Conditions: Trichomonas Infection
Keywords: Vaginal Itching Vaginal Discharge
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 147
Healthy volunteers: no

Brief summary:
This is a Phase 3, multi-center, prospective, randomized, placebo-controlled, delayed treatment, double-blind, study to evaluate the effectiveness, and safety of a single, oral dose of Solosec® containing 2 grams of secnidazole in female patients with trichomoniasis.

Detailed description:
The study will consist of a primary study phase (Visit 1 (baseline) to Visit 2 (Day 6-12)) and a follow-up phase (Visit 2 to Visit 3 (7-12 days post Visit 2)). During the primary phase patients will be randomly assigned in a 1:1 ratio to either Solosec or placebo. Patients will return to the clinic for the "test of cure" (TOC) visit to be conducted on Days 6-12 (Visit 2).

To ensure all patients receive treatment and to maintain the double-blind, after completion of the primary phase, patients will receive the opposite treatment , (placebo patients will receive Solosec and vice versa). Patients with V2 cultures that are subsequently positive for T. vaginalis will return to the clinic for Visit 3 (V3) assessments and investigator assessment of need for additional therapy (an additional Visit 4 may be scheduled at the investigator's discretion if culture at V3 is positive).

Summary of results includes data reported during the primary phase of the study \[Visit 1 (baseline) to Visit 2/TOC (Day 6-12)\]

Arms:
arm 1: Orally administered as a single dose with applesauce. arm 2: Orally administered as a single dose with applesauce.

Interventions: intervention 1: Secnidazole intervention 2: Placebo
Intervention descriptions: intervention 1: Oral Granules containing secnidazole intervention 2: Oral Granules of placebo manufactured to mimic secnidazole

Protocol document:
Prot_000.pdf: 




PROTOCOL NUMBER: SEC-WH-301 
 
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Lupin Inc. 
 
CONFIDENTIAL 
INVESTIGATOR 
AGREEMENT 
 
A Phase 3, Multi-center, Prospective, Randomized, Placebo-Controlled, Delayed 
Treatment, Double-Blind Study to Evaluate the Effectiveness and Safety of a Single Oral 
Dose of Solosec® Granules Containing 2 grams of Secnidazole for the Treatment of 
Trichomoniasis 
Protocol Number: SEC-WH-301 
IND Number: 117811 
 
 
I have carefully read the foregoing protocol including all appendices and agree that it 
contains all the necessary information for conducting the study safely. 
I will conduct this study in strict accordance with this protocol and according to the current 
GCP guidelines and will attempt to complete the study within the time designated. 
I will provide copies of the protocol and all other information submitted by the Sponsor 
relating to pre-clinical and prior clinical experience to all personnel for whom I am 
responsible that participate in the study.  I will discuss this information with them to assure 
that they are adequately informed regarding the drug and conduct of the study. 
I agree to keep records on all subject information (case report forms, shipment and drug 
return forms and all other information collected during the study) in accordance with the 
current GCP and local regulations. 
 
 
 
 
Principal Investigator’s name 
 
Lupin Representative's name 
 
 
 
Signature 
 
Signature 
 
 
 
Date (dd-Mmm-yyyy) 
 
Date (dd-Mmm-yyyy) 
 
 
 
Institution 
 
 
 
 
 
 


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TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT ...................................................................................3 
1. 
SYNOPSIS ..............................................................................................................7 
2. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .....................12 
3. 
INTRODUCTION................................................................................................14 
3.1 
Trichomoniasis ...........................................................................................14 
 Current Available Therapies ..........................................................15 
 Solosec ...........................................................................................15 
4. 
STUDY OBJECTIVES ........................................................................................17 
4.1 
PRIMARY OBJECTIVE(S) ......................................................................17 
4.2 
SECONDARY OBJECTIVE(S) ................................................................17 
4.3 
STUDY ENDPOINTS ...............................................................................17 
 Primary Efficacy Endpoints ...........................................................17 
 Exploratory Efficacy Endpoints .....................................................17 
 Safety Endpoints ............................................................................17 
5. 
STUDY DESIGN ..................................................................................................18 
5.1 
OVERALL STUDY DESIGN ...................................................................18 
5.2 
DOSE RATIONALE .................................................................................18 
6. 
SELECTION AND WITHDRAWAL OF SUBJECTS ....................................19 
6.1 
INCLUSION CRITERIA...........................................................................19 
6.2 
EXCLUSION CRITERIA .........................................................................20 
6.3 
RANDOMIZATION CRITERIA ..............................................................21 
6.4 
WITHDRAWAL CRITERIA ....................................................................21 
6.5 
REPLACEMENT OF SUBJECTS WHO WITHDRAW OR ARE 
DISCONTINUED ......................................................................................21 
7. 
TREATMENTS....................................................................................................23 
7.1 
TREATMENTS ADMINISTERED ..........................................................23 
7.2 
IDENTITY OF INVESTIGATIONAL PRODUCT ..................................23 
7.3 
SUPPLY OF STUDY MEDICATION ......................................................23 
7.4 
Method of Assigning Subjects to Treatment Groups .................................23 
7.5 
BLINDING ................................................................................................24 
7.6 
STUDY MEDICATION ACCOUNTABILITY........................................24 
7.7 
EMERGENCY CODE BREAKING .........................................................24 
8. 
PROHIBITED AND RESTRICTED MEDICATIONS AND 
PROCEDURES ....................................................................................................25 
9. 
STUDY CONDUCT .............................................................................................26 
9.1 
OVERVIEW ..............................................................................................26 


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9.2 
STUDY PROCEDURES ...........................................................................26 
 Screening/Baseline Visit (Study Day 1) ........................................26 
 Visit 2/Test of Cure Visit (Study Day 6-12) ..................................27 
 Visit 3 – Follow-up Visit (7-12 days post V2 visit).......................28 
 Unscheduled Visit ..........................................................................29 
10. 
SAFETY AND PHARMACOVIGILANCE ......................................................33 
10.1 
DEFINITION OF AN ADVERSE EVENT ..............................................33 
10.2 
INTENSITY OF ADVERSE EVENTS .....................................................33 
10.3 
RELATIONSHIP OF ADVERSE EVENTS TO STUDY DRUG ............33 
 Definition of “No Reasonable Possibility” ....................................34 
 Definition of “Reasonable Possibility” ..........................................34 
10.4 
RECORDING OF ADVERSE EVENTS ..................................................34 
 Clinical Laboratory Abnormalities and Other Abnormal 
Assessments as AE: .......................................................................35 
10.5 
DEFINITION OF A SERIOUS ADVERSE EVENT ................................36 
10.6 
SERIOUS ADVERSE EVENT REPORTING ..........................................36 
10.7 
REPORTING TO THE UNITED STATES FOOD AND DRUG 
ADMINISTRATION (US FDA) ...............................................................38 
11. 
DATA COLLECTION AND ANALYSIS .........................................................39 
11.1 
DATA COLLECTION METHODS ..........................................................39 
11.2 
SAMPLE SIZE CALCULATIONS ...........................................................39 
11.3 
POPULATIONS FOR ANALYSIS ...........................................................40 
11.4 
INTERIM ANALYSES .............................................................................40 
11.5 
STUDY ENDPOINT ANALYSES ...........................................................40 
 Efficacy Analyses ..........................................................................40 
 Safety Analyses ..............................................................................40 
11.6 
GENERAL ISSUES FOR DATA ANALYSIS .........................................41 
 Multiple Comparisons and Multiplicity .........................................41 
 Covariates ......................................................................................41 
 Planned Sub-Group Analyses ........................................................41 
 Missing Data ..................................................................................41 
 Pooling of Centers..........................................................................41 
12. 
STUDY ADMINISTRATION ............................................................................42 
12.1 
REGULATORY AND ETHICAL CONSIDERATIONS .........................42 
 Regulatory Authority Approval .....................................................42 
 Ethics Approval .............................................................................42 
 Subject Informed Consent..............................................................42 
 Investigator Reporting Requirements ............................................43 
12.2 
PROTOCOL AMENDMENTS .................................................................43 
12.3 
DECLARATION OF THE END OF THE CLINICAL TRIAL ................43 
12.4 
STUDY MONITORING ...........................................................................43 


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12.5 
QUALITY ASSURANCE .........................................................................44 
12.6 
STUDY TERMINATION AND SITE CLOSURE ...................................44 
12.7 
SITE TERMINATION ..............................................................................45 
12.8 
RECORDS RETENTION ..........................................................................45 
12.9 
CONFIDENTIALITY OF INFORMATION ............................................46 
12.10 PAYMENT TO SUBJECTS ......................................................................46 
12.11 CLINICAL TRIAL REGISTRATION ......................................................46 
13. 
REFERENCES .....................................................................................................47 
APPENDIX A - SOLOSEC PACKAGE INSERT ........................................................50 
 


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1. 
SYNOPSIS 
Protocol Number 
SEC-WH-301 
Title of Study 
A Phase 3, Multi-center, Prospective, Randomized, Placebo-Controlled, 
Delayed Treatment, Double-Blind Study to Evaluate the Effectiveness 
and Safety of a Single Oral Dose of Solosec® Granules Containing 2 
grams of Secnidazole for the Treatment of Trichomoniasis 
Name of Active Ingredient(s) 
secnidazole 
IND/EudraCT No. 
IND 117811 
Indication 
Solosec for the treatment of Trichomoniasis 
Phase of Development 
Phase 3 
Investigational Center(s) 
Approximately 10 study centers in the United States. 
Objectives  
 
Primary Objective 
The objective of this study is to evaluate the efficacy and safety of a 
single, oral dose of Solosec containing 2 grams of secnidazole compared 
to placebo for the treatment of trichomoniasis. 
 
Secondary Objective 
None 
Study Design Overview 
This is a Phase 3, multi-center, prospective, randomized, placebo-
controlled, delayed treatment, double-blind, study to evaluate the 
effectiveness, and safety of a single, oral dose of Solosec containing 2 
grams of secnidazole in female patients with trichomoniasis. 
Approximately 144 patients who test positive for trichomonas on 
OSOM® rapid test or via wet mount assessment or have positive T. 
vaginalis NAAT test within 30 days of screening (and have not been 
treated) and fulfill other eligibility criteria at the baseline visit will be 
enrolled in this study. The diagnosis of T. vaginalis will be confirmed 
by a positive culture for T. vaginalis. The study will consist of a primary 
study phase (Visit 1 (baseline) to Visit 2 (Day 6-12)) and a follow-up 
phase (Visit 2 to Visit 3 (7-12 days post Visit 2)). During the primary 
phase patients will be randomly assigned in a 1:1 ratio to either Solosec 
or placebo. The randomization will be stratified by site and based on the 
clinical symptoms of trichomoniasis (present or absent). Patients will 
return to the clinic for the “test of cure” (TOC) visit to be conducted on 
Days 6-12 (Visit 2). After all Visit 2 (V2) study procedures have been 
completed, patients will receive the opposite treatment (placebo patients 
will receive Solosec and vice versa). Patients with V2 cultures that are 
subsequently positive for T. vaginalis will return to the clinic for Visit 3 
(V3) assessments and investigator assessment of need for additional 
therapy (an additional Visit 4 may be scheduled at the investigator’s 
discretion if culture at V3 is positive).  Patients with cultures that are 
negative at V2 will be contacted by phone and discharged from the study 
(no V3 required). A Schedule of Assessments is provided in Table 1. 
Number of Patients Planned 
Approximately 144 patients will be enrolled in order to obtain 100 
patients (50 patients in each group) who will be included in the mITT 
study population (ie, culture-positive for trichomonas at baseline). 
 
 


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Diagnosis and Main 
Criteria for 
Enrollment 
Inclusion Criteria 
Patients will be eligible to participate in the study if they meet all of the following 
criteria: 
1. Are adult females or post-menarchal adolescent girls ≥ 12 years of age. 
2. Are willing and able to give written informed consent or, if < 18 years of age, 
are willing and able to give written informed assent with a written informed 
consent from a parent or legal guardian. 
3. Are in good general health including as confirmed by a medical history and 
physical examination, with no known medical or mental health conditions that, 
in the Investigator’s opinion, may interfere with study participation. 
4. Are willing and able to participate in the study as an outpatient, make required 
visits to the study center, and comply with all study requirements.  
5. Have a negative urine pregnancy test result prior to study treatment initiation.  
In addition, female patients of childbearing potential must be using an 
acceptable form of birth control as determined by the Investigator (e.g., oral 
contraception, implantable, injectable/transdermal hormonal contraception, 
intrauterine device (IUD), barrier methods), tubal ligation or have a 
vasectomized partner or are practicing abstinence.  
6. Have a diagnosis of trichomoniasis at the screening visit as determined by one 
of the following:  
• positive T. vaginalis NAAT test within 30 days of screening for which 
treatment has not been initiated.  
• positive OSOM® rapid test. 
• positive wet mount assessment. 
7. Agree to abstain from vaginal intercourse until the final study visit.  
8. Agree not to have any vaginal penetration or use of any vaginal products for 
the duration of the study (e.g., spermicides, condoms, diaphragms, vibrators, 
tampons, etc.).  
9. Agree not to use vaginal douches, lubricants, or similar products for the duration 
of the study. 
Exclusion Criteria 
Exclusion Criteria 
Patients will be excluded from study participation if they have any of the following 
criteria: 
1. Are pregnant, lactating, or planning to become pregnant during the study.   
2. Are suspected clinically (or confirmed diagnostically) of having alternative 
causes of vaginal symptoms including symptomatic vulvovaginal candidiasis, 
chlamydia, gonorrhea, or an active genital herpes outbreak (Note: Chlamydia 
trachomatis, Neisseria gonorrhoeae [by PCR] results will not be available at 
time of randomization).  Note: patients with bacterial vaginosis (BV) are eligible 
for this study. 
3. Are suspected clinically of having an acute urinary tract infection.  
4. Have active genital lesions, including primary syphilitic chancres and herpes 
simplex virus lesions, or other vaginal or vulvar conditions which could 
confound the interpretation of the clinical response, as determined by the 
Investigator (patients with genital warts may be enrolled).  
5. Have 
received 
systemic 
antibacterial 
therapy 
or 
topical 
antimicrobial/antifungal/ immunomodulatory therapies in the genital area 
(vagina, vulva and surrounding soft tissue), within 14 days prior to the Baseline 
Visit (Day 1).  
6. Have received secnidazole, metronidazole or tinidazole treatment within 30 
days prior to the Baseline Visit (Day 1) or any other medication for the treatment 
of trichomoniasis within 30 days prior to Baseline Visit. 
7. Are using NuvaRing® or any other vaginal ring products.  
8. Have a history of drug or alcohol abuse within the past 12 months, as determined 
by the Investigator. 


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9. Have participated in any investigational trial within 30 days before the Baseline 
Visit (Day 1).   
10. Are participating in any investigational, observational or non-interventional 
study (either currently or during the study). 
11. Have a known allergy to nitroimidazoles (e.g., metronidazole, tinidazole, 
nimorazole, secnidazole, etc.).  
12. Inability to consume apple sauce or comply with study medication dosing 
instructions.   
13. Have any history of cervical carcinoma or other carcinomas of the vagina or 
vulva or an abnormal Pap smear that may require colposcopic evaluation within 
the 3 months following the baseline visit (in the opinion of the investigator).  
14. Have undiagnosed abnormal vaginal bleeding.  
15. Are planning to undergo a surgical or vaginal procedure during the study. 
16. Have any condition that interferes with their ability to understand or comply 
with the requirements of the study. 
Study Endpoints 
Efficacy Endpoints 
The following primary endpoint will be evaluated at the TOC Visit (Study Day 6-
12): Microbiological Cure at the TOC Visit (Microbiological Cure is defined as a 
negative T. vaginalis culture). 
Safety Endpoints 
Includes treatment-emergent adverse events (TEAEs), serious adverse events 
(SAEs), treatment-related AEs, and AEs leading to study discontinuation. 
Exploratory 
Endpoints 
Symptom resolution and microbiologic cure in the subgroup of patients who have 
baseline symptoms attributable to trichomoniasis. 
Product, Dose, and 
Mode of 
Administration 
Solosec (secnidazole) oral granules, 2g. Study medication will be orally 
administered, under direct observation, as a single dose with approximately 4 
ounces of unsweetened applesauce. The study medication may be taken without 
regard to meals.  
Placebo Product, 
Dose, and Mode of 
Administration 
Matching placebo. Oral administration.  
Statistical Methods 
Sample Size 
Determination 
Assuming a responder rate (microbiological cure) of 75% in the Solosec treatment 
group and a 40% placebo response rate and based on the use of a two-sided, two-
sample comparison of proportions at the alpha=0.05 level of significance, a sample 
size of 100 patients (50 patients in each group) who meet the mITT criteria will 
provide approximately 95% power to demonstrate a statistically significant 
difference between Solosec and placebo. Assuming 70% of patients randomized in 
the study will meet the mITT criteria, approximately 144 patients will be enrolled 
into the study. 
Analysis of Primary 
Endpoint 
Study Populations: 
Intent-to-Treat (ITT):  The ITT population will include all randomized patients.   
Modified Intent-To-Treat (mITT):  The mITT population will include all 
randomized patients who were culture positive for Trichomonas vaginalis and 
negative for other sexually transmitted infections. The primary efficacy analysis 
will be conducted in the mITT population.  
Per-Protocol (PP):  The PP population will be composed of patients in the mITT 
population with consideration of the following criteria: received the study 
medication as randomized, met inclusion and exclusion criteria, had a TOC visit 
between Days 6-12, and had no major protocol violations. The composition of the 
PP population will be finalized and documented in a review of the data conducted 
prior to unblinding the study database. The PP population will be used for 
supportive efficacy analyses. 


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Safety:  The Safety population will be composed of all randomized patients who 
received any amount of study medication. 
The primary efficacy endpoint, Microbiological Cure (i.e., InPouch™ TV test 
negative for T. vaginalis) at the TOC visit, will be compared between the active 
and placebo treatment groups using a two-sided Cochran-Mantel-Haesnzel (CMH) 
test (stratified by the presence/absence of clinical symptoms of trichomoniasis at 
baseline ) at the alpha=0.05 level of significance. 


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Table 1 
Schedule of Assessments 
 
Assessment 
Screening/
Baseline 
Visit 
Visit 2 
Test of Cure 
(TOC)  
Visit 3/46 
(only for Patients 
culture + at Visit 2)8 
Day 1/Visit 1 
Day 6 -12 
7-12 days post Visit 
2 visit 
Informed consent 
X 
 
Inclusion/exclusion 
X 
 
Demographics 
X 
 
Medical history 
X 
 
Vital signs 
X 
X 
X 
Height/weight 
X 
 
Urine pregnancy test 
X1 
X1 
X1 
Physical examination 
X 
X7 
X7 
Pelvic examination 
X 
X 
X 
Clinical assessment of trichomoniasis 
symptoms (e.g., itching, discharge, odor) 
X 
X 
X 
OSOM® Trichomonas Rapid Test2 
X 
 
 
Vaginal wet mount 
X 
 
X5 
KOH Whiff Test 
X 
 
 
pH of vaginal fluid 
X 
 
 
T. vaginalis culture (BioMed InPouch™ 
TV test) 
X3 
X3 
X3 
STI Assessments 
X 
 
 
IWRS Randomization 
X 
 
Drug dosing 
X 
X4 
 
Concomitant medication  review 
X 
X 
X 
Adverse events query 
X 
X 
X 
Investigator’s clinical assessment of the need 
for further treatment 
 
X 
1. Performed by site personnel (not sent to central laboratory). 
2. OSOM® test not needed if patient has positive NAAT test within 30 days of screening for which treatment has not been initiated. 
The manufacturer of OSOM® Trichomonas Rapid Test, Sekisui Diagnostics, does not recommend the test be used as a test of 
cure. 
3. Results will not be available at the time of visit.  
4. Patients who received placebo at first visit will receive Solosec and those who received Solosec at first visit will receive placebo. 
5. For assessment of trichomonas only. 
6. At the discretion of the investigator a patient who is culture positive at visit 3 may return for an additional visit (Visit 4) for 
further evaluation and treatment (assessments may include all those listed but at the discretion of the investigator). 
7. A targeted physical examination is only needed per the Investigator’s discretion if a reported AE requires further evaluation. 
8. Patients with cultures that are negative at V2 or V3 will be contacted by phone and discharged from the study. Note: The 
telephone contact will include an assessment of safety and well-being. Subjects reporting any complaints, or an adverse event will 
be asked to return for an unscheduled visit for evaluation and safety assessment. 
 
 


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2. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
 
AE 
Adverse event 
ALT 
Alanine transaminase 
API 
Active pharmaceutical ingredient 
AST 
Aspartate transaminase 
BID 
Twice daily 
BMI 
Body mass index 
BP 
Blood pressure 
BV 
Bacterial vaginosis 
CFR 
Code of Federal Regulations 
CMH 
Cochran-Mantel-Haenszel 
CO2 
Carbon dioxide 
CRA 
Clinical research associate 
eCRF 
Electronic Case Report Form 
CRO 
Clinical Research Organization 
EDC 
Electronic Data Capture 
EOS 
End of Study Visit  
FDA 
Food and Drug Administration 
G 
Gram 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
GMP 
Good Manufacturing Practice 
HDPE 
High-density polyethylene 
HEENT 
Head, eyes, ears, nose, and throat 
HPV 
Human papillomavirus 
HSV-1 
Herpes simplex virus Type 1 
HSV-2 
Herpes simplex virus Type 2 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 


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Abbreviation 
Definition 
 
IUD 
Intrauterine Device 
IWRS 
Interactive Web Response System 
Kg 
Kilograms 
KOH 
Potassium Hydroxide 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
Milligram 
mITT 
Modified Intent-to-Treat 
mm Hg 
Millimeter of mercury 
NCE 
New chemical entity 
NF 
National Formulary 
OTC 
Over-the-counter 
PCR 
polymerase chain reaction 
PID 
Pelvic inflammatory disease 
PK 
Pharmacokinetic 
PO 
Oral 
RBC 
Red blood cell count 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
STI(s) 
Sexually transmitted infection(s) 
TMA 
Transcription-mediated amplification  
TOC 
Test of Cure 
US 
United States 
USP 
United States Pharmacopeia 
WBC 
White blood cell count 


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3. 
INTRODUCTION 
3.1 TRICHOMONIASIS  
Trichomoniasis is a sexually transmitted disease caused by the parasite, Trichomonas 
vaginalis (T. vaginalis, TV).  It is the most prevalent non-viral sexually transmitted infection 
in the United States, affecting an estimated 3.7 million persons (Satterwhite 2013). Health 
disparities persist in the epidemiology of T. vaginalis infection in the United States: TV 
infection prevalence was 4.2% among black males, 8.9% among black females, and 0.03% 
and 0.8%, respectively, among males and females of other races/ethnicities (Patel 2018). T. 
vaginalis infection affects >11% of women aged ≥40 years (Ginocchio 2012), and particularly 
high prevalence has been detected among STD clinic patients (Meites 2013) (26% of 
symptomatic women and 6.5% asymptomatic women tested) and incarcerated persons (9%–
32% of incarcerated women [Sutcliffe 2010; Sosman 2011] and 2%–9% of incarcerated men) 
(Shuter 1998; Sosman 2005).  
Some infected men have symptoms of urethritis, epididymitis, or prostatitis, and some 
infected women have vaginal discharge that might be diffuse, malodorous, or yellow-green 
with or without vulvar irritation. However, most infected persons (70%–85%) have minimal 
or no symptoms, and untreated infections might last for months to years (Peterman 2006; 
Sutton 2007). Although partners might be unaware of their infection, it is readily passed 
between sex partners during penile-vaginal sex (Sena 2007). Among persons who are sexually 
active, the best way to prevent trichomoniasis is through consistent and correct use of 
condoms during all penile-vaginal sexual encounters (Crosby 2012). Partners of men who 
have been circumcised might have a somewhat reduced risk of T. vaginalis infection 
(Sobngwi-Tambekou 2009; Gray 2009). Douching is not recommended because it might 
increase the risk for vaginal infections, including trichomoniasis (Tsai 2009). 
T. vaginalis infection is associated with two- to threefold increased risk for HIV acquisition 
(McClelland 2007; Van Der Pol 2008), preterm birth, and other adverse pregnancy outcomes 
among pregnant women. Among women with HIV infection, T. vaginalis infection is 
associated with increased risk for pelvic inflammatory disease (PID) (Minkoff 1984; Cotch 
1997, Moodley 2002).  
Diagnostic testing for T. vaginalis should be performed in women seeking care for vaginal 
discharge. Screening might be considered for persons receiving care in high-prevalence 
settings (e.g., STD clinics and correctional facilities) and for asymptomatic persons at high 
risk for infection (e.g., persons with multiple sex partners, exchanging sex for payment, illicit 
drug use, or a history of STD). However, data are lacking on whether screening and treatment 
for asymptomatic trichomoniasis in high prevalence settings or persons at high risk can reduce 
any adverse health events and health disparities or reduce community burden of infection. 
Decisions about screening might be informed by local epidemiology of T. vaginalis infection 
(CDC Guidelines 2015). 
 
 


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Current Available Therapies 
Current first-line therapeutic regimens recommended in the US by the Centers for Disease 
Control in their most recent Guideline, “Sexually Transmitted Diseases Treatment 
Guideline, 2015” (CDC 2015) for the treatment of trichomoniasis are as follows:  
• Metronidazole 2 g in a single dose orally; or 
• Tinidazole 2 g in a single dose orally; or  
• Alternative regimen: Metronidazole 500 mg orally twice daily (BID) for 7 days; 
3.2 
INVESTIGATIONAL PRODUCT AND BACKGROUND INFORMATION 
 
Solosec 
Solosec® (secnidazole, SYM-1219) oral granules 2 g is a FDA approved treatment for 
bacterial vaginosis (BV) in adult women. Solosec™ is a potent, 5-nitroimidazole antibiotic 
with enhanced pharmacokinetic properties that enable delivery in a single dose that has been 
shown to be efficacious and well tolerated.  
The FDA approval was supported by a comprehensive set of studies, including two pivotal 
trials in BV and an open label safety study, which found efficacy for single-dose secnidazole 
2 g (See the Solosec Package Insert, Appendix A for more detailed information). The efficacy 
of Solosec 2 g to treat patients with BV was demonstrated in two adequate and well-controlled 
studies; results were robust and consistent across all analyses in the two studies.  In both 
studies, a greater percentage of patients receiving a single oral administration of Solosec 2 g 
achieved clinical response compared to placebo, i.e., 67.7% and 17.7%, respectively in SYM-
1219-201 and 53.3% and 19.3%, respectively in SYM-1219-301.  The treatment effect was 
statistically significant, p < 0.001 (adjusted CMH test) when compared to placebo.  
Across the clinical studies, Solosec has been well tolerated.  The most extensive clinical safety 
experience has been with Solosec 2 g administered to women with BV (n=518).  Overall, with 
rare exception, AEs were mild or moderate in severity; severe AEs (n=9), SAEs (n=4), and 
study discontinuations due to AE (n=3) were rare across the BV studies.  The commonly 
reported AEs that represent adverse drug reactions of Solosec in patients with BV were 
nausea, headache, and dysgeusia.   Vulvovaginal mycotic infection and vulvovaginal 
candidiasis were reported in the BV studies but not in the healthy volunteer studies.  Review 
of these events indicate that almost all of these infections were mild or moderate, resolved 
with treatment, and occurred more commonly in women receiving Solosec 2 g compared to 
placebo indicating that they were consistent clinically with secondary vaginal yeast infections, 
a known risk in women receiving antimicrobial treatment.  No adverse trends were detected 
in hematology, chemistry, or vital signs parameters (See the Solosec Package Insert, 
Appendix A for more detailed information). 
3.3 
STUDY RATIONALE 
Trichomoniasis is the most prevalent nonviral sexually transmitted infection in the United 
States, affecting an estimated 3.7 million persons (Satterwhite 2013); Lupin is developing 
Solosec as an available treatment option to provide an alternative, effective, single dose 
therapy for women diagnosed with trichomoniasis that, in turn, should decrease the known 
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Drugs of the 5-nitroimidazole family are the only known medications to be effective 
against trichomoniasis (CDC 2015). Metronidazole, tinidazole, and secnidazole are 
reported to have about approximately 90-95% success rate in curing T. vaginalis 
(Cudmore 2004, Forna 2003, Hager 1980, Manorama 1978, Sobel 2015) depending on 
study design. Members of the 5-nitroimidazole family vary in half-life, Cmax, and side 
effects. Secnidazole has been widely used outside the U.S. for many years. CDC 
currently recommends metronidazole 2 g orally in a single dose or tinidazole 2 g orally 
in a single dose (CDC 2015); metronidazole 500 mg BID for 7 days is recommended as 
the alternative treatment regimen. 
Since cure rates with Solosec are anticipated to be high, this trial was designed to avoid the 
possibility of unprotected sex resulting in reinfection which becomes more likely the longer 
the interval between treatment and TOC.  Peterman et. al. found a reinfection rate of 16.5% 
among women initially diagnosed and treated for T. vaginalis at baseline (Peterman 2006). 
In light of these data on clearance and chance for re-infection, a window for the TOC visit 
to be 6-12 days was selected.  Since it is possible that this timing will create false positive 
NAAT (TMA) results and since reinfection in this group of women at high risk for STD is 
of greater importance to assess the efficacy of Solosec, trichomonas culture was selected 
as the criterion for cure. 
3.4 
DOSE SELECTION 
Solosec is a potent, 5-nitroimidazole antibiotic with enhanced pharmacokinetic properties 
that enable delivery in a single dose that has been shown to be efficacious and well tolerated.   
Secnidazole has been available for many years in Europe and other countries outside of the 
US as a single, oral 2 g dose, used as either monotherapy or in combination with other drugs. 
The drug has been used and investigated as a single or multiple dose regimen for the 
treatment of amebiasis, giardiasis, trichomoniasis and BV; there is a plethora of published 
literature on the use of secnidazole (Gillis 1996, Bravo 1978, Machado 1988, Moraes 2012, 
Piato 1977, Roche 1977, Siboulet 1977, Videau 1978). 
Data demonstrate that secnidazole is efficacious for the treatment of BV as well as other 
infections, including trichomoniasis. The efficacy profile of secnidazole coupled with the 
tolerable safety profile and convenience of the dosing regimen (i.e., 1 single oral dose) 
suggest that it is an attractive alternative to other drugs in this class. Clinical investigation 
of secnidazole in the US for the treatment of trichomoniasis is warranted. 


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4. 
STUDY OBJECTIVES 
4.1 PRIMARY OBJECTIVE(S) 
The objective of this study is to evaluate the efficacy and safety of a single, oral dose of 
Solosec containing 2 grams of secnidazole compared to placebo for the treatment of 
trichomoniasis. 
4.2 SECONDARY OBJECTIVE(S) 
None. 
4.3 STUDY ENDPOINTS 
 
Primary Efficacy Endpoints 
The following primary endpoint will be evaluated at the TOC Visit (Study Day 6-12):  
• Microbiological Cure at the TOC Visit (Microbiological Cure is defined as a 
negative T. vaginalis culture). 
 
Exploratory Efficacy Endpoints 
Symptom resolution and microbiologic cure in the subgroup of patients who have 
baseline symptoms attributable to trichomoniasis. 
 
Safety Endpoints 
Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), treatment-
related AEs, and AEs leading to study discontinuation. 


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5. 
STUDY DESIGN 
5.1 OVERALL STUDY DESIGN 
This is a Phase 3, multi-center, prospective, randomized, placebo-controlled, delayed 
treatment, double-blind, study to evaluate the effectiveness, and safety of a single, oral 
dose of Solosec containing 2 grams of secnidazole in female patients with trichomoniasis. 
Approximately 144 patients who test positive for trichomonas on OSOM® rapid test or 
via wet mount assessment or have positive T. vaginalis NAAT test within 30 days of 
screening (and have not been treated) and fulfill other eligibility criteria at the baseline 
visit will be enrolled in this study. The diagnosis of T. vaginalis will be confirmed by a 
positive culture for T. vaginalis. The study will consist of a primary study phase (Visit 1 
(baseline) to Visit 2 (Day 6-12)) and a follow-up phase (Visit 2 to Visit 3 (7-12 days post 
Visit 2)). During the primary phase patients will be randomly assigned in a 1:1 ratio to 
either Solosec or placebo. The randomization will be stratified by site and based on the 
clinical symptoms of trichomoniasis (present or absent). Patients will return to the clinic 
for the “test of cure” (TOC) visit to be conducted on Days 6-12 (Visit 2). After all Visit 2 
(V2) study procedures have been completed, patients will receive the opposite treatment 
(placebo patients will receive Solosec and vice versa). Patients with V2 cultures that are 
subsequently positive for T. vaginalis will return to the clinic for Visit 3 (V3) 
assessments and investigator assessment of need for additional therapy (an additional 
Visit 4 may be scheduled at the investigator’s discretion if culture at V3 is positive).  
Patients with cultures that are negative at V2 will be contacted by phone and discharged 
from the study (no V3 required). A Schedule of Assessments is provided in Table 1. 
5.2 DOSE RATIONALE 
Solosec (secnidazole) 2 g oral granules is a FDA approved treatment for bacterial 
vaginosis (BV) in adult women. Solosec is a potent, 5-nitroimidazole antibiotic with 
enhanced pharmacokinetic properties that enable delivery in a single dose that has been 
shown to be efficacious and well tolerated. 
 
 


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6. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Approximately 144 patients will be enrolled by approximately 10 investigative sites in 
the United States in order to obtain 100 patients (50 patients in each group) who will be 
included in the mITT study population (i.e., culture-positive for T. vaginalis at baseline).  
6.1 INCLUSION CRITERIA 
A subject will be eligible for enrollment if all of the following inclusion criteria apply: 
1. Are adult females or post-menarchal adolescent girls ≥ 12 years of age. 
2. Are willing and able to give written informed consent or, if < 18 years of age, are 
willing and able to give written informed assent with a written informed consent 
from a parent or legal guardian. 
3. Are in good general health including as confirmed by a medical history and physical 
examination, with no known medical or mental health conditions that, in the 
Investigator’s opinion, may interfere with study participation. 
4. Are willing and able to participate in the study as an outpatient, make required visits 
to the study center, and comply with all study requirements.  
5. Have a negative urine pregnancy test result prior to study treatment initiation.  In 
addition, female patients of childbearing potential must be using an acceptable form 
of birth control as determined by the Investigator (e.g., oral contraception, 
implantable, injectable/transdermal hormonal contraception, intrauterine device 
(IUD), barrier methods), tubal ligation or have a vasectomized partner or are 
practicing abstinence.  
6. Have a diagnosis of trichomoniasis at the screening visit as determined by one of 
the following:  
o positive T. vaginalis NAAT test within 30 days of screening for which treatment 
has not been initiated.  
o positive OSOM® rapid test. 
o positive wet mount assessment. 
Diagnosis will be confirmed by a positive culture for T. vaginalis obtained at the 
baseline visit (Note: The culture results will not be available at the time of study 
randomization and treatment).  
7. Agree to abstain from vaginal intercourse until the final study visit.  
8. Agree not to have any vaginal penetration or use of any vaginal products for the 
duration of the study (e.g., spermicides, condoms, diaphragms, vibrators, tampons, 
etc.).  
9. Agree not to use vaginal douches, lubricants, or similar products for the duration of 
the study. 
 
 


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6.2 EXCLUSION CRITERIA 
A subject who meets any of the following exclusion criteria must not be enrolled: 
1. Are pregnant, lactating, or planning to become pregnant during the study.   
2. Are suspected clinically (or confirmed diagnostically) of having alternative causes 
of vaginal symptoms including symptomatic vulvovaginal candidiasis, chlamydia, 
gonorrhea, or an active genital herpes outbreak (Note: Chlamydia trachomatis, 
Neisseria gonorrhoeae [by PCR] results will not be available at time of 
randomization).  Note: patients with bacterial vaginosis (BV) are eligible for this 
study. 
3. Are suspected clinically of having an acute urinary tract infection.  
4. Have active genital lesions, including primary syphilitic chancres and herpes 
simplex virus lesions, or other vaginal or vulvar conditions which could confound 
the interpretation of the clinical response, as determined by the Investigator 
(patients with genital warts may be enrolled).  
5. Have received systemic antibacterial therapy or topical antimicrobial/antifungal/ 
immunomodulatory therapies in the genital area (vagina, vulva and surrounding 
soft tissue), within 14 days prior to the Baseline Visit (Day 1).  
6. Have received secnidazole, metronidazole or tinidazole treatment within 30 days 
prior to the Baseline Visit (Day 1) or any other medication for the treatment of 
Trichomoniasis within 30 days prior to Baseline Visit. 
7. Are using NuvaRing® or any other vaginal ring products.  
8. Have a history of drug or alcohol abuse within the past 12 months, as determined 
by the Investigator. 
9. Have participated in any investigational trial within 30 days before the Baseline 
Visit (Day 1).   
10. Are participating in any investigational, observational or non-interventional study 
(either currently or during the study). 
11. Have a known allergy to nitroimidazoles (e.g., metronidazole, tinidazole, 
nimorazole, secnidazole, etc.).  
12. Inability to consume apple sauce or comply with study medication dosing 
instructions.   
13. Have any history of cervical carcinoma or other carcinomas of the vagina or vulva 
or an abnormal Pap smear that may require colposcopic evaluation within the 3 
months following the baseline visit (in the opinion of the investigator).  
14. Have undiagnosed abnormal vaginal bleeding.  
15. Are planning to undergo a surgical or vaginal procedure during the study. 
16. Have any condition that interferes with their ability to understand or comply with 
the requirements of the study. 


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6.3 RANDOMIZATION CRITERIA 
Subjects that meet all Inclusion/Exclusion criteria listed above will be enrolled in this 
double-blind study.  Upon approval by the medical monitor and sponsor, subjects who do 
not qualify based on a reversible medical condition or mild intercurrent illness may be re-
evaluated after further testing/examination or re-screened after the condition is resolved. 
6.4 WITHDRAWAL CRITERIA 
Patients may withdraw from the study at any time and for any reason. Reasons for 
discontinuation include, but are not limited to, the following: 
• Physician decision 
• Adverse Event any AEs continuing at the time of withdrawal should be followed 
until resolution or determined by the Investigator to be chronic or stable 
• Pregnancy 
• Withdrawal by subject 
• Study terminated by sponsor 
• Protocol violation 
• Disallowed concomitant medication. Patient’s use of, or need for, concomitant 
therapy liable to interfere with the interpretation of study endpoints.  The 
Investigator will report all such information on the electronic Case Report Form 
(eCRF) and decide, in accordance with the Medical Monitor, whether the patient 
should be withdrawn from the study. 
• Lost to follow-up.  The Investigator will try to reach the patient, at least twice by 
telephone and once by certified letter, before considering the patient lost-to-follow-
up.  These actions will be reported on the appropriate source documents, and a 
copy of the certified letter will be maintained in the Investigator’s file. 
All premature discontinuations and their causes must be documented by the Investigator 
on the appropriate eCRF page, and if need be, on the Adverse Event page of the eCRF.  
Patients not completing the entire study should be fully evaluated (i.e., final visit 
procedures performed), wherever possible.  
All patients are free to withdraw from participating in this study at any time and for 
whatever reason, specified or unspecified, and without prejudice to their medical care. 
Subjects may withdraw consent and/or may be discontinued by the investigator or 
Sponsor for any reason at any time. 
6.5 REPLACEMENT OF SUBJECTS WHO WITHDRAW OR ARE 
DISCONTINUED 
Subjects who withdraw, are discontinued, or are lost to follow-up may be replaced upon 
review/approval from the Sponsor. 
The date the subject is withdrawn from the study and the reason for discontinuation will 
be recorded in the CRF.  If there are multiple reasons for early discontinuation, the worst-
case scenario should be chosen. 
If a subject is withdrawn because of an adverse event, the event will be followed until the 
medical condition returns to baseline or is considered stable or chronic.  Discontinuation 


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of subjects due to adverse events, including those due to abnormal laboratory results, 
should be promptly reported to Sponsor. 


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7. 
TREATMENTS 
7.1 TREATMENTS ADMINISTERED 
Study medication [either Solosec (containing 2 grams of secnidazole) or matching 
placebo] will be orally administered, under direct observation, as a single dose with 
approximately 4 ounces of unsweetened applesauce. Upon completion of the primary 
phase (Visit 1 (baseline) to Visit 2 (Day 6-12)), patients will receive the opposite 
treatment (placebo patients will receive Solosec and vice versa). 
The study medication may be taken without regard to meals. Water may be taken after 
the administration of study medication to aid in swallowing (See the Solosec Package 
Insert, Appendix A for more detailed information). Administration of each dose of study 
drug will be witnessed by a qualified study site staff member and documented on the 
source document. 
All qualifying patients with T. vaginalis positive results at baseline will be asked to tell 
their sex partners (within at least 90 days) of their infection with T. vaginalis and to 
encourage them to seek appropriate treatment. Additionally, where allowed (based on 
legal and institutional restrictions) and at the discretion of the Investigator, all qualifying 
patients with T. vaginalis will be provided with a prescription for a medication for T. 
vaginalis (e.g., metronidazole 2g or tinidazole 2g) to deliver to their sex partner(s) (i.e., 
patient-delivered partner therapy).   
7.2 IDENTITY OF INVESTIGATIONAL PRODUCT 
The Solosec active formulation contains active secnidazole and excipients of sugar spheres, 
NF; povidone, USP; polyethylene glycol 4000, NF; Eudragit® NE30D (ethyl acrylate, 
methyl acrylate copolymer); talc, USP; and colloidal silicon dioxide, NF.  The matching 
placebo contains the same ingredients as the active formulation with the exception of 
Solosec.  Both the Solosec and placebo oral granules will be packaged in white packets 
with blinded packaging and labeling so they are indistinguishable. 
Study drug labels will be prepared in accordance with applicable Federal Regulations and 
will not bear any statement that is false or misleading in any manner or represents that the 
study drug is safe or effective for the purposes for which it is being investigated. 
Study medication must be stored at room temperature (20°- 25° C [68°- 77° F]); excursions 
permitted 15°C to 30°C (59°F to 86°F) [See USP Controlled Room temperature]  (See the 
Solosec Package Insert, Appendix A for more detailed information). 
7.3 SUPPLY OF STUDY MEDICATION 
All study medication supplies will be provided by the sponsor. 
7.4 METHOD OF ASSIGNING SUBJECTS TO TREATMENT GROUPS 
The randomization will be stratified by site and based on the clinical symptoms of a 
trichomoniasis vaginal infection (present or absent). 
Prior to the start of the study, a randomization list assigning kit numbers to one of two 
treatment groups in a 1:1 ratio will be generated by the CRO responsible for biostatistics 
in the trial.  This list will be used by the manufacturer to package study drug into 


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treatment kits.  Blinded study medication will be provided to the sites for each phase of 
the study (primary and follow-up phase). Study medication will be shipped to the study 
sites when IRB/IEC approval has been obtained and all required study documents are 
submitted to the sponsor. 
Once it has been established that a patient is eligible to participate in this study, the 
eligible patient will be assigned a patient number in the EDC system, and a Visit 1 
(primary phase) treatment kit from those kits that are available at the site will be assigned 
for that patient.  The kit number for the follow-up phase treatment will be provided by 
IWRS at Visit 2.  Treatment assignment must be assigned to patients using the IWRS.  
7.5 BLINDING 
This clinical trial is being conducted as a double-blind study; neither the investigator, 
supporting staff, nor the participant will be aware of the treatment the participant is 
receiving. 
7.6 STUDY MEDICATION ACCOUNTABILITY 
The US FDA requires accounting of all investigational drug received by each study 
center.  Records of drug disposition required by federal law include the date received by 
the center, date administered, quantity administered, and the patient to whom study drug 
was administered.  The Investigator is responsible for the accountability of all used and 
unused study drug containers and unused study drug. 
Each study center is to use a study drug accountability log to document study drug 
disposition.  All items on this form are to be completed in full.  
The investigator identification number and patient initials and identification number are 
to be recorded on each study drug accountability log.  Each time study personnel 
dispenses study drug for a patient, he or she is to record the date dispensed, and his or her 
initials.  Study personnel are to monitor the inventory of clinical supplies and maintain a 
count of all used and unused study drug.  The CRA is to review study drug accountability 
records and remaining drug supplies during routine monitoring visits. 
7.7 EMERGENCY CODE BREAKING 
In case of a serious adverse event or pregnancy, the investigator may un-blind the subject’s 
drug assignment when the study drug assignment is needed to make treatment decisions 
for the subject.  The Sponsor should be notified of the event prior to breaking the code, if 
possible.  If this is not possible, the Sponsor should be notified immediately afterwards, 
and the subject’s drug code assignment should not be revealed to the Sponsor.  The 
circumstances leading to the breaking of the code should be fully documented in the 
investigator’s study files and in the subject’s source documentation.  The subject’s 
treatment assignment should not be recorded in any study documents. 


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8. 
PROHIBITED AND RESTRICTED MEDICATIONS AND 
PROCEDURES 
All prescription and non-prescription medications and therapies, including vitamins, 
herbal medicines, or other non-traditional medicines, taken from 30 days prior to the first 
study drug dose through the end of the study must be recorded in the eCRF. 
The following medications and products are prohibited during study participation, as 
described below: 
• Systemic antimicrobial therapies for the duration of the study, with the exception 
of oral antifungal therapy (e.g., oral fluconazole) to treat intercurrent conditions 
(e.g., vulvovaginal candidiasis); 
• Topical antimicrobial/ antifungal / immunomodulatory therapies in the genital area 
(vagina, vulva and surrounding soft tissue), including treatments for external 
genital warts; 
• Secnidazole, metronidazole or tinidazole treatment. 
• Intravaginal paromomycin, intravaginal boric acid, nitazoxanide, intravaginal 
betadine (povidone-iodine), clotrimazole, acetic acid, furazolidone, gentian violet, 
nonoxynol-9, and potassium permanganate. 
• Systemic corticosteroids (intranasal and inhaled steroids are permitted). 
8.1 
DIET, FLUID, AND ACTIVITY CONTROL 
The following products are restricted during study participation, as described below: 
• Patients should not have vaginal intercourse until after the final study visit.  
• Patients should not have any vaginal penetration or use any vaginal products until 
after the study visit (e.g., spermicides, condoms, diaphragms, vibrators, tampons, 
etc.);  
• Patients should not use vaginal douches or similar products for the duration of the 
study. 
 
 


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9. 
STUDY CONDUCT 
9.1 OVERVIEW 
The time and events schedule for the study is presented in Table 1, Schedule of 
Assessments. 
9.2 STUDY PROCEDURES 
Patients will be scheduled to visit the clinic at least two times during the study (Baseline 
Visit and TOC Visit on Days 6-12). An additional visit (V3) will be scheduled for all 
patients who are determined to be culture positive for T. vaginalis at Visit 2 per Table 1, 
Schedule of Assessments.  
9.3 
STUDY VISITS 
 
Screening/Baseline Visit (Study Day 1) 
The following procedures should be completed prior to initiating study treatment: 
1. Obtain a signed and dated patient informed consent form/Authorization to disclose 
Health Information/assent and authorization to use and disclose medical 
information prior to performing any study-specific procedures; 
2. Collect demographic information including date of birth, sex, race, and ethnicity; 
3. Collect a medical history; 
4. Collect prior and concomitant medication use; 
5. Perform a urine pregnancy test; 
6. Perform a physical exam, including vital signs, weight and height; 
7. Perform a pelvic examination including assessment of vaginal discharge, and 
collection of vaginal samples as follows: 
a. Perform clinical assessment of trichomoniasis genital symptoms (e.g., itching, 
discharge, odor).  
b. Collect vaginal sample for T. vaginalis testing via: 
i. OSOM® Trichomonas Rapid test (If needed, see below). 
ii. BioMed InPouch™ TV test. 
c. Vaginal saline wet mount for assessment of clue cells and trichomonads; 
d. 10% KOH whiff test. 
e. pH of vaginal fluid; 
f. Collect samples for the assessment of other sexually transmitted infections 
(STIs) (Neisseria gonorrhoeae, Chlamydia trachomatis). Samples will be sent 
to central laboratory (results will not be available at time of enrollment); 
 
 


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8. Review inclusion and exclusion criteria. Note: Patients must have a diagnosis of 
trichomoniasis at the screening visit as determined by one of the following test 
results: 
i. Positive NAAT test within 30 days of screening for which treatment has 
not been initiated (NAAT test results must be available in the patient 
chart).  
ii. Positive wet mount assessment; 
iii. Positive OSOM® rapid test; note OSOM test not needed if patient has 
positive NAAT test within 30 days of screening for which treatment has 
not been initiated.  
Diagnosis will be confirmed by a positive culture for T. vaginalis obtained at the 
baseline visit. 
9. If the patient meets all clinically available inclusion/exclusion criteria, the site 
will use the IWRS to randomize the patient into the study.  IWRS will assign a 
unique kit number for the patient.  The following procedures will be performed 
after the patient has been successfully randomized and Visit 1 Kit Number has 
been assigned: 
1. The patient will self-administer the study medication (without regard to meals).  
(See Section 7.1 for drug administration instructions) 
2. Schedule the TOC Visit for Study Day 6-12. 
 
Visit 2/Test of Cure Visit (Study Day 6-12) 
The Test of Cure (TOC) Visit should be conducted between Study Day 6 and 12.   
The following procedures will be performed at the TOC Visit: 
1. Assess for adverse events; 
2. Review and record concomitant medications/treatments taken during the study; 
3. Perform a urine pregnancy test; 
4. Perform a targeted physical examination as needed to assess AEs. Collect vital 
signs; 
5. Perform a pelvic examination including assessment of vaginal discharge, and 
collection of vaginal samples as follows: 
a. Perform clinical assessment of trichomoniasis genital symptoms (e.g., itching, 
discharge, odor).  
b. Collect vaginal sample for T. vaginalis testing via: 
i. BioMed InPouch™ TV test. 
Upon completion of the primary phase (Visit 1 (baseline) to Visit 2 (Day 6-12)), the site 
will use IWRS to receive the Visit 2 kit number for the opposite treatment (placebo patients 
will receive Solosec and vice versa). Study treatment will be provided for the follow-up 
phase as described in section in Section 7 of the protocol. 
 
 


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The following procedures will be performed after the patient has been successfully 
completed the Day 6-12 TOC procedures described above:  
1. The patient will self-administer the study medication (without regard to meals).  
(See Section 7.1 for drug administration instructions). 
Patients with negative cultures for T. vaginalis at Visit 2 (i.e., negative InPouch™ TV test) 
will be contacted by phone and discharged from the study (no Visit 3 required).  Note: The 
telephone contact will include an assessment of safety and well-being. Subjects reporting 
any complaints, or an adverse event will be asked to return for an unscheduled visit for 
evaluation and safety assessment. 
A follow-up visit will be scheduled for all patients who have positive cultures for T. 
vaginalis (i.e., positive InPouch™ TV test at Visit 2). 
Note: patients who are subsequently found to have a negative culture for T. vaginalis (i.e., 
negative InPouch™ TV test) from the sample obtained at the Baseline Visit (Day 1) should 
remain in the study and complete all appropriate study visits. 
 
Visit 3 – Follow-up Visit (7-12 days post V2 visit)  
A follow-up visit (V3) will be scheduled for all patients who have positive cultures for T. 
vaginalis (i.e., positive InPouch™ TV test) at Visit 2. 
The following procedures will be performed at the Follow-up Visit: 
1. Assess for adverse events; 
2. Review and record concomitant medications/treatments taken during the study; 
3. Perform a urine pregnancy test; 
4. Perform a targeted physical examination as needed to assess AEs. Collect vital 
signs; 
5. Perform a pelvic examination including assessment of vaginal discharge, and 
collection of vaginal samples as follows: 
a. Perform clinical assessment of trichomoniasis symptoms (e.g., itching, 
discharge, odor).  
b. Collect vaginal sample for T. vaginalis testing via: 
ii. BioMed’s InPouch™ TV test. 
iii. Vaginal saline wet mount for assessment of trichomonads; 
6. Investigator’s assessment for the need of additional treatment. 
Additional alternative treatment should be determined by the investigator based on his/her 
review of the vaginal wet mount assessment for active trichomonads.  If clinical findings 
such as active trichomonads are not present on wet mount and the investigator does not 
believe patient should receive additional trichomoniasis treatment, then patient will be 
informed of findings and will await results of the Visit 3 InPouch TV test.  Patients with 
negative cultures for T. vaginalis (i.e., negative InPouch™ TV test) at Visit 3 will be 
contacted by phone and discharged from the study (no Visit 4 required).  Note: The 
telephone contact will include an assessment of safety and well-being. Subjects reporting 


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any complaints, or an adverse event will be asked to return for an unscheduled visit for 
evaluation and safety assessment. At the discretion of the investigator a patient who is 
culture positive at Visit 3 may return for an additional visit (V4) for further evaluation and 
treatment.  
 
Unscheduled Visit 
An unscheduled visit should be conducted for all patients with negative cultures for T. 
vaginalis at Visit 2 or Visit 3 (i.e., negative InPouch™ TV test) who report an adverse 
event during the post-visit telephone contact.  Unscheduled visit procedures include further 
assessment of the reported AE and any additional follow-up procedure as listed in Section 
9.3.3 above determined to be necessary by the study physician.  
An unscheduled visit may be conducted in patients with positive STI results from the 
baseline visit in order to avoid unnecessary delays in treatment (See Section 9.4.8.4), in 
patients who are suspected of being pregnant (see Section 9.4.4), or at the discretion of the 
investigator. 
9.4 
METHODS OF ASSESSMENTS  
 Demographics 
Patient demographics, including age, sex, race, and ethnicity, are to be documented 
during screening. 
 Patient Medical History 
A complete medical history is to be documented at the Baseline Visit (Day 1)  
 Vital Signs 
Vital signs, including seated systolic and diastolic blood pressure (mm Hg), pulse (beats 
per minute), and temperature are to be measured for all patients at the Baseline Visit (Day 
1) predose, and at the TOC Visit (and at the follow-up visits, if needed).   
Blood pressure (BP) and pulse will be measured using a BP recording device with an 
appropriate cuff size. 
 Urine Pregnancy Testing 
An in-office urine pregnancy test must be performed for all patients at the Baseline Visit 
(Day 1) and TOC Visit (Days 6-12) (and at the follow-up visits, if needed).  Patients must 
have a negative urine pregnancy test at the Baseline Visit prior to enrollment.  Urine 
pregnancy testing should also be conducted at an unscheduled visit for any patient who is 
suspected of being pregnant (additional pregnancy testing may be conducted at the 
Investigator’s discretion).  
 Physical Examination, Height, and Weight 
A physical examination which includes examination of head, eyes, ears, nose, and throat 
(HEENT); neck; cardiovascular; lungs; abdomen; extremities; skin; lymph nodes; and 
musculoskeletal, will be conducted for all patients during the Baseline Visit (Day 1). 
Height and weight are to be measured at the Baseline Visit. A targeted physical 


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examination at the TOC Visit is only needed per the Investigator’s discretion if a reported 
AE requires further evaluation. 
  Pelvic Examination, Vaginal Discharge Assessment and Testing 
A pelvic examination including vaginal discharge assessment and testing, will be 
performed at the Baseline Visit (Day 1) and TOC Visit (and at the follow-up visits, if 
needed).  A non-lubricated speculum must be used during the pelvic examination.  
Components of the pelvic examination are specified in the following sections.   
Prior to enrollment, if any test result is considered exclusionary it is not required to 
complete the evaluation of any additional samples.   
 Vaginal Discharge Assessment 
During the pelvic examination, conduct clinical assessment of trichomoniasis symptoms 
(e.g., itching, discharge, odor) (record as Normal, or Abnormal consistent with TV, or 
Abnormal Other). 
 Vaginal Discharge Testing 
Vaginal discharge testing will be performed at baseline and on each scheduled study day 
as indicated in the Schedule of Assessments, Table 1. 
9.4.8.1 Trichomonas Vaginalis 
OSOM® Trichomonas Rapid Test - Sekisui Diagnostics 
The presence or absence of T. vaginalis will be determined by the Investigator, or designee 
using the OSOM® Trichomonas Rapid Test kit.  Commercial test kits will be provided to 
the sites, and testing will be performed as described in the test instructions (refer to 
laboratory manual for instructions). 
The OSOM® Trichomonas Rapid Test will only be used at Visit 1 (baseline) to determine 
study eligibility. The OSOM test is not needed if patient qualifies for the study based on a 
positive NAAT test within 30 days of screening for which treatment has not been initiated. 
Patients must have a diagnosis of trichomoniasis at the screening visit as determined by 
one of the following test results: 
i. 
have positive NAAT test within 30 days of screening for which treatment has 
not been initiated (NAAT test results must be available in the patient chart).  
ii. 
wet mount assessment; 
iii. 
OSOM® rapid test; note OSOM test not needed if patient has positive NAAT 
test within 30 days of screening for which treatment has not been initiated.  
 
InPouch™ TV (Trichomonas vaginalis) - BioMed Diagnostics, Inc. 
The InPouch™ TV test will be utilized to determine the presence or absence of 
Trichomonas vaginalis. Commercial test kits will be provided to the sites, and vaginal 
samples will be obtained from the posterior fornix of the vagina by the Investigator, or 
trained designee according to the manufacturer’s instructions. Specimens will be sent to a 
central laboratory. Detailed procedures for sample collection, analysis, and reporting will 


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be provided in a separate laboratory manual. 
9.4.8.2 Wet Mount 
Wet mount assessments will be performed at the Baseline Visit (Day 1). Additional, 
vaginal wet mount testing may be conducted at Visit 3 for further evaluation of 
trichomoniasis (See Table 1, Schedule of Assessments). 
9.4.8.2.1 
Preparation of Slides for Vaginal Saline Wet Mount and Whiff Test 
Using sterile polyester-tipped swabs, swab the lateral vaginal walls with a polyester -tipped 
applicator and place polyester tip in a tube with approximately 6 drops of saline (~100 µl; 
enough to keep the swab moist, but not dilute the sample).  Remove the swab from the tube 
and place a liberal amount of discharge on each of the two glass slides immediately before 
testing as follows:  
9.4.8.2.2 
Slide #1 – KOH Whiff Test  
The Investigator, or designee, will mix approximately two drops of 10% potassium 
hydroxide (KOH) with the vaginal discharge sample and immediately smell the slide 
(Note: the assessor should not have any impairment to the sense of smell).  
• Assess for a fishy, amine-like odor (record as Positive or Negative; note that a 
Positive result indicates the presence of the odor). Note: patients with bacterial 
vaginosis (BV) are eligible for this study. 
9.4.8.2.3 
Slide #2 –Vaginal Saline Wet Mount 
The Investigator, or designee, will examine the second vaginal sample slide under a light 
microscope at 100X magnification and at 400X magnification.  Examine for the presence 
or absence of clue cells and motile trichomonads,  
• Clue cells: A minimum of 5 representative fields containing squamous epithelial 
cells should be examined and the ratio of clue cells to vaginal epithelial cells 
determined at 400X magnification. Clue cells will be identified as vaginal epithelial 
cells with such a heavy coating of bacteria surrounding them their peripheral borders 
are obscured.  Record clue cells as ≥ 20% of the total epithelial cells, or < 20% of 
the total epithelial cells. 
• Trichomonads: Record motile trichomonads as Present or Absent.  
9.4.8.3 Vaginal pH 
The pH of a vaginal sample will be obtained by the Investigator, or designee, at the Baseline 
Visit (Day 1) only, and the result will be recorded (recorded as < 4.7 or ≥ 4.7).  The 
necessary materials and instructions will be provided for vaginal pH testing (refer to 
laboratory manual for instructions).  
9.4.8.4 Sexually-transmitted Infection (STI) Assessments 
Assessments for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis will 
be performed at the Baseline Visit (Day 1). Patients with positive STI results from the 
baseline visit should remain in the study and complete all specified procedures.  An 
unscheduled visit may be conducted in order to avoid unnecessary delays in treatment. 


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Commercial test kits will be provided to the sites, and endocervical samples will be 
obtained by the Investigator, or trained designee according to the manufacturer’s 
instructions. Specimens will be sent to a central laboratory. The necessary materials and 
instructions will be provided for STI testing (refer to laboratory manual for instructions).  
9.5 
INVESTIGATOR’S CLINICAL ASSESSMENT 
At Visit 3 (if needed) the Investigator will answer the following question “In your opinion, 
does the patient require additional treatment for T. vaginalis infection at this time? The 
response will be recorded as Yes or No.  If the answer is Yes, the patient will be offered a 
prescription for a post-study treatment by the Investigator and followed-up outside of the 
study as they deem clinically necessary. 


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10. 
SAFETY AND PHARMACOVIGILANCE 
10.1 DEFINITION OF AN ADVERSE EVENT 
An AE is defined as any untoward medical occurrence in a clinical trial patient 
administered a medicinal product and which does not necessarily have a causal 
relationship with the treatment.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of an 
investigational medicinal product, whether or not considered related to the investigational 
medicinal product.  
A new medical condition or the worsening of a pre-existing condition will be considered 
an AE. Stable chronic medical conditions such as arthritis that are present prior to study 
entry and do not worsen during the study will not be considered AEs. Worsening of the 
disease under study should only be recorded as an AE if the outcome is more serious than 
would normally be expected from the normal course of the disease in a particular patient. 
In the study, any event occurring after the clinical trial subject has signed the study 
Informed Consent (ICF) should be recorded and reported as an AE.  Those events occurring 
prior to drug administration will be considered to be “Non-Treatment-Emergent” AEs and 
those occurring after drug administration as “Treatment-Emergent” AEs. 
10.2 INTENSITY OF ADVERSE EVENTS 
The intensity or severity of the AE will be characterized as: 
• Mild:  AE which is easily tolerated 
• Moderate:  AE sufficiently discomforting to interfere with daily activity 
• Severe:  AE which prevents normal daily activities 
The maximum severity for the event should be listed when the intensity changes during 
the course of an AE. If the change in severity represents distinct events rather than a 
single event, this should be recorded as separate AEs.  
10.3 RELATIONSHIP OF ADVERSE EVENTS TO STUDY DRUG 
The causal relationship of the investigational product to the AE(s) should be characterized 
as: 
Not Related: There is no reasonable possibility that the AE was caused by or 
attributed to the investigational product 
Related: 
There is a reasonable possibility that the AE was caused by or 
attributed to the investigational product.  A causal relationship cannot 
be ruled out. 
 
 


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Definition of “No Reasonable Possibility” 
The assessment term, “no reasonable possibility”, can only be applied to those AEs which, 
after careful consideration, are clearly due to extraneous causes (disease, environment, etc.) 
or to those AEs which, after careful medical consideration at the time they are evaluated, 
are judged to be unrelated to the study drug. 
An AE may be considered as being meeting the definition of “no reasonable possibility” 
if data are available to identify a clear alternative cause for the AE other than study drug; 
such as the patient’s clinical state, concomitant therapy, and/or other interventions or the 
AE/SAE has no plausible temporal relationship to administration of study drug.  
 
Definition of “Reasonable Possibility” 
The assessment term, “reasonable possibility”, can only be applied to those AEs which, 
after careful medical consideration at the time they are evaluated, a connection with the 
study drug administration cannot be ruled out with certainty or is felt with a high degree of 
certainty to be related to the study drug. 
An AE may be considered as meeting the definition of “reasonable possibility” if there is 
a plausible temporal relationship between the onset of the AE/SAE and study drug 
administration and the AE/SAE cannot be readily explained by the patient’s clinical state, 
intercurrent illness, or concomitant therapies; and/or the AE/SAE follows a known 
pattern of response to study drug; and/or the AE/SAE abates or resolves upon 
discontinuation of study drug or dose reduction and, if applicable, reappears upon re-
challenge.  
10.4 RECORDING OF ADVERSE EVENTS 
Adverse Events are illnesses or signs/symptoms that appear or worsen during the testing 
of a drug whether or not considered related to the investigational product (synonyms = 
medicinal or pharmaceutical product, study drug, clinical trial materials, etc.), including 
side effects, injury, toxicity, or hypersensitivity reactions. 
All adverse events, including observed, elicited, or volunteered problems, complaints or 
symptoms, are to be recorded on the Adverse Events page in the subject’s Case Report 
Form. 
The need to capture this information is not dependent upon whether adverse events are 
associated with use of the investigational product. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications progression of disease states should also be recorded.  
In order to avoid vague, ambiguous or colloquial expressions, adverse events should be 
recorded in standard medical terminology rather than the subject's own words.  Signs and 
symptoms should be reported individually unless, in the judgment of the investigator, they 
can be grouped under an inclusive term (e.g., gastroenteritis in lieu of abdominal pain, 
nausea, vomiting, and diarrhea). 
Each adverse event is to be evaluated for date/time of onset, duration, intensity, and causal 
relationship with the investigational product or other factors. 


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At every study visit, the investigator must document new AEs and the outcome of ongoing 
AEs.  Any subject with an AE (including SAEs) or any clinically significant abnormal 
laboratory result or physical finding reported as an AE will be followed by the investigator 
until the AE resolves, resolves with sequalae, is otherwise explained by a medical 
condition, follow-up is not possible (document), or the subject dies. 
 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
AE:  
Clinically significant abnormal laboratory findings or clinically significant abnormal 
findings from other assessments that are detected during the study or are present at baseline 
and significantly worsen following the start of the study will be reported as AEs. Abnormal 
laboratory findings or other assessments deemed as abnormal will not be reported as AEs 
if they are determined to be clinically insignificant.  
If an abnormal laboratory value or other assessment is clearly related to a medically-
defined diagnosis or syndrome, the diagnosis or syndrome will be recorded on the AE form, 
not the individual laboratory values or assessment.  
Clinically significant abnormal laboratory results or other clinically significant 
assessments will be followed until they resolve (return to normal or baseline values) or 
stabilize, or until they are judged by the Investigator to be no longer clinically significant.  
Clinically significant abnormal laboratory findings or abnormal findings from other 
assessments that are present at baseline will be recorded as medical history.  
10.4.1.1 
Clinical Laboratory Abnormalities  
It is the responsibility of the Investigator to assess the clinical significance of all 
abnormal laboratory values as defined by the appropriate reference range(s).  
An abnormal laboratory value is considered to be an AE if the abnormality meets any of 
the following conditions below:  
• results in discontinuation from the study  
• requires treatment, modification/interruption of study drug dose, or any other 
therapeutic intervention  
• is judged to be of significant clinical importance  
Laboratory abnormalities that fulfill a seriousness criterion need to be documented as a 
SAE.  
Merely repeating an abnormal test, in the absence of any of the above conditions, does 
not constitute an AE. Any abnormal test result that is determined to be an error, either by 
laboratory or by Investigator does not require reporting as an AE.  
10.4.1.2 
Other Safety Assessments:  
Any abnormal finding determined from physical examinations or from other safety 
assessments (e.g., vital signs, ECGs, diagnostic imaging, or any other potential safety 
assessment required or not required by protocol) should be assessed for clinical significance 
by the Investigator. Only clinically significant abnormal findings should be recorded as an AE. 
 
 


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10.5 DEFINITION OF A SERIOUS ADVERSE EVENT 
A Serious Adverse Event (SAE) is defined as an AE that results in any of the following: 
• Death 
• Life-threatening 
• Requires hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
• An important medical event which requires medical intervention to prevent any 
of the above outcomes 
Important medical events are those which may not be immediately life-threatening, but 
may jeopardize the subject and may require intervention to prevent one of the other serious 
outcomes listed above.  Examples of such events are intensive treatment in an emergency 
room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not 
result in hospitalization. 
Inpatient hospitalization or prolongation of existing hospitalization means that hospital 
inpatient admission and/or prolongation of hospital stay were required for treatment of AE, 
or that they occurred as a consequence of the event.  It does not refer to pre-planned elective 
hospital admission for treatment of a pre-existing condition that has not significantly 
worsened, or to diagnostic procedures. 
The term "life-threatening" in the definition of "serious" refers to an event in which the 
subject was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
The term “disability” in the definition of “serious” refers to an event in which the subject’s 
ability to conduct normal life functions was substantially disrupted. 
Severe vs. Serious AEs: The term “severe” is often used to describe the intensity (severity) 
of a specific event (as in mild, moderate, or severe headache).  This is not the same as 
“serious”, which is based on subject/event outcome or reaction criteria usually associated 
with events that pose a threat to a subject’s life or functioning.  Seriousness (not severity) 
serves as a guide for defining regulatory reporting obligations. 
Any new SAE that occurs after the study period and is considered to be related 
(possibly/probably) to the study drug or study participation should be recorded and 
reported immediately (Section 10.6).  The study period for the purpose of SAE reporting 
is defined as the period from the subject's signature on the informed consent form until the 
end of the protocol-defined follow-up visit/period. 
10.6 SERIOUS ADVERSE EVENT REPORTING 
In order to satisfy regulatory requirements, any Serious Adverse Event, whether deemed 
study drug-related or not, must be reported to the Sponsor’s Medical Monitor or designee 
as soon as possible after the investigator or site coordinator has become aware of its 
occurrence but no later than 24 hours of becoming aware of the event.   


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The SAE form completion and reporting must not be delayed even if all of the information 
is not available at the time of the initial contact. All completed SAE forms should be sent 
to sponsor’s pharmacovigilance unit on the email: T301@lupin.com 
Additional information (follow-up) about any SAE unavailable at the initial reporting 
should be forwarded by the site within 24 hours of the information becoming available to 
the Medical Monitor or designee. 
The following information should be provided by the investigator or designee to accurately 
and completely record the event: 
• Investigator name and center number 
• Subject number 
• Subject initials 
• Subject demographics 
• Clinical event 
o Description 
o Date of onset 
o Severity 
o Treatment (if blind needs to be broken) 
o Relationship to study drug (causality) 
o Action taken regarding study drug 
• If the AE results in death 
o Cause of death (whether or not the death was related to study drug) 
o Autopsy findings (if available) 
• Medical history case report form (copy) 
• Concomitant medication case report form (copy) 
• Any relevant reports (laboratory, discharge, x-ray, etc) 
Subjects who have had an SAE during the treatment period must be followed clinically 
until all parameters (including laboratory) have either returned to normal or have stabilized 
or are otherwise explained. 
The Medical Monitor for this study is: 
Brajesh Pandey, MD  
Title: Associate Medical Director, Lupin Inc.  
Tel: 443-531-1109  
Email: brajeshkumarpandey@lupin.com 
 


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Pregnancy reports: Pregnancy reports should be forward to the Sponsor 
pharmacovigilance unit for data-entry to the global safety database.  This includes 
pregnancies without AE. 
The pregnancy should be followed up to determine outcome, including spontaneous or 
voluntary termination, details of birth, and presence or absence of any birth defect, 
congenital abnormalities or maternal and newborn complications.   
The pregnancies reporting procedure should be the same as the SAE reporting procedure. 
10.7 REPORTING TO THE UNITED STATES FOOD AND DRUG 
ADMINISTRATION (US FDA)  
The sponsor will report expeditiously all Serious and Unexpected Suspected Adverse 
Reaction to the USFDA, Investigators & IRB’s as IND Safety Report according to 21 CFR 
312 regulations. 


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11. 
DATA COLLECTION AND ANALYSIS 
This section describes the biostatistical analysis as foreseen at the time of planning the 
study.  Changes, additions and further details about the analyses will be described in the 
Statistical Analysis Plan (SAP).  After finalization of the SAP and unblinding, any 
additional analyses or changes to analyses that may be required will be fully disclosed in 
the clinical trial report. 
11.1 DATA COLLECTION METHODS 
This study will use web-based, electronic case report forms (eCRFs) developed through a 
validated, Electronic Records / Electronic Signatures-compliant platform (US Title 21 CFR 
Part 11). 
All site personnel who will be using this system will receive formal training, after which 
each person will be issued a unique user name and password. Only the person who owns 
the user name and password will enter the system using that user name and password. For 
data security reasons and to be in compliance with regulatory guidelines, user names and 
passwords are not transferable. 
The Investigator is responsible for all data entered via the electronic data capture (EDC) 
system eCRFs and must confirm the accuracy of the data by electronically approving 
(signing) the eCRFs. This responsibility includes the timely completion and accuracy of 
the data entered into the eCRFs by their site personnel. 
The study center will be visited as documented in the Study Monitoring Plan to review the 
eCRFs for completeness and accuracy.  The CRA will highlight any omissions, apparent 
errors, and values requiring further clarification using computerized and manual 
procedures and ensure that appropriate site personnel address the discrepancies. When a 
discrepancy results in corrected eCRF data, the correction will be recorded in the eCRF 
audit trail.  Data collection procedures will be discussed during EDC system training. 
Data from eCRFs and other external data will be entered into a clinical database as 
specified in the data management plan. Quality control and data validation procedures will 
be applied to ensure the validity and accuracy of the clinical database. 
11.2 SAMPLE SIZE CALCULATIONS 
Assuming a responder rate (microbiological cure) of 75% in the Solosec treatment group 
and a 40% placebo response rate and based on the use of a two-sided, two-sample 
comparison of proportions at the alpha=0.05 level of significance, a sample size of 100 
patients (50 patients in each group) who meet the mITT criteria will provide approximately 
95% power to demonstrate a statistically significant difference between Solosec and 
placebo. Assuming 70% of patients randomized in the study will meet the mITT criteria, 
approximately 144 patients will be enrolled into the study. 
 
 


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11.3 POPULATIONS FOR ANALYSIS 
Study Populations: 
Intent-to-Treat (ITT):  The ITT population will include all randomized patients.   
Modified Intent-To-Treat (mITT):  The mITT population will include all randomized 
patients who were culture positive for Trichomonas vaginalis and negative for other 
sexually transmitted infections. The primary efficacy analysis will be conducted in the 
mITT population. 
Per-Protocol (PP):  The PP population will be composed of patients in the mITT 
population with consideration of the following criteria: received the study medication as 
randomized, met inclusion and exclusion criteria, had a TOC visit between Days 6-12, and 
had no major protocol violations. The composition of the PP population will be finalized 
and documented in a review of the data conducted prior to unblinding the study database.  
The PP population will be used for supportive efficacy analyses.  
Safety:  The Safety population will be composed of all randomized patients who received 
any amount of study medication.   All safety summaries will be based on the Safety 
population. 
11.4 INTERIM ANALYSES 
There will be no interim analyses performed in this study. 
11.5 STUDY ENDPOINT ANALYSES 
 
Efficacy Analyses 
Primary Efficacy Analysis 
The primary efficacy endpoint, Microbiological Cure (i.e., InPouch™ TV test negative 
for T. vaginalis) at the TOC visit (Study Day 6-12), will be compared between the active 
and placebo treatment groups using a two-sided Cochran-Mantel-Haesnzel (CMH) test 
(stratified by the presence/absence of clinical symptoms of trichomoniasis at baseline) at 
the alpha=0.05 level of significance. 
Exploratory Efficacy Analyses 
The following exploratory endpoint will be evaluated at the TOC Visit (Study Day 6-12) 
for the subgroup of patients who have clinical symptoms of trichomoniasis at baseline: 
• Outcome Responder: complete resolution of trichomoniasis symptoms (i.e., 
itching, discharge, and odor recorded as normal) and culture results (InPouch™ 
TV test) negative for T. vaginalis  
 
Safety Analyses 
Safety evaluations will be based on the incidence, intensity, and type of AEs.  Safety 
variables will be tabulated and presented for all patients in the Safety population. 
Summarization will focus on incidence of SAEs; treatment-emergent AEs by System 
Organ Class (SOC) and Preferred term; AEs that are considered study-drug related; and 
AEs leading to study discontinuation.  


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Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) for purposes of summarization.   
A Treatment-emergent AE is defined as any AE that occurs after administration of the 
study drug and through the final visit, any event that is considered study drug-related 
regardless of the start date of the event, or any event that is present at baseline but worsens 
in intensity or is subsequently considered study drug-related by the Investigator.  
11.6 GENERAL ISSUES FOR DATA ANALYSIS 
 
Multiple Comparisons and Multiplicity 
There is a single primary efficacy analysis, so no adjustment for multiplicity is required. 
 
Covariates 
The stratification variable of presence/absence of clinical symptoms of trichomoniasis at 
baseline will be included as a factor in the primary efficacy analysis. 
 
Planned Sub-Group Analyses 
The primary endpoint will be analyzed in each of the two randomization strata. 
 
Missing Data 
Subjects in the mITT population whose status for the primary endpoint is unknown will be 
assumed to be not cured.   Apart from this, no imputation of missing data will be performed. 
 
Pooling of Centers 
Due to the small number of patients per center, all analyses and data summaries will be 
pooled across centers. 


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12. 
STUDY ADMINISTRATION 
12.1 REGULATORY AND ETHICAL CONSIDERATIONS 
 
Regulatory Authority Approval 
This study will be conducted in accordance with Good Clinical Practice (GCP) 
requirements described in the current revision of International Conference on 
Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH) 
Guidelines and all applicable regulations, including current United States Code of Federal 
Regulations (CFR), Title 21, Parts 50, 54, 56, and 312 and Title 45, Part 164.  Compliance 
with these regulations and guidelines also constitutes compliance with the ethical principles 
described in the current revision of the Declaration of Helsinki.  This study will also be 
carried out in accordance with local legal requirements. 
 
Ethics Approval 
It is the Investigator’s responsibility to ensure that, prior to initiating the study, this protocol 
is reviewed and approved by the appropriate local IRB/IEC.  A non-local IRB/IEC may be 
used if the site of the study is not under the auspices of an IRB/IEC. 
The IRB/IEC must also review and approve the site’s informed consent form (ICF), other 
written information provided to the subject and all advertisements that may be used for 
subject recruitment.  The Investigator will provide the Sponsor or designee with copies of 
these documents and of dated IRB/IEC approval(s) prior to the start of the study. 
If it is necessary to amend the protocol or the ICF during the study, the Investigator will be 
responsible for ensuring that the IRB/IEC reviews and approves these amended documents.  
An IRB/IEC approval of the amended protocol and/or ICF must be obtained before 
implementation of the amended procedures and before new subjects are consented to 
participate in the study using the amended version of the ICF.  The Investigator will 
forward copies of the dated IRB/IEC approval of the amended protocol and/or ICF to the 
sponsor or designee as soon as available. 
 
Subject Informed Consent 
Before being admitted to the clinical study, all subjects must consent to participate.  An 
ICF will be given to each subject, which will contain all US federally required elements, 
all ICH-required elements, and Health Insurance Portability and Accountability Act 
Authorization (HIPAA) information in language that is understandable to the subject.  In 
addition, for those subjects who are 12-17 years old and are legally unable to sign an 
informed consent form,  an IRB-approved assent form will be provided. The consent should 
note that the Investigator is receiving compensation for the expenses of conducting the 
study. 
The process of obtaining the informed consent will be in compliance with all federal 
regulations, ICH requirements, and local laws. 
The Investigator or a designee will review the study and the consent form with each subject.  
The review will include the nature, scope, procedures, and possible consequences of the 
subject's participation in the study.  The consent and review must be in a form 


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understandable to the subject.  The Investigator or designee and the subject must both sign 
and date the ICF after review and before the subject can participate in the study.  The 
subject will receive a signed and dated form, and the original will be retained in the site’s 
study files.  The Investigator or designee must emphasize to the subject that study 
participation is entirely voluntary and that consent regarding study participation may be 
withdrawn at any time without penalty or loss of benefits to which the subject is otherwise 
entitled. 
 
Investigator Reporting Requirements 
In accordance with applicable regulatory requirements, the Investigator is solely and 
exclusively obligated to keep the IRB/IEC informed of progress on this study, and/or 
provide periodic safety updates at his/her site, and notify the IRB/IEC of study closure. 
The Investigator will provide the sponsor or designee with copies of all correspondence 
with, or from, the IRB/IEC that relates to study approvals, updates, or changes.  
Furthermore, the Investigator will be responsible for obtaining all IRB/IEC renewals 
according to applicable regulations for the duration of the study and to provide copies of 
any and all approval extensions to Lupin Inc. 
12.2 PROTOCOL AMENDMENTS 
Changes to the protocol can only be made by an approved protocol amendment.  Protocol 
amendments must be approved by the Sponsor and IRB/IEC prior to implementation. 
12.3 DECLARATION OF THE END OF THE CLINICAL TRIAL 
For clinical trial sites located in the EU, a declaration of the end of the clinical trial will be 
made according to the procedures outlined in Directive 2001/20/EC, Article 10(c) and, for 
those countries outside the EU, local regulations will be followed. 
12.4 STUDY MONITORING 
In accordance with applicable regulations, GCP, and the procedures of the Sponsor, or its 
designee, the Study Monitor will periodically contact the site, including conducting on-site 
visits.  The extent, nature, and frequency of on-site visits will be based on study complexity, 
enrollment rate, and data quality at the site.  Through frequent communications (e.g., letter, 
e-mail, and telephone), the Study Monitor will ensure that the investigation is conducted 
according to protocol and regulatory requirements. 
During these contacts, the monitoring activities will include: 
• Checking and assessing the progress of the study 
• Reviewing study data collected to date for completeness and accuracy 
• Conducting source document verification by reviewing each subject’s CRF 
against source documents (e.g., medical records, ICF, laboratory results 
reports, raw data collection forms), and  
• Identifying any issues and addressing resolutions. 
These activities will be done in order to verify that the: 


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• Data are authentic, accurate, and complete 
• Safety and rights of the subjects are being protected, and 
• Study is conducted in accordance with the currently approved protocol (and 
any amendments), GCP, and all applicable regulatory requirements. 
The Investigator will allow the Study Monitor direct access to all relevant documents, and 
allocate his/her time and the time of his/her staff to the Study Monitor to discuss findings 
and any relevant issues. 
In addition to contacts during the study, the Study Monitor will contact the site prior to the 
start of the study to discuss the protocol and data collection procedures with site personnel. 
12.5 QUALITY ASSURANCE 
At its discretion, the Sponsor or its designee may conduct a quality assurance audit of this 
study.  Auditing procedures of the Sponsor and/or its designee will be followed in order to 
comply with GCP guidelines and ensure acceptability of the study data for registration 
purposes.  If such an audit occurs, the Investigator will give the auditor direct access to all 
relevant documents, and will allocate his/her time and the time of his/her staff to the auditor 
as may be required to discuss findings and any relevant issues. 
Regulatory agencies (e.g., FDA) may conduct an inspection of this study.  In addition, EU 
clinical QP internal audit regulatory authorities may conduct an inspection for EU 
submission.  If such an inspection occurs, the Investigator will allow the inspector direct 
access to all source documents, CRFs, and other study documentation for source data check 
and/or on-site audit inspection.  The Investigator must allocate his/her time and the time of 
his/her staff to the inspector to discuss findings of any relevant issues. 
12.6 STUDY TERMINATION AND SITE CLOSURE 
Upon completion of the study, the following activities, when applicable, must be conducted 
by the Study Monitor in conjunction with the Investigator, as appropriate: 
• Return of all study data to the Sponsor or its designee 
• Data clarifications and/or resolutions 
• Accounting, reconciliation, and final disposition of used and unused study 
drug 
• Review of site study records for completeness; and  
• Shipment of blood samples to the clinical laboratory. 
Lupin Inc. reserves the right to temporarily suspend or prematurely terminate this study for 
any reason. 
If the study is suspended or terminated for safety reason(s), Lupin Inc. will promptly inform 
the Investigator, and will also inform the regulatory authorities of the suspension or 
termination of the study and the reason(s) for the action.  The Investigator is responsible 
for promptly informing the IRB/IEC, and providing the reason(s) for the suspension or 
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If the study is prematurely discontinued, all study data must be returned to the Sponsor or 
its designee.  In addition, the site must conduct final disposition of all unused study drug 
in accordance with Lupin Inc. procedures for the study. 
12.7 SITE TERMINATION 
Lupin Inc. may, in its sole discretion, terminate a single study site for various reasons, 
including, but not limited to, the following: 
• Failure of the Investigator to enroll subjects into the study at a reasonable 
rate 
• Failure of the Investigator to comply with pertinent FDA regulations  
• Submission of knowingly false information from the research facility to the 
Sponsor, Study Monitor, or FDA 
• Insufficient adherence to protocol requirements 
If the participation of a study site is terminated for reasons other than safety (e.g., 
uncorrected data acquisition or image quality issues), Lupin Inc. will issue a written notice 
to the Investigator.  The written notice will contain the reasons for taking such action.  If a 
study site is terminated for noncompliance, Lupin Inc. will also notify appropriate 
regulatory authorities.  Study termination and follow up will be performed in compliance 
with the conditions set forth in 21 CFR 312.50 and 21 CFR 312.56. 
12.8 RECORDS RETENTION 
In accordance with applicable regulatory requirements and following completion or 
termination of the study, the Investigator will retain a copy of all study records in a safe, 
secure, and accessible location for a minimum of 2 years after notification by Lupin Inc. 
that the investigations have been discontinued, or for 2 years after all marketing 
applications have been approved.  For EU submissions, retention of a minimum 5 years 
though it was post-submission is required. Study records will include at a minimum the 
following: 
• Signed ICFs for all subjects 
• Subject identification list 
• Record of all communications between the Investigator and the IRB/IEC 
• Record of all communications between the Investigator and the Sponsor or 
its designee 
• List of all sub-investigators and other key study personnel 
• Copies of all financial records related to the study including: financial 
arrangements for the study; financial payments made by the Sponsor or its 
designee to the Investigator; and financial interests held by the Investigator 
in the product or in Lupin Inc. 
• Copies of CRFs for all subjects, and 


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• All other source documents (e.g., subject records, hospital records, 
laboratory reports, and drug accountability records, etc.) 
To avoid any possible errors, the Investigator will contact Lupin Inc. prior to the 
destruction of any study records.  The Investigator must immediately notify Lupin 
Inc. in the event of accidental loss or destruction of any study records. 
12.9 CONFIDENTIALITY OF INFORMATION 
Subject names will remain confidential and will not be supplied to the Sponsor or its 
designee.  Only the subject number, subject initials, and birth date will be recorded in the 
CRF.  If the subject name appears on any other document collected (e.g., hospital discharge 
summary), it must be obliterated from the document before the document is transmitted to 
the Sponsor or its designee.  All study findings will be stored in electronic databases.  The 
subjects will give explicit written permission for representatives of the Sponsor, regulatory 
authorities, and the IRB/IEC to inspect their medical records to verify the information 
collected.  Subjects will be informed that all personal information made available for 
inspection will be handled in the strictest confidence and in accordance with all state, local, 
and federal data protection/privacy laws, including, without limitation, the HIPAA. 
When subjects complete the study, all contact information will be purged from all study 
files, and all subject identifiers (other than an assigned subject number) will be obliterated 
from documentation confirming a clinical endpoint event. 
12.10 PAYMENT TO SUBJECTS 
Subjects may be compensated for participating in this study and the amount of payment 
will be stated in the ICF approved by the IRB/IEC.   
12.11 CLINICAL TRIAL REGISTRATION 
This clinical trial will be registered on the “clinicaltrials.gov” clinical trial registry website 
as required by 42 USC 282(j). 
 


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13. 
REFERENCES 
Bravo AA, Vazquez RQ and Farugia DL (1978). Treatment of vaginitis due to 
trichomonas using a single dose of secnidazole. Investigación Médica Internacional 
[International Medical Research] 5: 476-482. 
Centers for Disease Control and Prevention (CDC) 2015 Sexually Transmitted Disease 
Treatment Guidelines (https://www.cdc.gov/std/tg2015/default.htm). 
Cotch MF, Pastorek JG, 2nd, Nugent RP, et al. Trichomonas vaginalis associated with 
low birth weight and preterm delivery. Sex Transm Dis 1997;24:353–60. 
Crosby RA, Charnigo RA, Weathers C, et al. Condom effectiveness against non-viral 
sexually transmitted infections: a prospective study using electronic daily diaries. Sex 
Transm Infect 2012;88:484–9. 
Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP and Garber GE (2004). 
Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis. Clin 
Microbiol Rev 17(4): 783-793, table of contents. 
Forna F and Gulmezoglu AM (2003).  Interventions for treating trichomoniasis in 
women. Cochrane Database Syst Rev(2): CD000218. 
Ginocchio CC, Chapin K, Smith JS, et al. Prevalence of Trichomonas vaginalis and 
coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States 
as determined by the Aptima Trichomonas vaginalis nucleic acid amplification assay. J 
Clin Microbiol 2012;50:2601–8. 
Gray RH, Kigozi G, Serwadda D, et al. The effects of male circumcision on female 
partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, 
Uganda. Am J Obstet Gynecol 2009;200:e41–7. 
Hager WD, Brown ST, Kraus SJ, et al. (1980).  Metronidazole for vaginal 
trichomoniasis. Seven-day vs single-dose regimens. JAMA 244(11): 1219-1220. 
Machado LE (1988). Single dose of secnidazole in the treatment of vaginal 
trichomoniasis a comparison between morning and evening doses. Jornal Brasileiro De 
Ginecologia 2: 83-86. 
Manorama HT and Shenoy DR (1978). Single-dose oral treatment of vaginal 
trichomoniasis with tinidazole and metronidazole. J Int Med Res 6(1): 46-49. 
McClelland RS, Sangare L, Hassan WM, et al. Infection with Trichomonas vaginalis 
increases the risk of HIV-1 acquisition. J Infect Dis 2007;195:698–702. 
Minkoff H, Grunebaum AN, Schwarz RH, et al. Risk factors for prematurity and 
premature rupture of membranes: a prospective study of the vaginal flora in pregnancy. 
Am J Obstet Gynecol 1984;150:965–72. 
Moodley P, Wilkinson D, Connolly C, et al. Trichomonas vaginalis is associated with 
pelvic inflammatory disease in women infected with human immunodeficiency virus. 
Clin Infect Dis 2002;34:519–22. 
 


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Moraes MEA, Cunha GH, Bezerra MM, et al. (2012). Efficacy of the Mentha crispa in 
the treatment of women with Trichomonas vaginalis infection. Arch Gynecol Obstet. 
286: 125-130. 
Patel EU, Gaydos CA, Packman ZR, et al. Prevalence and Correlates of Trichomonas 
vaginalis Infection Among Men and Women in the United States. Clin Infect Dis. 2018 
Jul 2;67(2):211-217. 
Peterman TA, Tian LH, Metcalf CA, et al. High incidence of new sexually transmitted 
infections in the year following a sexually transmitted infection: a case for rescreening. 
Ann Intern Med 2006;145:564–72. 
Piato S and Cymbalusta N (1977). Treatment of trichomoniasis with a single dose of 
secnidazole. Revista Brasileira de Medicina [Brazilian Journal of Medicine] 34(4): 197-
200. 
Rocha AM and Neto AS (1977). Treatment of urogenital trichomoniasis. Therapeutic 
themes; 34(6): 365-366. 
Satterwhite CL, Torrone E, Meites E, et al. Sexually transmitted infections among US 
women and men: prevalence and incidence estimates, 2008. Sex Transm Dis 
2013;40:187–93. 
Schwebke JR, Barrientes FJ. Prevalence of Trichomonas vaginalis isolates with 
resistance to metronidazole and tinidazole. Antimicrob Agents Chemother 
2006;50:4209–10. 
Schwebke JR, Desmond RA. A randomized controlled trial of partner notification 
methods for prevention of trichomoniasis in women. Sex Transm Dis 2010;37:392–6. 
Schwebke JR, Lensing SY, Sobel J. Intravaginal Metronidazole/Miconazole for the 
Treatment of Vaginal Trichomoniasis. Sexually Transmitted Diseases. 2013;40(9):710-
714. 
Sena AC, Miller WC, Hobbs MM, et al. Trichomonas vaginalis infection in male sexual 
partners: implications for diagnosis, treatment, and prevention. Clin Infect Dis 
2007;44:13–22. 
Shuter J, Bell D, Graham D, et al. Rates of and risk factors for trichomoniasis among 
pregnant inmates in New York City. Sex Transm Dis 1998;25:303–7. 
Siboulet A, Catalan F, Videau D and Niel G (1977). Urogenital trichomoniasis. Trials 
with a long half-life imidazole: secnidazole.*. Médecine et Maladies Infectieuses 7(9): 
400-409. 
Sobel J (2015). Trichomoniasis. UpToDate. R. L. Barvieri. March 15. 
Sosman J, Macgowan R, Margolis A, et al. Project START Biologics Study 
Group.  Sexually transmitted infections and hepatitis in men with a history of 
incarceration. Sex Transm Dis 2011;38:634–9. 
Sobngwi-Tambekou J, Taljaard D, Nieuwoudt M, et al. Male circumcision and Neisseria 
gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis: observations after a 
randomised controlled trial for HIV prevention. Sex Transm Infect 2009;85:116–20. 


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Sosman JM, MacGowan RJ, Margolis AD, et al. Screening for sexually transmitted 
diseases and hepatitis in 18-29-year-old men recently released from prison: feasibility 
and acceptability. International journal of STD and AIDS 2005;16:117–22. 
Sutcliffe S, Newman SB, Hardick A, et al. Prevalence and correlates of Trichomonas 
vaginalis infection among female US federal prison inmates. Sex Transm Dis 
2010;37:585–90. 
Sutton M, Sternberg M, Koumans EH, et al. The prevalence of Trichomonas vaginalis 
infection among reproductive-age women in the United States, 2001-2004. Clin Infect 
Dis 2007;45:1319–26. 
Tsai CS, Shepherd BE, Vermund SH. Does douching increase risk for sexually 
transmitted infections? A prospective study in high-risk adolescents. Am J Obstet 
Gynecol 2009;200:e31–8. 
Van Der Pol B, Kwok C, Pierre-Louis B, et al. Trichomonas vaginalis infection and 
human immunodeficiency virus acquisition in African women. J Infect Dis 
2008;197:548–54. 
Videau D, Niel G, Siboulet A and Catalan F (1978). Secnidazole. A 5-nitroimidazole 
derivative with a long half-life. Br J Vener Dis 54(2): 77-80. 
 
 
 


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APPENDIX A - SOLOSEC PACKAGE INSERT  

SAP_001.pdf: 
 
Confidential Document 
 
 
 
Statistical Analysis Plan 
 
Sponsor: 
Lupin Inc. 
Protocol No: 
SEC-WH-301 
Protocol Title: 
A Phase 3, Multi-center, Prospective, Randomized, 
Placebo-Controlled, Delayed Treatment, Double-
Blind Study to Evaluate the Effectiveness and 
Safety of a Single Oral Dose of Solosec® Granules 
Containing 2 grams of Secnidazole for the 
Treatment of Trichomoniasis 
Document Date: 
20-Mar-2020 
Document Revision 
2.0 
 
 




 
 
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DOCUMENT HISTORY 
 
Rev No 
Date 
Description 
1.0 
10-Apr-2019 
Original document 
2.0 
20-Mar-2020 Added clarification that the presence/absence of clinical 
symptoms of trichomoniasis is based on symptoms reported 
during the baseline vaginal assessment, with a sensitivity analysis 
if this differs from the randomized strata. 
 
 
 
 
 


 
 
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TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................................. 7 
1.1 
Study Background ............................................................................................................ 7 
1.2 
Study Design .................................................................................................................... 7 
1.3 
Study Objectives .............................................................................................................. 8 
1.3.1 
Primary Objectives.................................................................................................... 8 
1.3.2 
Secondary Objectives................................................................................................ 8 
2. 
STATISTICAL METHODOLOGY .................................................................................... 8 
2.1 
General Principles ............................................................................................................ 8 
2.2 
Sample Size Determination .............................................................................................. 8 
2.3 
Study Populations ............................................................................................................. 9 
2.4 
Patient Accounting and Baseline Characteristics ............................................................. 9 
2.5 
Efficacy Analyses ............................................................................................................. 9 
2.5.1 
Primary Efficacy Analyses ....................................................................................... 9 
2.5.2 
Additional Analyses of Primary Endpoint .............................................................. 10 
2.5.3 
Exploratory Efficacy Analyses ............................................................................... 10 
2.6 
Safety Analyses .............................................................................................................. 10 
2.6.1 
Adverse Events ....................................................................................................... 10 
2.6.2 
Vital Signs ............................................................................................................... 11 
2.7 
Interim Analyses ............................................................................................................ 11 
3. 
DATA HANDLING ............................................................................................................. 11 
3.1 
Baseline and Study Visits ............................................................................................... 11 
3.2 
Missing Data .................................................................................................................. 11 


 
 
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3.3 
Incomplete Medication Dates......................................................................................... 11 
4 
CHANGES FROM THE PROTOCOL ............................................................................. 12 
 
 
 
 


 
 
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List of Abbreviations 
AE 
Adverse Event 
BV 
Bacterial Vaginosis 
CMH 
Cochran Mantel Haenszel 
CRF 
Case Report Form 
EOS 
End of Study 
FDA 
Food and Drug Administration 
ITT 
Intent to Treat 
MedDRA Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent to Treat 
NAAT 
Nucleic Acid Amplification Testing 
PP 
Per-Protocol 
SD 
Standard Deviation 
SOC 
System Organ Class 
TOC 
Test of Cure 
TV 
Trichomonas Vaginalis 
WHO 
World Health Organization 
 
 


 
 
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1. 
INTRODUCTION 
1.1 Study Background 
Solosec® (secnidazole, SYM-1219) oral granules 2 grams is a Food and Drug Administration 
(FDA) approved treatment for bacterial vaginosis (BV) in adult women. Solosec™ is a potent, 5-
nitroimidazole antibiotic with enhanced pharmacokinetic properties that enable delivery in a 
single dose that has been shown to be efficacious and well tolerated. 
Trichomoniasis is the most prevalent nonviral sexually transmitted infection in the United States, 
affecting an estimated 3.7 million persons. Lupin is developing Solosec as an available treatment 
option to provide an alternative, effective, single dose therapy for women diagnosed with 
trichomoniasis that, in turn, should decrease the known serious sequelae that occur when this 
infection is left untreated or ineffectively treated. 
1.2 Study Design 
This is a Phase 3, multi-center, prospective, randomized, placebo-controlled, delayed treatment, 
double-blind, study to evaluate the effectiveness, and safety of a single, oral dose of Solosec 
containing 2 grams of secnidazole in female patients with trichomoniasis. Approximately 144 
patients who test positive for trichomonas on OSOM® rapid test or via wet mount assessment or 
have positive Trichomonas vaginalis (T. vaginalis, TV) Nucleic Acid Amplification Testing 
(NAAT) within 30 days of screening (and have not been treated) and fulfill other eligibility 
criteria at the baseline visit will be enrolled in this study. The diagnosis of T. vaginalis will be 
confirmed by a positive culture for T. vaginalis. 
The study will consist of a primary study phase (Visit 1 (baseline) to Visit 2 (Day 6-12)) and a 
follow-up phase (Visit 2 to Visit 3 (7-12 days post Visit 2)). During the primary phase patients 
will be randomly assigned in a 1:1 ratio to either Solosec or placebo. The randomization will be 
stratified by site and based on the clinical symptoms of trichomoniasis (present or absent). 
Patients will return to the clinic for the “test of cure” (TOC) visit to be conducted on Days 6-12 
(Visit 2). After all Visit 2 (V2) study procedures have been completed, patients will receive the 
opposite treatment (placebo patients will receive Solosec and vice versa). Patients with V2 
cultures that are subsequently positive for T. vaginalis will return to the clinic for Visit 3 (V3) 
assessments and investigator assessment of need for additional therapy (an additional Visit 4 
may be scheduled at the investigator’s discretion if culture at V3 is positive).  Patients with 


 
 
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cultures that are negative at V2 will be contacted by phone and discharged from the study (no V3 
required). 
1.3 Study Objectives 
1.3.1 Primary Objectives 
The objective of this study is to evaluate the efficacy and safety of a single, oral dose of Solosec 
containing 2 grams of secnidazole compared to placebo for the treatment of trichomoniasis. 
1.3.2 Secondary Objectives 
None. 
2. 
STATISTICAL METHODOLOGY 
2.1 General Principles 
All analyses will be performed using SAS® software version 9.4. Prior and concomitant 
medications will be coded using World Health Organization (WHO) Drug Dictionary Enhanced 
March 2019. Medical history and Adverse Events (AEs) will be coded using Medical Dictionary 
for Regulatory Activities (MedDRA) version 22.0. 
Continuous variables will be summarized by n (number of patients with non-missing results), 
mean, standard deviation (SD), median, minimum, and maximum.  Categorical variables will be 
summarized by count and percent (of patients in the population with a non-missing result). 
All data collected will be presented in data listings.  Data collected subsequent to TOC (Visits 3 
and 4) will be included in data listings but will not be used for any analyses. 
2.2 Sample Size Determination 
Assuming a responder rate (microbiological cure) of 75% in the Solosec treatment group and a 
40% placebo response rate and based on the use of a two-sided, two-sample comparison of 
proportions at the alpha=0.05 level of significance, a sample size of 100 patients (50 patients in 
each group) who meet the mITT criteria will provide approximately 95% power to demonstrate a 
statistically significant difference between Solosec and placebo. Assuming 70% of patients 
randomized in the study will meet the mITT criteria, approximately 144 patients will be enrolled 
into the study. 


 
 
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2.3 Study Populations 
Intent-to-Treat (ITT):  The ITT population will include all randomized patients.  Patients will be 
summarized based on the randomized treatment group. 
Modified Intent-To-Treat (mITT):  The mITT population will include all randomized patients 
who were culture positive for T. vaginalis and negative for STIs (lab results will not be known 
until after randomization). Patients will be summarized based on the randomized treatment group. 
Per-Protocol (PP):  The PP population will be composed of patients in the mITT population with 
consideration of the following criteria: received the study medication as randomized, met inclusion 
and exclusion criteria, had a TOC visit between Days 6-12, and had no major protocol violations. 
The composition of the PP population will be finalized and documented in a review of the data 
conducted prior to unblinding the study database. 
Safety:  The Safety population will be composed of all randomized patients who received any 
amount of study medication. Patients will be summarized based on the treatment group actually 
received. 
2.4 Patient Accounting and Baseline Characteristics 
Demographics will be summarized by treatment group for the mITT, PP, and safety populations. 
Other baseline characteristics (vaginal assessments, vital signs, laboratory results, medical 
history) and prior and concomitant medications will be summarized by treatment group for the 
safety population. Study completion status and primary reason for discontinuation will be 
displayed by treatment group for the ITT population.  
2.5 Efficacy Analyses 
The mITT population will be the primary efficacy population. The primary and exploratory 
efficacy analyses will also be conducted on the PP population. The presence/absence of clinical 
symptoms of trichomoniasis are based on symptoms reported during the baseline vaginal 
assessment. 
2.5.1 Primary Efficacy Analyses 
The primary efficacy endpoint, Microbiological Cure (i.e., InPouch™ TV test negative for T. 
vaginalis) at the TOC Visit (Study Day 6-12), will be compared between the active and placebo 
treatment groups using a two-sided Cochran-Mantel-Haesnzel (CMH) test (stratified by the 
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significance. In the event that there are subjects whose actual symptom strata differs from the 
strata used for randomization, a sensitivity analysis will be conducted using the randomized 
strata to assess the impact of the strata differences. 
2.5.2 Additional Analyses of Primary Endpoint 
For each treatment group, an exact 95% binomial confidence interval of the cure rate will be 
calculated.  Within each stratum, cure rates will be compared between the active and placebo 
treatment groups using a two-sided Fisher’s exact test. 
2.5.3 Exploratory Efficacy Analyses 
The exploratory endpoint, Outcome Responder, will be evaluated at the TOC Visit (Study Day 6-
12) for the subgroup of patients who have clinical symptoms of trichomoniasis at baseline.  A 
patient is considered a responder if they have complete resolution of trichomoniasis symptoms 
(i.e., itching, discharge, and odor recorded as normal) and culture results (InPouch™ TV test) 
negative for T. vaginalis.  Outcome Responders will be compared between the active and 
placebo treatment groups using a two-sided Fisher’s exact test.  For each treatment group, an 
exact 95% binomial confidence interval of the responder rate will be calculated. 
2.6 Safety Analyses 
Safety evaluations will be based on the incidence, intensity, and type of adverse events 
(AEs), and changes in vital signs. Safety summaries will be presented for all patients in the 
safety population. 
2.6.1 Adverse Events 
AEs that occur through the TOC Visit will be summarized by System Organ Class (SOC), 
Preferred Term, intensity, and treatment group for treatment-emergent AEs.  Summaries will 
also be provided for study drug-related AEs, serious AEs, and AEs leading to study 
discontinuation. Each patient will be counted only once for each of the incidence rates, 
regardless of the number of occurrences (events) the patient experiences. 
A Treatment-emergent AE is defined as any AE that occurs after administration of the study 
drug and through the final visit, or any event that is considered study drug-related regardless of 
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2.6.2 Vital Signs 
Actual values and changes from baseline to the TOC Visit will be summarized by treatment 
group for each vital sign assessment. 
2.7 Interim Analyses 
No interim analyses are planned. 
3. 
DATA HANDLING 
3.1 Baseline and Study Visits 
Visits for all analyses will be as recorded on the Case Report Form (CRF). Baseline is defined as 
the last assessment (including unscheduled assessments) prior to dosing. The day of dosing is 
considered Day 1.  Assessments will be considered Baseline if the assessment is before the date 
of dosing, or if the assessment was done on Day 1 and, according to the Study Schedule of 
Assessments, was supposed to be performed on Day 1 prior to treatment. 
3.2 Missing Data 
Patients in the mITT population whose status for the primary endpoint (Microbiological Cure) is 
unknown will be assumed to be not cured.  Patients in the mITT subgroup of patients who have 
clinical symptoms of trichomoniasis at baseline whose status for the exploratory endpoint 
(Outcome Responder) is unknown will be assumed to be a non-responder.  No other imputation 
of missing data will be performed. 
3.3 Incomplete Medication Dates 
If a medication has an incomplete start or stop date, the following rules will be used to determine 
if the medication is prior or concomitant: 
• If the stop year and month are both present, the stop date will be assumed to be the 
minimum of the last day of the given month for the given year and the patient’s final 
study date. 
• If the stop year is present and the stop month is missing, the stop date will be assumed to 
be the minimum of the last day of the given year and the patient’s final study date. 
• Otherwise, if the stop year is missing, the stop date will be assumed to be the patient’s 
final study date. 


 
 
SEC-WH-301 Statistical Analysis Plan  
Revision No.: 
2.0 
Document Date:   20-Mar-2020 
Page 12 of 12  
 
Confidential Document 
 
• An incomplete start date will be assumed to be the minimum of the date of study drug 
administration and the associated medication stop date. 
4 
CHANGES FROM THE PROTOCOL 
This analysis plan clarifies that data subsequent to the TOC visit (Visits 3 and 4) will be included 
in data listings but will not be used in any analyses. 
This analysis plan clarifies that the presence/absence of clinical symptoms of trichomoniasis is 
based on symptoms reported during the baseline vaginal assessment, with a sensitivity analysis if 
this differs from the randomized strata.