.  
The event requiring breaking the blind must be documented and reported appropriately, including the date 
the blind was broken.  
9.4 
STUDY INTERVENTION COMPLIANCE 
Participants will return their study drug tube and applicator following use.  Study drug compliance will be 
verified through confirmation of the weight of the study drug tube prior to dispensation and upon return to 
the study site.  Additional dosing information will be captured in real-time via patient reported eDiary 


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entries to ensure application procedures were properly followed. Finally, compliance information will be 
recorded for each patient on a study-specific drug accountability log. 
Instances of significant over- or under-dosing are considered protocol deviations but will not be 
automatically recorded as AEs. Any undesirable medical occurrence resulting from significant over- or 
under-dosing is an AE and should be recorded and reported on the AE eCRF. The Investigator should record 
the event in the source document and should monitor the subject. 
9.5 
ELECTRONIC DIARY 
Patients will be instructed on how to use their daily eDiary at Visit 1. Site staff will review eDiary entries 
with patients at each study visit and ensure that any relevant information pertaining to new medications or 
AEs has been appropriately captured in the eCRF. 
9.6 
CONCOMITANT THERAPY 
Concomitant medications include any medication or health product (any prescription medications or over-
the-counter preparations) taken from the time the patient signs the informed consent documents until 
study exit and must be reported appropriately on the eCRF. Information on prior medications taken within 
30 days of consent should be collected (including supplements and herbal remedies in addition to 
prescription and over-the-counter medications). 
Recording of all concomitant treatments will occur on the patient’s source and eCRF, including the name 
of the drug, dose, start and stop dates, and reason for use, from the time the ICF is signed through 
completion or discontinuation from the trial. Any other investigational product must have been stopped at 
least 30 days before the start of screening for this trial. Other medications for the treatment of inter-
current medical conditions will be permitted and recorded as detailed above unless identified as 
prohibited medications.  
Patients should not have received antifungal or antibacterial therapy (systemic or intravaginal) during the 
14 days prior to the Screening/Randomization Visit (Visit 1). Patients on suppressive antiviral therapy for 
herpes simplex infections are considered eligible for the study provided they have remained 
asymptomatic for at least 6 months prior to screening (as per Exclusion Criterion #1) and antiviral therapy 
is expected to continue in a stable fashion for the duration of the study. Patients receiving antiviral 
therapy for other indications at the time of screening should be assessed on a case-by-case basis and 
discussed with the Medical Monitor prior to randomization. Oral probiotics are permitted, provided usage 
has been stable for at least 1 month prior to randomization and is intended to remain stable during the 
patient’s study participation.  
Patients enrolled and treated in this study who have lack of relief of BV symptoms at or prior to Visit 3 
and are treated with other BV therapy should not be discontinued from the study. The same is generally 
true for patients requiring any other antimicrobial therapy during their study participation. Patients who 
satisfy all eligibility criteria based on clinical and microscopic assessments at screening, but then, after 
randomization and dosing, are discovered to be positive for Chlamydia (CT), gonorrhea (NG), or Candida 
based on their screening NAATs or Candida culture, should be encouraged to complete the study; i.e., 
they should not be discontinued solely due to positive screening laboratory results--unless there are 
reasons why it is not in the patient’s best interest to continue in the study.  The goal is for all patients to 
complete the study whenever feasible and appropriate; therefore, any patient requiring antifungal, 
antibacterial (whether for BV or an unrelated indication), or antiviral therapy should be assessed on a 
case-by-case basis, and if in doubt, discussed with the Medical Monitor, to determine if/when it is not 
appropriate for the patient to continue in the study.  


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9.7 
PATIENT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Each patient will be informed of her right to withdraw from the study at any time and for any reason. A 
patient may be discontinued from the study at any time if the patient, the Investigator, or the Sponsor feels 
that it is not in the patient’s best interest to continue in the study.  
Patients who sign the ICF and agree to participate in the study, but do not meet eligibility criteria, will be 
considered screen failures.  
Following enrollment, patients may be discontinued from the study for the following reasons:  
 
Lack of compliance (i.e., failure to follow protocol requirements that is judged severe enough by 
the Investigator to significantly affect study outcomes) 
 
Any AE or intercurrent illness that would jeopardize the patient’s health or the interpretation of 
the results of the study 
 
Lost to follow-up 
 
Patient withdrawal of consent  
 
Treatment failure 
 
Retrospective discovery of an entry criterion violation 
 
Pre-existing condition or abnormality, including abnormal laboratory or microbiological result 
obtained at screening 
 
Other (e.g., sponsor decision, pregnancy during the study, logistical issues related to Covid-19, 
etc.) 
Prior to discontinuing a patient from the study, the site should contact Daré or designee. The reason for 
discontinuation must be recorded on the appropriate section of the patient’s eCRF and Early 
Discontinuation procedures should be performed. 
9.8 
LOST TO FOLLOW-UP 
A patient cannot be considered withdrawn due to becoming lost to follow-up (LTFU) until the research 
site performs and documents at least 3 attempts to contact her. Documentation must include at least 
1 letter sent via a method that allows a “return receipt,” e.g., certified mail, to be requested with 
instructions provided to the patient to contact the research site. Every reasonable effort must be made to 
follow up with patients who discontinue with study drug-related AEs in order to determine the final 
outcome. 
Patients designated as LTFU who later resume contact with the site should be requested to come in for an 
unscheduled visit to complete early discontinuation procedures. Documentation should include the period 
of time they were out of contact with the site (after last contact). If the Investigator anticipates future 
problems with follow up, then the patient should be withdrawn from the study. 
10 
STUDY ASSESSMENTS AND PROCEDURES 
10.1 
STUDY VISITS 
The study will include 3 scheduled in-clinic visits for all patients, plus a follow-up phone call for patients 
who discontinue prematurely: 
 
Visit 1: Screening/Randomization for all patients 


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 
Visit 2 (Days 7-14): Interim Assessment for all patients 
 
Visit 3 (Days 21-30): TOC for all patients 
 
Safety Follow-up Phone Visit (Days 21-30) for all prematurely discontinued patients 
For patients in the PK subset only, there will be additional blood draws and vaginal clindamycin 
concentration collections at the Screening/Randomization Visit (Day 1) as well as 5 additional visits 
between Visit 1 and Visit 2 (Visits PK1-PK5 on Days 2 through 6). The assessments for the Interim 
Assessment Visit (Day 7-14) may be done on the same day as the Day 7 PK draw. 
Refer to the Schedule of Assessments for the study (Table 1) and for the PK subset (Table 2) as well as 
the by-visit descriptions below for additional details. 
10.1.1 
Visit 1: (Day 1) Screening/Randomization  
All Visit 1 (Screening/Randomization) procedures should be completed on the same day when feasible. If 
it is not feasible to complete all assessments on the same day, or if the patient’s menstrual cycle requires a 
delay in randomization, then confirmation of eligibility must be repeated at the time of randomization. 
The specific assessments that must be performed on the day of randomization are identified below; the 
Investigator may use clinical judgment to decide whether other assessments should also be repeated. If 
randomization does not occur on same day as the initial screening visit, the patient should return no later 
than 14 days from start of screening (i.e., the signing of the ICF) for randomization. 
During Visit 1, the following procedures should be performed. All assessments must be completed prior 
to randomization; however, if randomization must be delayed and a split screening visit is utilized, then 
the asterisked and italicized assessments below must then be completed (or repeated) on the day of 
randomization.  
 
Written informed consent administration 
 
Demographics 
 
Collection of medical, gynecological, contraceptive, menstrual, and relevant sexual history 
 
Height 
 
Weight* 
 
Vital signs* 
 
Prior and concomitant medications assessment* 
 
Adverse events assessment* 
 
Urine pregnancy test* 
 
In clinic urine dipstick* 
 
Urinalysis 
 
Hematology/chemistry 
 
Complete physical examination 
 
Pelvic examination* 
 
Amsel’s criteria assessments*: 
o Vaginal discharge evaluation* 
o KOH whiff test* 
o Clue cells (wet mount)* 
o Vaginal secretion pH* 
 
Evaluate signs and symptoms of BV, including color, odor, and consistency of vaginal discharge, 
vulvovaginal itching, and irritation* 


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 
Assessment of patient-reported and Investigator-assessed local site reactions* (i.e., patient-
reported burning/stinging, vulvovaginal pain or pruritus, and Investigator-assessed vulvovaginal 
erythema, edema, petechiae or erosions/ulcers). 
 
Utilizing a swab of the vaginal pool, prepare a KOH wet mount for microscopic yeast assessment 
(this may be performed on the same sample used for the KOH whiff test)* 
 
Collect swab for vaginal Candida culture* 
 
Swab the lateral vaginal wall and prepare slides for centralized Nugent scoring as outlined in the 
study procedures manual* 
 
Perform OSOM® test for Trichomonas vaginalis* 
 
Collect swabs for Chlamydia trachomatis and Neisseria gonorrhoeae NAATs* 
 
Review eligibility criteria* 
 
Randomize patient (if patient meets all eligibility requirements)* 
 
Review instructions and provide training on use of eDiary* 
 
Dispense study drug and provide instructions to randomized patients. Under all circumstances 
study drug should be applied within 1 day of randomization.* 
 
PK subset patients only: PK blood draws for plasma clindamycin assessment taken at 0 hours 
(pre-dose) and then at 2, 4, 6, and 8 hours (±15 minutes) post-dose. A baseline swab sample for 
vaginal clindamycin concentration assessment will be taken at Visit 1/Day 1 at 0 hours (pre-dose) 
only; vaginal clindamycin samples will not be taken at post-dose timepoints during 
Visit 1/Day 1.* 
10.1.2 
Visits PK1-PK5 (Days 2, 3, 4, 5, and 6): Pharmacokinetic Draw Visits 
(for Pharmacokinetic Subset Only) 
During Visits PK1-PK5 for patients in the PK subset only: 
 
PK blood draws for clindamycin plasma level assessment and swab samples for vaginal 
clindamycin concentration assessment will be done at:  
o Visit PK1 (Day 2, 24 hours [±2 hour] post-dose) 
o Visit PK2 (Day 3, 48 hours [±2 hour] post-dose) 
o Visit PK3 (Day 4, 72 hours [±2 hour] post-dose) 
o Visit PK4 (Day 5, 96 hours [±2 hour] post-dose) 
o Visit PK5 (Day 6, 120 hours [±2 hour] post-dose) 
 
Concomitant medications assessment 
 
Adverse events assessment 
10.1.3 
Visit 2 (Days 7-14): Interim Assessment 
During Visit 2 (Days 7-14)/Interim Assessment, the following procedures should be performed: 
 
Vital signs 
 
Record treatment application date 
 
Concomitant medications assessment 
 
Adverse events assessment 
 
Urine pregnancy test 
 
In clinic urine dipstick 
 
Pelvic examination 
 
Assessment of patient-reported and Investigator-assessed local site reactions 
 
Amsel’s criteria assessments: 


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o Vaginal discharge evaluation 
o KOH whiff test 
o Clue cells (wet mount) 
o Vaginal secretion pH 
 
Evaluate signs and symptoms of BV, including color, odor, and consistency of vaginal discharge, 
vulvovaginal itching, and irritation 
 
Swab the vaginal pool and prepare KOH wet mount for microscopic yeast assessment (this may 
be performed on the same sample used for the KOH whiff test) 
 
Swab the lateral vaginal wall and prepare slides for centralized Nugent scoring as outlined in the 
study procedures manual 
 
Collect used/unused study drug and perform compliance assessment by weighing the returned 
used tube; record weight in the eCRF 
 
Review eDiary 
 
Administer Acceptability Questionnaire 
 
PK subset patients only: PK blood draw should be done on Day 7 (144 hours [±2 hour] post-
dose). Also, for the PK subset only, collect samples for vaginal clindamycin concentration 
assessment. The other assessments for the Day 7 – 14 visit may be done on the same day as the 
Day 7 PK draw 
10.1.4 
Visit 3 (Days 21-30): Test of Cure (TOC) 
During Visit 3 (Days 21-30)/TOC, the following procedures should be performed: 
 
Vital signs 
 
Concomitant medications assessment 
 
Adverse events assessment 
 
Urine pregnancy test 
 
In clinic urine dipstick 
 
Urinalysis 
 
Hematology/chemistry 
 
Directed physical examination 
 
Pelvic examination 
 
Assessment of patient-reported and Investigator-assessed local site reactions 
 
Amsel’s criteria assessments: 
o Vaginal discharge evaluation 
o KOH whiff test 
o Clue cells (wet mount) 
o Vaginal secretion pH 
 
Evaluate signs and symptoms of BV, including color, odor, and consistency of vaginal discharge, 
vulvovaginal itching, and irritation 
 
Swab the vaginal pool and prepare KOH wet mount for microscopic yeast assessment (this may 
be performed on the same sample used for the KOH whiff test) 
 
Swab the lateral vaginal wall and prepare slides for centralized Nugent scoring as outlined in the 
study procedures manual 
 
Review eDiary 
 
Administer Acceptability Questionnaire 


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10.1.5 
Early Discontinuation Visit 
At Early Discontinuation visits, the following procedures should be performed: 
 
Vital signs 
 
Concomitant medications assessment 
 
Adverse events assessment 
 
Urine pregnancy test 
 
In clinic urine dipstick 
 
Urinalysis 
 
Hematology/chemistry 
 
Directed physical examination 
 
Pelvic examination 
 
Assessment of patient-reported and Investigator-assessed local site reactions 
 
Amsel’s criteria assessments: 
o Vaginal discharge evaluation 
o KOH whiff test 
o Clue cells (wet mount) 
o Vaginal secretion pH 
 
Evaluate signs and symptoms of BV, including color, odor, and consistency of vaginal discharge, 
vulvovaginal itching, and irritation 
 
Swab the vaginal pool and prepare KOH wet mount for microscopic yeast assessment (this may 
be performed on the same sample used for the KOH whiff test) 
 
Swab the lateral vaginal wall and prepare slides for centralized Nugent scoring as outlined in the 
study procedures manual 
 
Collect PK sample if patient was enrolled in that subset and discontinuation was within the first 
7 days 
 
Review eDiary 
 
Administer Acceptability Questionnaire 
10.1.6 
Safety Follow-up Phone Call 
Patients who discontinue early from the study will receive a follow-up phone call from the site staff 
between Study Day 21-30. Patients will be asked questions regarding AEs, concomitant medications and 
the status of their BV symptoms. 
10.1.7 
Unscheduled Visits 
Unscheduled visits are allowed at the discretion of the Investigator for safety assessments or 
administrative reasons. During unscheduled visits, the Investigator will perform any study assessments or 
other safety assessments as necessary to provide appropriate treatment.  
10.2 
EFFICACY ASSESSMENTS 
The primary efficacy endpoint (Clinical Cure at the TOC visit [Day 21-30]) is the resolution of the 
following 3 BV signs included in Amsel’s criteria (Amsel, 1983): abnormal vaginal discharge associated 
with BV as determined by the Investigator, positive KOH whiff test, and the presence of clue cells at 
>20% of the total epithelial cells on microscopic examination of the saline wet mount. 


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The supportive secondary efficacy endpoints are the Bacteriological Cure and the Therapeutic Cure. The 
bacteriological cure is defined as Nugent’s score <4 (via Gram stain performed by a central laboratory). A 
Nugent score ≥4 is considered abnormal and represents an imbalance in vaginal flora that permits BV to 
manifest (Nugent, 1991). Patients who are responders are expected to achieve a normal Nugent score 
(i.e., 0 through 3) following treatment. 
Therapeutic cure is defined as having achieved both Clinical Cure (i.e., resolution of abnormal discharge 
associated with BV, negative whiff test and <20% clue cells on wet mount) and Bacteriological Cure 
(i.e., Nugent score of <4). 
10.3 
SAFETY AND OTHER ASSESSMENTS 
10.3.1 
Medical, Gynecological, Contraceptive, and Relevant Sexual History 
A complete medical, gynecological, contraceptive, and relevant sexual history will be collected at Visit 1, 
including prior and concomitant illnesses. The recorded information will include: acute and chronic 
history of medical and gynecological conditions (including history of BV), smoking, illicit drug and 
alcohol use history, menstrual cycle history (start date of last menstrual cycle and expected timing of next 
menses will be collected), medically relevant sexual history including history of sexually-transmitted 
infections (STIs), current sexual activity, previous/current contraceptive use, and pregnancy history. 
10.3.2 
Demographics 
The date of birth, race, ethnicity, and sex of the patient are to be recorded at Visit 1. 
10.3.3 
Vital Signs, Height, and Weight 
Vital sign measurements will be taken at each visit and include sitting (after 5 to 10 minutes in this 
position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature per 
standard of care. Height and weight will be measured only at Visit 1. 
10.3.4 
Urine Pregnancy Test 
Pregnancy testing via urine human chorionic gonadotropin (hCG) testing will be performed for each 
patient, unless the patient is not of childbearing potential as defined in Inclusion Criterion #5, at each visit 
(serum hCG testing will be done only if deemed necessary by the Investigator). Additional pregnancy 
testing may also be performed if there is any suspicion or clinical concern that a woman might be 
pregnant at any time during the study. 
10.3.5 
Urinalysis 
Onsite dipstick urinalysis will be performed at Visit 1 (Screening), Visit 2 (Interim Assessment), Visit 3 
(TOC), and at the Early Discontinuation Visit as specified in the Schedule of Assessments (Table 1 and 
Table 2 [for PK subset]). In addition, a full urinalysis will be performed by the central laboratory for 
Visit 1 (Screening), Visit 3 (TOC), and at the Early Discontinuation visit. If an abnormal laboratory result 
from the screening assessment is judged by the Investigator as being clinically significant but not 
exclusionary, it should be reported as medical history. If clinical symptoms or urinalysis results at 
screening suggest that the patient may have a urinary tract infection that could require antibiotic therapy, 
then the patient should be screen failed and referred for further evaluation.  


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10.3.6 
Hematology/Chemistry 
Samples for hematology and clinical chemistry assessments will be collected at Visit 1 (Screening), 
Visit 3 (TOC), and the Early Discontinuation visit as specified in the Schedule of Assessments (Table 1 
and Table 2 [for PK subset]). If an abnormal laboratory result from the screening assessment is judged by 
the Investigator to be clinically significant, it should be reported as medical history.  
10.3.7 
Physical Examination 
A complete physical examination should be performed at Visit 1. A directed physical exam should be 
performed at Visit 3 and at the Early Discontinuation visit (if applicable), in accordance with the 
Investigator’s judgment. Clinically significant physical examination findings should be reported as 
medical history or AEs, as appropriate. Rectal and breast examinations are not required for either the 
complete or directed physical exams. 
10.3.8 
Pelvic Examination 
A pelvic examination will be performed at each visit and will include a vaginal wall inspection as well as 
an examination of the cervix, and confirmation that all findings are consistent with BV, versus 
Candidiasis or other causes of the patient’s vaginal signs or symptoms. Any observed abnormalities will 
be assessed and documented in the source document and eCRF.  
10.3.9 
Specimen Collection  
At Screening, swabs will be collected and submitted for the Candida culture, Chlamydia trachomatis and 
Neisseria gonorrhoeae NAATs, and the OSOM® test for Trichomonas vaginalis (which will be 
performed onsite). A swab of the vaginal pool should be utilized to perform a microscopic wet mount 
evaluation for clue cells (as part of Amsel’s criteria) as well as other elements (e.g., white blood cells, 
trichomonads, yeast, bacteria, etc.). Vaginal samples will also be used for microscopic KOH wet mount 
evaluations to assess the presence of Candida species.  
A swab of the lateral vaginal wall should be utilized for the slides to be submitted for centralized Gram 
staining for Nugent scoring. Instructions for the sampling for all procedures, including vaginal Candida 
cultures, preparation of slides for Nugent scoring, and NAAT and OSOM® testing, will be included in the 
laboratory manual and/or other study documents.  
10.3.10 
Prior and Concomitant Medications 
All medications taken during the 30 days prior to signing the ICF or used during the patient’s study 
participation will be recorded at each visit and documented in the eCRF. 
10.3.11 
Adverse Events 
Assessment of AEs will be completed at all visits. Any untoward events reported by the patient or 
observed by the study staff during or following treatment are to be recorded as AEs. (Events that occur 
after signing the ICF but before treatment with study drug are to be recorded and reported either as 
medical history or pre-treatment AEs, as appropriate.) Refer to Section 10.4 for details regarding 
definitions, documentation, and reports of AEs and SAEs. 


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10.3.12 
Local Site Reactions 
At each visit the Investigator or designee will perform a vulvar-vaginal examination to assess the 
treatment area and rate the following on a scale of 0 = absent, 1 = mild (slight, barely perceptible), 2 = 
moderate (distinct presence), and 3 = severe (marked, intense):  
 
Erythema  
 
Petechiae  
 
Erosion/ulceration  
 
Edema  
The patient will be queried by the Investigator or designee for presence of the following and, if present, 
the patient will be asked to rate as described above:  
 
Burning/stinging  
 
Pain  
 
Pruritus (itching)  
A separate eCRF will be designed to identify, track and characterize all local site reactions; therefore, 
vulvovaginal symptoms should be reported as TEAEs only if they are of a magnitude suggesting a 
clinically significant worsening compared to the patient’s baseline condition, or they require medical 
intervention.  
10.3.13 
Acceptability Assessment 
Patients will provide responses to questions of product acceptability, including the patient’s experience 
with changes in odor and discharge. Additionally, information will be collected to understand the 
patient’s experience with the study drug itself, e.g., ease of application, messiness or lack thereof, etc.  
10.3.14 
Pharmacokinetics and Vaginal Clindamycin Assessments 
For patients that have agreed and consented to participate in the PK subset group, PK blood draws will be 
done at 0 hours (pre-dose) and then at 2, 4, 6, and 8 hours (±15 minutes) post-dose (Day 1), as well as at 
24, 48, 72, 96, 120, and 144 hours (±2 hours) post-dose (Days 2-7).  
Also in the PK subset, samples will be collected for assessment of vaginal clindamycin concentrations at 
baseline (pre-dose only on Day 1; i.e., vaginal clindamycin samples will not be collected at post-dose 
time points on Day 1) as well as post-treatment on Days 2-7. 
10.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
10.4.1 
Definition of Adverse Events 
An AE in a study of an investigational drug is any untoward medical occurrence, unintended disease or 
injury or any untoward clinical signs (including an abnormal laboratory finding) associated with the use 
of a drug in humans, whether or not considered related to the drug. 
10.4.2 
Definition of Serious Adverse Events 
An event is considered an SAE if, in the view of either the Investigator or Sponsor, it meets the criteria as 
outlined in 21 CFR 312.32 (a) as per the following:  


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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 
adverse event, 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 hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the patient or 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.  
10.4.3 
Classification of an Adverse Event 
10.4.3.1 
Severity of Event 
The Investigator is responsible for assessing the severity of each AE using the following definitions: 
 
Mild: Symptoms causing no or minimal interference with usual social and functional activities 
with intervention not indicated. 
 
Moderate: Symptoms causing greater than minimal interference with usual social and functional 
activities with intervention indicated. 
 
Severe: Symptoms causing inability to perform usual social and functional activities with 
intervention or hospitalization indicated. 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity whereas 
seriousness is defined by the criteria under Section 10.4.2. An AE of severe intensity may not be 
considered serious. 
If there is a change in severity of an AE, it must be recorded as a separate event. 
10.4.3.2 
Relationship to Study Intervention 
An Investigator who is qualified in medicine (e.g., MD, NP, DO) must make the determination of 
relationship to the study drug for each AE. The Investigator should decide whether, in his or her medical 
judgment, there is a reasonable possibility that the event may have been caused by the investigational 
product. For each AE, the assessment of relatedness should be made using the following scale: 
 
Unrelated: Onset of the AE had no reasonable temporal relationship to administration of the study 
product or a causal relationship to administration of the study product is biologically implausible 
or the event is attributed to an alternative etiology. 
 
Possibly Related: Onset of the AE has a reasonable temporal relationship to study product 
administration and a causal relationship is not biologically implausible. 
 
Probably Related: Onset of the AE has a strong temporal relationship to administration of the 
study product that cannot be explained by the patient’s clinical state and a causal relationship is 
not biologically implausible. 
 
Definitely Related: Onset of the AE shows a distinct temporal relationship to administration of 
the study product that cannot be explained by the patient’s clinical state or other factors or the AE 
is a known reaction to the product or chemical group or can be predicted by the product’s 
pharmacology. 


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If the relationship between the AE/SAE and the investigational product is determined to be “possible,” 
“probable,” or “definite” the event will be considered related to the investigational product for the 
purposes of expedited regulatory reporting. 
10.4.4 
Time Period and Frequency for Event Assessment and Follow-up 
All AEs must be recorded in detail in the source documentation, reported on the appropriate page in the 
eCRF, and followed to satisfactory resolution, until the Investigator deems the event to be chronic or not 
clinically significant, until the patient is considered to be stable, or when a plan for appropriate follow-up 
has been approved by the Medical Monitor. 
10.4.5 
Adverse Event Reporting 
All AEs reported or observed during the study shall be recorded in the source documentation and reported 
on the AE page in the eCRF. Information to be collected includes the patient’s study ID number, age, site, 
concomitant drug treatment, and dose (if available), event term, time of onset, Investigator-specified 
assessment of severity and relationship to study drug, time of resolution of the event, seriousness, any 
required treatment or evaluations, outcome, and period of study at onset (at screening, during treatment, 
or at follow-up). Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concomitant medications, or progression of disease states must also be reported. All AEs 
shall be followed-up until adequate resolution. The Medical Dictionary for Regulatory Activities 
(MedDRA) shall be used to code all AEs. 
Any medical condition that is present at the time the patient is screened but does not deteriorate after 
treatment shall not be reported as an AE. However, if it deteriorates at any time during the study, it shall 
be recorded as an AE. 
10.4.6 
Serious Adverse Event Reporting 
Any AE that meets SAE criteria must be reported to the Sponsor or designee immediately (within 
24 hours) after the time site personnel first learn about the event.  
The study clinician shall immediately report to the Sponsor or designee any SAE, whether or not 
considered study intervention related, including those listed in the protocol or Investigator’s Brochure, 
and must include an assessment of whether there is a reasonable possibility that the study intervention 
caused the event.  
All SAEs shall be followed-up until satisfactory resolution or until the site Investigator deems the event to 
be chronic or the patient is stable. Other supporting documentation of the event may be requested by the 
study Sponsor or designee and shall be provided as soon as possible. 
The study Sponsor or designee shall be responsible for notifying the U.S. 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 or designee’s initial receipt of the information. In addition, the Sponsor or designee 
must notify the U.S. FDA and all participating Investigators in an Investigational New Drug (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 or designee determines that the information qualifies for 
reporting. 
The Sponsor or designee and all applicable Investigators are also responsible for reporting new safety 
information to regulatory agencies as required in accordance with applicable local laws and regulations. 


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10.4.7 
Reporting of New Information to Patients 
Study patients will be notified in a timely manner of any new safety information that may affect their 
consent to participate in the study. 
10.4.8 
Reporting of Pregnancy 
All pregnancies that occur while a patient is participating in the study will be reported immediately 
(within 24 hours) to the Sponsor or designee and monitored until outcome. Information from medical 
records will also be collected on pregnancy outcome data including maternal or fetal complications, 
spontaneous or elective abortions, ectopic pregnancies, stillbirths, and live preterm and full-term births. 
Although pregnancy itself is not an AE, any complications during pregnancy should be recorded as AEs 
or SAEs (if they fulfill the SAE criteria). Offspring should be followed for a minimum of 8 weeks. Any 
congenital anomaly/birth defect in a child born to a patient exposed to the test article(s) should be 
recorded as a SAE and details appropriately documented. Spontaneous abortions will be considered 
non-serious unless associated with consequences that meet seriousness criteria. 
Patients who are pregnant at the time of study enrollment will also be followed until delivery/termination 
of pregnancy and their offspring followed for a minimum of 8 weeks.  The same information collected for 
patients who become pregnant during the study will be collected on patients who enter the study while 
pregnant.   
11 
STATISTICAL CONSIDERATIONS 
A detailed statistical analysis plan (SAP) will be finalized before the treatment assignments for all 
patients are unblinded and prior to locking the database to expand upon the statistical methods presented 
below. 
11.1 
STATISTICAL HYPOTHESES 
The hypothesis test for the primary endpoint will be done to determine if DARE-BV1 is superior to 
placebo for Clinical Cure at the TOC visit (Visit 3; Day 21-30). 
11.2 
RANDOMIZATION AND STRATIFICATION 
Randomization will be done in a 2:1 ratio (DARE- BV1 [clindamycin phosphate vaginal gel. 2%]: 
placebo vaginal gel). The randomization schedule will be generated using SAS® version 9.4 or higher. 
The randomization schedule will be stratified by site and race (African-American/Black versus all others). 
11.3 
SAMPLE SIZE DETERMINATION 
The sample size calculations were performed using SAS® version 9.4 for the 2-group chi-square test. It is 
expected that this test will provide approximately the same power as the Cochran-Mantel-Haenszel 
(CMH) test stratified by analysis center and race. A sample size of 188 DARE-BV1 versus 94 placebo 
patients (282 patients total) will have 90% power to detect a statistically significant difference at a 
significance level of 0.05 (2-tailed) under the assumption the clinical cure rates will be 55% and 30% for 
DARE-BV1 and placebo, respectively. This sample size assumes 35% of randomized patients will not be 
in the mITT population. 


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11.4 
POPULATIONS FOR ANALYSES 
Intent-to-Treat (ITT): All randomized patients 
Safety: All ITT population patients who applied study drug 
PK Subset (PKS): All Safety population patients who are enrolled into the PK subset 
Modified Intent-to-Treat (mITT): All Safety population patients except those excluded due to 
demonstrating a positive test result for other concomitant vaginal or cervical infections at baseline 
(e.g., T. vaginalis, N. gonorrhoeae, C. trachomatis, Candida species) or who are determined to have a 
baseline Nugent score of < 7. If the Nugent score at baseline is missing, then the patient is excluded from 
the mITT population.  
Per-Protocol (PP): The PP population will include patients from the mITT population who either receive 
other BV therapy during the study for any reason, or meet the following criteria: 
 
Meet all 4 Amsel’s criteria at screening 
 
Apply study drug within 1 day of randomization 
 
Do not use a prohibited medication prior to the Day 21-30 visit 
 
Attended the Day 21-30 visit  
 
Have no other major protocol violations that impacted the primary or secondary endpoints. 
For the mITT and PP populations, if the patient receives other BV therapy for any reason, the patient will 
be included in the analysis as a treatment failure for all visits on or after receipt of the other therapy. 
Patients will be excluded from the PP population if they received study treatment that was not the 
treatment to which they were randomized. A review of the data will be performed prior to locking the 
database and unblinding the study to determine which medications and major protocol violations would 
impact the primary and secondary endpoints and cause a patient to be excluded from the PP population. 
11.5 
STATISTICAL ANALYSES 
11.5.1 
General Approach 
All statistical processing will be performed using SAS®, Version 9.4, or later. Continuous variables will 
be summarized with number of patients (N), mean, median, standard deviation (SD), minimum (Min), 
and maximum (Max). Categorical variables will be summarized with frequency counts and percentages. 
All efficacy analyses will be conducted using a 2-sided test at an alpha level of 0.05. The primary efficacy 
analyses will be conducted on the mITT population. Additionally, efficacy analyses will be performed on 
the PP population and will be considered supportive. Safety analyses will be performed on the Safety 
population. Patients will be analyzed according to the treatment to which they were randomized for ITT 
and mITT analyses, regardless of actual treatment received. For all other analysis populations, patients 
will be analyzed according to the treatment they received. 
11.5.2 
Analysis of the Primary Efficacy Endpoint 
All efficacy endpoints will be summarized for each treatment group using descriptive statistics, including 
95% confidence intervals (within treatment group), as appropriate. 
The primary efficacy analysis of Clinical Cure at Day 21-30 will be analyzed for the mITT population 
with a CMH test stratified by study center and race (African-American/Black versus all others). The 


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Daré Bioscience, Inc. 
 
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method for handling of patients in the mITT analysis without a Clinical Cure result at Day 21-30 will be 
included in the final SAP. 
Patients who receive other BV treatment(s) for any reason will be included in the analysis as treatment 
failures for all visits on or after receipt of the other therapy(ies). 
11.5.3 
Analysis of the Secondary Endpoints 
Hypothesis testing for the secondary efficacy endpoints will be conducted in a sequential manner to 
control the Type 1 error rate, in the order presented below: 
1. Proportion of patients in the mITT population with Bacteriological Cure at the TOC visit 
(Day 21-30). Bacteriological Cure is defined as a Nugent score < 4. 
2. Proportion of mITT patients with Therapeutic Cure at the TOC visit (Day 21-30). Therapeutic 
Cure is defined as both a Clinical Cure and Bacteriological Cure (Nugent Score < 4). 
3. Proportion of mITT patients with Clinical Cure at the Interim Assessment visit (Day 7-14). 
4. Proportion of mITT patients with Bacteriological Cure (Nugent score < 4) at the Interim 
Assessment visit (Day 7-14). 
5. Proportion of mITT patients with Therapeutic Cure at the Interim Assessment visit 
(Day 7-14).  
Analysis of the secondary endpoints will follow the same method as the analysis of the primary endpoint, 
including patients being included in the analysis as treatment failures if other BV treatments were 
received (i.e., treatment failure status will be applied to all visits on or after receipt of the other BV 
treatment).  
The PP population will be used to perform sensitivity analyses of the above primary and secondary 
efficacy analyses. Patients in the PP population without a Clinical Cure result at Day 21-30 will be 
excluded from the PP analyses. 
11.5.4 
Safety Analyses 
Descriptions of AEs will include the date of onset, the date the AE ended, the maximum severity of the 
AE, relationship to study drug, seriousness, any action taken, and the outcome. 
All TEAEs occurring during the study will be recorded and classified on the basis of MedDRA 
terminology. Treatment-emergent AEs are those AEs with an onset at the time of or after the application 
of study drug. All reported TEAEs will be summarized by treatment group, system organ class and 
preferred term. Adverse event summaries will include severity, relationship to study drug, and 
seriousness. When summarizing events by causality and severity, each patient will be counted only once 
within a system organ class or a preferred term by using the event with the greatest relationship and 
highest severity within each classification. In addition, a list of patients who had an SAE or who 
prematurely discontinued from the study due to an AE will be provided. 
Changes from baseline and shifts from baseline will be summarized for safety laboratory results. A listing 
that displays all out-of-range laboratory test results will also be provided.  
Local site reactions will be summarized at each visit. 
Changes from baseline to each visit will be summarized for other safety parameters (e.g., vital signs, 
pelvic examination). 


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11.5.5 
Pharmacokinetic Analysis 
The following PK parameters will be summarized for the PKS population to assess plasma and vaginal 
clindamycin concentration levels for Days 1-7:  
 
minimum concentration (Cmin)  
 
maximum concentration (Cmax)  
 
area under the curve (AUC0-t), where t is the last time-point with measurable concentration)  
 
time to maximum concentration (Tmax)  
 
elimination half-life (t1/2) 
Descriptive summaries of plasma clindamycin levels will be presented for each timepoint. 
11.5.6 
Baseline Descriptive Statistics 
Demographic data and other baseline characteristics including medical and medication history will be 
summarized as appropriate. 
11.5.7 
Product Acceptability  
Patients will provide responses to questions of product acceptability, including the patient’s experience 
with changes in odor and discharge. Additionally, information will be collected to understand the 
patient’s experience with the study drug itself, e.g., ease of application, messiness or lack thereof, etc. The 
results will be summarized for the Safety population. 
11.5.8 
Planned Interim Analyses 
No interim analyses are planned. 
11.5.9 
Sub-group Analyses 
Any sub-group analyses will be defined in the SAP that will be finalized prior to database lock. 
11.5.10 
Tabulation of Individual Patient Data 
By-patient data listings will be provided to support all tabulated output. 
12 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
12.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
12.1.1 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, ICH Guideline for Good Clinical Practice (GCP) E6 (R2), and all applicable 
regulations. 
12.1.2 
Institutional Review Board 
Federal (U.S.) regulations, applicable laws and regulations in Canada and Europe, and ICH guidelines 
require that approval be obtained from an IRB before participation of human subjects in research studies. 


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Before study onset, the protocol, ICF, advertisements to be used for the recruitment of study subjects, and 
any other written information regarding this study to be provided to the subject or the subject’s legal 
guardian must be approved by the IRB. Documentation of all IRB approvals and of the IRB compliance 
with ICH Harmonised Tripartite Guideline E6 (R2): GCP will be maintained by the site and will be 
available for review by the Sponsor or its designee. 
All IRB approvals must identify the IRB name and address, the clinical protocol by title or protocol 
number or both, and the date approval or a favorable opinion was granted. 
The Investigator is responsible for providing written summaries of the progress and status of the study as 
specified by the IRB. The Investigator must promptly supply the Sponsor or its designee, the IRB, and, 
where applicable, the institution, with written reports on any changes significantly affecting the conduct 
of the study or increasing the risk to subjects. 
12.1.3 
Informed Consent Process 
A written ICF in compliance with ICH Guideline for GCP E6 (R2) and U.S. Title 21 CFR Part 50 will be 
obtained from each patient before entering the study. No study-related procedures or activities will be 
performed until each patient is fully informed about the study and the ICF is properly signed and dated. 
An ICF template will be provided by the Sponsor or designee to investigative sites. If any institution-
specific modifications to study-related procedures are proposed or made by the site, the ICF will be 
reviewed by the Sponsor and/or its designee before IRB submission. Once reviewed, the ICF will be 
submitted by the Investigator or Sponsor/designee (as applicable) to the IRB, and when applicable to 
regulatory authorities, for review and approval before the start of the study. If the ICF is revised during 
the course of the study, all active participating patients to whom the change is applicable must sign the 
revised form. Reconsent will be needed before rescreening a patient. 
Before enrollment, each prospective patient and/or her parent(s)/legal guardian(s) will be given a full 
explanation of the study and be allowed to read the IRB-approved ICF. Once the Investigator is assured 
that the patient/legal guardian understands the implications of participating in the study, the patient, 
parent(s), and/or legal guardian(s) will be asked to give consent/assent to participate in the study by 
signing the ICF. 
The Investigator will retain the signed original ICF and give a copy of the signed original ICF to the 
patient or legal guardian. 
Patients aged 12 through 17 years old may participate where permitted by applicable local regulations and 
IRB approval. All applicable laws and regulations regarding the informed consent of minors are to be 
strictly observed. 
12.1.4 
Study Discontinuation and Closure 
The Sponsor reserves the right to modify or terminate the study at any time. Possible reasons for 
termination are unsatisfactory enrollment of patients, new scientific knowledge becomes known that 
makes the objectives of the study no longer feasible, efficacy or safety reasons, e.g., if the incidence of 
AEs in this study or another study using the same investigational product indicates there is a potential 
health risk for patients. 
The Sponsor or designee will provide a written statement to the IRB and the relevant regulatory authority 
with the reasons for modification or termination of the study. If the study is terminated, a closeout visit 
will be performed at each active site at which study investigational product was received and at least 


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Daré Bioscience, Inc. 
 
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1 patient was screened, and applicable procedures will be carried out to close the trial site(s). The Sponsor 
reserves the right to discontinue the study at any time for clinical or administrative reasons. 
The end of the study is defined as the date on which the last patient completes the last visit or the last 
contact by which study-related data is conveyed. 
12.1.5 
Potential Impact of the COVID-19 Pandemic 
The DARE-BV1-001 study is being conducted while the United States is contending with the COVID-19 
pandemic.  In March 2020, the FDA released a document entitled “FDA Guidance on Conduct of Clinical 
Trials of Medical Products during COVID-19 Public Health Emergency;” this document was then further 
updated on April 16, 2020.  This guidance acknowledges various ways in which the pandemic could 
impact clinical trials, as per the following excerpt:  
“FDA recognizes that the COVID-19 public health emergency may impact the conduct of clinical 
trials of medical products. Challenges may arise, for example, from quarantines, site closures, travel 
limitations, interruptions to the supply chain for the investigational product, or other considerations 
if site personnel or trial subjects become infected with COVID-19. These challenges may lead to 
difficulties in meeting protocol-specified procedures, including administering or using the 
investigational product or adhering to protocol-mandated visits and laboratory/diagnostic testing. 
FDA recognizes that protocol modifications may be required, and that there may be unavoidable 
protocol deviations due to COVID-19 illness and/or COVID-19 public health control measures.” 
In addition to the need for sites to implement procedures to ensure the safety of its patients and staff, the 
sponsor and CRO study teams have taken additional steps to contend with the potential consequences of 
the pandemic.  For example, there will be increased reliance on remote monitoring, and additional 
documentation will be maintained to track operational disruptions or other study issues secondary to the 
consequences of the COVID-19 pandemic.  Additional details are provided in the study Clinical 
Management Plan.   
12.1.6 
Confidentiality and Privacy 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain patient confidentiality. All records shall be kept in a secure storage area with limited 
access. Clinical information shall not be released without the written permission of the patient (or the 
patient’s legal guardian), except as necessary for monitoring and auditing by the Sponsor, its designee, the 
IRB, or applicable regulatory authorities (e.g., the U.S. FDA), or unless otherwise required by law. 
The Investigator and all employees and coworkers involved with this study may not disclose or use for 
any purpose other than performance of the study any data, record, or other unpublished, confidential 
information disclosed to those individuals for the purpose of the study. Prior written agreement from the 
Sponsor or its designee must be obtained for the disclosure of any said confidential information to other 
parties. 
12.1.7 
Future Use of Stored Specimens and Data 
No laboratory specimens will be retained after the end of the study. 


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12.1.8 
Key Roles and Study Governance 
The Medical Monitor, or a designated backup, will serve as the primary contact for site medical questions 
related to the study. 
12.1.9 
Safety Oversight 
The Medical Monitor, or a designated backup, will conduct periodic reviews of study safety data to 
identify any potential safety concerns.  
12.1.10 
Clinical Monitoring 
The clinical monitor, as a representative of the Sponsor, has the obligation to follow the study closely. In 
doing so, the monitor shall visit the Investigator and study site at periodic intervals, in addition to 
maintaining necessary telephone and other contacts. At sites where in-person monitor visits are not 
feasible due to the COVID-19 pandemic, virtual monitor visits will be permitted.  The monitor shall 
maintain current personal knowledge of the study through observation, review of study records and 
source documentation, and discussion of the conduct of the study with the Investigator and personnel. 
Remote monitoring of the eCRF will also be employed for this trial.  Additional details regarding clinical 
monitoring can be found in the trial Clinical Management Plan. 
All aspects of the study shall be carefully monitored, by the Sponsor or its designee, for compliance with 
applicable regulations. 
12.1.11 
Quality Assurance and Quality Control 
This study shall adhere to U.S. FDA standards as well as other applicable local standards of conduct 
regarding quality assurance. All parts of the U.S. CFR applicable to clinical studies, including 
21 CFR Parts 50, 56, and 312, must be followed, along with ICH E6 (R2). 
Suitably qualified and trained clinical research personnel of the Sponsor or designee shall visit the trial 
site at regular intervals during the trial for monitoring purposes and to assist the research staff with any 
queries. The eCRFs and source documentation shall be available for review during monitoring visits to 
the trial site. The function of this monitoring is to ensure compliance with the protocol and study 
procedures, applicable regulatory and GCP obligations, proper maintenance of records including study 
drug accountability records, correct administration of study drug including storage conditions, and 
accurate reporting of AEs. After data from the patient’s records have been entered onto the database, they 
shall be reviewed and the data verified against the patient’s source data (details of data verification, 
including the percentage of data fields requiring source verification, shall be documented in a Monitoring 
Plan). Any discrepancies shall be tracked by paper or electronically with an electronic audit trail. 
The Sponsor, an independent auditor, or a regulatory authority may audit the trial site and trial 
documentation. These audits may take place while the trial is being conducted or up to several years later. 
12.1.12 
Data Handling and Record Keeping 
Investigators and institutions involved in the study shall permit study-related monitoring, audits, IRB 
review, and regulatory inspections by providing direct access to all study records. In the event of an audit, 
the Investigator agrees to allow the Sponsor, representatives of the Sponsor, or a regulatory agency (i.e., 
U.S. FDA or other regulatory agency) access to all study records. 


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The Investigator shall promptly notify the Sponsor or designee of any audits scheduled by any regulatory 
authorities and promptly forward copies of any audit reports received to the Sponsor or designee. 
12.1.12.1 Data Collection and Management Responsibilities 
As part of the responsibilities assumed by participating in the study, the Investigator agrees to maintain 
adequate case histories for the patients treated as part of the research under this protocol. The Investigator 
agrees to maintain accurate source documentation as part of the case histories. These source documents 
may include, but are not limited to, laboratory reports, histology reports, and ultrasound findings. 
Investigative site personnel shall enter patient data into the eCRF. Clinical data management shall be 
performed in accordance with applicable standards and data cleaning procedures to ensure the integrity of 
the data, e.g., removing errors and inconsistencies in the data. Adverse events will be coded using 
MedDRA and concomitant medication terms will be coded using the World Health Organization Drug 
Dictionary (WHO-DD). 
12.1.12.2 Study Records Retention 
Following completion of the study, the Investigator shall retain copies of the approved study protocol, 
ICF, relevant source documents, and all other supporting documentation related to the study according to 
the ICH guidelines. 
If the Investigator can no longer maintain the archive of study records (i.e., due to retirement or 
relocation), the Sponsor must be informed in writing about any change in responsibility for record 
retention, including the name of the new responsible party, contact information, and location of the study 
records. Records may not be destroyed without prior written consent from the Sponsor. 
12.1.13 
Protocol Deviations 
A protocol deviation occurs when the patient, Investigator, or Sponsor fails to adhere to significant 
protocol requirements affecting the inclusion, exclusion, patient safety and primary endpoint criteria. 
Protocol deviations for this study include, but are not limited to, the following: 
 
Failure to meet inclusion/exclusion criteria 
 
Enrolling a patient into the study without securing proper consent 
 
Deviating from the protocol-defined study procedures 
Certain protocol deviations may require the patient to be discontinued early from the study. The Sponsor, 
in conjunction with the Investigator, will determine if a protocol deviation should result in withdrawal of 
a patient.  
Failure to comply with GCP guidelines will also result in a protocol deviation. It is the responsibility of 
the research sites to report all protocol deviations to their IRB according to IRB policy. 
12.1.14 
Publication and Data Sharing Policy 
All information concerning the study supplied by the Sponsor to the Principal Investigator and not 
previously published is considered confidential. No data collected in this study will be presented or 
published without prior approval from the Sponsor. 


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Daré Bioscience, Inc. 
 
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12.1.15 
Conflict of Interest Policy 
Investigators are required to provide financial disclosure information to allow the Sponsor to submit the 
complete and accurate certification or disclosure statements required under U.S. FDA 21 CFR 54. In 
addition, the Investigator must provide to the Sponsor a commitment to promptly update this information 
if any relevant changes occur during the course of the investigation and for 1 year following the 
completion of the study. 


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Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
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12.2 
PROTOCOL SIGNATURE PAGE - SPONSOR 
Protocol Number: 
DARE-BV1-001 
Study Title: 
A Phase 3 Multi-center, Double-blind, Placebo-controlled, Randomized 
Study of DARE-BV1 in the Treatment of Bacterial Vaginosis 
Sponsor: 
Daré Bioscience, Inc. 
3655 Nobel Drive, Suite 260 
San Diego, CA 92122 
Version Number: 
4.0 
Version Date: 
14 Aug 2020 
This study will be carried out in compliance with the International Council for Harmonisation 
(ICH) E6 (R2) guidance on Good Clinical Practice (GCP) and the United States (U.S.) Code of 
Federal Regulations (CFR) applicable to clinical studies (21 CFR Part 50, 21 CFR Part 56, and 
21 CFR Part 312). 
 
Except for a change that is intended to eliminate an immediate hazard to patients, the approved 
protocol shall be conducted as described. All protocol deviations must be documented. 
 
 
 
 
_________________________________________________________________________________ 
David Friend, PhD, Chief Scientific Officer, Daré Bioscience, Inc.                       Date 
 
 
 
 
_________________________________________________________________________________ 
Nadene Zack, MS, Vice President, Clinical Operations, Daré Bioscience, Inc.    Date 
 
08/20/2020
08/20/2020


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DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 55 of 56 
12.3 
PROTOCOL SIGNATURE PAGE – PRINCIPAL INVESTIGATOR 
Protocol Number: 
DARE-BV1-001 
Study Title: 
A Phase 3 Multi-center, Double-blind, Placebo-controlled, Randomized 
Study of DARE-BV1 in the Treatment of Bacterial Vaginosis 
Sponsor: 
Daré Bioscience, Inc. 
3655 Nobel Drive, Suite 260 
San Diego, CA 92122 
Version Number: 
4.0 
Version Date: 
14 Aug 2020 
This study will be carried out in compliance with the International Council for Harmonisation 
(ICH) E6 (R2) guidance on Good Clinical Practice (GCP) and the United States (U.S.) Code of 
Federal Regulations (CFR) applicable to clinical studies (21 CFR Part 50, 21 CFR Part 56, and 
21 CFR Part 312). 
 
Except for a change that is intended to eliminate an immediate hazard to patients, the approved 
protocol shall be conducted as described. All protocol deviations must be documented. Any 
protocol-related issues that pose an immediate or significant hazard to patients must be reported to 
the Sponsor or designee. 
 
 
 
 
_________________________________________________________________________________ 
Principal Investigator Name (Print) 
 
 
 
 
_________________________________________________________________________________ 
Principal Investigator Signature                                                                            Date 
 
 


Clinical Study Protocol 
DARE-BV1-001 
Daré Bioscience, Inc. 
 
Version/Date: 4.0/14 Aug 2020 
Page 56 of 56 
13 
REFERENCES 
Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. (1983). Nonspecific vaginitis: 
diagnostic criteria and microbial and epidemiologic associations. Am J Med. 74(1):14-22. 
Centers for Disease Control and Prevention (CDC). (2017, June). Bacterial Vaginosis - CDC Fact Sheet. 
https://www.cdc.gov/std/bv/BV-FS.pdf. Retrieved 29 May 2019. 
Donders GGG, Zodzika J, and Rezeberga D. (2014). Treatment of bacterial vaginosis: what we have and 
what we miss. Expert Opin Pharmacother 15(5):645-657. 
Hay P. (2014). Bacterial vaginosis. Medicine 42(7):359-363. 
Lowe NK, Neal JL, Ryan-Wenger NA. (2009). Accuracy of the clinical diagnosis of vaginitis compared 
with a DNA probe laboratory standard. Obstet Gynecol 111(1):89-95. 
Mondal P, Alur HH, Johnston TP. (2011). Evaluation of TRI-726 as a drug delivery matrix. Drug Dev Ind 
Pharm 37(8):995-1001. 
Nugent RP, Krohn MA, and Hillier SL. (1991). Reliability of diagnosing bacterial vaginosis is improved 
by a standardized method of gram stain interpretation. J Clin Microbiol 29(2):297-301. 
Perrigo Specialty Pharmaceuticals. (2014). Clindesse (clindamycin phosphate) Vaginal Cream, 2%, 
Prescribing Information. https://www.clindesse.com/pdf/PI.pdf. Retrieved 08 April 2019. 
Schwebke JR, Taylor SN, Ackerman R, et al. (2020). Clinical validation of the Aptima bacterial vaginosis 
and Aptima Candida/Trichomonas vaginitis assays: results from a prospective multicenter clinical study. 
J Clin Microbiol 58(2):1-10.  
Sobel R, Sobel JD. (2015). Metronidazole for the treatment of vaginal infections. Expert Opin 
Pharmacother 16(7):1109-1115. 
Taylor BD, Darville T, Haggerty CL. (2013). Does bacterial vaginosis cause pelvic inflammatory 
disease? Sex Transm Dis 40(2):117-122. 
 

SAP_001.pdf: 
Daré Bioscience                                           CONFIDENTIAL                                           DARE-BV1-001 
Statistical Analysis Plan, v3.0 
 
 
 
Protocol D ARE-BV1-001 
 
A Phase 3 Multi-Center, Double-Blind, Placebo-Controlled, 
Randomized Study of DARE-BV1 in the Treatment of 
Bacterial Vaginosis 
 
 
Statistical Analysis Plan 
 
 
 
 
 
 
 
Prepared for: 
 
Daré Bioscience, Inc. 
3655 Nobel Drive, Suite 260 
San Diego, CA 92122 
 
 
 
 
 
Prepared by: 
 
Health Decisions, Inc. 
2510 Meridian Parkway, Suite 100 
Durham, NC 27713 
 


Daré Bioscience                                           CONFIDENTIAL                                           DARE-BV1-001 
TEM BM-001.06 (Eff. 06JUN2018)                           Statistical Analysis Plan, v3.0 – Page i 
STATISTICAL ANALYSIS PLAN APPROVAL 
 
RESPONSIBILITY 
NAME AND 
COMPANY 
SIGNATURE 
DATE 
(DDMMMYYYY) 
Principal 
Biostatistician, 
Biostatistics and 
Programming 
 
 
 
Hongsheng Wu 
Health Decisions 
 
 
Associate Director,  
Biostatistics and 
Programming 
 
 
 
Phil Custodio 
Health Decisions 
 
 
Sr. Project 
Manager, 
Clinical Operations 
 
 
 
 
Jessica Hatheway 
Health Decisions 
 
 
Vice President,  
Clinical Operations 
 
 
 
 
Nadene Zack 
Daré Bioscience 
 
 
 
 






Daré Bioscience                                           CONFIDENTIAL                                           DARE-BV1-001 
TEM BM-001.06 (Eff. 06JUN2018)                           Statistical Analysis Plan, v3.0 – Page ii 
TABLE OF CONTENTS 
 
STATISTICAL ANALYSIS PLAN APPROVAL ............................................................... i 
TABLE OF CONTENTS .................................................................................................. ii 
LIST OF ABBREVIATIONS ........................................................................................... iv 
1.0 
INTRODUCTION .................................................................................................. 5 
2.0 
PROTOCOL SUMMARY ...................................................................................... 5 
2.1 
Background ....................................................................................................... 5 
2.2 
Objectives ......................................................................................................... 5 
2.3 
Trial Design ....................................................................................................... 5 
2.4 
Study Efficacy Endpoints .................................................................................. 6 
2.4.1 
Primary Efficacy Endpoint .......................................................................... 6 
2.4.2 
Secondary Efficacy Endpoints ................................................................... 6 
2.5 
Sample Size Consideration ............................................................................... 7 
3.0 
STATISTICAL METHODS ................................................................................... 7 
3.1 
Statistical Handling Policy ................................................................................. 7 
3.1.1 
Interim Safety Review ................................................................................ 7 
3.1.2 
Analysis Conventions................................................................................. 7 
3.2 
Subject Disposition ........................................................................................... 8 
3.3 
Protocol Deviations ........................................................................................... 9 
3.4 
Analysis Populations ......................................................................................... 9 
3.5 
Demographics and Pre-Treatment Characteristics ......................................... 10 
3.5.1 
Demographics .......................................................................................... 10 
3.5.2 
Medical History ........................................................................................ 10 
3.5.3 
BV History ................................................................................................ 11 
3.5.4 
Sexual, Contraceptive, and Pregnancy History ........................................ 11 
3.5.5 
Prior Medications ..................................................................................... 12 
3.6 
Concomitant Medications ................................................................................ 12 
3.7 
Efficacy Analyses ............................................................................................ 12 
3.7.1 
Primary Efficacy Analyses ....................................................................... 12 
3.7.2 
Secondary Efficacy Analyses ................................................................... 16 
3.8 
Safety Analyses .............................................................................................. 17 


Daré Bioscience                                           CONFIDENTIAL                                           DARE-BV1-001 
TEM BM-001.06 (Eff. 06JUN2018)                           Statistical Analysis Plan, v3.0 – Page iii 
3.8.1 
Treatment Exposure and Compliance...................................................... 17 
3.8.2 
Adverse Events and Serious Adverse Events .......................................... 17 
3.8.3 
Local Site Reactions ................................................................................ 18 
3.8.4 
Vital Signs and Weight ............................................................................. 19 
3.8.5 
Physical Examination ............................................................................... 19 
3.8.6 
Pelvic Examination .................................................................................. 19 
3.8.7 
Hematology, Chemistry, and Urinalysis ................................................... 20 
3.8.8 
Safety Phone Follow-Up .......................................................................... 20 
3.8.9 
Other Safety Assessments ...................................................................... 20 
3.9 
User Acceptability Assessments ..................................................................... 21 
3.9.1 
User Acceptability Questionnaire ............................................................. 21 
3.10 
Pharmacokinetics Analyses ............................................................................ 22 
4.0 
REFERENCES ................................................................................................... 22 
5.0 
APPENDICES .................................................................................................... 23 
5.1 
Study Schedule of Assessments ..................................................................... 23 
5.2 
Table of Contents for Data Display ................................................................. 25 
5.2.1 
Planned Tables ........................................................................................ 25 
5.2.2 
Planned Data Listings .............................................................................. 28 
 


Daré Bioscience                                           CONFIDENTIAL                                           DARE-BV1-001 
TEM BM-001.06 (Eff. 06JUN2018)                           Statistical Analysis Plan, v3.0 – Page iv 
LIST OF ABBREVIATIONS  
 
AE 
Adverse Event 
BMI 
Body Mass Index 
BV 
Bacterial Vaginosis 
CC 
Clinical Cure 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel test 
CSR 
Clinical Study Report 
eCRF 
Electronic Case Report Form 
eDiary 
Electronic Diary 
ED 
Early Discontinue 
HEC 
Hydroxyethylcellulose 
HEENT 
Head, Eyes, Ears, Nose and Throat 
IRT 
Interactive Response Technology 
ITT 
Intent-To-Treat 
KOH 
Potassium Hydroxide 
MAR 
Missing At Random 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
Min 
Minimum 
MITT 
Modified Intent-To-Treat 
MNAR 
Missing Not At Random 
PK 
Pharmacokinetics 
PKS 
Pharmacokinetics Subset (population) 
PP 
Per-Protocol 
PT 
Preferred Term 
QD 
One a day (from the Latin quaque die) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SE 
Standard Error 
SOC 
System Organ Class 
STI 
Sexual Transmitted Infection 
TOC 
Test Of Cure 
TEAE 
Treatment Emergent Adverse Event 
WHO DDE 
World Health Organization Drug Dictionary Enhanced 
 
 
 
 


Daré Bioscience                                           CONFIDENTIAL                                           DARE-BV1-001 
TEM BM-001.06 (Eff. 06JUN2018)                             Statistical Analysis Plan, v3.0 – Page 5 
1.0 
INTRODUCTION 
The purpose of this document is to detail the planned statistical analysis and data 
presentations that will be performed to support the Clinical Study Report (CSR) for Daré 
Bioscience study protocol DARE-BV1-001.  The analyses detailed herein are based on 
the study protocol (Version 4.0, dated 14AUG2020) and electronic case report forms 
(eCRFs, dated 24JUL2020).  Any post-hoc or unplanned analyses not identified in this 
statistical analysis plan (SAP) will be clearly identified in the CSR. 
 
2.0 
PROTOCOL SUMMARY 
2.1 
Background 
Bacterial vaginosis (BV) is a common bacterial infection in postmenarchal women.  BV is 
typically diagnosed using Amsel’s criteria (Amsel 1983). The four Amsel’s criteria used to 
determine a clinical diagnosis of BV are as follows:  
a) homogenous, non-viscous, off-white (milky or gray) thin discharge; 
b) the presence of > 20% clue cells;  
c) vaginal pH > 4.5;  
d) positive “whiff” test (“fishy” odor of the vaginal discharge with the addition of a drop 
of 10% potassium hydroxide [KOH]). 
Currently, oral and intravaginal metronidazole, intravaginal clindamycin, oral tinidazole, 
and oral secnidazole are used as the treatment of BV in the United States. DARE-BV1 is 
a thermosetting bioadhesive intravaginal gel formulated with 2% clindamycin phosphate 
designed to release the active ingredient for an extended period of time (Mondal, Alur, & 
Johnston, 2011). The extended period of time is approximately 7 days, based on in vitro 
data, and will be better defined in this study with the pharmacokinetics (PK) data from a 
subset of participants. Research has shown that effective drug delivery is essential to 
optimize the therapy for BV. 
2.2 
Objectives 
The primary objective of this study is to assess the efficacy of DARE-BV1 for the treatment 
of BV in postmenarchal females. 
The primary efficacy endpoint is the proportion of subjects with Clinical Cure at the test 
of cure (TOC) visit (Day 21-30).  Clinical cure is defined as: 
x Resolution of the abnormal vaginal discharge associated with BV, 
x Negative 10% KOH whiff test, and 
x Clue cells < 20% of the total epithelial cells in the saline wet mount. 
The secondary efficacy objectives of the study include assessment of Bacteriological 
Cure and Therapeutic Cure of BV (defined in Section 2.4.2) and the safety and 
acceptability of DARE-BV1 (listed in Section 3.7.3) in postmenarchal females. 
2.3 
Trial Design 
This is a multicenter (with approximately 36 study sites), randomized, double-blind (for 
both subjects and investigators), placebo-controlled study of DARE-BV1 clindamycin 


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phosphate vaginal gel, 2% (QD × 1 day) compared to placebo vaginal gel 
(hydroxyethylcellulose [HEC] Universal Placebo Gel) (QD × 1 day). Total 240 Subjects 
will be evaluated at 3 time points: a Day 1 Screening/Randomization visit, a Day 7-14 
Interim Assessment visit, and a Day 21-30 TOC visit (or a Day 21-30 Safety Follow-up 
phone call for subjects who are prematurely discontinued).  The total study duration will 
be up to approximately 30 days for a subject, with a minimum age of 12 years old.  
Females of 12 to 17 years old may participate where permitted by applicable local 
regulations and Institutional Review Board approval, also with consent from the 
parent(s)/guardian(s) and assent from themself. 
Eligible subjects will be randomly assigned, stratified by study site and subject race (either 
African American or Not-African American), via Interactive Response Technology (IRT, 
by Suvoda LLC, Conshohocken, Pennsylvania) to one of the following treatment groups 
in the ratio of 2:1 of either:  
A. clindamycin phosphate vaginal gel, 2% (DARE-BV1; 1 dose is 5 g gel = 100 mg 
clindamycin) QD × 1 day, or  
B. placebo vaginal gel (Universal HEC Placebo Gel), 5 g, QD × 1 day.  
Assigned product will be applied intravaginally within 1 day of randomization. 
Approximately 20 subjects at selected study sites (1-3 sites are anticipated) will 
participate in a PK study.  The subjects in this subset will apply the study drug at the study 
clinic during Visit 1 (randomization) and will have blood draws for plasma clindamycin 
assessment taken at 0 hours (pre-dose) and then at 2, 4, 6, and 8 hours (±15 minutes) 
post-dose, as well as at 24 (±1 hour), 48, 72, 96, 120, and 144 hours (±2 hours) post-
dose (Days 2-7).  In addition, samples for vaginal clindamycin concentrations will be 
collected on Days 1-7, with the Day 1 sampling schedule starting pre-dose; no post-dose 
vaginal clindamycin samples will be collected on Day 1. 
All procedures and assessments associated with each study visit are shown in the 
Appendix 5.1 of this SAP. 
 
2.4 
Study Efficacy Endpoints 
2.4.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of subjects with Clinical Cure at the TOC 
visit (Day 21-30). Here Clinical Cure is defined as all of the following 3 criteria being met: 
x Resolution of abnormal vaginal discharge associated with BV, 
x Negative 10% KOH whiff test, 
x Clue cells < 20% of the total epithelial cells in the saline wet mount. 
2.4.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
x Proportion of subjects with Clinical Cure at the Interim Assessment visit (Day 7-
14). 
x Proportion of subjects with Bacteriological Cure at the TOC visit (Day 21-30). 
Bacteriological Cure is defined as a Nugent score < 4. 


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x Proportion of subjects with Therapeutic Cure at the TOC visit (Day 21-30). 
Therapeutic Cure is defined as both a Clinical Cure and Bacteriological Cure 
(Nugent Score < 4). 
x Proportion of subjects with Bacteriological Cure (Nugent score < 4) at the Interim 
Assessment visit (Day 7-14). 
x Proportion of subjects with Therapeutic Cure at the Interim Assessment visit (Day 
7-14). 
2.5 
Sample Size Consideration 
The sample size calculations were performed using SAS® version 9.4 for the 2 group chi-
square test. It is expected that this test will provide approximately the same power as the 
CMH test stratified by analysis center and race.  Under the assumption that the Clinical 
Cure rates of 55% for DARE-BV1 and 30% for placebo, a sample size of 188 DARE-BV1 
versus 94 placebo subjects will have 90% power to detect a statistically significant 
difference at a significance level of 0.05 (2-tailed).  This sample size assumes 35% of 
randomized subjects will not be in the modified intent-to-treat (MITT) population (see 
Section 3.4 for analysis population definition) which is used for the primary efficacy 
analysis. 
3.0 
STATISTICAL METHODS 
3.1 
Statistical Handling Policy 
3.1.1 
Interim Safety Review 
This is a short-duration study - a subject will be in the study for approximately 30 days.  
No formal interim analysis will be conducted for this short duration study. 
3.1.2 
Analysis Conventions 
This section details general approaches to be used for the statistical analyses.  
Departures from these general approaches may be outlined in the specific detailed 
sections of this SAP, and will take precedence over the general approaches. The 
following approaches will be applied to all data presentations and analyses. 
x Data listings will be provided for all CRF data with one listing for one CRF panel. All 
data listings will be sorted for presentation in the order of, treatment assignment, site 
identifier (ID), subject ID, and date of procedure or event. 
x Statistical summary tables will be provided for most CRF data, and generated for each 
of the 2 treatment groups, and for all subjects (i.e., 2 groups combined, presented in 
a column labelled “Total”) when appropriate. 
x Summary statistics will consist of the number and percentage of responses in each 
category for discrete (categorical) variables, and the number of non-missing 
observations (n), mean, median, standard deviation (SD), 25th, 75th percentiles, 
minimum, and maximum (abbreviated as “8-number statistics”) for continuous 
variables.  Some parameters valued as integers (0, 1, 2, etc.) may be summarized as 
both categorical variable with counts and percentage of subjects and continuous 
variables with 8-number statistics. 


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x All mean values will be formatted to one more decimal place than the measured value, 
and standard deviation values will be formatted to two more decimal places than the 
measured value.  For median values, the same decimal place as the measured values 
will be reported, if that is feasible without losing accuracy; otherwise, median values 
will be formatted to one more decimal place than the measured values. 
x All percentages will be rounded to one decimal place.  The number and percentage 
of categorical responses will be presented in the form XX (XX.X), where the 
percentage is in the parentheses.  The denominator for percentage calculations will 
be the number of non-missing observations (n) when this number is shown, or will be 
the total sample size of the relevant treatment group for tables like adverse events, 
medical histories, or other tables where this number of non-missing observations (n) 
is not presented. 
x All statistical tests will use a significance level of D = 0.05.  Two-tailed tests will be 
performed for all analyses that use statistical testing. 
x All p-values will be rounded to 3 decimal places.  All p-values that round to 0.000 will 
be presented as ‘<0.001’, and p-values that round to 1.000 will be presented as 
‘>0.999’.  Any p-value d 0.05 will be considered statistically significant and will be 
marked with one asterisk (e.g., 0.025*). 
x All analysis and summary tables will have the population sample sizes in the column 
headings. 
x Summary by visit tables will not include unscheduled visit(s); those unscheduled visit 
data will be included in relevant data listings. 
x Baseline is defined as the last data point on or before the day of randomization. 
x Calculating change from baseline to a visit will be performed as “Observed value at 
the visit – Baseline value”.  As a result of this approach, for those subjects who have 
only baseline, or conversely are missing a baseline value and only have a post-
baseline value for a parameter, calculating Change from Baseline for that parameter 
at that visit will not be possible. 
x Version 9.4 of SAS£ or higher will be the statistical software package used to produce 
all statistical analysis tables and data listings. 
3.2 
Subject Disposition 
Subject disposition will be summarized for ITT population as follows: 
x Number of subjects who have signed informed consent in each of the following 3 
groups for the All Screened population: 
o Screen failures 
o DARE-BV1 
o Placebo 
x Summary of screen failures by the reason for ineligibility for screen failed subjects 


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x The number and percentage of randomized subjects who completed or discontinued 
prematurely from the study, the number and percentage of subjects who discontinued 
by each reason for all subjects. 
x A listing of randomized subjects who discontinued prematurely from the study. The 
listing will include information about treatment assignment, study site ID number, 
subject ID number, age, number of days in the study (calculated as Date of Last Visit 
– Date of randomization + 1.), and reason for discontinuation. 
x The number and percentage of randomized subjects at each study visit.  This table 
will also be repeated for the MITT population. 
x The number of randomized subjects who were enrolled, had completed, or 
discontinued prematurely at each study site. 
The Disposition page of the CRF will be used to determine who discontinued prematurely 
from the study. 
3.3 
Protocol Deviations 
Protocol deviations data, collected during the clinical monitoring process, will be classified 
into different types of deviations, such as informed consent process not conducted per 
ICH/GCP Guidelines, patient did not meet eligibility criteria, scheduled visit completed out 
of specified window, deviation from protocol-defined procedure, clinical assessment not 
done, lab processing error, lab assessment not completed, use of prohibited medication, 
study medication not returned/lost, etc.  These data will be summarized categorically with 
number and percentage of distinct subjects for each type of deviations by treatment group 
and all subjects.  All deviations will be reviewed prior to database lock, and each will be 
prospectively designated as either “minor” vs “major” to define whether the deviation 
warrants excluding the patient from the Per Protocol Population.   
 
3.4 
Analysis Populations 
All Screened Population: all subjects who signed Consent Form and screened at the 
study sites. 
Intent-to-Treat (ITT) Population: All randomized subjects. 
Safety Population:  All randomized subjects who applied assigned study drug.  If the drug 
accountability is unknown (e.g., due to being lost to follow-up after being randomized) the 
subjects will be assumed to have taken study drug and included in the safety population.  
Subjects with confirmation of 0 doses taken will be excluded. 
Pharmacokinetic Subset (PKS) Population: Safety population subjects who are enrolled 
into the PK sub-study and have at least one post-baseline PK measurement. 
Modified Intent-to-Treat (MITT) Population: All Safety population subjects except those 
excluded due to demonstrating a positive test result for other concomitant vaginal or 
cervical infections at baseline (e.g., T. vaginalis, N. gonorrhoeae, C. trachomatis, Candida 
species) or who are determined to have a baseline Nugent score of < 7 
(https://www.fda.gov/media/129530/download). If the Nugent score at baseline is 
missing, then the subject is excluded from the MITT population. 


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Per Protocol (PP) Population: subjects in MITT population who either receive other BV 
therapies during the study for any reason, or meet the following criteria: 
1. Meet all 4 Amsel’s criteria at screening 
2. Apply assigned study drug within 1 day of randomization 
3. Do not use a prohibited medication prior to the Day 21-30 visit 
4. Attend the Day 21-30 visit  
5. Have no other major protocol violations that impact the primary or secondary 
endpoints. 
For the MITT and PP populations, if the subject receives other BV therapy for any reason, 
the subject will be included in the analysis as a treatment failure for all visits on or after 
receipt of the other BV therapy.  Subjects will be excluded from the PP population if they 
receive study treatment that was not the treatment to which they were randomized. A 
review of the data will be performed prior to locking the database and unblinding the study 
to determine which medications and major protocol violations would impact the primary 
and secondary efficacy endpoints and cause a subject to be excluded from the PP 
population. Safety endpoints will not be impacted. 
3.5 
Demographics and Pre-Treatment Characteristics 
Subject demographics and pre-treatment characteristics will be summarized for the ITT 
population, and some of these summaries may also be done for other populations, such 
as MITT and PP populations, when deemed important. 
3.5.1 
Demographics 
A summary of demographics and subject characteristics will be created for the ITT, MITT, 
and PP populations, and include age, race, ethnicity, height, weight, and body mass index 
(BMI) at the screen visit with: 
x 8-number statistics (number of non-missing observations, mean, median, SD, 25th 
percentile, 75th percentile, minimum, and maximum) for age, height, baseline weight, 
baseline BMI by treatment group and for all subjects.  
x Age will also be categorized as ≤ 20, 21-30, 31-40, 41-50, ≥ 51, and then summarized 
categorically along with race, ethnicity. 
x BMI at the study entry visit, which will also be categorized as: Underweight (< 18.5), 
Normal (18.5 – 24.9), Overweight (25.0 – 29.9), and Obese (≥ 30.0). The number and 
percentage of subjects in each of these categories will be presented by treatment 
group and for all subjects. 
3.5.2 
Medical History 
Medical history data will be coded by using the Medical Dictionary for Regulatory Activities 
(MedDRA) Version 23.0. The codings will be reviewed by qualified medical personnel, 
and then summarized by system organ class (SOC) and preferred term (PT) and by the 
medical history status “Ongoing”, or “Resolved” by treatment group and for all subjects in 
the ITT population.  If a subject reports the same SOC/PT more than once in a status, 
that subject will be counted only once toward that status. 


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3.5.3 
BV History 
BV history data will be summarized categorically for the following parameters for ITT and 
MITT populations: 
x Number of previously diagnosed BV episodes - lifetime (≤10, >10.), 
x Number of previously diagnosed BV episodes in the past 12 months (≤3, >3), 
x Treatment used in the last 12 months (Metronidazole vaginal, Metronidazole oral, 
Clindamycin vaginal, Clindamycin oral, Secnidazole, Tinidazole, Don’t remember, 
or Other), 
and also summarized with 8-number statistics, with n (number of non-missing), mean, 
SD, median, tertiles (33.3th and 66.7th percentiles), minimum, and maximum for: 
x Number of previously diagnosed BV episodes - lifetime 
x Number of previously diagnosed BV episodes in the past 12 months 
x Approximate number of years since last diagnosed BV episode. 
The last parameter “Approximate number of years past since last diagnosed BV episode” 
= 2020 – “Year of previous (last) BV episode” in BV CRF; but if the Year of previous (last) 
BV episode = 2020, this will be expressed as a fraction based on the number of months 
since last BV episode (e.g., 0.3 for 3.6 months), instead of as a whole number of 0. 
3.5.4 
Sexual, Contraceptive, and Pregnancy History 
Gynecological history data will be summarized for key parameters collected in the CRFs, 
with categorical (qualitative) parameters as follows for ITT populations:  
x What sanitary products does the subject currently use? (Tampons, Sanitary Pads, 
Menstrual cup, and Other, in Demographics CRF) 
x Subject sexually active 
x Previously diagnosed with other sexually transmitted infections 
x Form of contraception to be used during the study (Oral contraceptive, Hormonal 
contraception (transdermal or implanted), Intrauterine device (IUD), Non-
polyurethane condom, Vasectomy of partner, Abstinence, Surgically sterile, 
Postmenopausal, Other, or None)  
x Had previous pregnancies 
x Number of previous pregnancies (0, 1, 2, etc.) 
x Number of C-sections and vaginal deliveries 
and continuous (quantitative) parameters as: 
x Approximate length of menstrual cycle (in days)  
x Number of previous pregnancies 
x Number of current sexual partners 
The number and percentage of subjects will be provided by treatment group and for all 
subjects for each response to the question for categorical data, and 8-number statistics 
for continuous data. 


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3.5.5 
Prior Medications 
All medications taken by the subject during the 30 days prior to randomization (pre-study) 
and during the study will be recorded on the prior and concomitant medication CRF page. 
Prior medications are medications that were taken during the 30 days before 
randomization, and concomitant medications are medications taken after randomization. 
Medications will be coded to the therapeutic drug classes and preferred names by using 
the World Health Organization (WHO) Drug Dictionary Enhanced (DDE) B3 March 2020 
version.  The codings will be reviewed by qualified medical personnel, and then 
summarized by treatment group and for all subjects with the number and percentage of 
ITT subjects who had prior medications that were coded to each preferred name and 
therapeutic drug class (Level 2), as well as the number and percentage of subjects who 
had at least one prior medication.  Subjects reporting more than one drug in each drug 
class/generic name are only counted once to that drug class/generic name. 
Prior medications will be also be summarized by the descending order of frequencies 
(total number of ITT subjects) for drug class (i.e., no preferred names provided). 
3.6 
Concomitant Medications 
As defined in the above Section 3.5.4, concomitant medications are medications taken 
on or after the subject applied study treatment.  Similar to prior medications, concomitant 
medications will be summarized for Safety populations by the number and percentage of 
subjects in each coded drug name (preferred name) and drug class. They will also be 
summarized by the descending order of frequencies (total number of subjects with DARE-
BV1 and placebo groups combined) for drug class (i.e., no preferred names provided). 
A medication may be both “prior” and “concomitant” if a subject took it prior to the study 
product use (pre-study) and also used it again on/after study product use.  Another 
summary table with unique number and percentage of subjects for each treatment group 
and all subjects will be presented for medications belonging to both “prior” and 
“concomitant” (i.e., a medication will not be included in the table unless a subject took it 
before randomization as well as on or after randomization).  
3.7 
Efficacy Analyses 
The primary efficacy analyses will be conducted on the modified intent-to-treat (MITT) 
population.  Additionally, efficacy analyses will be performed on the ITT and per-protocol 
(PP) population and will be considered supportive. 
3.7.1 
Primary Efficacy Analyses 
The primary efficacy endpoint of this study is the proportion of Clinical Cure (CC) at the 
TOC visit (Day 21-30). CC is defined using the criteria of following 3 parameters from the 
Study Procedure CRF: 
x Abnormal Vaginal discharge consistent with BV, defined as presence of off-white 
(milky or gray) thin homogenous discharge, should have value of “No”, 
x 10% KOH whiff test, which is from the variable Whiff test, should have value of 
“Negative”, 


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x Clue cells < 20% of the total epithelial cells in the saline wet mount, which is from 
the variable Percentage of Clue Cells, and should have value below 20.  
The Clinical Cure will be “Yes” when all of the above 3 conditions are met; otherwise 
Clinical Cure will be “No” (this includes data missing in one or more of these 3 
components).  A Cochran-Mantel-Haenszel (CMH) test, stratified by study center and 
race (African-American/Black versus all others), will be performed to test the association 
between Clinical Cure and treatment assignment (either DARE-BV1, or placebo) for the 
subjects in MITT population.   Subjects who received other BV therapy for any reason will 
be included in the analysis as a treatment failure (Clinical Cure will be “No”) for all visits 
on or after receipt of the other BV therapy. Additionally, non-study treatments that might 
interfere with the assessment of the subject’s BV will cause the subject to be analyzed as 
a treatment failure for all visits on or after receipt of the non-study treatment.  The following 
non-study treatments will be considered to interfere with BV assessments and will cause 
a subject to be a failure on or after receipt of the non-study treatment: 
x 
metronidazole  
x tinidazole 
x secnidazole 
x clindamycin  
x Intravaginal probiotics 
x Intravaginal  boric acid 
If the p value from CMH (general association) chi-square test is ≤ to 0.05, then we will 
reject the null hypothesis that the 2 Clinical Cures rates in DARE-BV1 and placebo groups 
are equal.  
A 95% confidence interval (CI), using Yates’ correction, for the difference, pT – pR, in 
proportion of subjects achieving Clinical Cure will be calculated. 
Furthermore, 2-sided 95% CI for the Clinical Cure rate of each individual treatment group, 
estimated as pT and pR for DARE-BV1 and placebo, respectively, will also be presented 
by using PROC FREQ in SAS£.  
Sensitivity Analysis by Multiple Imputation for Missing Data 
If some of the 3 components of Clinical Cure are missing, conventional analysis method 
only uses complete cases, which would reduce the sample size. Multiple Imputation (MI) 
is a way to make use of all records, including partially complete records.  The imputed 
values are drawn from a distribution, so they inherently contain some variation. It replaces 
each missing variable with acceptable values, representing a distribution of possibilities. 
Here are the 3 parameters that will be missing for subject who prematurely discontinued 
study, and all are categorical variables. 
x Abnormal Vaginal Discharge consistent with BV  (Yes, No) 
x Whiff test (Negative, Positive) 
x Less than 20% of clue cells (Yes, No, derived from the quantitative value) 
MI is a simulation-based procedure. Its purpose is to handle missing data to achieve valid 
statistical inference. First, the methodology is described, and then SAS code fragments 
will be provided. MI involves 3 steps: 


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a. Running an imputation model defined by the chosen variables to create imputed 
datasets. In other words, the missing values are filled in m times to generate m 
complete datasets. 
b. The m complete datasets are analyzed by using standard procedures. 
c. The parameter estimates from each imputed dataset are combined to get a final 
set of parameter estimates. 
The aforementioned method for non-missing data will be repeated m times by using m 
imputed datasets for each of the 3 parameters that make up Clinical Cure.  Then a final 
Clinical Cure will be determined for each imputation for each subject by combining the 
datasets for the 3 clinical cure parameters.  The multiple imputation solves the limitations 
of single imputation by introducing an additional form of error based on variation in the 
parameter estimates across the imputation, which is called “between imputation error”. 
The final results will be summarized by MIANALYZE Procedure in SAS£.  The number of 
imputations will be determined once the number of subjects with missing Clinical Cure at 
Day 21-30 Visit is known.  The decision on the number of imputations will be determined 
prior to database lock and unblinding.  The number of imputations performed will be equal 
to the percentage of missing data to target a 99% imputation efficiency rate (e.g., if 10% 
of the subjects have missing data then 10 imputations will be performed: 
https://documentation.sas.com/?docsetId=statug&docsetTarget=statug_mi_details54.ht
m&docsetVersion=14.3&locale=en ). 
Imputation is only being done within each treatment group (since the treatment group 
variable is a factor in the modeling) because assigned drug dosing is complete for each 
subject once the subject takes 1 dose of study drug. Parameter Race is used as 
randomization strata, it will also be used in the MI process as a factor in the modeling.  
Missing data in subjects who prematurely discontinue from the study will be designated 
as either missing at random (MAR) or missing not at random (MNAR), depending on the 
relationship between the subject’s treatment with study drug (i.e., its effectiveness, safety 
and/or tolerability) and her reason for early discontinuation (ED).  The sponsor and CRO 
will conduct a careful review of each discontinued subject’s CRF data, in blinded way, 
i.e., before unblinding the randomization codes, to ensure that the ED reason is 
appropriately categorized; this review will include a review of AEs, efficacy data, medical 
history and medication usage in addition to the ED reason. However, for subjects 
discontinued study due to treatment failure, the analysis value for CC will be imputed as 
“No”, and none of the 3 individual components will be separately imputed. 
Any drop out reason can fall into either of the following two scenarios: 
x Subjects prematurely discontinued due to reasons that are related or potentially 
related to their use of study drug will be assumed to be missing not at random 
(MNAR); these will include the CRF-defined ED reasons of “Occurrence of other 
vaginal infection requiring treatment” and “Other Adverse Event” if/when the 
causality designation is “Probably Related”, “Possibly Related”, or “Definitely 
Related” to study treatment.   
x The remaining CRF-defined ED reasons will be assumed to be missing at random 
(MAR), including: “Retrospective discovery of an entry criterion violation;” “Pre-
existing condition or abnormality, including abnormal laboratory or microbiological 


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result obtained at screening;” “Other adverse event” with causality = “Unrelated;” 
“Withdrawal of consent;” “Lack of compliance;” “Lost to follow-up;” and “Other.” 
The current COVID-19 pandemic may also impact subjects’ ability to complete the study 
for reasons unrelated to the efficacy, safety, or tolerability of the study treatment.  In the 
event that a subject must discontinue specifically due to a COVID-19-related illness, an 
ED reason of AE (causality = unrelated) will be recorded, and hence assumed to be MAR.  
In the event a subject must discontinue due to other consequences of the pandemic (e.g., 
illness in a close family member necessitating self-quarantine, or changes in the 
investigative site’s ability to conduct business), then other MAR reasons will be utilized 
as appropriate (e.g., Other).  In all such cases, reference to COVID-19 will be made in 
the CRF (or the study’s deviation log, if appropriate) to ensure that the impact of the 
pandemic can be understood and characterized.         
The complete data will be pooled from the 2 different missing pattern’s imputation as the 
input data for efficacy analysis.  First, we make the observed data into two subsets:  
1) one subset with completers and early terminated subjects with termination reasons 
considered to be MAR,  
2) the other with completers and early terminated subjects with termination reasons 
considered to be MNAR.  
Note that we need to use completers, i.e., those not missing values for the clinical cure 
at Day 21-30, in both subsets to predict the missing values.  Overlap data from completers 
(same data appear in both subsets) will be removed when pooling all together after 
separately running MI process for the above two subsets. 
If there are subjects with a missing result at the Interim Assessment visit (Day 7-14) and 
a result at the TOC visit (Day 21-30), then the MCMC procedure within PROC MI will be 
used to turn the arbitrary missing patterns to monotone missing patterns under MAR 
assumption 
(https://www.pharmasug.org/proceedings/2019/ST/PharmaSUG-2019-ST-
103.pdf). 
Here are SAS£ code fragments of the first subset data (with MAR) by PROC MI 
(https://documentation.sas.com/?docsetId=statug&docsetTarget=statug_mi_syntax09.ht
m&docsetVersion=14.3&locale=en ) for Clinical Cure parameter “Whiff Test”: 
PROC MI data=Observed1 out=Imputed1 seed=s nimpute=m; 
CLASS Trt01PN Race WHIFF_Day7_14 WHIFF_Day21_30; 
MONOTONE logistic(WHIFF_7_14 = Trt01PN Race); 
MONOTONE logistic(WHIFF_21_30 = WHIFF_7_14 Trt01PN Race); 
VAR Trt01PN Race WHIFF_Day7_14 WHIFF_Day21_30; 
RUN; 
where WHIFF_Day7_14 and WHIFF_Day21_30 is the “Whiff Test” at Interim Assessment 
visit (Day 7-14) and TOC visit (Day 21-30), respectively; s is a randomization seed; m is 
the number of imputations (to be determined prior to database lock once the number of 
subjects without a clinical cure at day 21-30 is known); Trt01PN is the treatment group 


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indicator (1 for DARE-BV1, 2 for Placebo); Race is indicator (either “African-American”, 
or “Not- African-American”). 
SAS codes for the second subset, missing not at random (MNAR): 
PROC MI data=Observed2 out=Imputed2 seed=s nimpute=m; 
CLASS Trt01PN Race WHIFF_Day7_14 WHIFF_Day21_30; 
MNAR MODEL (WHIFF_Day7_14 WHIFF_Day21_30 / MODELOBS=CCMV); 
MONOTONE logistic(WHIFF_Day7_14 = Trt01PN Race); 
MONOTONE logistic(WHIFF_Day21_30 = WHIFF_Day7_14 Trt01PN Race); 
VAR Trt01PN Race WHIFF_Day7_14 WHIFF_Day21_30;  
RUN; 
For the first subset, there is no need to use MNAR statement for this part of the data.  
This way we impute missing values using MAR assumption for each treatment group 
separately. 
Similarly, the MI process will be done for the other 2 parameters - Vaginal discharge, and 
Percentage of Clue Cells. The primary endpoint Clinical Cure will be calculated from the 
3 parameters, and the analysis for complete cases (no missing values) will be performed 
as aforementioned by using each of the m data sets.  Final summary of the analysis result 
will utilize MIANALYZE Procedure in SAS£.  
3.7.2 
Secondary Efficacy Analyses 
Regardless of the outcome and conclusion from the primary efficacy endpoint, the 
following secondary efficacy analysis tables will be presented.  Statistical testing of the 
secondary efficacy endpoints will only be done if the p-value for the primary endpoint is 
≤0.05. Hypothesis testing for the secondary efficacy endpoints will be conducted in a 
sequential manner to control the overall Type 1 error rate in the order presented below: 
1. Proportion of MITT subjects with Clinical Cure at the Interim Assessment visit (Day 
7-14). 
2. Proportion of subjects in the MITT population with Bacteriological Cure at the TOC 
visit (Day 21-30). Bacteriological Cure is defined as a Nugent score < 4. 
3. Proportion of MITT subjects with Therapeutic Cure at the TOC visit (Day 21-30). 
Therapeutic Cure is defined as both a Clinical Cure and Bacteriological Cure 
(Nugent Score < 4). 
4. Proportion of MITT subjects with Bacteriological Cure (Nugent score < 4) at the 
Interim Assessment visit (Day 7-14). 
5. Proportion of MITT subjects with Therapeutic Cure at the Interim Assessment visit 
(Day 7-14).  
Analysis of the secondary endpoints will follow the same method as the analysis of the 
primary endpoint, including subjects being included in the analysis as treatment failures 
if other BV treatments were received (i.e., treatment failure status will be applied to all 
visits on or after receipt of the other BV treatments) as well as non-study treatments that 
might interfere with the assessment of the subject’s BV (as outlined in Section 3.7.1 


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above) will cause the subject to be analyzed as a treatment failure for all visits on or after 
receipt of the non-study treatment.  
The ITT and PP populations will be used to perform sensitivity analyses of the above 
primary and secondary efficacy analyses.  Subjects in the PP population without a Clinical 
Cure result at Day 21-30 will be excluded from the PP analyses thus no imputation as a 
failure due to missing results (i.e., CC = “No”) will be used for the PP analyses. 
Nugent score will also be summarized categorically by its raw score (0, 1, 2, …,10).  All 
results from the Amsel’s 4 criteria will also be summarized categorically (“Yes”/ “No”) by 
study visit and treatment group for both MITT and PP populations.  Clue cell summary of 
“Yes”/”No” response will be derived using the percentage of clue cells and will be 
presented as <20 being the Yes response and ≥20 being the No response. 
3.8 
Safety Analyses 
All safety analyses will be performed for the Safety population, and summaries will be 
presented by treatment group and all subjects, unless noted otherwise. 
3.8.1 
Treatment Exposure and Compliance 
Each eligible subject should apply only one dose of the assigned drug, either (active) 
DARE-BV1, or placebo gel. Compliance with use of the study drug will be verified through 
collection and assessments of dispensed weight and returned weight of study product via 
Investigational Product (IP) CRF.    The number and percentage of subjects that have a 
tube weight change (between dispense and return) of <4 grams or >6 grams will be 
summarized. 
3.8.2 
Adverse Events and Serious Adverse Events 
A treatment-emergent adverse event (TEAE) is any symptom, sign, illness, or experience 
that develops or worsens in severity and/or frequency after the study treatment started. 
A serious adverse event (SAE) is any adverse event that results in any of the following 
outcomes: Death; immediate threat to life; inpatient hospitalization or prolongation of an 
existing hospitalization; persistent or significant disability/incapacity; congenital 
anomaly/birth defect; other serious (medical important) AEs. All AEs will be coded with 
system organ class (SOC) and preferred term (PT) from the MedDRA Version 23.0. The 
codings will be reviewed by qualified medical personnel. 
Incidence of AEs and SAEs will be summarized by SOC and PT with the number and 
percentage of subjects with each SOC and PT by treatment group.  The following tables 
will be presented: 
x Overall number and percent of subjects with AEs without presenting SOC or 
preferred term, which includes AE severity (Unknown, Mild, Moderate, Severe), 
AE relatedness (Unrelated, Possibly Related, Probably Related, Definitely 
Related); SAE; Death, or discontinued study due to any AE 
x AEs by SOC and preferred term 
x Study product-related AEs (including Possibly Related, Probably Related, and 
Definitely Related) by SOC and preferred term 


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x AEs presented in descending order of frequency by preferred term (without 
showing SOC), in which the most frequent one appears at first, and least frequent 
one will appear in the last 
x AEs by SOC and preferred term and by severity 
x AEs by SOC and preferred term and by relatedness to the study product 
All the above tables (except for where specified) are counting number of distinct subjects 
in each SOC and PT. Subjects reporting more than one AE/SAE in each PT will be 
counted only once to that PT, using the most severe intensity, for unique number of 
subjects counting, while “Unknown” intensity will be an independently counted.  The only 
exception to this will be for the summary by relatedness to the treatment, where subjects 
will be counted only once using the strongest relatedness to the treatment for the purpose 
of counting distinct number of subjects. The same principle also will be applied to the 
summary at the SOC level. 
An overall AE high-level summary table will also be provided (without showing SOC and 
PT) for Safety population with total number and percentage of distinct subjects by 
treatment group. 
Another high-level summary table will present the counts of events (i.e., not distinct 
subjects) similar to the following chart for each treatment group. 
 
Relatedness (to the 
study treatment) 
AE Severity 
Unknown 
Mild 
Moderate 
Severe 
Total # (%) 
of Events 
Unrelated 
xx 
xx 
xx 
xx 
xx (x.x) 
Possibly Related 
xx 
xx 
xx 
xx 
xx (x.x) 
Probably Related 
xx 
xx 
xx 
xx 
xx (x.x) 
Definitely Related 
xx 
xx 
xx 
xx 
xx (x.x) 
Total # of Events 
xx 
xx 
xx 
xx 
xx (100.0) 
 
Note that percentages at “Total # (%) of Events” column are based on the number on the 
one where “(100.0)” is displayed. This AE summary table, populated for each treatment 
group and all Safety population subjects, provides the cross reference between every 
level of relatedness and severity. If there are not any AEs of “Unknown” severity in the 
final analysis data, this “Unknown” column will not be presented in the final table. 
Two listing-style tables, one for SAEs, and the other for AEs that led to premature study 
discontinuation, will also be presented, with the details about the event onset date, 
resolved date, study day of onset since the study treatment (calculated as Onset Date – 
Study Product Use Date +1), severity, outcome, medical intervention needed for the AE, 
and relatedness to the study treatment, as well as other supportive data such as the 
subject’s age and number of days on the study.  
3.8.3 
Local Site Reactions 
At each visit the Investigator or designee will perform a vulvar-vaginal examination to 
assess the treatment area and rate the following on a scale of 0 = absent, 1 = mild (slight, 
barely perceptible), 2 = moderate (distinct presence), and 3 = severe (marked, intense): 


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TEM BM-001.06 (Eff. 06JUN2018)                             Statistical Analysis Plan, v3.0 – Page 19 
x Erythema 
x Edema 
x Petechiae 
x Erosion/ulceration 
Subjects will also be queried by the Investigator or designee for presence of the following 
symptoms either at the visit (for Randomization visit) or since the last visit (for post-
treatment visits), and to do the severity rating (on the scale of 0 to 3 as described above) 
for: 
x Burning/stinging 
x Vulvovaginal Pain 
x Pruritus (itching)  
Summary will be the number and percentage of subjects in each treatment group with the 
categorical results of 0 = absent, 1 = mild, 2 = moderate, and 3 = severe, for each of the 
7 symptoms at each visit. 
3.8.4 
Vital Signs and Weight 
Vital signs measurements, including pulse rate (heart rate), oral temperature, systolic and 
diastolic blood pressures will be presented.   Weight and BMI  (unit: kg/m2) = weight (kg) 
/ [ height (m) ] 2, obtained at the screening visit only, will be summarized.  BMI will be 
categorized as: Underweight (< 18.5), Normal (18.5 – 24.9), Overweight (25.0 – 29.9), 
and Obese (≥30.0). Both numerical and categorical summaries for BMI will be presented. 
The 8-number summary statistics for continuous variables and their changes from 
baseline will be presented by study visit. 
3.8.5 
Physical Examination 
A complete physical examination in body areas such as dermatological, respiratory, etc., 
will be performed at Visit 1, and a directed physical exam will be performed at Visit 3 and 
at the Early Discontinuation visit (if applicable).  
If any “Abnormality” is reported, the examination result is “Abnormal”; otherwise, it is 
“Normal”. Number and percentage of subjects in the categories of “Normal” and 
“Abnormal” will be presented by visit and examined body area. 
For “Abnormal” findings, clinical significance (either Clinically Significant, or Not Clinically 
Significant) will also be summarized categorically. 
3.8.6 
Pelvic Examination 
Pelvic examination will be done at each study visit, evaluating the vulva, vaginal wall, and 
cervix, etc. The examination results are “Normal”, or “Abnormal”. Number and percentage 
of subjects in these categories will be presented by visit for each examined pelvic area.   
For “Abnormal” results, a further question “Was the result clinically significant?” will also 
be summarized categorically (“Yes”, “No”). 
A summary of shifts from Baseline will also be presented. 


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3.8.7 
Hematology, Chemistry, and Urinalysis 
Hematology and chemistry observed values and changes from screening to TOC visit (or 
early discontinuation visit) visit will be summarized by 8-number statistics. A summary of 
shifts from Baseline will be presented for each lab test parameter. The normal range for 
each parameter will be used to create categories of Low, Normal, or High.  Any result that 
is higher (lower) than the upper (lower) limit of normal will be categorized as High (Low), 
and any result within the lower and upper limits of normal will be categorized as Normal.  
The number and percent of subjects in each category (Low, Normal, or High) from 
Baseline to TOC visit (or early discontinuation visit) will be presented for each lab test 
parameter. 
Urinalysis data will be summarized categorically with counts and percentages of subjects 
for discrete data and 8-number statistics for continuous parameters. 
3.8.8 
Safety Phone Follow-Up 
Safety phone follow-up data will be summarized categorically for  
1. Did safety follow-up phone visit occur? (Yes, No) 
2. Did subject experience any additional adverse events since last visit? (Yes, No) 
3. Did subject take any additional concomitant medications/therapies/procedures 
since last visit? (Yes, No) 
4. Does subject report they currently have abnormal vaginal discharge consistent 
with BV symptom (milky or gray, thin, homogeneous discharge)? (Yes, No) 
5. Does patient report they currently have a “fishy” or unpleasant vaginal odor? 
(Yes, No) 
6. Subject experienced burning/stinging since last visit? (Absent, Mild, Moderate, 
Severe) 
7. Subject experienced vulvovaginal pain since last visit? (Absent, Mild, Moderate, 
Severe) 
8. Subject Experienced pruritus (itching) since last visit? (Absent, Mild, Moderate, 
Severe) 
9. Subject requires additional follow-up for signs/symptoms of BV? (Yes, No) 
Data from the 4th question’s sub-question “Number of days symptom present” will be 
summarized as a continuous parameter with 8-number statistics. 
3.8.9 
Other Safety Assessments 
On-Study Conduct CRF data will be summarized categorically for: 
x Did patient abstain from vaginal sexual intercourse and/or sexual activity since the 
last study visit? (Yes, No) 
x Did menstruation occur between the previous and the current study visit? (Yes, 
No) 
x What sanitary product(s) did the subject use, or is using? (Tampons, Sanitary 
Pads, Menstrual cup, Other) 
x Subject currently on menstrual cycle (Yes, No) 
Other study assessments, such as pregnancy tests, will be provided in data listings. 


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3.9 
User Acceptability Assessments 
3.9.1 
User Acceptability Questionnaire 
All treated subjects will provide responses to questions related to their experience with 
the study drug (e.g., ease of application, messiness or lack thereof, etc.) and overall 
product acceptability at the Interim and TOC/End of Trial visits (a subset of the questions 
asked at the Interim Visit will be repeated at the TOC/ET visit).  Responses will be 
summarized categorically for Safety population subjects at each visit.  
1. How would you describe the process of filling the applicator with the study drug? 
(Very easy, Fairly easy, Neither easy nor difficult, Fairly difficult, Very difficult) 
2. How would you describe the process of putting the study drug into your vagina? 
(Very easy, Fairly easy, Neither easy nor difficult, Fairly difficult, Very difficult) 
3. How would you describe the process of removing the applicator from your vagina? 
(Very easy, Fairly easy, Neither easy nor difficult, Fairly difficult, Very difficult) 
4. How would you describe your overall experience with the study drug in terms of 
neatness of applying it? (Clean, Fairly clean, Neither clean nor messy, Fairly 
messy, Messy) 
5. Did you experience leakage in the days following using the study drug? (If yes, 
answer question 5a.  If No, skip to question 6 (Yes, No) 
5a. When you experienced leakage, was it Bothersome, or Not Bothersome? 
6.  Have you used other vaginally applied BV products in the past? (Yes - answer 
question 6a, 6b and 6c), No (skip to question 7) 
6a. Compared to all other vaginally applied products you have used for BV, your 
overall experience with the study drug is (Much better, Better, Neither better nor 
worse, Worse, Much worse) 
6b. Compared to all other vaginally applied products you have used for BV; the study 
treatment is: Much cleaner, Slightly cleaner, Neither cleaner nor messier, Slightly 
messier, or Much messier? 
6c. Compared to other vaginally applied BV drugs, the leakage experienced was 
(Much less bothersome, Less bothersome, About the same, More bothersome, 
Much more bothersome) 
7. Considering your overall experience with the study drug treatment, were you (Very 
satisfied, Somewhat satisfied, Neither satisfied nor dissatisfied, Somewhat 
dissatisfied, Very dissatisfied) 
8. How likely is it that you would recommend this treatment to a friend who has BV? 
(Very likely, Likely, Neither likely nor unlikely, Unlikely, Very unlikely) 
9. How likely would you be to use this treatment again if it were available after the 
study and you had BV again? (Very likely, Likely, Neither likely nor unlikely, 
Unlikely, Very unlikely). 
A subset of the same questions, as follows, is asked at TOC Visit, which will be 
summarized categorically too: 


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1. Considering your overall experience with the study drug treatment, were you? 
(Very satisfied, Somewhat satisfied, Neither satisfied nor dissatisfied, Somewhat 
dissatisfied, Very dissatisfied) 
2. How likely is it that you would recommend this treatment to a friend who has BV? 
(Very likely, Likely, Neither likely nor unlikely, Unlikely, Very unlikely) 
3. How likely would you be to use this treatment again if it were available after the 
study and you had BV again? (Very likely, Likely, Neither likely nor unlikely, 
Unlikely, Very unlikely). 
3.9.1.1 
Product Attribute Ranking 
As part of the Acceptability Questionnaire, all treated subjects will also be asked to rank 
the following five attributes of the study product in the order of their preference from 1 to 
5, with 1 being the attribute they liked the most and 5 being the least, at both Interim 
Assessment and TOC visits for 
x One-time dosing 
x Vaginal drug delivery to the site of infection versus taking something orally 
x Clear gel versus a colored or opaque cream 
x Odorless 
x Resolved bothersome symptoms quickly 
These ranking data will be summarized by 8-number statistics at the 2 visits.  
3.10 
Pharmacokinetics Analyses 
PK analysis will not be done in this study and a separate PK study protocol will perform 
the PK analysis. All collected plasma and vaginal clindamycin concentration data will be 
presented in data listings.  
 
4.0 
REFERENCES 
1. Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis: diagnostic criteria and 
microbial and epidemiologic associations. Am J Med. 1983;74(1):14-22. 
2. Center for Drug Evaluation and Research. Application Number 205223 Orig1s000. 
Statistical Reviews. Statistical Review and Evaluation of metronidazole vaginal gel 
1.3%. Review date January 18, 2014. 
3. Mondal P, Alur HH, Johnston TP. (2011). Evaluation of TRI-726 as a drug delivery 
matrix. Drug Dev Ind Pharm 37(8):995-1001. 
4. https://www.fda.gov/media/129530/download 
5. https://go.documentation.sas.com/?cdcId=pgmsascdc&cdcVersion=9.4_3.5&docset
Id=statug&docsetTarget=statug_mi_syntax01.htm&locale=en 
6. https://www.pharmasug.org/proceedings/2019/ST/PharmaSUG-2019-ST-103.pdf 
7. https://www.pharmasug.org/proceedings/2013/SP/PharmaSUG-2013-SP03.pdf 
8. https://documentation.sas.com/?docsetId=statug&docsetTarget=statug_mi_details5
4.htm&docsetVersion=14.3&locale=en 
 


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5.0 
APPENDICES 
5.1 
Study Schedule of Assessments 
Visit 
Visit 1 
Visit 2 
Visit 3 
Safety Follow-up 
Phone Visit 
 
 
Early 
Disconti-
nuation 
Visit Name 
Screening/ 
Randomization 
Interim 
Assessment 
Test of 
Cure 
(TOC) 
 (FU after Early 
Discontinuation)1  
+5 days 
Study Day(s) 
1 
7-14 
21-30 
21-30 
 
 
Written informed consent 
administration 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical, gynecological, 
contraceptive, & relevant 
sexual history2 
X 
 
 
 
 
Height 
X 
 
 
 
 
Weight 
X 
 
 
 
 
Vital signs 
X 
X 
X 
 
X 
Concomitant medications 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
Urine pregnancy test3 
X 
X 
X 
 
X 
Urinalysis4  
X 
X 
X 
 
X 
Hematology/chemistry 
X 
 
X 
 
X 
Physical examination5 
X 
 
X 
 
X 
Pelvic examination6 
X 
X 
X 
 
X 
Assessment of local site 
reactions7 
 
X 
X 
 
X 
Amsel’s criteria assessments: 
 
 
 
 
 
-Vaginal discharge 
evaluation 
X 
X 
X 
 
X 
-KOH whiff test  
X 
X 
X 
 
X 
-Clue cells (wet mount) 
X 
X 
X 
 
X 
-Vaginal secretion pH 
X 
X 
X 
 
X 
Signs and symptoms of BV, 
including color, odor, and 
consistency of vaginal 
discharge, vulvovaginal 
itching, and irritation 
X 
X 
X 
X 
X 
KOH wet mount for microscopic 
yeast assessment8 
X 
X 
X 
 
X 
Vaginal culture for Candida 
species9  
X 
 
 
 
 
Collect sample/prepare slides 
for Nugent score9 
X 
X 
X 
 
X 
Perform OSOM® test for 
Trichomonas vaginalis9 
X 
 
 
 
 
Collect samples for Chlamydia 
trachomatis and Neisseria 
gonorrhoeae NAATs9 
X 
 
 
 
 
Review eligibility criteria 
X 
 
 
 
 
Randomization 
X 
 
 
 
 
Review of eDiary 
X 
X 
X 
 
X 
Dispense study drug and 
instructions 
X 
 
 
 
 
Collect study drug and perform 
compliance assessment10 
 
X 
 
 
 
Record treatment application 
date 
 
X 
 
 
 
Acceptability Questionnaire 
 
X 
X 
 
X 


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Abbreviations:  
BV = bacterial vaginosis; eDiary = electronic diary; FU = follow-up; KOH = potassium hydroxide; NAAT = nucleic acid 
amplification test; TOC = Test of Cure 
Notes:  
If necessary due to persistent symptoms of BV, patients may be offered other BV treatment prior to completion of the 
study; however, whenever feasible, other BV therapy should not be initiated until the patient has completed the final 
TOC Visit (Visit 3, Day 21-30). If initiated prior to Visit 3, then the patient should remain in the study and return to the 
clinic for the final TOC Visit (Visit 3, Day 21-30). If other treatment is prescribed at Visit 3, then the patient should 
either be followed by the study doctor (if the patient is regularly treated at their clinic), or be referred back to their local 
health care provider for further follow-up, as appropriate. The choice of other BV therapy is left up to the Investigator 
in collaboration with the patient, based on the current standard of care.  
Any other medications received for treatment of BV should be recorded as concomitant medications. 
1 Patients who are discontinued early from the study will be contacted by phone between study Day 21-30 to assess 
BV symptoms, adverse events, and concomitant medications.  
2 For medical, gynecological, contraceptive, and relevant sexual history, the recorded information will include: acute 
and chronic history of medical and gynecological conditions (including history of BV), smoking, illicit drug and alcohol 
use history, menstrual cycle history (start date of last menstrual cycle and expected timing of next menses will be 
collected), medically relevant sexual history including history of sexually-transmitted infections (STIs), current sexual 
activity, previous/current contraceptive use, and pregnancy history. 
3 Pregnancy testing via urine human chorionic gonadotropin (hCG) testing will be performed for each patient, 
regardless of childbearing potential, at each visit (serum hCG testing will be done only if deemed necessary by the 
Investigator). 
4 At all visits an in-clinic urine dipstick will be performed. At Visit 1, Visit 3, and the Early Discontinuation visit a central 
laboratory urinalysis will also be performed. 
5 A complete physical examination should be performed at Visit 1; at Visit 3 and at the Early Discontinuation visit (if 
applicable), a directed physical examination should be performed in accordance with the Investigator’s judgment. 
Rectal and breast examinations are not required for the complete or directed physical examinations. 
6 Pelvic examination will include a vaginal wall inspection as well as an examination of the cervix and will include 
assessment and appropriate reporting of any abnormalities, and confirmation that all findings are consistent with BV, 
versus Candidiasis or other causes of the patient’s vaginal signs or symptoms. 
7 A review of patient-reported and Investigator-assessed local site reactions will occur at each visit after 
randomization and treatment. 
8 The microscopic yeast assessment may be done on the same sample obtained for the 10% KOH whiff test. A swab 
of the vaginal pool should be utilized for both assessments.  
9 Diagnostic assessments for Candida spp, C. trachomatis, N. gonorrhoeae, or T. vaginalis may be repeated after 
baseline if changes in the patient’s clinical condition warrant re-testing. Full instructions for the collection of all 
samples will be provided in the study procedures manual.  
10 Perform compliance assessment by weighing the returned used tube and recording the weight in the eCRF. 
 
 
Additional Sampling for PK Subset Subjects 
 
Visit 
Visit 1 
Visits 
PK1-PK5 
Visit 2 
Visit 3 
Safety 
Phone  
Follow-up 
Early 
Disconti-
nuation 
Visit Name 
Screening/ 
Randomization 
PK1-PK5 
Interim 
Assessment  
Test of 
Cure 
FU after 
Early 
Disconti-
nuation 
+ 5 days 
Study Day(s) 
1 
2,3,4,5,6 
7-14 
21-30 
21-30 
 
Plasma samples for 
clindamycin level 
X 
X 
X  
(only at  
Day 7) 
 
 
X  
(if within 
the first 7 
days) 


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Visit 
Visit 1 
Visits 
PK1-PK5 
Visit 2 
Visit 3 
Safety 
Phone  
Follow-up 
Early 
Disconti-
nuation 
Visit Name 
Screening/ 
Randomization 
PK1-PK5 
Interim 
Assessment  
Test of 
Cure 
FU after 
Early 
Disconti-
nuation 
+ 5 days 
Study Day(s) 
1 
2,3,4,5,6 
7-14 
21-30 
21-30 
 
Vaginal samples for 
clindamycin 
concentration 
X 
X 
X  
(only at  
Day 7) 
 
 
X 
 (if 
applicable) 
 
 
5.2 
Table of Contents for Data Display 
Tables and data listings will be numbered according to the nomenclature used to support 
the final CSR. 
5.2.1 
Planned Tables 
The format of each unique table is provided in a separate document of “Table Shells”, but 
no data listing shells are provided. Final outputs may be slightly different in layout from 
that of illustrated in “Table Shells”. The table shells will not be amended to match the 
actual tables in such cases.  
 
Table  
Number 
Table Title 
Analysis 
Population 
14.1.1 
Summary of Subject Disposition and Reasons for 
Discontinuation 
All Screened 
14.1.1.1 
Screen Failure Reason Summary 
All Screened 
14.1.2 
List of Subjects Who Prematurely Discontinued the Study 
ITT 
14.1.3 
Summary of Subject Disposition by Study Site 
ITT 
14.1.4 
Number and Percentage of Randomized Subjects at Each 
Visit 
ITT 
14.1.4M 
Number and Percentage of Randomized Subjects at Each 
Visit 
MITT 
14.1.5 
Summary of Protocol Deviations 
ITT 
14.1.6 
Summary of Analysis Populations 
ITT 
14.1.7 
Demographics 
ITT 
14.1.7M 
Demographics 
MITT 
14.1.7P 
Demographics 
PP 
14.1.8.1 
Medical History 
ITT 
14.1.8.2 
Sexual, Contraceptive and Pregnancy History 
ITT 
14.1.8.3 
BV History 
ITT 


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14.1.8.3M 
BV History 
MITT 
14.1.9.1C 
Number and Percentage of Subjects with Prior 
Medication Use by Drug Class in Descending Order of 
Frequencies 
ITT 
14.1.9.1N 
Number and Percentage of Subjects with Prior 
Medication Use by Preferred Name in Descending Order 
of Frequencies 
ITT 
14.1.9.1 
Number and Percentage of Subjects with Prior 
Medication Use by Drug Class and Preferred Name 
ITT 
14.1.9.2C 
Number and Percentage of Subjects with Concomitant 
Medication Use by Drug Class in Descending Order of 
Frequencies 
Safety 
14.1.9.2N 
Number and Percentage of Subjects with Concomitant 
Medication Use by Preferred Name in Descending Order 
of Frequencies 
Safety 
14.1.9.2 
Number and Percentage of Subjects with Concomitant 
Medication Use by Drug Class and Preferred Name 
Safety 
14.1.9.3C 
Number and Percentage of Subjects with Prior 
Medications Also Used After the Study Treatment Applied 
by Drug Class in Descending Order of Frequencies 
Safety 
14.1.9.3N 
Number and Percentage of Subjects with Prior 
Medications Also Used After the Study Treatment Applied 
by Preferred Name in Descending Order of Frequencies 
Safety 
14.1.9.3 
Number and Percentage of Subjects with Prior 
Medications Also Used After the Study Treatment Applied 
by Drug Class and Preferred Name 
Safety 
14.2.1 
Primary Analysis of Clinical Cure 
MITT 
14.2.1Sen 
Sensitivity Analysis of Clinical Cure through Multiple 
Imputation Method 
MITT 
14.2.1T 
Analysis of Clinical Cure for Intent-to-Treat Population 
ITT 
14.2.1Sen-T 
Sensitivity Analysis of Clinical Cure through Multiple 
Imputation Method for Intent-to-Treat Population 
ITT 
14.2.1P 
Analysis of Clinical Cure for Per-Protocol Population 
PP 
14.2.2 
Summary of Clinical Cure, Bacteriological Cure and 
Therapeutic Cure at the Interim Assessment Visit 
MITT 
14.2.2T 
Summary of Clinical Cure, Bacteriological Cure and 
Therapeutic Cure at the Interim Assessment Visit for 
Intent-to-Treat Population 
ITT 
14.2.2P 
Summary of Clinical Cure, Bacteriological Cure and 
Therapeutic Cure at the Interim Assessment Visit for Per-
Protocol Population 
PP 


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14.2.3 
Summary of Bacteriological Cure and Therapeutic Cure 
at the Test of Cure Visit 
MITT 
14.2.3T 
Summary of Bacteriological Cure and Therapeutic Cure 
at the Test of Cure Visit for Intent-to-Treat Population 
ITT 
14.2.3P 
Summary of Bacteriological Cure and Therapeutic Cure 
at the Test of Cure Visit for Per-Protocol Population 
PP 
14.2.4 
Nugent Score and Amsel’s Criteria Summary by Visit 
MITT 
14.2.4T 
Nugent Score and Amsel’s Criteria Summary by Visit for 
Intent-to-Treat Population 
ITT 
14.2.4P 
Nugent Score and Amsel’s Criteria Summary by Visit for 
Per-Protocol Population 
PP 
14.2.5.1 
Summary of User Acceptability at the Interim Assessment 
Visit  
Safety 
14.2.5.2 
Summary of User Acceptability at the Test of Cure Visit 
Safety 
14.2.5.3 
Summary of Product Attribute Rankings 
Safety 
14.3.0 
Treatment Exposure and Compliance 
Safety 
14.3.1.1 
Overall Number and Percentage of Subjects with Adverse 
Events 
Safety 
14.3.1.2 
Overall Number of Adverse Events by Severity and 
Relatedness to the Study Treatment 
Safety 
14.3.1.3C 
Summary of Adverse Events by System Organ Class in 
Descending Order of Frequencies 
Safety 
14.3.1.3P 
Summary of Adverse Events by Preferred Term in 
Descending Order of Frequencies 
Safety 
14.3.1.4 
Summary of Adverse Events by System Organ Class and 
Preferred Term 
Safety 
14.3.1.5C 
Summary of Adverse Events by System Organ Class and 
by Severity 
Safety 
14.3.1.5 
Summary of Adverse Events by System Organ Class and 
Preferred Term and by Severity 
Safety 
14.3.1.6C 
Summary of Adverse Events by System Organ Class and 
by Relatedness to the Study Treatment 
Safety 
14.3.1.6 
Summary of Adverse Events by System Organ Class and 
Preferred Term and by Relatedness to the Study 
Treatment 
Safety 
14.3.2.1 
List of Serious Adverse Events 
Safety 
14.3.2.2 
List of Adverse Events that Led to Premature Study 
Discontinuation 
Safety 
14.3.5 
Local Site Reaction 
Safety 


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14.3.6 
Vital Signs and Weight 
Safety 
14.3.7 
Physical Examination 
Safety 
14.3.8.1 
Pelvic Examination 
Safety 
14.3.8.2 
Shift of Pelvic Examination from Baseline 
Safety 
14.3.9.1 
Hematology Test Results and Changes from Baseline 
Safety 
14.3.9.2 
Hematology Test Results and Shifts from Baseline 
Safety 
14.3.9.3 
Chemistry Test Results and Changes from Baseline 
Safety 
14.3.9.4 
Chemistry Test Results and Shifts from Baseline 
Safety 
14.3.9.5 
Summary of Urinalysis 
Safety 
14.3.10 
Summary of Safety Phone Follow-Up 
Safety 
14.3.11 
Summary of On-Study Conduct Questions 
Safety 
 
 
 
5.2.2 
Planned Data Listings 
No data listing shells are provided. A data listing may be split into 2 or more sub-listings 
(as Part A, Part B, etc.) when there are too many columns (variables) and the labels are 
lengthy, thus it is difficult to fit all headers in the same page. All data collected during the 
course of this study, including eDiary, will be presented in data listings. 
 
Listing  
Number 
Listing Title 
Analysis 
Population 
16.2.1.1 
Subject Information 
All Screened 
16.2.1.2 
Inclusion/Exclusion Criteria Not Met 
All Screened 
16.2.1.3 
Subject Disposition 
All Screened 
16.2.1.4 
Subject Study Visits 
All Screened 
16.2.1.5 
Reconsent 
All Screened 
16.2.2 
Protocol Deviations 
All Screened 
16.2.3 
Safety Subjects Excluded from MITT or PP Populations 
Safety 
16.2.4.1 
Demographics  
All Screened 
16.2.4.2 
Medical History 
All Screened 
16.2.4.3 
BV History 
All Screened 
16.2.4.4 
Sexual, Contraceptive, and Pregnancy History 
All Screened 
16.2.4.4 
Prior and Concomitant Medications 
All Screened 
16.2.5.1 
Investigational Product 
Safety 
16.2.5.2 
On-Study Conduct 
All Screened 
16.2.6.1 
Study Procedures 
All Screened 
16.2.6.2.1 
User Acceptability at Interim Assessment Visit  
Safety 
16.2.6.2.2 
User Acceptability at Test of Cure Visit 
Safety 


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16.2.6.3 
Unscheduled Assessments 
All Screened 
16.2.6.4.0 
PK Samples 
PKS 
16.2.6.4.1 
Plasma Clindamycin Levels 
PKS 
16.2.6.4.2 
Vaginal Clindamycin Concentration 
PKS 
16.2.7.1A 
Adverse Events – Part A 
Safety 
16.2.7.1B 
Adverse Events – Part B 
Safety 
16.2.7.2 
Local Site Reaction 
Safety 
16.2.8.0 
Lab Samples 
All Screened 
16.2.8.1 
Hematology 
All Screened 
16.2.8.2 
Chemistry 
All Screened 
16.2.8.3 
Urinalysis 
All Screened 
16.2.8.4 
Nugent Scores 
All Screened 
16.2.8.5 
Chlamydia and Gonorrhea 
All Screened 
16.2.8.6 
Trichomonas Vaginalis 
All Screened 
16.2.8.7 
Candidiasis 
All Screened 
16.2.8.8 
eDiary 
All Screened 
16.2.9.1 
Vital Signs 
All Screened 
16.2.9.2 
Physical Examination 
All Screened 
16.2.9.3 
Pelvic Examination 
All Screened 
16.2.10 
Pregnancy Test 
All Screened 
16.2.11 
Safety Follow-Up Phone Contact 
Safety