Clinical trial NCT05033743
Conditions: Recurrent Bacterial Vaginosis
Sponsor: Indiana University
Start date: 2021-07-09; Completion date: 2022-10-07
Enrollment: 24 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to test the effectiveness Secnidazole to treat recurrent BV. Secnidazole is approved for one-time use in acute BV. In this study, the drug will be used for recurrent BV, and given weekly for 18 weeks.

Detailed description:
A single-center prospective pilot study with once-weekly oral secnidazole granule treatment of acute condition for two-weeks followed by prophylactic treatment of asymptomatic responders with once-weekly secnidazole for 16 weeks, followed by no therapy for 12 weeks. The final follow-up evaluation is at week 28.

Eligible women with a current symptomatic bacterial vaginosis infection (\> or = 3 Amsel criteria) and a history of at least 2 previous episodes of bacterial vaginosis in the past year will be enrolled in the open-label treatment study. All women will be treated with 2g of secnidazole granules orally once-weekly for 2 weeks. At the second visit, 3-5 days after completion of treatment, women who have a resolution of bacterial vaginosis (asymptomatic and \< or = 2 Amsel criteria) will continue on once-weekly secnidazole for 16 weeks.

Patients will be evaluated every 4 weeks for recurrence of bacterial vaginosis. This will include questions about symptoms as well as a pelvic examination for assessment of vaginal discharge (\> or = 3 Amsel criteria). We will also collect any information on other clinical evaluations for recurrence and the dates of diagnoses and types of treatments they may have received. Those who remain without recurrence during the 16-week suppressive phase will be followed for an additional 12 weeks off therapy, with assessment for recurrence at weeks 22 and 30. Throughout the study, data will be collected on participants' compliance and on the occurrence of adverse events.

Arms: arm 1: Secnidazole treatment
Interventions: intervention 1: Secnidazole 2 GM Oral Granules
Intervention descriptions: intervention 1: Once weekly 2g oral secnidazole for 18 weeks

Protocol documents:
ICF_002.pdf: 
 
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Suppressive Antibacterial Therapy with Once-weekly Solosec®(secnidazole) Oral Granules to 
Prevent Recurrent Bacterial Vaginosis  
Drug Name: Solosec®(secnidazole) Oral Granules, 2 g 
 
 
NCT # 05033743 
Document Date: 08/17/2021 
 
 
 
 
 
 
Chemen M. Neal MD, Associate Professor 
Department of Obstetrics & Gynecology 
550 N. University Ave Suite 2440 
Indianapolis, IN 46202 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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INDIANA UNIVERSITY INFORMED CONSENT STATEMENT FOR RESEARCH 
 
Suppressive Antibacterial Therapy with Once-Weekly Secnidazole Granules to Prevent Recurrent 
Bacterial Vaginosis; a Pilot Study  
Lupin Pharmaceuticals, Inc. 
ABOUT THIS RESEARCH  
You are being asked to participate in a research study.  Scientists do research to answer important 
questions which might help change or improve the way we do things in the future.  
 
This consent form will give you information about this study to help you decide whether you want to 
participate.  It is your choice whether or not you want to be in this research study.  Please read this 
form, and ask any questions you have, before agreeing to be in this study.   
 
WHY IS THIS STUDY BEING DONE? 
Bacterial vaginosis (BV) is the most common cause of vaginal symptoms in women in the United States. 
Many women will have repeat episodes of BV after receiving standard treatment and there are limited 
options for treating women with recurrent BV.  
 
The purpose of this study is to test the effectiveness of a medication called “Secnidazole” to treat 
recurrent BV. Secnidazole is approved for one-time use in acute BV. In this study, the drug will be used 
for recurrent BV, and given weekly for 18 weeks.  
 
We are asking you if you want to be in this study because you currently have symptoms of BV, have a 
history of at least two previous episodes of BV in the past year, and are 18-50 years old.   
 
The study is being conducted by Dr. Chemen Neal at Indiana University Department of Obstetrics and 
Gynecology.  It is funded by Lupin Pharmaceuticals, Inc who manufactures secnidazole. 
 
HOW MANY PEOPLE WILL TAKE PART? 
You will be one of 50 participants taking part in this study.  
 
WHAT WILL HAPPEN DURING THE STUDY? 
All visits will occur at IU Health Coleman Center 
Visit 1 – Enrollment - Baseline Assessment 
• For research purposes the study team will collect information about you from your medical 
records. 
• You will answer questions about your symptoms. 
• We will perform a symptom assessment, pelvic exam, and obtain vaginal swabs to evaluate 
your symptoms. The pelvic exam of the vagina is like pelvic examinations performed clinically at 
most annual gynecologic examinations. The pelvic exam will take about 2 minutes. 


 
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• You will have a basic neurological exam. The neurological exam will take about 2 minutes. The 
neurological exam will take about 2 minutes. Cranial nerves 2-12 will be evaluated (nerves that 
are in your face and head), and your arm and leg strength and reflexes will be tested. 
• We will perform STI testing for gonorrhea/chlamydia/trichomonas. 
• We will perform a urine pregnancy test. If you are pregnant, you will not continue with study 
drug. 
• We will provide you with secnidazole and you will be instructed in the use of the secnidazole 
granules by trained study personnel or your medical provider. You will take secnidazole orally, 
once a week - initially for 2 weeks. 
• You will be asked to attend follow-up clinic visits throughout the study to undergo additional 
pelvic exams, assess your symptoms and evaluate your vaginal discharge, vaginal irritation, 
bleeding, redness, or itching as well as medication intake, tolerance, and any potential side 
effects.  
• Each study visit will last about 30 minutes to 1 hour. 
• Any testing performed that is part of the standard evaluation of your symptoms will be billed to 
you and/or your insurance. Study related testing and examinations will not be charged to you. 
Your provider will explain which parts of your examination are standard or study related.  
Visit 2 – 3 to 5 days after the 2-week treatment period 
• You will attend a follow-up visit, where we will again assess your symptoms, perform a pelvic 
exam, and evaluate your symptoms. 
• You will have a basic neurological exam at follow-up clinic visits. 
• You will also complete a questionnaire that asks about symptoms, the use of contraception, 
and any side effects you may have experienced.  
• If we find that secnidazole is not treating your symptoms of bacterial vaginosis at this visit or 
subsequent follow-up visits, your participation in the study will be considered complete and 
you will be placed on standard therapy for recurrent BV.  
• If you show signs of resolution, you will continue to take secnidazole once a week up until week 
16. 
Visit 3 through 6 – Weeks 6, 10, 14, and 18 
• Every 4 weeks up until Week 16, you will attend follow-up visits to assess your symptoms, and 
make sure you are taking the study drug. 
Visit 7 and 8 – Weeks 22 and 30 
• If you remain without recurrence during the 16-week treatment phase, you will be followed for 
an additional 12 weeks (about 3 months) off therapy with follow-up visits at weeks 22 and 30. 
• You will be followed for up to 30 weeks (about 7 months) total if you remain symptom free. 
 
If you participate in this study, we may learn things about you from the study procedures that could be 
important or interesting to you. Depending on the information, you might need to meet with 
professionals with expertise to help you decide what to do with the information. We do not have 
money or funds available to cover the costs of any follow-up consultations or actions.  We will share 
the following information with you: 


 
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• Any information that might be immediately critical to your health will be shared with you or 
your health care provider. 
 
WHAT ARE THE RISKS OF TAKING PART IN THE STUDY? 
While participating in the study, the risks, side effects, and/or discomforts include: 
• A risk of completing the survey is being uncomfortable answering the questions. You can 
skip any questions that make you uncomfortable or that you do not want to answer. 
• There is a risk someone outside the study team could get access to your research or medical 
information from this study. More information about how we will protect your information 
to reduce this risk is described later in this document. 
• The risks of a speculum pelvic exam include pain and discomfort. 
• Previous trial data shows that 30% of all treated individuals will report a side effect to 
secnidazole. The side effects associated with taking secnidazole include (in parenthesis are 
the percentage of individuals who reported that side effect): 
o Vaginal candida infection (9.6%) 
o Headache (3.6%) 
o Nausea (3.6%) 
o Temporary loss of taste (3.4%) 
o Vomiting (2.5%) 
o Diarrhea (2.5%) 
o Abdominal pain (2%) 
o Vaginal itching (2%) 
• Prior clinical studies of secnidazole reported mild prolongation of QTc (a portion of the 
heartbeat) after single 2g or 6g doses. While this was found to be clinically insignificant, it is 
still a symptom that you might encounter. 
• Animal trials in rats and dogs demonstrated neurological adverse events in toxicity studies. 
No significant accumulation of the drug is expected in humans when treated weekly for 18 
weeks, but multi-dose regimens of secnidazole have not been studied in humans. 
• You should avoid pregnancy during the active treatment period of participation in this study 
since secnidazole has not been studied in pregnancy. Effective contraception includes 
condoms, implants, intrauterine devices, injectable medications, pills, and patches. 
• Animal trials in mice and rats have demonstrated cancer-causing effects with nitroimidazole 
derivatives (chemicals similar to secnidazole) after lifetime exposure and when used at very 
high doses (1.4 times the normal human dose). Up to the present, no carcinogenic effects 
have been observed in humans. It is unclear if the rodent studies indicate risks to patients 
taking secnidazole.  
• Alcoholic beverages and preparations containing ethanol or propylene glycol should be 
avoided during secnidazole therapy and for 2 days after treatment is stopped. Nausea, 


 
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vomiting, diarrhea, abdominal pain, dizziness, and headache have been reported when 
secnidazole was taken at the same time as alcohol. 
• Whenever an antibiotic is used, there is potential for the development of drug-resistant 
bacteria. Secnidazole should only be used when an infection is proven or strongly 
suspected. 
 
To reduce the potential for these risks the following measures will be employed: 
• While completing the survey, you can tell the researcher that you feel uncomfortable or 
that you do not want to answer a particular question. 
• Speculum exams will be completed by experienced providers and, whenever possible, it will 
be collected at a time when you are already having a speculum exam. 
• While you are receiving secnidazole, you will be questioned weekly about side effects, and 
you will be monitored utilizing a speculum exam. 
 
There also may be other side effects that we cannot predict. If you become pregnant while you are 
participating in this study, this may include risks to your unborn baby. 
 
WHO WILL PAY FOR MY TREATMENT IF I AM INJURED?  
If you are injured as a result of participating in this study necessary medical treatment will be provided 
to you and billed as part of your medical expenses.  Costs not covered by your health care insurer will 
be your responsibility.  Also, it is your responsibility to determine the extent of your health care 
coverage.  No money or funds are set aside to pay for these types of injuries.  However, you are not 
giving up any legal rights or benefits to which you are otherwise entitled by signing this Informed 
Consent form.   
 
WHAT ARE THE BENEFITS OF TAKING PART IN THE STUDY? 
Participating in this study may reduce the recurrence of your bacterial vaginosis. However, we do not 
know for sure. We are doing this research study to find out if this treatment helps or not. 
 
WILL I BE PAID FOR PARTICIPATION?  
You will be compensated $30 for each study visit you attend. If you are eligible after visit 2 you could 
attend up to 8 study visits for a total of $240. If you develop symptoms of bacterial vaginosis at visits 2 
through 6 you will not be able to continue with study visits. 
 
WILL IT COST ME ANYTHING TO PARTICIPATE?  
There is no cost to you for taking part in this study. Any testing performed that is part of the standard 
evaluation of your symptoms will be billed to you and/or your insurance. Study related testing and 
examinations will not be charged to you. Your provider will explain which parts of your examination 
are standard or study related. 
 


 
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WHAT ARE THE OTHER TREATMENT OPTIONS? 
There may be other options for treatment of your bacterial vaginosis. There are other antibiotic 
therapies and treatment durations available to you should you choose to not participate in this 
research study. 
 
HOW WILL MY INFORMATION AND SPECIMENS BE USED? 
The following individuals and organizations may receive or use your identifiable health information: 
• The researchers and research staff conducting the study 
• The Institutional Review Boards (IRB) or its designees that review this study  
• Indiana University 
• US or foreign governments or agencies as required by law 
• Data safety monitoring boards and others authorized to monitor the conduct of the study  
• The following research sponsors: Lupin Pharmaceuticals, Inc. 
• State or Federal agencies with research oversight responsibilities, including but not limited to:  
o The United States Food and Drug Administration (FDA)  
 
The study sponsor, Lupin Pharmaceuticals, Inc, will access research information to monitor safety and 
progress of the study. 
 
Information and specimens collected for this study may be used for other research studies or shared 
with other researchers for future research. If this happens, information that could identify you, such as 
your name and other identifiers, will be removed before any information or specimens are shared. 
Since identifying information will be removed, we will not ask for your additional consent.  
 
A description of this clinical trial will be available on ClinicalTrials.gov, as required by U.S. law. This 
website will not include information that can identify you. At most, the website will include a summary 
of the results. You can search this website at any time.  
 
HOW WILL MY INFORMATION BE PROTECTED? 
Every effort will be made to keep your personal information confidential, but we cannot guarantee 
absolute confidentiality. No information which could identify you will be shared in publications about 
this study. Your personal information may be shared outside the research study if required by law 
and/or to individuals or organizations that oversee the conduct of research studies. 
 
WHAT WILL YOU DO WITH MY GENETIC INFORMATION? 
We will not use the specimens collected as a part of this study for whole genome sequencing, which 
involves mapping all of your DNA.  
  
 


 
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WHO SHOULD I CALL WITH QUESTIONS OR PROBLEMS? 
For questions about the study or a research-related injury, contact the researcher, Dr. Chemen Neal, at 
317-948-3148. After hours, please call 317-944-8231. 
 
In the event of an emergency, please call 911. 
 
If you are unable to reach the investigator at the above number(s) in an emergency, you may contact 
the University Hospital pharmacy at 317-944-0362 and ask them to page the IDS pharmacist on call. 
 
For questions about your rights as a research participant, to discuss problems, complaints, or concerns 
about a research study, or to obtain information or to offer input, please contact the IU Human 
Research Protection Program office at 800-696-2949 or at irb@iu.edu. 
 
WHAT IF I DO NOT PARTICIPATE OR CHANGE MY MIND? 
After reviewing this form and having your questions answered, you may decide to sign this form and 
participate in the study.  Or you may choose not to participate in the study. This decision is up to you. If 
you choose not to participate in this study or change your mind after signing this document, it will not 
affect your usual medical care or treatment or relationship with Indiana University or University 
Hospital. 
 
If you change your mind and decide to leave the study in the future, the study team will help you 
withdraw from the study safely. If you withdraw from the study, you may experience a recurrence of 
BV symptoms. If you decide to withdraw, notify Dr. Neal via phone or at your next visit to determine if 
additional or alternative treatment will be necessary. You may also contact the study team at 317-948-
3148 or in writing at 550 University Blvd Ste 2440, Indianapolis, IN 46202.  
   
The researchers may stop your participation in the study even if you do not want to stop if you 
experience unexpected side effects such as an allergic reaction or other adverse reaction.  
 
PARTICIPANT’S CONSENT 
In consideration of all the above, I agree to participate in this research study. I will be given a copy of 
this document to keep for my records.  
 
 
 
 
 
 
 
_________________________                   ____ 
Printed Name of Person Obtaining Consent      Date         
 
_______________                              __________   
Signature of Person Obtaining Consent                       
 
_______________________                              __   
Participant’s Printed Name                           Date         
 
__________________                              _______   
Participant’s Signature                                                                 
                       

Prot_000.pdf: 
 
 
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IRB# 10283 
 
 Suppressive Antibacterial Therapy with Once-weekly Solosec®(secnidazole) Oral Granules to Prevent Recurrent 
Bacterial Vaginosis  
Drug Name: Solosec®(secnidazole) Oral Granules, 2 g 
 
 
NCT # 05033743 
Document Date: 06/01/2021 
 
 
 
 
 
 
Chemen M. Neal MD, Associate Professor 
Department of Obstetrics & Gynecology 
550 N. University Ave Suite 2440 
Indianapolis, IN 46202 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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IRB# 10283 
 
STUDY PROTOCOL 
Suppressive Antibacterial Therapy with Once-Weekly Secnidazole Granules to Prevent Recurrent Bacterial 
Vaginosis; a Pilot Study 
 
Chemen M. Neal MD, Assistant Professor 
Department of Obstetrics & Gynecology 
550 N. University Ave Suite 2440 
Indianapolis, IN 46202 
 
Sub-Investigators and their affiliations: 
Jeffrey Peipert, MD, Ph.D., Professor  
Obstetrics & Gynecology 
Indiana University School of Medicine 
 
David Haas, MD, MS, Professor 
Obstetrics & Gynecology 
Indiana University School of Medicine 
 
IRB# 10283 
IND/IDE#: 155940 
 
 


 
 
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IRB# 10283 
 
Table of Contents: 
 
Study Schema 
1.0 
Background & Rationale 
2.0 
Objective(s) 
2.1 
Primary Objective 
2.2 
Secondary Objective 
2.3 
Tertiary/Exploratory/Correlative Objectives 
3.0 
Outcome Measures 
3.1 
Primary Outcome Measures 
3.2 
Secondary Outcome Measures 
3.3 
Tertiary/ Exploratory/ Correlative Outcome Measures 
4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
4.2 
Exclusion Criteria 
5.0 
Study Design 
6.0 
Enrollment/Randomization 
7.0 
Study Procedures 
8.0 
Study Calendar 
9.0 
Reportable Events 
10.0 
Data Safety Monitoring 
11.0 
Study Withdrawal/Discontinuation 
12.0 
Statistical Considerations 
13.0 
Data Management 
14.0 
Privacy/Confidentiality Issues 
15.0 
Follow-up and Record Retention 
16.0 
References 
17.0 
Appendix 
 


 
 
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IRB# 10283 
 
1. Background & Rationale 
Forty to fifty percent of women with vaginal complaints will be diagnosed with bacterial vaginosis (BV) making 
it the most prevalent cause of vaginal symptoms in women nationally. Greater than 50% of women will have a repeat 
episode of BV within 1 year of standard treatment. 1 Recurrent BV, defined as three or more symptomatic episodes within 
1 year, may be associated with multiple treatment failures over periods of several years or months. While there are no 
universally agreed upon treatment protocols for recurrent BV, the current CDC referenced treatment regimens include a 
14-day course of metronidazole or tinidazole followed by twice-weekly or daily nitroimidazole therapy for up to six 
months.2  
Secnidazole is a nitroimidazole antimicrobial indicated for the treatment of bacterial vaginosis in adult women 
with a much longer half-life than both metronidazole and tinidazole. While suppressive therapy can be curative or can 
increase symptom free intervals, patient compliance with complicated and prolonged treatment regimens are barriers to 
successful outcomes. Compared to metronidazole and tinidazole, secnidazole has a much longer half-life (metronidazole 
and tinidazole: 8 hours and 12-14 hours vs. secnidazole: 17-29 hours).   
To date, there are no studies that have evaluated secnidazole for suppressive therapy of recurrent BV.  In a 
randomized double-blind trial, clinical cure and/or symptom improvement rates were similar in women with bacterial 
vaginosis treated with a single dose of secnidazole (90.8%) or tinidazole (87.5%). Data from two non-blinded studies 
indicated that a single dose of secnidazole was at least as effective as 7-day treatment with metronidazole (secnidazole 
73.3 to 93.1%; metronidazole 58.5 to 95.8%). 3  
From this data, it is reasonable to speculate that once weekly dosing of secnidazole for suppressive therapy of 
recurrent BV may be at least as effective as the current more complex therapies and would be a valuable treatment 
alternative to women suffering with recurrent BV due to the more simplified dosing regimen.  
Simplifying suppressive protocols could improve patient compliance and decrease the recurrence of disease. Poor 
adherence increases with longer durations of treatment and studies of compliance rates show that 50% of women do not 
adhere to 5-7 day treatments for BV.4,5 Poor adherence leads to treatment failures and recurring infections and increases 
the potential for resistant organisms.6 Utilizing a drug such as secnidazole, which has a much longer half-life may provide 
an improved therapeutic window for suppression of causative microorganisms and could prevent a recurrence.  
 
2. Objectives 
2.1 Primary Objective. To determine the efficacy and safety of once-weekly oral secnidazole granules for 
suppressive therapy of recurrent BV to previously published efficacy and safety data of multiple-dose 
nitroimidazole suppressive regimens for the treatment of recurrent BV.  
2.2 Secondary Objective. To determine the meantime to recurrence of BV after treatment. 
2.3 Tertiary/Exploratory/Correlative Objectives. To evaluate participant compliance, tolerance, and 
occurrence of adverse events. 
 
3. Outcome Measures/Endpoints 
3.1 Primary Outcome Measures To estimate the efficacy and safety of once-weekly oral secnidazole granules 
for suppressive therapy of recurrent BV and to qualitatively compare to previously published efficacy and 
safety data of multiple-dose nitroimidazole suppressive regimens for the treatment of recurrent BV to aid in 
the design of a larger comparative trial.  
3.1.1 
 Efficacy: The primary efficacy endpoint is failed treatment, defined as having at least 1 episode 
of RBV in the 30 week follow-up period. An episode of RBV (failed treatment) will be diagnosed 
if the subject has a Amsel score of 3 or higher. We will report total number of RBV episodes, 
overall failure rate, and time to failure after initial treatment. We will also report rates of RBV if 
diagnosed as >=1 Amsel criteria is met per FDA recommendations, but the primary outcome will 
be >=2 criteria to be consistent with prior literature and recommendations. 
3.1.2  
3.1.2.1 The Amsel criteria: 
3.1.2.1.1 
Thin, white, yellow, homogeneous discharge 
3.1.2.1.2 
Clue cells on wet mount microscopy 
3.1.2.1.3 
a vaginal fluid pH of over 4.5 when placing the discharge on litmus paper 


 
 
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IRB# 10283 
 
3.1.2.1.4 
Release of fishy odor when adding 10% potassium hydroxide (KOH) solution 
to wet mount - also known as “whiff test.” 
3.1.3 Safety: adverse events via MedDRA criteria. 
3.2 Secondary Outcome Measures Time to recurrence measured by failure rates and time-to-failure. Defined by 
Amsel’s criteria or by Nugent criteria (gram stain results).  To be measured at visit 2 (3-5 days after initial 
treatment), visits 3-6 (week 6, 10, 14, and 18 during suppressive treatment), visits 7 & 8 (22 & 30 weeks after 
initiation of treatment).  
3.3 Tertiary/Exploratory/Correlative Outcome Measures Participant compliance, tolerance, and adverse event 
data to be collected via a patient questionnaire at each visit. The safety of secnidazole was evaluated in five Phase 
1 clinical trials before FDA approval. The five most common treatment-associated adverse events were: 
vulvovaginal candidiasis, headache, nausea, diarrhea, abdominal pain, and vulvovaginal pruritis. We will monitor 
for the frequency and severity of these events and any other subject-related side effects. 
 
4. Eligibility Criteria 
4.1 Inclusion Criteria 
• 
Age 18 -50 
• 
Ability to consent in English 
• 
Current symptomatic bacterial vaginosis infection (> 3 Amsel criteria). 
 
Amsel’s criteria: Homogenous vaginal discharge, vaginal pH >4.5, positive amine odor, and/or 
presence of >20% clue cells /hpf on saline mount microscopy 
• 
History of at least 2 previous episodes of BV in the past 1 year.  
 
Continuation after Second Visit 
• 
Clinical resolution of bacterial vaginosis defined as:  (asymptomatic and < 2 Amsel criteria, will also 
be reported as asymptomatic and < 1 Amsel criteria). 
 
4.2 Exclusion Criteria 
• 
Current gynecologic infection or condition, including candida vaginitis, gonorrhea, chlamydia, 
trichomonas, desquamative inflammatory vaginitis, atrophic vaginitis. 
• 
Pre-existing heart conditions 
• 
Pre-existing neurological conditions 
• 
Currently Pregnant or breastfeeding 
• 
Women taking anticoagulants, lithium, metoclopramide, or disulfiram therapy 
• 
Hypersensitivity to secnidazole or other drugs in the same class. 
 
5. 
Study Design 
A single-center prospective pilot study with once-weekly oral secnidazole granule treatment of an acute condition for two 
weeks followed by prophylactic treatment of asymptomatic responders with once-weekly secnidazole for 16 weeks, 
followed by no therapy for 12 weeks. The final follow-up evaluation is at week 30. 
Eligible women with a current symptomatic bacterial vaginosis infection (> 3 Amsel criteria) and a history of at least 2 
previous episodes of bacterial vaginosis in the past year will be enrolled in the open-label treatment study. All women will 
be treated with 2g of secnidazole granules orally once weekly for 2 weeks. At the second visit, 3-5 days after completion 
of treatment, women who have a clinical resolution of bacterial vaginosis (asymptomatic and <2 Amsel criteria, will also 
be reported as asymptomatic and < 1 Amsel criteria) will continue on once-weekly secnidazole for 16 weeks.  
Patients will be evaluated at week 6, 10, 14, and 18 for recurrence of bacterial vaginosis.  This will include questions 
about symptoms as well as a pelvic examination for assessment of vaginal discharge (> 3 Amsel criteria). We will also 
collect any information on other clinical evaluations for recurrence and the dates of diagnoses and types of treatments they 
may have received. Those who remain without recurrence during the 16-week suppressive phase will be followed for an 
additional 12 weeks off therapy, with assessment for recurrence at weeks 22 and 30. Throughout the study, data will be 
collected on participants’ compliance and on the occurrence of adverse events. 
 
 
 
 


 
 
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IRB# 10283 
 
 
 
Flow diagram: 
 
At Enrollment 
 
 
 
 
Visit 1 
 
 
 
 
 
Visit 2  
 
 
 
Visits 3 – 6 
(wk 6, 10, 14, 18)  
 
 
 
 
 
 
 
 
6. 
Enrollment 
Participants presenting to the IU Coleman Center with a history of recurrent bacterial vaginosis who are currently 
symptomatic will be evaluated for enrollment in the study. Informed consent will be obtained. 
 
7. 
Study Procedures 
At each visit where women are evaluated for BV they will be asked about vaginal discharge. Then they will undergo a 
speculum examination of the vagina similar to pelvic examinations performed clinically at most annual gynecologic 
examinations. Any vaginal discharge present will be collected by a swab for assessment of pH, odor, and presence of clue 
cells on microscopy. The speculum examination should take ~2 minutes. 
At the initial enrollment visit, subjects will be given a point-of-care pregnancy test. If the test is positive, the subject will 
not be placed on study drug, and will receive alternate, traditional suppressive therapy. Women enrolled will be instructed 
in the use of the secnidazole granules by trained study personnel or the medical provider. If a subject becomes pregnant 
during the study, we will terminate study drug for the subject and follow the subject for any adverse pregnancy outcomes 
for safety reporting. The subject will have a basic neurological test at enrollment. 
At follow up visits, women will again be queried about vaginal discharge and will undergo a speculum examination as 
above, even if they do not endorse vaginal discharge. Subject will have a basic neurological test at follow up visits. 
Women will be asked about any adverse side effects of the secnidazole including vaginal irritation, bleeding, redness, or 
itching. If the subject presents with vulvovaginal candidiasis, they will be treated with oral or vaginal fluconazole, per 
patient preference, if they present to the PI, or with the standard of care if they present elsewhere. The treatment will be 
noted. 
If the subject or potential subject has any history of heart disease or disorders of the heart, they will be excluded from 
participation. 
If a study participant has recurrence of bacterial vaginosis while on protocol, the subject will fail study treatment, and will 
be placed on alternate, traditional suppressive therapy. The participant will have completed the study at this point. 
 
 
Total N: 50   
Obtain informed consent. Screen potential participants by inclusion and exclusion criteria.   
Obtain history.  Document. 
Perform baseline assessments 
Symptom assessment, pelvic exam, gonorrhea/chlamydia/trichomonas PCR, pH, UPT, wet mount, whiff test, Gram 
stain, neurological exam  
Dispense 2 packets of 2g dose of Secnidazole granules (will be taken 1 packet weekly for 2 weeks) 
Follow-up assessments of study endpoints and safety 
Symptom assessment, pelvic exam, pH, wet mount, whiff test, Gram 
stain, neurological exam 
Follow-up assessments of study endpoints and safety 
Symptom assessment, compliance assessment, pelvic exam, pH, wet mount, whiff test, Gram stain, 
neurological exam 
Assessment for bacterial vaginosis  
Symptom assessment, pelvic exam, pH, wet mount, whiff test, Gram stain, neurological exam 
If < 1 Amsel criteria, continue to next phase 
Dispense 16 packets of 2g dose of Secnidazole (will be taken 1 packet weekly for 16 weeks)  
3-5 days post treatment 
Every 4 weeks x 16 weeks 
At Visit 6 
Asymptomatic & < 1 
Amsel Criteria 
Visit 7-8  
(week 22, 30) 


 
 
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IRB# 10283 
 
 
 
8. 
Study Calendar 
 
 
Treatment 
Follow Up 
Unscheduled 
Event/Procedure 
Enrollment/V1 
Day 1 
V2 
Day 18 
V3 
Week 6 
 
V4 
Week 10 
 
V5 
Week 14 
 
V6 
Week 18 
 
V7 
Week 22 
 
V8 
Week 30 
 
Unscheduled 
Window 
 
+/- 1 
day 
+/- 5 
days 
+/- 5 
days 
+/- 5 
days 
+/- 5 
days 
+/- 5 
days 
+/- 5 
days 
 
Screening 
x 
 
 
 
 
 
 
 
 
Confirm 
eligibility 
x 
 
 
 
 
 
 
 
 
Informed 
consent 
x 
 
 
 
 
 
 
 
 
Collection of 
MHx 
x 
 
 
 
 
 
 
 
 
Symptom 
Assessment 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Pelvic Exam 
x 
x 
x 
x 
x 
x 
x 
x 
Per SOC 
STI Testing 
SOC 
 
 
 
 
 
 
 
Per SOC 
Whiff test 
x 
x 
x 
x 
x 
x 
x 
x 
Per SOC 
Vaginal pH 
x 
x 
x 
x 
x 
x 
x 
x 
Per SOC 
Wet mount 
x 
x 
x 
x 
x 
x 
x 
x 
Per SOC 
Gram stain 
x 
x 
x 
X 
x 
x 
x 
x 
Per SOC 
Study Drug 
Administration 
x 
X* 
X* 
X* 
X* 
X* 
 
 
 
Med compliance 
assessment 
 
 
x 
x 
x 
x 
 
 
 
*study drug provided to asymptomatic subjects only at V2 - V6. 
 
 
9. 
Reportable Events 
The study is expected to be only slightly greater than minimal risk as the study medications and examinations are those 
that are commonly used during routine clinical care and evaluations. Secnidazole (study drug) has FDA approval for the 
treatment of acute BV with minimal side effects reported.  
 
Any severe adverse effects including unexpected hospitalization due to treatment will be reported per IRB guidelines. Any 
non-severe Adverse Events (“AE”s) such as sensitivity or side effects will be reported in aggregate at annual reviews. 
Expected/common side effects of the examinations are discomfort and irritation. There is a minimal risk of vaginal 
bleeding. Side effects reported with secnidazole include vulvovaginal candidiasis, headache, mild gastrointestinal 
discomfort, and vaginal itching.  
 
An adverse event (“AE”) is defined as any untoward medical occurrence associated with the use of a drug in humans, 
whether or not the event is considered drug-related. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding that is unrelated to the intent of the study), symptom, or disease temporally 
associated with the use of a drug. An adverse reaction means any adverse event caused by a drug. Adverse reactions are a 
subset of all suspected adverse reactions for which there is reason to conclude that the drug caused the event. A suspected 
adverse reaction implies a lesser degree of certainty about causality than an adverse reaction. 
Pre-existing conditions are not considered adverse events unless there is an unexpected change in the frequency, intensity, 
or nature of the condition. A newly diagnosed pregnancy during study enrollment will not be considered an adverse event. 
If a pregnancy occurs during the treatment or maintenance phases of the study, the subject will be asked to discontinue the 
study drug and be terminated from the study. 
 
Pregnancy reports: 
Pregnancy reports of subjects should be forwarded to Lupin Research Inc. This also includes normal pregnancies without 
AE. If a pregnancy occurs during the treatment or maintenance phases of the study, the subject will be asked to 
discontinue study drug and be terminated from the study.   
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. 
Pregnancy follow-up should be conducted until the outcome. 


 
 
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IRB# 10283 
 
The pregnancy reporting procedure should be the same as the Serious AE reporting procedure set out in Section 2.7 of the 
Agreement. 
 
 
Additional Notes on Adverse Events and Serious Adverse Events: 
For the purposes of this study, changes in clinical criteria (i.e. Amsel criteria and/or symptoms) from baseline that are 
associated with BV will be captured on the corresponding case report forms and should not be recorded as an adverse 
event with the following exception: 
• 
If in the investigator/clinician’s opinion a subject treated for BV gets a secondary infection (e.g. yeast infection), 
the yeast infection should be captured as an adverse event. 
Each AE or suspected adverse reaction must be assessed for its seriousness. The term “serious” is not synonymous with 
“severe” that may be used to describe the intensity of an event or reaction. An AE or suspected adverse reaction is 
considered serious if in the view of either the investigator: 
• 
Results in death 
• 
Is life threatening (referring to an adverse event or suspected adverse reaction in which either the investigator or 
the sponsor believes the subject was at risk of death at the time of the event or reaction; it does not refer to an 
event that hypothetically might have caused death if it were more severe). 
• 
Requires inpatient hospitalization or prolongs an existing hospitalization 
• 
Results in a persistent or significant disability/incapacity 
• 
Is considered medically important  
 
Important medical events are those that may not be immediately life threatening but are of major clinical significance and 
may require intervention to prevent one of the other serious outcomes listed above. Examples include a seizure that did 
not require in-subject hospitalization or allergic bronchospasm that needed emergency treatment. 
 
All adverse events or suspected adverse reactions that do not meet the criteria for serious will be regarded as non-serious.  
Definition of Unexpectedness: An adverse event or suspected adverse reaction is considered unexpected if the 
nature/specificity or severity of the event or reaction is not consistent with applicable product information.  
Documentation of Adverse Events: All adverse events (serious and non-serious) that occur from the time informed 
consent is signed through Visit 8 must be reported and recorded in source documentation and the appropriate page(s) of te 
CRF. Information to be documented for each AE includes the following:  
• 
Adverse event term 
• 
Severity of the event (mild, moderate, or severe) 
• 
Start and stop date (if applicable) 
• 
Time of the event if it occurred on the first day of study drug administration 
• 
Relationship to study drug (none, possible, probable, definite) 
• 
Action taken with the study drug (none, study drug interrupted, study drug discontinued) 
• 
Action taken (none, new medication/treatment, termination from study, hospitalization, other) 
• 
Outcome of the event (resolved, resolved with sequalae, ongoing, death, or unknown) 
• 
Whether or not the event meets serious criteria.  
 
If AE signs and symptoms are the result of a specific diagnosis, the diagnosis only (and not the cluster of signs and 
symptoms that make up the diagnosis) should be reported on the CRF.  
Severity criteria: Severity criteria for adverse events will be defined as follows: 
• 
Mild: awareness of signs/symptoms that are easily tolerated causing minimal discomfort and not interfering with 
normal daily activities 
• 
Moderate: Sufficient discomfort is present and may interfere with normal daily activities 
• 
Severe: Extreme distress is present causing significant impairment of functioning or incapacitation preventing 
normal daily activities. 
The investigator should use clinical judgement in assessing the intensity of adverse events not directly experienced by the 
subject (e.g., lab abnormalities). 
Relatedness Criteria: An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable, or definite. Attribution definitions for the relatedness of adverse events will be defined as follows: 
• 
None: An adverse event that is not related to the use of study drug. 


 
 
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IRB# 10283 
 
• 
Possible: An adverse event that might be due to the use of the drug; an alternative explanation (e.g. a concomitant 
drug or illness) is inconclusive. The relationship to time is reasonable. 
• 
Probable: An adverse event that might be due to the use of the drug; an alternative explanation (e.g. a concomitant 
drug or illness) is less likely. The relationship in time is suggestive. 
• 
Definite: An adverse event that cannot be reasonably explained with an alternate explanation (e.g. a concomitant 
drug or illness). The relationship in time is very suggestive. A direct cause and effect relationship between the 
study drug and the adverse event exists. 
 
Serious Adverse Event Reporting: All serious adverse events (SAE) that occur during the trial regardless of their 
relationship to the study drug must be reported to the IRB (and sponsor) as soon as possible but no later than 24 hours 
after learning of the event. A Serious Adverse Event (SAE) Report form must be filed and sent to the sponsor as soon as 
possible. Information included with the initial notification should include as much of the information requested in the 
form as possible. The SAE Report form should not be held up if all the information regarding the SAE is not yet available.   
The Investigator will be responsible for reporting to the regulatory authorities, Lupin and all participating investigators all 
serious adverse events associated with the use of the study drug. The Investigator will report such SAEs using the FDA 
MedWatch form, CIOMS, etc. The Investigator will report safety reports to the IRB and institution in accordance with 
IRB regulations and institutional policies.  
The Investigator will also record all non-serious adverse events and share with Lupin as a part of the final study report. 
When additional/new information regarding the SAE becomes available, an updated SAE Report form should be 
submitted to the sponsor/IRB. Copies of any relevant data from hospital notes (e.g. laboratory tests, discharge summary, 
ECGs, ER records, etc.) should also be submitted when they become available. 
All serious adverse events should be followed and treated appropriately until there is satisfactory resolution of the adverse 
event, the adverse event becomes stable or can be explained by other causes, clinical judgment indicates further evaluation 
is not needed, or it appears unlikely that additional information can be obtained given due diligence has been done.  
Rates of SAE will be examined after the first 5 subjects are completed, then at 10, 20, and 30 subjects. If greater than 25% 
of subjects have an occurrence of a SAE at any of these milestones, the study team will work with the IRB to determine 
whether the trial should stop.  If CTCAE grade 3 or higher events occur, we will consult the IRB and FDA and halt the 
trial if either entity recommends stopping the trial. 
 
10. 
Data Safety Monitoring 
Lupin will perform a monthly reconciliation with the investigator for the SAEs that were shared with Lupin in the given 
month. 
A clinical monitor will perform on-site and/or remote monitoring visits as often as necessary to ensure that all aspects of 
the protocol are followed. Monitors will record their visits on a site visit log that will be kept on-site, and may be recorded 
electronically. During monitoring visits, source documentation will be reviewed for verification of data entered on the 
CRF. Source documents include, but are not limited to, clinic and office charts (paper and/or electronic), laboratory and 
vaginal culture results, Gram stain results, and any electronic records generated from computerized medical record 
systems used at investigational sites that may serve as source documentation for the purposes of this protocol.  
The review of regulatory documents, informed consents, and drug storage and accountability records will also be done 
during monitoring visits. Monitors will meet with the principal investigator periodically throughout the study to provide 
feedback on the study and performance.  
Direct access to source documentation and to the drug storage and dispensing area must be allowed during monitoring 
visits. It is also expected that investigator/study staff will be available to assist the monitor in his/her activities, CRFs will 
be completed, and ICFs, drug accountability, and regulatory records will be available for review. A suitable area should 
be provided for the monitor to work during monitoring visits.  
 
11. 
Study Withdrawal/Discontinuation 
 
All subjects are free to withdraw from participation in the study at any time, and for whatever reason, specified or 
unspecified, and without prejudice. The reason for discontinuation will be entered onto the study termination page of the 
CRF. 
No constraints will be placed on ordinary subject management, and subjects may be placed on other conventional therapy 
upon request or whenever clinically necessary, as determined by the investigator/clinician.  
 
12. 
Statistical Considerations 


 
 
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IRB# 10283 
 
 
As this is a pilot project to determine the rates of recurrence with this therapy, no a priori sample size was calculated. We 
aim to recruit 50 women to determine this rate. That is a similar sample size to other studies in this area. The rates 
determined by this pilot study will be used in sample size calculations for a larger comparative trial.  If the patient 
population behaves similarly to other BV studies, this study can expect to lose 15% immediately after enrollment as a loss 
to follow-up. In similar studies, 25.5% had recurrence of BV at the end of the 16-week maintenance phase. A total of 51% 
had recurrence of BV by the end of the 28-week follow-up phase. In a 50-subject trial, if secnidazole has a similar 
performance, this would yield approximately 21 subjects that have resolved symptoms through the full 30 weeks of 
participation.7 For this pilot study, we anticipate this 50% symptom resolution rate ± 15%. In consideration of this, 21/42 
= 0.50 with 95% CI of 0.34 to 0.66 (exact) at 30 weeks, the half-width would be 0.16.  We will report rates as point 
estimates and 95% confidence intervals. For proportions/rates, we will use exact binomial confidence intervals, and, for 
time to event, we will estimate the confidence intervals using the Kaplan-Meier method. 
 
13. 
Statistical Data Management 
Primary data will be collected via subject self-report and EMR review and stored electronically in REDCap electronic 
CRF.  A backup of the CRF data in REDCap will be saved on a nightly basis to a secure environment maintained by the 
Research Technologies division of University Information Technology Services (UITS)..   
 
Quality assurance steps will include: 
• 
Testing of database prior to being placed into production mode 
• 
Automated range checks. 
• 
Manual verification of any self-reported subject data; clinical notes/ electronic medical 
chart will take precedence over self-reported data, except when overridden by PI or their 
designee. 
• 
Single entry with random checks of accuracy and extraction and cleaning of data that will 
be used for analysis every 6 months. 
 
 
14. 
Privacy/Confidentiality Issues 
Only study staff involved in the study will have access to study records. Subjects will be given a unique subject number 
once they sign consent. All study staff will complete and maintain the required Indiana University training and study-
specific training prior to interacting with subjects.  Study data will be maintained on a secure, password-protected 
REDCap database. 
 
15. 
Follow-up and Record Retention 
We expect to complete study enrollment in 12 months. Subjects will be followed for up to 9 months. Hard copy records 
will be kept in secure areas. Electronic records will be kept on password protected systems. Records will be kept until the 
study ends and follow current guidance. This study utilizes secure IT systems for data gathering, data transfer, data 
management, and analysis. All data transfers are encrypted. Transfers from data sources are governed by an approved 
honest data broker process, ensuring data transfers are in accordance with research protocol and relevant data usage 
agreements. All IT systems used for data gathering, management, and analysis are secure as per HIPAA. Access to patient 
data and research applications is administered to ensure research teams only have access to patient data for which they are 
approved. 
 
16. 
References 
 
1. Allsworth JE, Peipert JF. Prevalence of bacterial vaginosis: 2001-2004 National Health and Nutrition 
Examination Survey data. Obstet Gynecol. 2007;109(1):114-120. 
2. Prevention CfDCa. 2015 Sexually Transmitted Diseases Treatment Guidelines. 2015. 
3. Gillis, J.C., Wiseman, L.R. Secnidazole. Drugs 1996;51, 621–638.. 
4. Pentikis, H., Adetoro, N., Tipping, D. et al. An Integrated Efficacy and Safety Analysis of Single-Dose 
Secnidazole 2 g in the Treatment of Bacterial Vaginosis. Reprod. Sci. 2020;27, 523–528.  
5. Cockburn J, Gibberd R W, Reid A L, Sanson-Fisher R W. Determinants of non-compliance with short term 
antibiotic regimens. Br Med J (Clin Res Ed) 1987;295:814. 
6. Przemyslaw Kardas, Patient compliance with antibiotic treatment for respiratory tract infections, Journal of 
Antimicrobial Chemotherapy  2002;49,897–903. 


 
 
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IRB# 10283 
 
7. Sobel JD, Ferris D, Schwebke J, Nyirjesy P, Wiesenfeld HC, Peipert J, Soper D, Ohmit SE, Hillier SL. 
Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. 
Am J Obstet Gynecol. 2006 May;194(5):1283-9. 

SAP_001.pdf: 
Seconidazole BV 
Sponsor: Lupin Pharmaceuticals, Inc. 
1 | P a g e
Suppressive Antibacterial Therapy with Once-weekly Solosec®(secnidazole) Oral Granules 
to Prevent Recurrent Bacterial Vaginosis  
Drug Name: Solosec®(secnidazole) Oral Granules, 2 g 
NCT # 05033743 
Document Date: 02/17/2023 
Chemen M. Neal MD, Associate Professor 
Department of Obstetrics & Gynecology 
550 N. University Ave Suite 2440 
Indianapolis, IN 46202 


Seconidazole BV 
Sponsor: Lupin Pharmaceuticals, Inc. 
2 | P a g e
1.1. 
Statistical Methods 
To assess the efficacy of secnidazole, we estimated failure rates and 95% exact confidence 
intervals for initial treatment, suppression therapy following initial resolution of BV symptoms, 
and overall. For the time-to-failure analysis, time was defined as the number of days since the 
second visit where clinical resolution of initial BV was confirmed. The non-parametric maximum 
likelihood estimate (NPMLE) of the survival curve was estimated using the interval package in R 
to account for the interval censored data. Results are presented using an Amsel criteria score of 
≥3 as well as ≥1 for BV diagnosis. All analyses were conducted using R 4.2.2 (R Core Team, 
2020) in RStudio (RStudio Team 2021).