Clinical trial NCT03840616
Conditions: Recurrent Vulvovaginal Candidiasis
Sponsor: Mycovia Pharmaceuticals Inc.
Start date: 2019-03-13; Completion date: 2020-12-02
Enrollment: 219 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Recurrent vulvovaginal candidiasis (RVVC), also known as recurrent yeast infections, is defined as at least 3 episodes of acute vulvovaginal candidiasis (VVC) in the past 12 months. Several properties of oteseconazole (VT-1161) suggest it might be a safer and more effective treatment of RVVC than other oral antifungal medications.

This study will evaluate the effectiveness and safety of oteseconazole (VT-1161) for the treatment of acute VVC episodes in patients with RVVC and consists of 2 parts. The first part of the study is a 2-week induction phase for the treatment of the patient's current VVC episode when the patient will take either fluconazole or oteseconazole (VT-1161) according to a random assignment. The second part consists of an 11-week maintenance phase, when the patient will take either oteseconazole (VT-1161) or a placebo according to the random assignment from the first part of the study, and then a 37-week follow-up period.

Detailed description:

Arms: arm 1: 600mg oteseconazole administered on Day 1 and 450mg administered on Day 2, followed by 150mg administered once weekly for 11 weeks staring on Day 14 arm 2: 150mg fluconazole administered every 72 hours in 3 sequential doses starting on Day 1, followed by placebo administered once weekly starting on Day 14
Interventions: intervention 1: Oteseconazole (VT-1161) 150mg capsule intervention 2: Fluconazole 150mg capsule intervention 3: Placebo
Intervention descriptions: intervention 1: 600mg administered on Day 1 and 450mg administered on Day 2, followed by 150mg administered once weekly for 11 weeks staring on Day 14. intervention 2: 150mg administered every 72 hours in 3 sequential doses starting on Day 1. intervention 3: Administered once weekly starting on Day 14.

Protocol documents:
Prot_000.pdf: 
PRS COVER PAGE for PROTOCOL 
 
TITLE: A Phase 3, Randomized, Double-Blind Study to Evaluate the 
Efficacy and Safety of VT-1161 Oral Capsules versus Fluconazole and 
Placebo in the Treatment of Acute Vulvovaginal Candidiasis Episodes in 
Subjects with Recurrent Vulvovaginal Candidiasis (VMT-VT-1161-CL-017) 
 
DATE: 17 January 2019 
 
CLINICALTRIALS.GOV ID: NCT03840616 
 
 


PROPRIETARY INFORMATION: This document and the contents hereof are considered proprietary and confidential information of 
Mycovia Pharmaceuticals, Inc. Disclosure to unauthorized individuals or dissemination, publication or copying is prohibited without the
prior written consent of Mycovia Pharmaceuticals, Inc.
A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and 
Safety of VT-1161 Oral Capsules versus Fluconazole and Placebo in the 
Treatment of Acute Vulvovaginal Candidiasis Episodes in Subjects with 
Recurrent Vulvovaginal Candidiasis
Study Number: VMT-VT-1161-CL-017
Version: 2  
Date of Issue: 17 January 2019
Mycovia Pharmaceuticals, Inc
4505 Emperor Boulevard, Suite 300 
Durham, NC USA 27703 
Confidentiality Statement
This document and the information it contains are confidential and the proprietary property of 
Mycovia Pharmaceuticals, Inc. The information is not to be disclosed or transmitted to any party 
without the written approval of Mycovia Pharmaceuticals, Inc. or its agents, and any such 
unauthorized use or disclosure is expressly prohibited.  




CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
3 
This study is to be performed in accordance with Good Clinical Practice, the ethical principles that 
have their origin in the Declaration of Helsinki, Title 21 of the Code of Federal Regulations, 
Parts 11 (Electronic Records; Electronic Signatures), 50 (Protection of Human Subjects), 
54 (Financial Disclosure by Clinical Investigators), 56 (Institutional Review Boards), and 
312 (Investigational New Drug Application), and International Conference on Harmonisation E6 
(Guideline for Good Clinical Practice). 
 
 
Study Sponsor: 
Mycovia Pharmaceuticals, Inc. 
 
4505 Emperor Boulevard, Suite 300, Durham, NC USA 27703 
 
 
 
 
 
 
Sponsor Contact: 
Stephen Brand, Ph.D. 
 
Senior VP of Clinical Development 
 
4505 Emperor Boulevard, Suite 300, Durham, NC USA 27703 
 
 
 
 
 
 
 
 
Medical Responsible: 
Claude Hughes, M.D., Ph.D. 
Medical Consultant 
4820 Emperor Blvd., Durham, NC USA 27703 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
4 
Investigator’s Statement 
 
I have reviewed the protocol VMT-VT-1161-CL-017 entitled “A Phase 3, Randomized, Double-
Blind Study to Evaluate the Efficacy and Safety of VT-1161 Oral Capsules versus Fluconazole 
and Placebo in the Treatment of Acute Vulvovaginal Candidiasis Episodes in Subjects with 
Recurrent Vulvovaginal Candidiasis” and agree that it contains all the information necessary to 
conduct the study as required. I will conduct the study in accordance with the principles of 
International Conference on Harmonisation, Good Clinical Practice, and the Declaration of 
Helsinki. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, 
including but not limited to, the protocol, case report forms, Investigational Brochure, material 
supplied at investigator meetings, minutes of teleconferences, etc. I agree that such material will 
only be provided as necessary to site personnel involved in the conduct of the study, the 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), regulatory authorities, or 
agencies as required by local law. 
I will obtain written informed consent or assent (for those ages 12-17) from each prospective study 
subject or each prospective study subject’s legal representative prior to conducting any protocol-
specified procedures. The consent form used will have the approval of the IRB/IEC. 
I will maintain adequate source documents and record all observations, treatments, and procedures 
pertinent to study subjects in their medical records. I will accurately complete the case report forms 
supplied by the Sponsor in a timely manner. I will ensure that my facilities and records are 
available for inspection by representatives of the Sponsor, the IRB/IEC, or other applicable 
regulatory authorities. I will ensure that my staff and I are available to resolve queries and meet 
with representatives of the Sponsor during regularly scheduled monitoring visits. 
I will notify the Sponsor within 24 hours of any serious adverse events. Following this notification, 
a written report describing the serious adverse event will be provided to the Sponsor within 1 
business day following the initial notification. 
I acknowledge that I am responsible for the overall study conduct, and I agree to personally 
conduct and/or supervise the study. I will ensure that all associates, colleagues, and employees 
assisting in the conduct of the study, are informed and trained as necessary about their obligations 
and that there are adequate mechanisms in place for the site staff to receive the appropriate 
information throughout the study. 
 
 
 
 
 
Name 
 
 
 
 
 
Signature 
 
Date 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
5 
PROTOCOL SYNOPSIS 
Title of Study: A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of 
VT-1161 Oral Capsules versus Fluconazole and Placebo in the Treatment of Acute Vulvovaginal 
Candidiasis Episodes in Subjects with Recurrent Vulvovaginal Candidiasis 
Protocol Number: VMT-VT-1161-CL-017 
Interim Analysis: No 
Investigational Medicinal Product: VT-1161 capsules 
Non-Investigational Medicinal Product: Fluconazole tablets 
Planned Number of Sites: Approximately 45 U.S.  
Planned Number of Subjects: 360 screened; 180 randomized 
Phase of Development: 3 
Introduction: 
VT-1161 is an orally-available inhibitor of fungal CYP51 that has shown high potency and selectivity in 
in vitro studies.  VT-1161 blocks the production of ergosterol, an essential component of the fungal cell 
membrane, which is critical to fungal growth.  In vitro and in vivo pharmacology studies have 
demonstrated that VT-1161 is highly active against Candida albicans, including fluconazole-resistant 
C. albicans, and non-albicans Candida species that cause vulvovaginal candidiasis (VVC).  VT-1161 is 
highly selective for fungal CYP51 relative to off-target human CYP enzymes, and data to date suggest 
that it may avoid the side-effect profile that limits the use of commonly prescribed azole antifungal 
agents. 
Oral VT-1161 has been evaluated in Phase 1 and 2 studies and shown to be safe, well tolerated, and 
highly effective in the treatment of vulvovaginal infections caused by Candida species.  For example, in 
a Phase 2b study in subjects with recurrent VVC (RVVC), subjects in the 12-week VT-1161 treatment 
group (150 mg VT-1161 once daily for 7 days followed by 150 mg VT-1161 once weekly for 11 weeks) 
showed a 4.8% recurrence rate through Week 48 compared with a 52% recurrence rate in the placebo 
group in the intent-to-treat analysis.  
RVVC, defined as 3 or more acute VVC episodes over a 12-month period, is experienced by 5 to 
7 million women each year in the US.  Candida albicans is the leading cause of recurrent vulvovaginal 
yeast infections in the United States.  However, there has been an increasing trend in the number of 
vaginal yeast infections attributable to non-albicans species such as C. glabrata and C. tropicalis.  In 
addition to the use of topical products to treat VVC, the majority of the women visiting healthcare 
professionals receive fluconazole for the treatment of each acute episode.  A smaller percentage are 
prescribed a fluconazole maintenance regimen although fluconazole is not currently approved for the 
treatment of RVVC.  Since some of the C. albicans and the majority of non-albicans isolates are resistant 
to fluconazole, the management of RVVC has become even more challenging.  
In both nonclinical studies and clinical trials conducted to date, VT-1161 has demonstrated a favorable 
safety and tolerability profile, with no discernable adverse effect on liver function.  In reproductive 
toxicity studies in pregnant rats or rabbits, VT-1161 was not teratogenic at any exposure studied.  In a 
recent CYP3A4 drug-drug interaction study utilizing midazolam as the substrate, no clinically significant 
inhibition and only weak induction of midazolam metabolism was observed.  These data are favorable 
when compared to other oral antifungal agents such as fluconazole.  This study is to evaluate the efficacy 
and safety of VT-1161 compared to fluconazole in treating acute VVC infections in RVVC subjects. 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
6 
Objectives: 
Primary:  
• 
To evaluate the efficacy of oral VT-1161 in the prevention of culture-verified acute episodes 
of VVC through Week 50 in RVVC subjects. 
• 
To compare the efficacy of oral VT-1161 and fluconazole in the treatment of an acute VVC 
episode in RVVC subjects. 
Secondary:  
• 
To evaluate the safety and tolerability of oral VT-1161 through Week 50. 
Methodology: 
Study Design: 
This is a Phase 3, multicenter, randomized, double-blind study to evaluate the efficacy and safety of 
VT-1161 oral capsules versus fluconazole in the treatment of acute vulvovaginal candidiasis episodes in 
subjects with recurrent vulvovaginal candidiasis.  In addition, the study will evaluate the efficacy of oral 
VT-1161 compared to placebo in the prevention of RVVC through Week 50 after treating the acute 
episodes of VVC with treatment of VT-1161 or fluconazole.  Approximately 180 subjects will be 
randomized, 120 subjects in the VT-1161 arm and 60 subjects in the fluconazole and placebo arm. 
Subjects must have a history of RVVC, defined as at least 3 episodes of acute VVC in the past 12 months, 
as described below: 
• 
Subjects must have an acute VVC episode at the time of Screening, with a documented positive 
potassium hydroxide (KOH) performed at the investigative site 
• 
Subjects must also have had 2 or more additional episodes of acute VVC in the past 12 months, 
with at least 1 of the episodes documented by a positive confirmatory laboratory test (i.e., culture, 
PCR, Affirm test, KOH test, a documented Papanicolaou (Pap) test, or other approved diagnostic 
tests) 
Subjects must also have an acute VVC episode at Screening, defined as a total signs and symptoms score 
of ≥3. 
The study consists of two Phases:  
1) an Induction Phase for the treatment of the acute VVC episode in which subjects will be randomized 
to receive one of the following: 
• 
600 mg VT-1161 (4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) 
on Day 2, or  
• 
3 sequential 150 mg oral doses (every 72 hours) of over-encapsulated fluconazole. 
2) a Maintenance Phase in which subjects initially randomized to receive VT-1161 in the Induction Phase 
will receive 150 mg VT-1161 (1 x 150 mg capsule) weekly for 11 weeks and will then enter a 37-week 
follow-up period.  Subjects randomized to receive over-encapsulated fluconazole in the Induction Phase 
will receive placebo weekly for 11 weeks and will then enter a 37-week follow-up period. 
Once subjects have provided informed consent or assent (for those ages 12-17) the investigational site 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
7 
will evaluate all subjects by completing a review of pertinent medical history, obtaining vital signs, 
weight and height, electrocardiogram (ECG) and laboratory tests, reviewing clinical signs and symptoms 
of vulvovaginitis, performing a complete physical examination including speculum examination of the 
vagina, performing a KOH wet mount test from a vaginal smear to confirm the presence of yeast, and 
collecting vaginal swabs to establish a baseline culture for identification of fungal species.  Eligible 
subjects must have an acute VVC episode at Screening, defined as a total signs and symptoms score of 
≥3 and a positive local KOH wet mount preparation from a vaginal smear revealing filamentous 
hyphae/pseudohyphae and/or budding yeast cells, and must meet other initial entry criteria.  Once 
eligibility is confirmed, subjects will be randomized to enter the Induction Phase.  
At Screening (Day 1), subjects presenting with an acute infection and meeting all study eligibility criteria 
will enter the Induction Phase where they will be randomized 2:1 ratio to receive either 600 mg VT-1161 
(4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) on Day 2, or 3 sequential 
150 mg oral doses (every 72 hours) of over-encapsulated fluconazole.  Subjects will return approximately 
14 days after the first dose of VT-1161 or over-encapsulated fluconazole to determine if the acute VVC 
infection has resolved (defined by a signs and symptoms score of <3).  If the acute VVC has not resolved, 
the subject will be considered a screen failure and encouraged to see their physician for follow-up care. 
All subjects in which the acute VVC infection has resolved will continue into a Maintenance Phase. 
Subjects initially randomized to receive VT-1161 in the Induction Phase will receive 150 mg VT-1161 
(1 x 150 mg capsule) weekly for 11 weeks and will then enter a 37-week follow-up period.  Whereas 
subjects randomized to receive over-encapsulated fluconazole in the Induction Phase will receive 
placebo weekly for 11 weeks and will then enter a 37-week follow-up period. 
Subject’s Day 1 (Screening) is defined as the first day of investigational medicinal product (IMP) 
administration and subsequent study days are defined by the number of consecutive days thereafter.  
Subject’s Day 14 is defined as the first day of weekly dosing of IMP administration.  
Study Duration: 
The study duration is expected to be approximately 18 months from screening of the first subject until 
last follow-up of the last subject. 
Subject Participation: 
The duration of individual subject participation will be approximately 50 weeks.  See Table 1 for the 
Schedule of Assessments and Procedures which will be performed.  After Screening, subjects will return 
to the clinic on Day 14 (±2 days), the start of the Maintenance Phase.  Subjects will then have visits on 
Weeks 8 (±7 days), 14 (±14 days) (end of treatment [EOT]), 20 (±14 days), 26 (±14 days), 32 (±14 days), 
38 (±14 days), 44 (±14 days) and 50 (±14 days) (end of study [EOS]).  Subjects who return to the clinic 
for a recurrent acute VVC episode should be evaluated as per the unscheduled visit noted in the Schedule 
of Assessment and Procedures.  
 
 
 
 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
8 
Scoring of Vulvovaginal Signs and Symptoms: 
Vulvovaginal signs and symptoms will be evaluated at Screening and at each subsequent study visit. 
Each of the following vulvovaginal signs and symptoms will be scored and the individual scores 
combined, for a maximum score of 18 using the following scale: 
a. Signs: erythema, edema, and excoriation 
b. Symptoms: itching, burning, and irritation 
 
Scoring Scale: Each score should be graded on a scale of 0 to 3 as follows: 
0 = none (complete absence of any sign or symptom) 
1 = mild (slight) 
2 = moderate (present) 
3 = severe (marked, intense) 
 
Mycology Assessment: 
A local mycological assessment using KOH wet mount followed by microscopy will be evaluated at the 
Screening (Day 1) and at any study visit where a recurrent acute VVC episode is suspected.  In addition, 
a vaginal swab for culture testing will be obtained and sent to the central mycology laboratory at the 
Screening and each subsequent study visit. 
Plasma Pharmacokinetics: 
Blood samples for assay of VT-1161 plasma concentrations will be collected from subjects at Day 14, 
Week 14 and Week 50 visits. 
Intense sampling will be obtained from approximately 12 consenting subjects at participating sites on 
Day 1 and on Day 2, at time points predose and 1, 2, 4, and 8 hours after dosing.   
Safety: 
Subject safety will be monitored by collection of adverse events (AEs), changes in vital signs, physical 
and vaginal exam parameters, ECGs, and safety laboratory parameters, including pregnancy tests for 
women of childbearing potential (WOCBP). 
Concomitant Medications: 
The following prescription and over-the-counter drug products are prohibited during the study and will 
be considered a protocol deviation: 
1. Topical or oral antifungal drugs (with the exception of fluconazole when prescribed by the 
Investigator to treat a subject with a recurrent VVC episode.  If subject fails to respond to 
fluconazole treatment, the Investigator may employ treatment options corresponding to the site’s 
standard of care treatment to treat the infection upon consult with the Medical Monitor.)  
2. Topical products applied to the vulva or vagina (e.g. antibiotic, antitrichomonal, corticosteroids, or 
anti-inflammatory agents). 
3. Oral antibacterial or antitrichomonal agents for the treatment of bacterial vaginosis, trichomonas, 
or other concomitant urogenital infection unless prescribed by the Investigator. 
4. Oral or injectable corticosteroid or immunosuppressive drugs for the duration of the study. Use of 
topical (no vulvar or vaginal steroids), inhaled, ophthalmic, or intraarticular and intralesional 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
9 
steroids is permitted. 
5. Drugs with a narrow therapeutic index that are metabolized by CYP3A4 and sensitive to induction 
of CYP3A4 (carbamazepine, cyclosporine, fentanyl, quinidine, sirolimus and tacrolimus). 
Number of Subjects (Planned):  
Approximately 180 randomized subjects are planned for this study.  Assuming a 20% discontinuation 
rate for the duration of the study, approximately 144 subjects are expected to complete the study. 
Criteria for Inclusion and Exclusion: 
Criteria for Inclusion: 
1. Subjects must be generally healthy, post-menarchal females 12 years of age and older as of 
Screening (Day 1). 
2. Subjects must have a history of recurrent VVC as defined by three (3) or more episodes of acute 
VVC in the past 12 months, including the episode confirmed at Screening, with at least one episode 
(not including the current episode) documented by a positive culture, PCR, Affirm test, KOH test, 
or a documented Pap test in the prior 12 months revealing filamentous hyphae/pseudohyphae 
and/or budding yeast cells. 
3. Subjects must have an acute VVC episode at Screening, defined as a total signs and symptoms 
score of ≥3 and a positive KOH wet mount preparation from a vaginal smear revealing filamentous 
hyphae/pseudohyphae and/or budding yeast cells. 
4. Subjects must have a composite vulvovaginal signs and symptoms score of <3 at the Day 14 Visit. 
5. Subjects must have a documented Pap test results at Screening or within the current standard of 
care guidelines for the appropriate age requirement, reported as either “negative for intraepithelial 
lesion or malignancy” or “ASCUS-atypical squamous cells of undetermined significance” (not 
applicable to subjects with a history of total hysterectomy). 
6. Subjects must be suitable candidates for oral therapy and be able to swallow capsules intact.  
7. Subjects must be willing and able to provide written informed consent or assent (for those ages 12-
17) and authorization for use of protected health information. 
8. Subjects must be willing and able to comply with protocol requirements, instructions, and protocol-
stated restrictions and be likely to complete the study as planned. 
9. Subjects of non-childbearing potential must meet the requirements defined below: 
a. Pre-menopausal with documentation of surgical sterilization (i.e., hysterectomy, bilateral 
tubal ligation, bilateral oophorectomy, or bilateral salpingectomy) at least 3 months prior to 
study entry.  
b. Post-menopausal defined as amenorrhea for at least 12 months following cessation of all 
exogenous hormonal treatments at Screening. 
10. Subjects of childbearing potential (includes ages 12-17) must use 1 of the following methods of 
contraception during the study through Week 50: 
OPTION 1 - Highly effective methods that can be used alone: 
1. 
Copper intrauterine device used continuously and successfully for at least 
90 days prior to first dose of study druga 
2. 
Levonorgestrel-releasing intrauterine system used successfully for at least 
90 days prior to first dose of study druga 
3. 
Progestin implant used successfully for at least 90 days prior to first dose 
of study druga 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
10 
4. 
Monogamous with a vasectomized male partner (vasectomy performed at 
least 6 months prior to first dose of study drug)a 
5. 
Abstinenceb 
OPTION 2 – Acceptable first and second barrier methods to be used in combination: 
FIRST (Hormonal Contraception)a 
1. Estrogen & progestin oral contraceptives, transdermal patch or vaginal ring 
used successfully for at least 90 days prior to first dose of study drug 
2. Progestin only oral contraceptives or injection used successfully for at least 
90 days prior to first dose of study drug 
SECOND (Barrier Method) 
1. Diaphragm (with spermicide) 
2. Cervical cap (with spermicide) 
3. Male condom (with or without spermicide) 
 
In addition to OPTIONS 1 and 2, subjects of childbearing potential (includes ages 12-17) may 
also use 1 of the following methods of contraception after completing the Induction Phase on 
Study Day 14 through Week 50: 
OPTION 3 (Day 14 – Week 50)c – Acceptable first and second barrier methods to be used in 
combination: 
FIRST (Barrier Method) 
1. Diaphragm (with spermicide) 
2. Cervical cap (with spermicide) 
SECOND (Barrier Method) 
1. Male condom (with or without spermicide) 
a Subjects who started using an intrauterine device or any of the hormonal contraceptive methods 
described above less than 3 months prior to the first dose of study medication must agree to use a double-
barrier method (i.e., diaphragm plus spermicide or condom) through 3 months after start of the use of the 
IUD or hormonal contraceptive. Similarly, subjects that claim a monogamous relationship with a 
vasectomized male partner where the vasectomy was performed less than 6 months prior to the first dose 
of study medication, must agree to use a double-barrier method (i.e., diaphragm plus spermicide or 
condom) through 6 months after the date of the vasectomy.  
b Sexual abstinence is defined as refraining from heterosexual intercourse during the entire study period 
and where this is the usual life style of the subject. Periodic abstinence (calendar, symptothermal, 
postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method are not considered to be acceptable methods of contraception. 
c Because of the teratogenic risk associated with repeat dosing of fluconazole, OPTION 3 contraceptive 
methods cannot be used during Screening and the Induction Phase of the study [from Screening (Day 1) 
until Day 14 of the study].   
 
Criteria for Exclusion: 
1. Subjects must not have the presence of concomitant vulvovaginitis caused by other pathogens (e.g., 
bacterial vaginosis, Trichomonas vaginalis, Chlamydia trachomatis, or Neisseria gonorrhoeae) at 
Screening (Day 1) visit. 
2. Subjects must not have an active HPV infection as evidenced by visible condylomas on 
vulvovaginal examination at Screening (Day 1) visit. 
3. Subjects must not have the presence or a history of another vaginal or vulvar condition(s) that in 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
11 
the Investigator’s opinion would confound the interpretation of clinical response. 
4. Subjects must not have a history of cervical cancer.  
5. Subjects must not use any systemic (e.g., oral or injectable) corticosteroid therapy during the study 
or within 30 days prior to Screening visit; nor use of topical vulvar or vaginal steroids during the 
study or within 7 days prior to Screening visit. However, use of topical (no vulvar or vaginal 
steroids), inhaled, ophthalmic, collunarium/nasal, intraarticular and intralesional steroids is 
permitted.  
6. Subjects must not use any systemic (e.g., oral or injectable) or topical (applied to the vulva or 
vaginal area) antifungal, antibacterial, or antitrichomonal drugs for the treatment of bacterial 
vaginosis, trichomonas, or other concomitant urogenital infection during the study (unless 
prescribed by the Investigator) or within 7 days prior to Screening. 
7. Subjects must not be using drugs with a narrow therapeutic index that are metabolized by CYP3A4 
and sensitive to induction of CYP3A4 during the study (carbamazepine, cyclosporine, fentanyl, 
quinidine, sirolimus and tacrolimus). 
8. Subjects must not use any vaginal estrogen replacement therapy, ospemifene, Vitamin E gel 
capsules (vaginally) or lubricants within 7 days prior to Screening. 
9. Subjects must not have a condition that would require treatment during the study with concomitant 
topical (applied to vulva and vagina) or systemic antimicrobial therapy for any reason. 
10. Subjects must not have received an immunosuppressive medication (e.g. cyclosporine, tacrolimus, 
methotrexate, 6-mercaptopurine, mycophenolate, etc.), or radiation therapy within 3 months prior 
to Screening or have a medical condition where it would be likely that the subject may need to use 
these therapies during the study. 
11. Subjects must not have evidence of any clinically significant major organ disease or current 
clinically significant infection or any other conditions (with the exception of acute VVC) that may 
affect the clinical assessment of RVVC per investigator judgment. 
12. Subjects must not have any comorbid condition that in the opinion of the Investigator would 
preclude the safe participation of the subject in the study or would prevent the subject from meeting 
the study requirements. 
13. Subjects must not have any condition that in the opinion of the investigator could impact drug 
absorption (e.g. gastrectomy, Roux-en-Y gastric bypass surgery, gastric bands or staples, etc.), 
distribution, or elimination. 
14. Subjects must not have poorly controlled diabetes mellitus (HbA1c ≥8.5% at Screening; performed 
only on known diabetics or subjects suspected to have diabetes by the investigative site).  
15. Subjects must not have moderate or severe hepatic and/or renal disease (defined in Appendix B 
and Appendix C). 
16. Subjects must not have a laboratory abnormality that in the opinion of the Investigator is likely to 
introduce additional risk to the subject or might interfere with data interpretation. The specific 
findings listed below are excluded at Day 1 (a single repeat laboratory evaluation is allowed for 
eligibility determination, except for HIV, HBsAg and antibodies to hepatitis C virus): 
a. Serum alanine aminotransferase (ALT) ≥2.0x the upper limit of normal (ULN) of the 
reference range.  
b. Serum aspartate aminotransferase (AST) ≥2.0x the ULN of the reference range.  
c. Serum total bilirubin ≥1.5x the ULN of the reference range, unless the elevation is consistent 
with Gilbert’s Syndrome.  
d. Electrocardiographic QTc interval >470 msec as corrected by the Fridericia formula, or any 
clinically significant electrocardiographic abnormality. 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
12 
e. Positive test for antibodies to human immunodeficiency virus (HIV), hepatitis B surface 
antigen (HBsAg), or antibodies to hepatitis C virus. 
17. Subjects of childbearing potential must not be pregnant (positive pregnancy test at Screening), 
lactating, or planning to become pregnant during the study period. 
18. Subjects must not have planned surgery or other medical procedures that in the Investigator’s 
opinion would impact compliance with the protocol. 
19. Subjects must not have active substance abuse (e.g., drugs of any kind, including alcohol) or any 
other medical, psychiatric or social condition that in the Investigator’s opinion would preclude 
compliance with the protocol.   
20. Subjects must not have received VT-1161 study medication in a previous study. 
21. Subjects must not have received any IMP in a clinical trial within 5 half-lives of that IMP prior to 
Screening (if unknown, 60 days prior to Screening). 
22. Subjects must not have a known history of intolerance or hypersensitivity to azole antifungal drugs 
(e.g., fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole), or any excipients 
of the capsule formulation. 
Induction Treatment Phase 
Investigational Medicinal Product: VT-1161 150 mg capsules 
Dose and Mode of Administration:  
Oral administration of 600 mg VT-1161 (4 x 150 mg capsules) on Day 1, and 450 mg VT-1161 (3 x 150 
mg capsules) on Day 2. 
Oral administration of IMP within 30 minutes after ingestion of the subject’s main meal of the day (as 
determined by the subject and kept consistent throughout the duration of the study).  Approximately 240 
mL (approx. 8oz) of water is to be consumed with each dose of IMP. 
 
Placebo capsules matching the VT-1161 capsules will be administered on Day 1 (4 capsules) and Day 2 
(3 capsules) to maintain study blind for those subjects randomized to the fluconazole treatment arm. 
 
Investigational Medicinal Product: Fluconazole 150 mg tablets, over-encapsulated  
Dose and Mode of Administration:  
Oral administration of 3 sequential doses (every 72 hours) of fluconazole 150 mg starting on Day 1. 
Oral administration of IMP within 30 minutes after ingestion of the subject’s main meal of the day (as 
determined by the subject and kept consistent throughout the duration of the study).  Approximately 240 
mL (approx. 8oz) of water is to be consumed with each dose of IMP. 
 
Placebo capsules matching the over-encapsulated fluconazole IMP will be administered on Day 1, 4 and 
7 to maintain study blind for those subjects randomized to the VT-1161 treatment arm.  
 
Maintenance Treatment Phase 
Maintenance Phase Test Product: VT-1161 150 mg capsules 
Dose and Mode of Administration:  
Oral administration of VT-1161 within 30 minutes after ingestion of the subject’s main meal of the day 
(as determined by the subject and kept consistent throughout the duration of the study).  Approximately 
240 mL (approx. 8oz) of water is to be consumed with each dose of IMP. 


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Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
13 
Starting on Day 14, VT-1161 150 mg (1 capsule) will be given once weekly for 11 weeks. 
Duration of Administration: 11 weeks 
Maintenance Phase Reference Product: Matching Placebo capsules 
Dose and Mode of Administration:  
Oral administration of placebo within 30 minutes after ingestion of the subject’s main meal of the day 
(as determined by the subject and kept consistent throughout the duration of the study).  Approximately 
240 mL (approx. 8oz) of water is to be consumed with each dose. 
Starting on Day 14, placebo (1 capsule) will be given once weekly for 11 weeks. 
Duration of Administration: 11 weeks 
Study Populations: 
Intent-to-Treat (ITT) Population: All randomized subjects. 
Safety Population: All randomized subjects who received at least 1 dose of study drug.  
Per Protocol Population (PP): All randomized subjects who had the following:  
• 
Had no deviations to inclusion/exclusion criteria that could impact treatment outcome. 
• 
Were compliant with the assigned study treatment, defined as ≥80% compliance during the 
Induction Phase and ≥50% compliance during the Maintenance Phase. 
• 
Had the Week 50 visit completed within the acceptable time window (±14 days). 
• 
Had no major protocol violations that would impact treatment outcome. 
Modified ITT: All enrolled subjects who had the following: 
• 
Positive KOH at Screening. 
• 
Positive culture at Screening. 
• 
Negative culture at Day 14. 
Criteria for Evaluation:  
Efficacy: 
Clinical and mycological assessments will be conducted as outlined in Table 1. 
Schedule 
of 
Assessments and Procedures. 
All efficacy analyses will be performed on the ITT, PP, and mITT Populations. 
The primary efficacy outcome measure is the proportion of subjects with one or more culture-verified 
acute VVC episodes (post-randomization through Week 50) in the ITT population, which will include 
the subjects who failed clearing their infection during the Induction Phase. An acute VVC episode 
(considered a recurrent episode) is defined as a positive culture for Candida species and a clinical signs 
and symptoms score of ≥3. 
The key secondary efficacy outcome measures include the following: 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
14 
a. The proportion of subjects with resolved acute VVC infections (clinical signs and symptoms 
score of <3) at Day 14 following treatment with VT-1161 or fluconazole. 
b. The proportion of subjects with at least one culture-verified acute VVC episode with signs and 
symptoms of ≥3 during the Maintenance Phase (post Day 14 through Week 50). 
c. Time to first recurrence of a culture-verified acute VVC episode with signs and symptoms score 
≥3 during the Maintenance Phase (post Day 14 through Week 50). 
d. The proportion of subjects with at least one positive culture for Candida during the Maintenance 
Phase. 
Safety: 
All safety analyses will be performed on the Safety Population.  AEs will be collected throughout the 
study.  Physical and vaginal examination findings and vital signs will be recorded at Screening and 
throughout the study per Table 1. 
Schedule 
of 
Assessments 
and 
Procedures.  
ECGs and safety laboratory tests (hematology, chemistry, and urinalysis) will be obtained throughout 
the study. All concomitant medications taken during the period from 30 days prior to Screening through 
the Week 50 (EOS) visit will be recorded in the case report form (CRF).  Pertinent and all major medical 
conditions will be recorded on the Medical History CRF.    
Subjects who want to discontinue from the study should be encouraged to remain in the study for all 
remaining visits through Week 50 for safety and efficacy assessments.  All subjects who discontinue 
early from the study should have all EOS procedures performed on the day of discontinuation.  
Statistical Methods and Data Analysis:  
A statistical analysis plan will be finalized before 50% of subjects are enrolled. 
Efficacy Analysis: 
The statistical objectives of this study will be: 
1. To determine if there is a difference in the proportions of subjects with one or more episodes of 
culture-verified acute VVC in those receiving VT-1161 compared to those receiving placebo  
2. To determine if there is a difference in the ability of VT-1161 and fluconazole to resolve acute 
episodes in subjects with RVVC. 
A sample size of 82 subjects in the VT-1161 arm and 41 subjects in the fluconazole/placebo arm provides 
at least 90% power to detect a treatment difference between the VT-1161 treatment group and the 
fluconazole /placebo treatment group with a type 1 error rate of 0.05.  Sample size calculation assumes 
50% of the subjects in the placebo arm will have at least one culture-verified acute VVC episode post-
randomization through Week 50. For the first key secondary endpoint, the proportion of subjects with 
resolved acute VVC infections (clinical signs and symptoms score of <3) at Day 14 following treatment 
with VT-1161 or fluconazole,  a sample size of 120 subjects in the VT-1161 arm and 60 subjects in the 
fluconazole/placebo arm provides at least 88% power to detect non-inferiority between the VT-1161 
treatment group and the fluconazole treatment group with a non-inferiority margin of 15% and a type 1 
error rate of 0.05. The sample size calculation assumes that 90% of the subjects in the fluconazole arm 
will resolve their acute VVC infection by Day 14. 
For the efficacy analyses, missing values for the investigator’s assessment of clinical signs and symptoms 
or the culture result will be imputed using the method of multiple imputation.  For subjects who 
discontinue the study early and have missing assessments for all visits after discontinuation, the missing 


CONFIDENTIAL 
 
Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
Protocol Synopsis 
Protocol VMT-VT-1161-CL-017 
IND 111675 
Version 2, 17 January 2019 
 
15 
values for the expected scheduled visits will be imputed using the method of multiple imputation.  
The missing values will be imputed using the following auxiliary information: region, treatment, baseline 
BMI, baseline age, ethnicity, and visit.   
A chi-square test will be used to compare the proportion of subjects with one or more culture-verified 
acute VVC in those receiving VT-1161 compared to those receiving fluconazole and placebo.  The 
proportion of subjects who have cleared their infection at Day 14 in those receiving VT-1161 will be 
evaluated for non-inferiority versus those receiving fluconazole utilizing a non-inferiority margin of 
15%. 
Safety Analysis: 
AEs will be coded using the Medical Dictionary for Regulatory Activities® dictionary.  The number and 
percentage of subjects reporting treatment-emergent AEs will be tabulated by system organ class, 
preferred term, and greatest severity with a breakdown by treatment group.  Mean changes from pre-
treatment in vital signs, ECG, and clinical laboratory variables will be summarized by treatment group. 
Pharmacokinetics: 
No formal statistical hypothesis testing related to pharmacokinetics will be conducted.  VT-1161 
concentrations will be presented by visit with descriptive statistics.  The pharmacokinetic data will be 
used in a cross-population pharmacokinetic analysis that will be presented in a separate report. 
Blood samples for assay of VT-1161 plasma concentrations will be collected from subjects prior to IMP 
on Day 14 and Week 14 and at Week 50. Intense sampling will be obtained only from consenting subjects 
at participating sites on Day 1 and Day 2 (predose and 1, 2, 4, and 8 hours after dosing, with ±10-minute 
window per timepoint).   




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Product: VT-1161  
 
Protocol VMT-VT-1161-CL-017 
IND 111675 
       Version 2, 17 January 2019 
 
17 
a. 
All medication taken 30 days prior to Screening and all non-pharmacologic treatments received 72 hours prior to Screening will be recorded through the EOS 
visit. 
b. Weight only. 
c. 
Vital signs include sitting heart rate, blood pressure, temperature, and respiratory rate.  
d. Limited physical examination, i.e. vaginal speculum examination plus a symptom directed physical examination. 
e. 
Subjects participating in the intense Day 1 and Day 2 PK collection will have samples taken predose and 1, 2, 4, and 8 hours after dosing.  All subjects will 
have PK draws prior to IMP on Day 14 and Week 14 and at Week 50. 
f. 
Serum chemistry (creatinine, BUN, AST, ALT, alkaline phosphatase, total bilirubin, conjugated bilirubin, albumin, total protein, total carbon dioxide, glucose, 
sodium, potassium, chloride, calcium, and phosphorus, creatine phosphokinase [CK], cholesterol and triglycerides). Testing for HbA1c is performed only in 
known or suspected diabetic subjects at Screening. Cultures to test for Chlamydia trachomatis and Neisseria gonorrhoeae will be taken at Screening and sent 
to the central lab. Testing for bacterial vaginosis will be done locally at Screening. An OSOM® Rapid test or similar test will be performed for Trichomonas 
vaginalis locally at Screening. 
g. For WOCBP, a local lab urine and central lab serum pregnancy test will be obtained at the Screening Day 1 visit. A central lab serum pregnancy test will be 
performed at Weeks 14, 26, and 50. 
h. IMP is to be administered within 30 minutes after the subject’s main meal of the day (as determined by the subject) at approximately the same time of the day 
consistently throughout the study. Approximately 240 mL (approx. 8 oz.) of water is to be consumed with each dose of IMP.  
Subject will be randomized to receive either 600 mg VT-1161 (4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) on Day 2 followed 
by 11 weekly doses of 150 mg VT-1161, or 3 sequential 150 mg oral doses (every 72 hours) of over-encapsulated fluconazole followed by 11 weekly doses 
of placebo. In the Induction Phase, IMP may be over-encapsulated and matching placebo capsules will be provided to maintain study blind. Subjects 
participating in the intense PK collection will be required to take the Days 1 and 2 IMP at the Investigational site.  
Remind subject to bring IMP to each visit to assess compliance.  
i. 
Only subjects participating in the intense PK will come in for the Day 2 visit. 
j. 
All procedures listed are to be completed only for unscheduled visits where a recurrent VVC episode is suspected. If the unscheduled visit is for repeat 
procedures (i.e., ECG, safety labs, etc.), only those specific procedures need to be performed, along with collection of any changes in medical treatments or 
medications and collection of any AEs. 
 
 
 
 
 
 
 


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Mycovia Pharmaceuticals, Inc. 
 
Product: VT-1161  
 
Protocol VMT-VT-1161-CL-017 
IND 111675 
       Version 2, 17 January 2019 
 
18 
TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE .................................................................................................2 
PROTOCOL SYNOPSIS ................................................................................................................5 
TABLE OF CONTENTS ...............................................................................................................18 
LIST OF APPENDICES ................................................................................................................23 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ..................................................24 
1 
INTRODUCTION ......................................................................................................26 
1.1 
Background Information .............................................................................................26 
1.1.1 
Vulvovaginal Candidiasis ...........................................................................................27 
1.2 
VT-1161 ......................................................................................................................29 
1.2.1 
Non-Clinical Pharmacology .......................................................................................30 
1.2.2 
Clinical Studies ...........................................................................................................34 
1.3 
Study Rationale ...........................................................................................................42 
1.3.1 
Rationale for Induction Phase Treatment ...................................................................43 
1.3.2 
Dosing Regimen for VT-1161 and Fluconazole with Matching Placebo ...................43 
1.4 
Potential Risks and Benefits of Participating in the Study .........................................44 
2 
OBJECTIVES .............................................................................................................45 
3 
STUDY ENDPOINTS ................................................................................................46 
4 
STUDY DESIGN .......................................................................................................47 
4.1 
Overall Study Design ..................................................................................................47 
4.2 
Treatment Arms and Duration of Study .....................................................................48 
4.3 
Number of Subjects ....................................................................................................48 
4.4 
Design Justification ....................................................................................................48 
4.4.1 
Justification for Inclusion of Adolescents in the Study ..............................................50 
5 
SELECTION OF STUDY POPULATION ................................................................51 
5.1 
Inclusion Criteria ........................................................................................................51 
5.2 
Exclusion Criteria .......................................................................................................53 
6 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................57 
6.1 
Description of Investigational Medicinal Product ......................................................57 
6.1.1 
VT-1161 ......................................................................................................................57 


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6.1.2 
Fluconazole .................................................................................................................57 
6.1.3 
Placebo ........................................................................................................................57 
6.2 
Investigational Medicinal Product Labeling and Packaging ......................................57 
6.3 
Investigational Medicinal Product Storage Conditions ..............................................58 
6.4 
Receipt of Supplies/Handling/Storage ........................................................................58 
6.5 
Investigational Medicinal Product Accountability .....................................................58 
6.6 
Investigational Medicinal Product Return ..................................................................58 
7 
TREATMENT OF SUBJECTS ..................................................................................59 
7.1 
Investigational Medicinal Product Administration and Dosing Schedule ..................59 
7.1.1 
Induction Phase (Screening/Randomization to Day 14) .............................................59 
7.1.2 
Maintenance Phase (Day 14 to Week 14) ...................................................................60 
7.2 
Method of Assigning Subjects to Treatment Groups .................................................60 
7.3 
Dose Interruptions and Modifications ........................................................................60 
7.4 
Prohibited and Permitted Medications/Non-Medications ..........................................61 
7.4.1 
Prohibited Medications/Non-Medications ..................................................................61 
7.4.2 
Permitted Medications/Non-Medications ...................................................................61 
7.5 
Treatment Compliance ................................................................................................62 
7.6 
Replacement of Study Subjects ..................................................................................62 
7.7 
Randomization and Blinding ......................................................................................62 
7.8 
Conditions for Breaking the Blind ..............................................................................63 
7.9 
Treatment After the End of the Study .........................................................................63 
8 
STUDY PROCEDURES ............................................................................................64 
8.1 
Assessments and Procedures ......................................................................................64 
8.1.1 
Screening (Day 1) Assessments and Procedures ........................................................67 
8.1.2 
Day 2 Assessments and Procedures – Intense PK Sampling ......................................69 
8.1.3 
Day 14 (±2 Days) Assessments and Procedures .........................................................69 
8.1.4 
Week 8 (±7 Days) Assessments and Procedures ........................................................70 
8.1.5 
Week 14 (±14 Days) Assessments and Procedures (End of Treatment) ....................71 
8.1.6 
Week 20 (±14 Days) Assessments and Procedures ....................................................72 
8.1.7 
Week 26 (±14 Days) Assessments and Procedures ....................................................73 
8.1.8 
Week 32 (±14 Days) Assessments and Procedures ....................................................73 


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8.1.9 
Week 38 (±14 Days) Assessments and Procedures ....................................................74 
8.1.10 
Week 44 (±14 Days) Assessments and Procedures ....................................................75 
8.1.11 
Week 50 (±14 Days) Assessments and Procedures (End of Study) ...........................76 
8.1.12 
Unscheduled Visit Assessment and Procedures .........................................................77 
8.2 
Exercise .......................................................................................................................78 
9 
SAFETY ASSESSMENTS ........................................................................................79 
9.1 
Safety Tests and Assessments ....................................................................................79 
9.1.1 
Height and Weight ......................................................................................................79 
9.1.2 
Vital Signs ..................................................................................................................79 
9.1.3 
Physical Examination .................................................................................................79 
9.1.4 
Electrocardiograms .....................................................................................................79 
9.1.5 
Laboratory Determinations .........................................................................................80 
9.1.6 
KOH Wet Mount Tests and Fungal Cultures .............................................................81 
9.1.7 
Vulvovaginitis Clinical Assessment ...........................................................................81 
9.2 
Adverse Event Reporting ............................................................................................82 
9.2.1 
Definition of Adverse Events .....................................................................................82 
9.2.2 
Definition of a Serious Adverse Event .......................................................................83 
9.2.3 
Recording of Adverse Events .....................................................................................84 
9.2.4 
Severity of Adverse Events ........................................................................................85 
9.2.5 
Causality Assessment .................................................................................................86 
9.2.6 
Action Taken Following Adverse Events ...................................................................88 
9.2.7 
Outcome of Adverse Events .......................................................................................88 
9.2.8 
Other Reportable Events .............................................................................................89 
10 
PHARMACOKINETIC ASSESSMENTS .................................................................90 
10.1 
Sample Collection and Handling ................................................................................90 
10.2 
Analytical Procedures .................................................................................................90 
10.3 
Pharmacokinetic Parameters .......................................................................................90 
11 
STUDY TERMINATION AND SUBJECT DISCONTINUATION .........................91 
11.1 
Screening/Baseline Failures........................................................................................91 
11.2 
Subject Withdrawal or Premature Discontinuation from the Study ...........................91 
11.3 
Subject and Study Completion ...................................................................................92 


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11.4 
Premature Study Termination .....................................................................................93 
12 
STATISTICAL ANALYSIS ......................................................................................94 
12.1 
Determination of Sample Size ....................................................................................94 
12.2 
Analysis Populations ..................................................................................................94 
12.3 
Missing Data ...............................................................................................................95 
12.4 
Multiple Testing ..........................................................................................................95 
12.5 
Demographic and Baseline Characteristic Analyses ..................................................96 
12.6 
Efficacy Analyses .......................................................................................................96 
12.7 
Safety Analyses ..........................................................................................................98 
12.8 
Pharmacokinetic Analyses ..........................................................................................99 
13 
CLINICAL STUDY ADMINISTRATION/STUDY GOVERNANCE 
CONSIDERATIONS ................................................................................................100 
13.1 
Ethical Conduct of Study ..........................................................................................100 
13.2 
Informed Consent or Assent .....................................................................................100 
13.3 
Quality Control (Study Monitoring) .........................................................................100 
13.4 
Quality Assurance .....................................................................................................101 
13.5 
Compliance with Standards of Medical Research/ Deviations .................................101 
13.6 
Data Management .....................................................................................................102 
13.7 
Study and Site Closure..............................................................................................103 
13.8 
Records Retention .....................................................................................................103 
13.9 
Disclosure of Data ....................................................................................................104 
13.10 
Financial Disclosure .................................................................................................104 
13.11 
Publication Policy .....................................................................................................105 
13.12 
Confidentiality ..........................................................................................................105 
13.12.1 
Data ...........................................................................................................................105 
13.12.2 
Subject Anonymity ...................................................................................................105 
14 
REFERENCES .........................................................................................................106 
 
 
 
 


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Protocol VMT-VT-1161-CL-017 
IND 111675 
       Version 2, 17 January 2019 
 
22 
List of Tables  
Table 1. 
Schedule of Assessments and Procedures ..................................................................16 
Table 2. 
Oral Agents Commonly Used to Treat VVC ..............................................................29 
Table 3. 
VT-1161 Antifungal MIC50 or Range (μg/mL) ..........................................................31 
Table 4. 
MIC Values of VT-1161 and Fluconazole in µg/mL for 413 Candida spp. 
Isolates Derived From Phase 2b RVVC Study ...........................................................43 
Table 5. 
Number of Capsules Taken Per Treatment Group During Induction Phase ..............59 
 
 


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Product: VT-1161  
 
Protocol VMT-VT-1161-CL-017 
IND 111675 
       Version 2, 17 January 2019 
 
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LIST OF APPENDICES 
Appendix A.   Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table 
(Draft November 2007) 
Appendix B.   Grading of Renal Impairment 
Appendix C.   Child-Pugh Classification of Hepatic Impairement 
Appendix D. Protocol Amendment 1, Version 2 Summary of Protocol Changes 
  
 


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Product: VT-1161  
 
Protocol VMT-VT-1161-CL-017 
IND 111675 
       Version 2, 17 January 2019 
 
24 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition or Term 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
CK 
creatine phosphokinase 
Cmax 
maximum plasma concentration 
CRF 
case report form 
CYP51 
lanosterol demethylase 
DDI 
drug-drug interaction 
DMID 
Division of Microbiology and Infectious Diseases 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
end of study 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
HBsAg 
hepatitis B surface antigen 
HIV 
human immunodeficiency virus 
IC50 
half maximal inhibitory concentration 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IMP 
investigational medicinal product 
IRB 
institutional review board  
ITT 
intent-to-treat 
IWRS 
interactive web response system 
KOH 
potassium hydroxide 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC50 
minimum inhibitory concentration 
NOAEL 
no-observed-adverse-effect-level 
OM 
Onychomycosis 
Pap 
Papanicolaou 
PK 
Pharmacokinetic 
PKE 
pharmacokinetic evaluation 
PP 
per protocol 
QTc 
duration of the QT interval adjusted for heart rate (Fridericia correction) 
RVVC 
recurrent vulvovaginal candidiasis 


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Protocol VMT-VT-1161-CL-017 
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       Version 2, 17 January 2019 
 
25 
Abbreviation 
Definition or Term 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
TEAE 
treatment-emergent adverse event 
Tmax 
time to reach maximum plasma concentration 
TOC 
test of cure 
ULN 
upper limit of normal 
VVC 
vulvovaginal candidiasis 
WOCBP 
women of childbearing potential 
 


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Protocol VMT-VT-1161-CL-017 
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       Version 2, 17 January 2019 
 
26 
1 
INTRODUCTION 
Lanosterol demethylase (CYP51), an enzyme essential for fungal growth, catalyzes an early step 
in the biosynthetic pathway of ergosterol, a sterol required for fungal cell membrane formation 
and integrity (Yoshida, 1988).  Inhibition of CYP51 results in the accumulation of 14-methylated 
sterols, some of which are toxic to the fungus.  CYP51 is the molecular target of the class of drugs 
referred to as ‘azole antifungals’.  All currently approved azole drugs contain either an imidazole 
or triazole ring system that binds tightly to the catalytic heme-iron of fungal CYP51 as well as to 
the heme-iron of many off-target mammalian cytochrome P450 enzymes.  This inherent lack of 
selectivity is responsible for many of the side effects associated with the azole antifungals.  
For example, the potent inhibition of one or more human cytochrome P450 metabolizing enzymes 
found in the liver (e.g. CYP3A4, CYP2C9, CYP2C19) or in the adrenal and sex organs 
(e.g. CYP19, CYP17, CYP21), is the basis for azole drug-drug interactions (Bates and Yu, 2003) 
and reproductive warnings (Zarn et al., 2003), respectively.  Additional azole class toxicities that 
are less well understood but may be related to off-target protein interactions include hepatic 
toxicities, skin photosensitivity, and vision impairment.  In the acute care setting, these dose-
limiting side effects prevent attainment of plasma drug levels that might reduce the longstanding 
40% mortality rate attributed to invasive fungal infections.  The safety profile of the class similarly 
limits its use for chronic treatment of non-life-threatening fungal infections, such as recurrent 
vulvovaginal candidiasis (RVVC) and onychomycosis (OM).  A safer antifungal drug would also 
improve treatment options for infections seen in otherwise healthy individuals, such as RVVC and 
OM, which require protracted treatment in a patient population where significant side-effect risks 
are unacceptable. 
1.1 
Background Information 
Mucosal candidiasis, also known as thrush, describes a group of yeast-like fungal infections that 
involve the mucous membranes including the mouth, urinary tract and genitals, notably the vagina 
and surrounding skin in women.  Infection is typically caused by Candida albicans, however more 
rare and difficult-to-treat Candida strains such as C. glabrata are becoming more prevalent.  
Mucosal candidiasis occurs more frequently in immunocompromised patients but may also arise 
in immunocompetent individuals. 
 


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1.1.1 Vulvovaginal Candidiasis 
1.1.1.1 Epidemiology 
Symptoms of vulvovaginitis (inflammation of the vagina and vulva) are common and are among 
of the most frequent reasons for women’s visits to physicians.  Vulvovaginitis is associated with 
considerable morbidity including genital discomfort, decrease in sexual pleasure, loss of 
productivity, and psychological distress (Eschenbach, 2004).  There are several etiologies for 
vulvovaginitis; candidiasis being the second most common after bacterial vaginitis.  Vulvovaginal 
candidiasis is a common disorder, with nearly 75% of all adult women having had at least one 
“yeast infection” in their lifetime.  Approximately half of these women experience a recurrence, 
with 5 to 8% developing recurrent VVC, defined as 3 or more episodes in one year (Sobel, 2016).  
Estrogen increases the glycogen concentration of the vaginal lining; glycogen is a substrate on 
which C. albicans thrives.  As estrogen levels are significantly lower in both pre-menarchal and 
post-menopausal females, the incidence of VVC is lower in these populations.  Vulvovaginal 
candidiasis is most common in women aged 25 to 34 years (Foxman et al., 2013). 
1.1.1.2 Pathophysiology 
Vulvovaginal candidiasis occurs when there is an overgrowth of the normal yeast in the vagina.   
Most cases (85% - 95%) are caused by C. albicans, followed by C. glabrata, and infrequently by 
C. parapsilosis, C. tropicalis, and C. krusei.  Vulvovaginitis caused by non-albicans Candida 
species, in particular C. glabrata, is clinically indistinguishable from C. albicans VVC but is more 
resistant to current treatments. 
Candida organisms gain access to the lumen and secretions of the vagina primarily from the 
adjacent perianal region.  Normal anti-Candida defense mechanisms allow for long-term 
persistence of Candida as commensal organisms in the vagina without signs or symptoms of 
vaginitis.  Factors predisposing to VVC versus asymptomatic colonization include those attributed 
to the health (immunosuppression, use of antibacterial agents, pregnancy, uncontrolled diabetes 
mellitus) and behavior (frequent intercourse, orogenital sexual activity, use of oral contraceptives 
or estrogen-based hormonal replacement therapy) of the host.  Other dermatologic conditions such 
as psoriasis, lichen planus, and lichen sclerosus also predispose women to VVC (Goncalves et al., 
2016). 
1.1.1.3 Presentation and Diagnosis 
The clinical array of signs and symptoms of VVC include genital pruritus associated with edema, 
an erythematous rash and excoriation of the vulva and surrounding skin, a burning sensation in the 
vagina and vulva, and a vaginal discharge.  These symptoms may persist for days to weeks and 


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Protocol VMT-VT-1161-CL-017 
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       Version 2, 17 January 2019 
 
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may also recur with each menstrual cycle.  Women with VVC typically most commonly present 
with acute pruritus and a vaginal discharge, though neither is specific for candidiasis.  
The discharge may range from being watery to quite thick and “cottage-cheese-like”.  
Common symptoms include vaginal soreness, irritation, vulvar burning, dyspareunia, and external 
dysuria.  Physical examination typically reveals erythema and edema of the vulva with fissures 
and a pustulopapular rash, vaginal erythema, and a normal cervix.  Symptoms often worsen the 
week prior to menses. 
The diagnosis of VVC requires more than a history and physical examination as symptoms and 
signs, in particular pruritus, are often non-specific.  Diagnosis is made by microscopic examination 
of a 10% potassium hydroxide (KOH) wet mount showing the presence of yeast cells and mycelia 
and the absence of both clue cells (pathognomonic of bacterial infection) and trichomonads.  
The vaginal pH is normal, approximately 4.0%.  A vaginal culture should also be performed, 
particularly for women with negative microscopy, as up to 50% of patients with culture-positive 
VVC will have no findings on microscopy (Sobel, 2007); additionally, a culture will precisely 
identify the organism. Papanicolaou (Pap) smears are also not reliable, typically positive in only a 
quarter of patients with VVC. 
As up to 15% of asymptomatic women are colonized with Candida species and are thus culture 
positive, the final diagnosis of VVC requires a comprehensive assessment of clinical findings, 
microscopic examination, and vaginal culture. 
1.1.1.4 Treatment and Outcome 
In general, women who are asymptomatic carriers of Candida do not require treatment.  
Acute VVC in symptomatic women requires individualized treatment, the selected agent and 
duration of therapy being based on whether the VVC is categorized as either: 
• Uncomplicated, defined as having all of the following characteristics: (mild or moderate in 
symptom severity, sporadic in frequency, C. albicans as the infecting organism, in non-
pregnant women with normal immune function), or 
• Complicated, defined as having any one or more of the following characteristics: severe in 
symptom severity, recurrent, a non-C. albicans organism as the infecting agent, abnormal 
immune function, or pregnant (Eschenbach, 2004). 
Women with uncomplicated VVC can be treated with single-dose or short-course treatments, while 
those with complicated VVC require longer-term therapy, at least 5 to 7 days and possibly 


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maintenance therapy up to 6 months (Sobel et al., 2004).  Pregnant women, who are at higher risk 
of developing VVC, can only be treated with topical agents because of the potential teratogenic 
effects of azoles when administered systemically.  Topical agents are limited by local side effects, 
especially burning, and are messy to apply; therefore, most patients prefer the oral regimens.  
However, the systemically administered azoles listed in Table 2 are characterized by systemic 
toxicities and drug-drug-interactions (DDIs) and have poor activity against C. glabrata and 
fluconazole resistant C. albicans. 
Table 2. 
Oral Agents Commonly Used to Treat VVC 
Agent 
Formulation 
Dose and Schedule 
Fluconazole (Diflucan®) 
150 mg tablet (Rx) 
Single dose 
Ketoconazole (Nizoral®) 
200 mg tablet (Rx) 
2 tablets q.d. x5d 
Itraconazole (Sporanox®) 
100 mg tablet (Rx) 
2 tablets q.d. x3d 
Abbreviations: mg = milligrams; d = day; q.d. = once daily; Rx = prescription. 
 
1.1.1.5 Recurrent, Resistant and Non-Albicans VVC 
Up to 20% of women will develop recurrent, resistant, or complicated VVC.  In a study that 
compared a 6-month maintenance weekly fluconazole regimen to placebo in patients with 
recurrent VVC, the time to recurrence increased from 4.0 to 10.2 months, and the cure rate at 
12 months doubled versus placebo from 22% to 43% (Sobel et al., 2004).  However, fewer than 
half of patients remained disease-free after discontinuation of fluconazole which highlights the 
unmet medical need for these patients. 
The prevalence of infection with non-albicans species, in particular C. glabrata, is increasing, 
especially in patients who are immunosuppressed and/or are diabetics; C. glabrata is poorly 
sensitive to current azole antifungal agents. 
1.2 
VT-1161 
VT-1161 is a novel oral antifungal agent with a lower affinity for heme-iron and a greater affinity 
for the fungal lanosterol 14 α-demethylase (CYP51) than the currently available azole drugs.  
As a result, VT-1161 more potently inhibits fungal CYP51 than current azoles and less potently 
inhibits host cytochrome P450 enzymes, resulting in greater cytochrome selectivity.  
These properties should translate to greater efficacy with an improved safety and tolerability 
profile. 


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VT-1161 is being developed for the treatment of patients with mucosal or superficial fungal 
infections.  It is formulated with standard excipients known to be chemically stable when combined 
with VT-1161 into tablets or capsules for the investigational drug product. 
A detailed description of the non-clinical binding and inhibition, metabolism, microbiology, 
toxicology, safety pharmacology, Phase 1 clinical studies in which 72 subjects were exposed to 
VT-1161 and Phase 2a proof-of-concept studies, in which 78 subjects were exposed to VT 1161 
can be found in the VT-1161 Investigational Brochure.  In the Phase 2b studies, 378 subjects were 
exposed to VT-1161.  These studies are summarized below.  The following sections provide data 
from non-clinical, Phase 1 and Phase 2 clinical trials supporting the use of VT‑1161 for patients 
with RVVC. 
1.2.1 Non-Clinical Pharmacology 
1.2.1.1 Binding and Inhibition 
In vitro pharmacology studies demonstrated that VT-1161 is a potent inhibitor of fungal CYP51 
and binds more than 2200-fold more tightly to fungal CYP51 than to human CYP51.  VT-1161 is 
also highly selective for fungal CYP51 versus key human cytochrome P450 enzymes, non-
cytochrome metalloenzymes, and a broad panel of receptors, ion channels, and transporters. 
1.2.1.2 Metabolism 
VT-1161 was not significantly metabolized when incubated with mouse, rat, dog or human 
hepatocytes.  Only 1 possible metabolite consistent with hydroxylation and glucuronidation of 
VT-1161 was detected in dog hepatocytes.  No additional metabolites were detected in any of the 
4 species. 
1.2.1.3 Microbiology 
VT-1161 was tested against a broad range of Candida clinical isolates and showed potent activity 
( 
 
 
 
Table 3).  It was also active against dermatophytes, including Trichophyton rubrum, 
T. mentagrophytes, and T. tonsurans. 


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Table 3. 
VT-1161 Antifungal MIC50 or Range (μg/mL) 
Fungus (# of clinical isolates) 
VT-1161 
Comparator 
C. albicans (N=10) 
≤ 0.03 
Fluconazole 
≤ 0.125 
C. glabrata (N=10) 
0.25 
4 
C. parapsilosis (N=10) 
≤0.03 
0.125 
C. guilliermondii (N=3) 
0.125-0.25 
2-8 
T. mentagrophytes (N=12) 
0.25 
Itraconazole 
0.06 
T. rubrum (N=41) 
0.03 
≤ 0.03 
T. tonsurans (N=5) 
0.06-0.5 
≤0.03-0.06 
Abbreviations: C. = Candida; T. = Trichophyton; MIC50 = minimum inhibitory concentration for 50% of isolates;  
μg = microgram; mL = milliliter; N = number (of clinical isolates). 
 
 
In the Phase 2b RVVC study (VMT-VT-1161-CL-006), 413 clinical isolates were collected from 
subjects at screening visits until the end of the study.  The minimum inhibitory concentration 
(MIC) ranges for VT-1161 and fluconazole for the isolates collected were; <0.0005 – >0.5 µg/ml 
and <0.06-32 µg/ml, respectively.  The MIC50 values for VT-1161 and fluconazole were 
0.004 µg/ml and 0.125 µg/ml, respectively, and the MIC90 values for VT-1161 and fluconazole 
were 0.06 µg/ml and 4 µg/ml, respectively. These data further demonstrated that VT-1161 has 
potent in vitro activity against the Candida strains obtained from clinical strains.  For all tested 
isolates, VT-1161 demonstrated MIC50 and MIC90 that were 5 dilutions lower than those 
demonstrated by fluconazole.   
1.2.1.4 Activity in Animal Models of VVC 
VT-1161 was evaluated as an oral treatment of vaginal candidiasis (C. albicans) in a murine model 
(Garvey et al., 2012).  Three days after infection, VT-1161 was dosed orally once daily at 4, 10, 
or 25 mg/kg daily for 4 days.  Fungal burden measured in vaginal lavage fluid was highly 
significantly suppressed (p <0.0002) compared to vehicle-treated controls at all doses and when 
measured 1 or 4 days after treatment ended.  Plasma and vaginal tissue levels of the lowest dose 
of VT-1161 indicated that levels as low as 1 µg/mL resulted in this high degree of efficacy. 
1.2.1.5 Pharmacokinetics 
VT-1161 formulated as a suspension in carboxymethylcellulose was well absorbed and exhibited 
approximately dose linear pharmacokinetics (PK) and a long plasma half-life in both rats and dogs.  


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There was no evidence of an effect of gender on the PK of VT-1161 in either rats or dogs.  
VT-1161 accumulated during repeat-dosing in rats and dogs as expected based on the long 
half-life.  VT-1161 was widely distributed into tissues and was mostly excreted in bile and feces 
in the rat.  In vitro plasma protein binding of VT-1161 is high with approximately 99.5% binding 
to rat, dog and human plasma and slightly lower binding in mice (97.6%).  The absolute oral 
bioavailability of the capsule formulation used in Phase 1 studies administered to dogs was 
approximately 40% in the fasted state and approximately 100% when administered in the fed state. 
1.2.1.6 General Toxicology 
Oral VT-1161 was evaluated in general Good Laboratory Practice toxicity studies of up to 
6 months and 9 months in duration in rats and dogs, respectively.  Rats were more sensitive to the 
toxicological effects of oral administration of VT-1161 than dogs.  The no observable adverse 
effect level (NOAEL) for the 6-month rat toxicity study was determined to be 0.5 mg/kg/day, 
based on an increase in incidence and severity of chronic progressive nephropathy, a rat-specific 
finding.  The NOAEL for liver findings was 1.5 mg/kg, based on adverse findings at the high dose 
of 5 mg/kg/day including a minimal increase in serum alanine aminotransferase (ALT) and 
aspartate aminotransferase (AST) and an increase in frequency of minimal focal necrosis and 
single cell necrosis.  Findings of liver hypertrophy, sub-capsular necrosis and multinucleated 
hepatocytes were considered rat-specific and associated with metabolic adaptation.  Focal necrosis 
may be an exaggerated response to hepatocellular hypertrophy which is known to cause 
sub-capsular and single cell necrosis.  The findings were reversible and similar to the findings 
observed in a prior 28-day study in the rat, providing support that the increased treatment duration 
in the 6-month rat study did not result in new findings of clinical concern.  At the 1.5 mg/kg dose 
at steady state on Day 182, maximum plasma concentration (Cmax) was 4,055 ng/mL and area 
under the curve (AUC0-24) was 81,900 ng·h/mL.  The NOAEL for the 9-month dog study was 
determined to be the high dose of 17 mg/kg/day (Day 273 Cmax was 74,700 ng/mL and AUC0-24 
was 1,675,000 ng·h/mL), as no adverse findings were identified.  The NOAEL in the previous 
28-day dog study was 10 mg/kg/day, based on decreased body weight and mild effects on 
lymphoid organs including increased tingible body macrophages in the mandibular and mesenteric 
lymph nodes and in the Peyer’s patches at 30 mg/kg and higher.  These findings were largely 
reversed during the recovery period. 
1.2.1.7 Genotoxicity 
VT-1161 was found to be negative for genotoxicity in the Ames bacterial reverse mutation assay, 
the chromosome aberration assay in human peripheral lymphocytes and the in vivo bone marrow 
micronucleus assay in rats. 


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1.2.1.8 Reproductive Toxicology 
VT-1161 at doses resulting in maternal toxicity (clinical signs and decrease in body weights) did 
not cause alterations in uterine and ovarian parameters in embryofetal development studies in rats 
and rabbits.  Mean fetal body weights were slightly reduced in rabbits in the high dose group as a 
direct result of maternal toxicity and decreased maternal body weights.  No external, visceral and 
skeletal malformations and variations were observed at any of the dose levels evaluated. 
There were no effects on male or female fertility at clinically relevant doses.  
1.2.1.9 Safety Pharmacology 
The effects of VT-1161 on the neurological and pulmonary systems were evaluated in 
Sprague-Dawley rats.  The data demonstrated that there were no VT‑1161-related effects in either 
the neuropharmacological or pulmonary studies in rats given an oral dose of up to 1,000 mg/kg 
VT-1161, the highest dose tested.  
Evaluation of cardiovascular function in telemetered dogs revealed no treatment-related changes 
in heart rate, blood pressure, cardiac rhythm or morphology, including the QT/QTc (Fridericia 
correction) interval, at oral doses up to 300 mg/kg, the highest dose tested. 
1.2.1.10 In Vitro Cytochrome P450 Interactions 
VT-1161 
inhibited 
cytochrome 
P450 
enzymes 
with 
the 
following 
potencies:  
CYP1A2 (half maximal inhibitory concentration [IC50] ≥10 µM), CYP2B6 (IC50 = 4.0 µM), 
CYP2C8 (IC50 = 1.4 µM), CYP2C9 (IC50 ≥10 µM), CYP2C19 (IC50 = 9.7 µM), 
CYP2D6 (IC50 = 9.4 µM), and CYP3A4 (IC50 = 9.6 µM [testosterone], IC50 ≥10 µM [midazolam]).  
Based on the high plasma protein binding of VT-1161, no clinically significant drug-drug 
interactions are expected. 
1.2.1.11 Effects of VT-1161 on Cardiac Repolarization 
An in vitro human ether-à-go-go related gene study was conducted to assess the potential of 
VT-1161 to inhibit the repolarizing current of the cardiac action potential.  VT-1161 inhibited the 
human ether-à-go-go related gene potassium current by 94.7 ± 1.3% at 6 µM.  The IC50 was 
calculated to be 1.9 µM (Hill coefficient = 2).  However, a cardiovascular safety study in dogs 
showed that VT-1161 was well tolerated and did not induce any deleterious cardiovascular effects 
or affect QT intervals at test doses of up to 300 mg/kg, the highest dose tested, with exposures 
reaching 24,000 ± 6,881 ng/mL at 30 hours post-dose. 


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1.2.2 Clinical Studies 
1.2.2.1 Phase 1 Studies 
VT-1161 has been evaluated in 4 Phase 1 trials, a single ascending dose trial, a multiple ascending 
dose trial, a DDI study with midazolam as a sensitive substrate, and an ethnic PK study comparing 
Japanese and Western subjects.  The primary objectives of these studies were to evaluate the safety 
and tolerability, PK and drug interaction potential of VT-1161 in healthy adult subjects.  Detailed 
descriptions of the trials can be found in the VT-1161 Investigational Brochure. 
1.2.2.1.1 Single Dose-Escalation Study (Study VMT-VT-1161-CL-001) 
Study VMT-VT-1161-CL-001 was a single-center, Phase 1, double-blind, randomized, placebo-
controlled, dose-escalating study in healthy adult subjects.  The study was designed to evaluate the 
safety, tolerability, and PK of single oral doses of VT-1161.  Sixty-four subjects (43 males and 
21 females) between 18 and 55 years of age were enrolled in 8 dose groups.  Within each dose-
group, 6 subjects received VT-1161 and 2 subjects received placebo.  In the first 7 cohorts, 
escalating single oral doses (5, 10, 20, 40, 80, 160, and 320 mg) or matching placebo were 
administered in the fasted state.  An 8th cohort received a single 320 mg oral dose of VT-1161 or 
matching placebo after ingesting a high-fat breakfast.  Subjects in Cohorts 1 to 6 were followed 
for 14 days for safety and PK assessments.  Visits on Days 28 and 42 were added for Cohorts 7 
and 8.  Dose escalation proceeded only after safety and PK of the previous dose was determined.   
There were no deaths or serious adverse events (SAEs) reported.  There were no treatment-
emergent adverse events (TEAEs) that led to discontinuation from the study.   
Overall, mean changes from baseline in safety parameters (hematology, chemistry, urinalysis, vital 
signs, and electrocardiogram [ECG]s) were generally small and were considered not clinically 
significant.  None of the treatment-emergent physical examination abnormalities were of clinical 
significance.  The maximum tolerated dose for the study was the highest dose administered, 
320 mg, administered in the fed state. 
Following oral administration of VT‑1161 in the fasted state, median time to reach maximum 
plasma concentration (Tmax) ranged from 4 to 10 hours.  Overall, Cmax increased slightly less than 
proportional to dose. The area under the plasma concentration versus time curve from time zero to 
infinity (AUCinf) values generally increased with increase in dose, ranging from an average of 
16,145 ng•hr/mL at 20 mg to 241,971 ng•hr/mL at 320 mg.  The mean half-life ranged from 393 to 
1,467 hours.  Administration of 320 mg VT-1161 with a standard high-fat meal resulted in higher 
plasma concentrations than those observed following 320 mg in the fasted state in a separate group 


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of subjects.  Average fasting Cmax was 338 ng/mL and this increased to 988 ng/mL in the fed state.  
AUCinf also increased from 241,971 ng•hr/mL when subjects were fasted to 953,119 ng•hr/mL 
with a high-fat meal. 
1.2.2.1.2 Multiple Dose-Escalation Study (Study VMT-VT-1161-CL-002) 
Study VMT-VT-1161-CL-002 was a Phase 1, single-center, randomized, double blind, placebo-
controlled, multiple dose-escalating study in healthy adult subjects.  The study was designed to 
evaluate the safety, tolerability, and PK of multiple oral doses of VT-1161.  In addition to plasma 
PK, concentrations of VT-1161 in nails and skin were assessed.  A total of 32 subjects participated 
in the study and received VT-1161 at 40, 80, 160 or 320 mg or placebo once daily for 7 days after 
ingestion of a high-fat meal.  In each cohort of 8 subjects, 6 subjects received VT-1161, and 2 
subjects received placebo.  Subjects were followed for safety and PK assessments for 42 days after 
the last dose of study drug. 
There were no deaths or SAEs reported.  Most TEAEs were mild in intensity and no severe TEAEs 
were reported. 
Mean changes from baseline in safety parameters (hematology, chemistry, coagulation, urinalysis, 
vital signs, and ECGs) were generally small and not considered clinically significant.  There was 
no evidence of any clinically significant effect of VT-1161 on physical examinations in any dose 
group at any time point.  The maximum tolerated dose for the study was the highest dose 
administered, 320 mg, administered once daily for 7 days in the fed state. 
Following oral administration of VT-1161 in the fed state, median Tmax values ranged from 4 to 
6 hours after dosing.  The increase in mean Cmax was nearly proportional to dose over the 40 to 
320 mg dose range.  The concentrations were 3 to 4-fold higher on Day 7 than they were on Day 1, 
indicating accumulation during the 7-day dosing interval, with a mean Cmax of 3,300 ng/mL on 
Day 7 at 320 mg.  The area under the plasma concentration versus time curve over the dosing 
interval (AUCτ) values on Day 7 also increased nearly proportionally to dose over the 40 to 320 mg 
dose range.  The mean half-life ranged from 1,905 to 3,046 hours.   
1.2.2.1.3 Drug-Drug Interaction Study (Study VMT-VT-1161-CL-007) 
Study VMT-VT-1161-CL-007 was a Phase 1, single-center, open-label study in healthy adult 
subjects to evaluate the effect of single and multiple oral doses of VT‑1161 when co-administered 
with single oral doses of midazolam (DDI cohort) and to evaluate the PK of a single oral dose of 
an alternate strength of VT-1161 alone (pharmacokinetic evaluation [PKE] cohort).  All dosing 


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was conducted 30 minutes after the start of a high-fat, high-calorie meal.  A total of 36 subjects 
were enrolled in the study.   
In the DDI cohort, 28 subjects were enrolled in a fixed-sequence design to receive a 2-mg oral 
dose of midazolam on Day 1, followed by 14 daily 600 mg oral doses of VT‑1161 (4 x 150 mg 
tablets) on Day 3 through Day 16 with single 2 mg oral doses of midazolam on Day 3 and Day 16.  
Subjects were followed for safety, tolerability and PK assessments through Day 17, 1 day after the 
last dose of study drug.  Twenty-four subjects in the DDI cohort completed the study and 4 subjects 
withdrew from the study prior to completion; 2 subjects voluntarily withdrew consent and 
2 subjects withdrew due to an AE (discussed in more detail below).   
There were no deaths reported in the study.  One SAE (acute psychosis) was reported in a subject 
in the DDI cohort on Day 11 of the study, leading to discontinuation.  The Investigator determined 
the subject likely had a pre-existing psychiatric condition based on patient report and assessed 
causality as unlikely-related to VT-1161.  One additional subject in the DDI cohort withdrew from 
the study due to an AE of abnormal ECG on Day 3 of the study.  The AE occurred prior to the first 
dose of VT-1161; the Investigator assessed causality as unrelated to study drug.  Otherwise, mean 
changes from baseline in safety parameters (hematology, chemistry, coagulation, urinalysis, vital 
signs, and ECGs) in both the DDI and PKE cohorts were generally small and not considered 
clinically significant and there was no evidence of any clinically significant effect of VT-1161 on 
physical examinations in either cohort. 
In the DDI cohort, midazolam mean plasma Cmax increased 30% and AUCinf decreased 15% on 
Day 3 (after the first dose of VT‑1161) relative to Day 1 (midazolam alone).  Midazolam mean 
plasma Cmax decreased 3% and AUCinf decreased 37% on Day 16 (after 14 daily doses of VT‑1161) 
relative to Day 1 (midazolam alone). 
In the PKE cohort, 8 subjects were enrolled to receive a single 600 mg oral dose of VT-1161 (2 x 
300 mg tablets) on Day 1.  Subjects in the PKE cohort were followed for safety, tolerability and 
PK assessments through Day 2, 1 day after the dose of study drug.  All 8 subjects in the PKE 
cohort completed the study.  VT-1161 mean plasma Cmax and AUC0-24 values after a single oral 
administration of 600 mg VT‑1161 (2 x 300 mg) on Day 1 were 1,946 ng/mL and 
28,070 ng•hr/mL, respectively.  These values are similar to VT-1161 mean plasma Cmax and 
AUC0-24 values after a single oral administration of 600 mg VT‑1161 (4 x 150 mg) in the DDI 
cohort (1,994 ng/mL and 25,330 ng•hr/mL, respectively), indicating the bioavailability of the 2 
strengths of tablets is similar. 


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1.2.2.1.4 Japanese Bridging Study (Study VMT-VT-1161-CL-008) 
Study VMT-VT-1161-CL-008 was a single-center, open-label study in healthy adult Japanese and 
Western subjects.  The objective of this ethno-bridging study was to evaluate the safety, 
tolerability, and PK of VT-1161 in these 2 ethnic populations after subjects received 14 once daily 
oral doses of VT-1161 administered in the fed state.  There was a total of 51 subjects enrolled. 
In the 300-mg dosage-group, there were 13 Japanese and 14 Western subjects.  In the 600 mg 
dosage group, there were 12 Japanese and 12 Western subjects.  The mean age of subjects was 
36.5 years, ranging from 19 to 55 years across treatment groups.  The subjects were evenly divided 
by sex across all groups and the race of the Western subjects was evenly divided by white and 
black.  
The study drug was overall well tolerated by both Western and Japanese subjects.  There were no 
significant differences between the 2 populations in any of the safety assessments.  A slight 
increase in AEs was seen in the 600 mg dosage group as compared with the 300 mg dosage group, 
but no SAEs were observed.  Only 1 subject was withdrawn from the study for an AE of rash 
(subject request), which was categorized as an unlikely-related TEAE.  There was 1 pregnancy in 
a subject who was non-compliant with contraception requirements, which was electively 
terminated by the subject. 
Of the 51 subjects enrolled in the study, 11 Japanese subjects from both dose groups and 
12 Western subjects from both dose groups were included in the full PK analysis population. 
Trough concentrations on Days 1 through 14 rose each day; thus, steady-state conditions had not 
been met by Day 14.  Larger differences between the 2 ethnic groups were seen in Cmax and 
AUC0-72 following the 300 mg dose compared with the 600 mg dose. At the 300 mg dose, Cmax and 
AUC0-72 were approximately 40% higher in Japanese subjects compared with Western subjects. 
At the 600-mg dose, Cmax and AUC0-72 were approximately 10% higher in Japanese subjects 
compared with Western subjects. However, median Tmax was similar across doses at 4 hours for 
Japanese subjects at both the 300 mg and 600 mg dosages and 6 hours for Western subjects at both 
the 300 mg and 600 mg dosages. The terminal elimination phase was very flat and half-life 
exceeded 1800 hours. Total clearance following the 300-mg dose was 1.642 L/hr for the Japanese 
subjects compared with 2.332 L/hr for the Western subjects.  Following the 600 mg dose, clearance 
was similar for the Japanese and Western subjects (2.000 and 2.086 L/hr, respectively). 


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1.2.2.2 Phase 2 Studies 
1.2.2.2.1 Dose Ranging Study in Tinea Pedis (Study VMT-VT-1161-CL-003) 
VMT-VT-1161-CL-003 was a Phase 2a, randomized, double-blind, dose-ranging study to evaluate 
the efficacy and safety of VT-1161 over-encapsulated tablets compared to placebo in the treatment 
of subjects with moderate to severe interdigital tinea pedis.  A total of 50 subjects participated in 
the study across 4 dose groups: 1) VT-1161 200 mg once daily for 4 days, followed by 50 mg once 
daily for 10 days (low dose); 2) VT-1161 600 mg once daily for 4 days, followed by 150 mg once 
daily for 10 days (mid-dose); 3) 600 mg twice daily for 4 days, followed by 300 mg once daily for 
10 days (high dose; or 4) placebo matching the VT-1161 treatment regimen.  VT-1161 plasma 
concentrations increased with dose and were as high as 6,230 ng/mL on Day 14 in the 600 mg 
twice daily/300 mg once daily dose group. Subjects were enrolled into the high-dose cohort 
following an interim analysis that included safety data generated through the test of cure (TOC) 
visit (Day 42) of the 2 lower dose groups.   
VT-1161 was safe and well tolerated at all dose levels through 6 months of follow-up.  No SAEs 
were reported.  Most AEs reported were mild to moderate in severity and considered unrelated to 
study drug.  A single VT-1161 treatment related AE was reported (rash) that was considered by 
the Investigator to be “possibly related.”  The subject discontinued treatment after the first dose, 
and the rash completely resolved by the following day.  There were no clinically significant 
treatment-emergent changes in vital signs, physical findings, ECGs, or laboratory parameters.  
One subject experienced a significant elevation of creatine kinase (CK) along with a slight increase 
in ALT and AST that was associated with a rigorous exercise program.  These changes were 
considered unrelated to treatment and all enzyme levels returned to normal at a subsequent follow-
up visit.   
At the Day 42 TOC visit, 42%, 42%, 50% and 0% of subjects receiving low dose, mid-dose or 
high dose VT-1161 or placebo were determined to have achieved effective therapeutic cure 
(defined as having a total severity score of ≤2 with no individual severity score of >1, and also, 
having negative mycology [culture and KOH]) in the intent-to-treat (ITT) population.   
1.2.2.2.2 Dose Ranging Study in Acute Vulvovaginal Candidiasis (Study VMT-VT-1161-
CL-004)  
VMT-VT-1161-CL-004 was a randomized Phase 2a, double-blind, dose ranging study to evaluate 
the efficacy and safety of VT-1161 over-encapsulated tablets compared to fluconazole in the 
treatment of 55 subjects with moderate to severe acute VVC.  A total of 55 subjects with moderate-
to-severe acute VVC (severity score ≥6 and a positive fungal KOH test) participated in the study 


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across 4 dose groups: 1) VT 1161 300 mg once daily for 3 days, 2) 600 mg once daily for 3 days, 
3) 600 mg twice daily for 3 days, or 4) a single dose of fluconazole 150 mg followed by matching 
placebo.  Subjects were enrolled into the high-dose cohort following an interim analysis that 
included safety data generated through the TOC visit (Day 28) of the 2 lower dose groups.  
An additional interim analysis was conducted when the high-dose subjects had completed their 
TOC visit.   
VT-1161 was determined to be safe and well tolerated at all dose levels through Day 28.  No SAEs 
were reported and no subjects discontinued because of an AE.  Most AEs reported were considered 
unrelated to study drug and were mild in severity.  There were few treatment-related TEAEs of 
clinical concern.  Most TEAEs were reported in the low- and mid-dose cohorts and only 1 TEAE 
(insomnia) was noted in the high-dose cohort.  One subject developed urticaria that was considered 
possibly related to study drug and which resolved with prednisone.  There were no clinically 
significant treatment-emergent changes in vital signs, physical findings, ECGs or laboratory 
parameters. 
The efficacy of VT-1161 in the treatment of moderate-to-severe acute VVC was evaluated at the 
TOC visit in the ITT population (defined as all randomized subjects receiving at least 1 dose of 
study drug) and the per protocol (PP) population (defined as subjects that were compliant with all 
key aspects of the protocol).  Subjects in the ITT population were randomized into the 
VT-1161 300 mg once daily for 3 days (n = 14), VT-1161 600 mg once daily for 3 days (n = 12), 
VT-1161 600 mg twice daily for 3 days (n = 14) or fluconazole (n = 15).  Effective clinical cure 
rate (defined as having a total severity score of 0 or 1 and a negative culture) were 29%, 83%, 86% 
and 73%, respectively.  Subjects in the PP population achieved effective therapeutic cure at a rate 
of approximately 87%, 86%, 86% and 75%, respectively, in the low-dose, mid-dose, or high-dose 
VT-1161 or fluconazole groups at the Day 28 TOC visit. 
1.2.2.2.3 Phase 2b Study in Subjects with Distal and Lateral Subungual Onychomycosis of 
the Toenail (VMT-VT-1161-CL-005) 
In this Phase 2b study, the safety, tolerability, PK and efficacy of VT-1161 in subjects with distal 
and lateral subungual onychomycosis of the toenail were evaluated.  A total of 259 subjects 
participated in the study in 5 treatment groups and were administered either: 
• 
Low dose 12-week: Loading doses of 300 mg once daily for 2 weeks, then 300 mg once weekly 
for 10 weeks, followed by placebo for 12 weeks. 


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• 
Low dose 24-week: Loading doses of 300 mg once daily for 2 weeks, then 300 mg once weekly 
for 22 weeks. 
• 
High dose 12-week: Loading doses of 600 mg once daily for 2 weeks, then 600 mg once weekly 
for 10 weeks, followed by placebo for 12 weeks. 
• 
High dose 24-week: Loading doses of 600 mg once daily for 2 weeks, then 600 mg once weekly 
for 22 weeks. 
• 
Matching placebo 
Subjects in all cohorts were followed for 60 weeks.  Consenting subjects were enrolled into an 
extension study to assess the long-term safety and PK of VT-1161 through Week 96.   
The incidence of adverse events (AEs) was balanced across the VT-1161 treatment arms and 
placebo.    A total of 148 subjects (57%) had at least 1 TEAE, and the frequency was within the 
range of 49% to 67% for all treatment groups.  The majority of TEAEs were considered by the 
Investigator to be mild or moderate and unrelated to study drug.  Most TEAEs were transient and 
occurred during the first 12 weeks of treatment for all treatment groups, including placebo.  
Nineteen subjects reported related TEAEs through Week 60.  Sixteen subjects were on VT-1161 
and three subjects were on placebo.  The only related TEAE reported by more than 2 subjects was 
nausea.  Eleven subjects reported a total of 16 SAEs, which were considered unrelated to study 
drug.   
The incidence of study drug related TEAEs was within the range of 6% to 11% for all treatment 
groups, with the highest frequency in the 600 mg 24-week group.  The most common (≥2 total 
subjects) TEAEs that were considered related to VT-1161 were nausea, dysgeusia, dizziness, 
constipation, and decreased appetite.  The most common TEAE that was considered related to 
placebo was dizziness. 
The incidence of TEAEs leading to study drug discontinuation was low, in the range of 0% to 6% 
for all treatment groups. 
There were no clinically-relevant findings noted by the Investigators with vital signs, physical 
exam findings or ECGs. 
There was no obvious clinically-relevant effect of VT-1161 on chemistry, hematology or urinalysis 
parameters.  


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Overall, VT-1161 was safe and well-tolerated at all doses and treatment durations including the 
highest dose and longest duration evaluated of 600 mg 24-week treatment group.  The TEAEs 
were typical of the subject population being studied and were generally balanced across the 
VT-1161 treatment and placebo group. 
The primary efficacy endpoint was complete cure at Week 48.  The proportion of subjects in the 
ITT population with complete cure at Week 48 ranged from 32% to 42% in the VT-1161 treatment 
groups, with the lowest rate in the 300 mg 12–week treatment group and the highest rate in the 
600 mg 12–week treatment group. No subjects receiving placebo experienced complete cure at 
Week 48.  The proportion of ITT subjects with complete cure was statistically significantly higher 
for all VT-1161 treatment groups compared with placebo at Week 48 (p<0.001). 
Overall, the efficacy at Week 48 was clearly demonstrated in all the VT-1161 treatment groups, 
with little to no improvement seen in the placebo group.   
1.2.2.2.4 Phase 2b Study in Subjects with Recurrent Vulvovaginal Candidiasis 
In this Phase 2b study, the safety, tolerability, PK and efficacy of VT-1161 in subjects with 
recurrent vulvovaginal candidiasis was evaluated.  A total of 215 subjects participated in the study, 
were randomized to 5 treatment groups and were administered either: 
• 
Low dose 12-week: Loading doses of 150 mg once daily for 7 days, then 150 mg once weekly 
for 11 weeks, followed by placebo for 12 weeks. 
• 
Low dose 24-week: Loading doses of 150 mg once daily for 7 days, then 150 mg once weekly 
for 23 weeks. 
• 
High dose 12-week: Loading doses of 300 mg once daily for 7 days, then 300 mg once weekly 
for 11 weeks, followed by placebo for 12 weeks. 
• 
High dose 24-week: Loading doses of 300 mg once daily for 7 days, then 300 mg once weekly 
for 23 weeks. 
• 
Matching placebo 
In general, the incidence of AEs was balanced across the VT-1161 treatment arms and placebo. 
Two subjects discontinued VT-1161 because of a TEAE.  Of these two, only one TEAE was 
considered related to VT-1161 by the study investigator.  Most TEAEs were considered unrelated 
to study drug and were mild or moderate in severity.  Six SAEs were reported through Week 48 


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of the study, none of which were considered related to study drug by the investigator.  Interestingly, 
a higher incidence of bacterial vaginosis and urinary tract infections was reported in the placebo 
arm.   
There were no clinically-relevant findings noted by the investigators regarding vital signs, physical 
exam findings or ECGs. There was no obvious clinically-relevant effect of VT-1161 on chemistry, 
hematology or urinalysis parameters. 
The primary efficacy outcome measure was the proportion of subjects with one or more culture-
verified acute VVC episodes during the Maintenance Phase through Week 48 of the study in the 
ITT population.  Culture-verified acute VVC was defined as a positive fungal culture for Candida 
species associated with a clinical signs and symptoms score of ≥ 3.  The proportion of subjects 
with one or more culture-verified acute VVC episode through Week 48 was lower in VT-1161 
dosing regimens: 4.8% in 150 mg 12 weeks, 7.0% in 150 mg 24 weeks, 0.0% in 300 mg 12 weeks, 
and 4.9% in 300 mg 24 weeks, treatment groups compared with 52.2% in the placebo group. 
The difference was statistically significant in the VT-1161 dosing regimens compared with 
placebo (p<0.0001). 
In conclusion, VT-1161 was determined to be efficacious, safe and well tolerated at all dose levels 
through the final visit at Week 48 of the study. 
1.3 
Study Rationale  
RVVC can be treated with topical and/or oral agents and patients may receive maintenance 
treatment for up to 6 months or longer once the acute infection has resolved.  For most patients, 
available agents do not provide the desired delay to recurrence of an acute VVC episode, 
underlining the need for more effective treatments for RVVC.  Fluconazole has been used to treat 
acute VVC episodes in patients with recurrent disease. However, fluconazole has relatively lesser 
activity against some non-albicans species that are more common in patients with complicated 
VVC.  The current study has been designed to compare the ability of a short dosing regimen of 
VT-1161 or fluconazole in their ability to effectively treat the acute VVC infection in women with 
RVVC. 
VT-1161 has demonstrated superior in vitro antifungal activity when compared to fluconazole 
when tested against clinical isolates collected in the recently completed Phase 2b RVVC study 
VMT-VT-1161-CL-006. The MIC ranges for VT-1161 and fluconazole against the C. albicans 
isolates collected during the study (n = 355) were between <0.0005 – 0.125 µg/mL and 
<0.06 – 4 µg/mL, respectively. When all 413 collected Candida spp. isolates were considered, the 


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MIC ranges for VT-1161 and fluconazole were <0.0005 – >0.5 µg/mL and <0.06 – 32 µg/mL, 
respectively.  The mean MIC50 values for VT-1161 and fluconazole were 0.004 µg/mL and 
0.125 µg/mL, respectively, and the MIC90 values for VT-1161 and fluconazole were 0.06 µg/mL 
and 4 µg/mL, respectively (Table 4). 
Table 4. 
MIC Values of VT-1161 and Fluconazole in µg/mL for 413 Candida spp. 
Isolates Derived From Phase 2b RVVC Study 
MIC Values 
VT-1161 
Fluconazole 
Range 
<0.0005 – >0.5 
<0.06 – 32 
MIC50 
0.004 
0.125 
MIC90 
0.06 
4 
Source: Report VMT-CWRU-VT-1161-CL-006; Determination of the Minimum Inhibitory Concentration of VT-1161 Against Candida Strains 
Obtained from Clinical Trial VMT-VT-1161-CL-006. 
Abbreviations: MIC, minimum inhibitory concentration. 
 
These data suggest that VT-1161 has the ability to treat the acute infection in the RVVC patient 
population and warrant further clinical investigation evaluating its effectiveness compared to 
current standard-of-care. 
While approved oral antifungal agents often offer improved efficacy, they suffer from safety issues 
associated with their narrow therapeutic windows and off target toxicity.  Since VT-1161 is much 
more selective for fungal CYP51 and CYP metabolizing enzymes than currently used oral agents, 
the probability of safety issues, including hepatotoxicity and DDIs, should be significantly 
reduced, as evidence in the clinical safety data generated with VT-1161 to date.  The PK profile 
and extended half-life associated with VT-1161 should also limit recurrence of VVC. 
1.3.1 Rationale for Induction Phase Treatment 
Fluconazole is an approved treatment for acute VVC and is used off-label to treat patients with 
recurrent disease.  The proposed dose regimen of 3 doses of over-encapsulated fluconazole taken 
72 hours apart corresponds to a regimen that is often used as the standard of care and has been 
regularly employed during the induction phase of similar clinical studies designed to study RVVC.   
1.3.2 Dosing Regimen for VT-1161 and Fluconazole with Matching Placebo 
At Screening, subjects will be randomly assigned to receive one of the following treatment groups:  
• VT-1161: Loading dose of 600 mg on Day 1 and 450 mg on Day 2, then 150 mg once 
weekly for 11 weeks. 


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• Fluconazole: Three doses of 150 mg every 72 hours, then placebo once weekly for 11 
weeks. 
The rationale for dose selection is provided in Section 4.4, Design Justification.     
1.4 
Potential Risks and Benefits of Participating in the Study 
The Phase 1, Phase 2a, and Phase 2b studies with VT-1161 incorporated monitoring for AEs often 
reported with other azole antifungal drugs.  No clinically significant study drug related AEs were 
observed in clinical studies with VT-1161, suggesting that it may be better tolerated than 
commonly used azole agents.  


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2 OBJECTIVES 
Primary:  
• To evaluate the efficacy of oral VT-1161 in the prevention of culture-verified acute episodes 
of VVC through Week 50 in RVVC subjects. 
• To compare the efficacy of oral VT-1161 and fluconazole in the treatment of an acute VVC 
episode in RVVC subjects. 
 
Secondary:  
• To evaluate the safety and tolerability of oral VT-1161 through Week 50. 
 


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3 
STUDY ENDPOINTS 
The primary efficacy outcome measure is the proportion of subjects with one or more culture-
verified acute VVC episodes (post-randomization through Week 50) in the ITT population, which 
will include the subjects who failed clearing their infection during the Induction Phase.  An acute 
VVC episode (considered a recurrent episode) is defined as a positive culture for Candida species 
and a clinical signs and symptoms score of ≥3.  
Secondary:  
• The proportion of subjects with resolved acute VVC infections (clinical signs and symptoms 
score of <3) at Day 14 following treatment with VT-1161 or fluconazole. 
• The proportion of subjects with at least one culture-verified acute VVC episode with signs and 
symptoms of ≥3 during the Maintenance Phase (Post Day 14 through Week 50). 
• Time to first recurrence of a culture-verified acute VVC episode with signs and symptoms 
score ≥3 during the Maintenance Phase (post Day 14 through Week 50). 
• The proportion of subjects with at least one positive culture for Candida during the 
Maintenance Phase. 


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4 
STUDY DESIGN 
4.1 
Overall Study Design 
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. 
The study is designed to evaluate the efficacy and safety of VT-1161 oral capsules versus 
fluconazole and placebo in the treatment of acute vulvovaginal candidiasis episodes in subjects 
with RVVC. 
Subjects must have a history of RVVC, defined as at least 3 episodes of acute VVC in the past 
12 months, as described below:   
• Subjects must have an acute VVC episode at the time of Screening, with a documented 
positive KOH performed at the investigative site 
• Subjects must also have had 2 or more additional episodes of acute VVC in the past 12 
months, with at least 1 of the episodes documented by a positive confirmatory laboratory 
test (i.e., culture, PCR, Affirm test, KOH test, a documented Pap test, or other approved 
diagnostic test) 
The study consists of two Phases: 1) an Induction Phase for the treatment of the acute VVC 
infection in which subjects will be randomly assigned to receive with either 600 mg VT-1161 
(4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) on Day 2 and 
matching placebo capsules or 3 sequential 150 mg oral doses (every 72 hours) of over-
encapsulated fluconazole together with matching placebo capsules, and 2) a Maintenance Phase in 
which subjects will receive VT-1161 or placebo for 11 weeks and will then enter a 37-week follow-
up period. 
Once subjects have provided informed consent or assent (for those ages 12-17), the investigational 
site will evaluate all subjects by completing a review of pertinent medical history, obtaining vital 
signs, weight and height, ECG and laboratory tests, reviewing clinical signs and symptoms of 
vulvovaginitis, performing a complete physical examination including speculum examination of 
the vagina, performing a KOH wet mount test from a vaginal smear to confirm the presence of 
yeast, and collecting vaginal swabs to establish a baseline culture for identification of fungal 
species.  Eligible subjects will have a composite vulvovaginal signs and symptom score of ≥3 as 
outlined in Section 9.1.7, a positive local KOH that confirmed the presence of yeast, and must 
meet other initial entry criteria.  


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Once eligibility is confirmed, subjects will be randomized and enter the Induction Phase.  
During the Induction Phase, the presenting acute VVC infection will be treated with either 600 mg 
VT-1161 (4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) on Day 2 
or 3 sequential 150 mg oral doses (every 72 hours) of over-encapsulated fluconazole.  Subjects 
will return approximately 14 days after the first dose of VT-1161 or over-encapsulated fluconazole 
for evaluation and, if the acute VVC infection has resolved (defined by a signs and symptoms 
score of <3), they will enter into the Maintenance Phase to receive either VT-1161 or a matching 
placebo regimen.  Day 1 (Screening) is defined as the first day of investigational medicinal product 
(IMP) administration and subsequent study days are defined by the number of consecutive days 
thereafter.  If the acute VVC has not resolved (defined by a signs and symptoms score of ≥3), the 
subject will be considered an Induction failure and encouraged to see their physician for further 
evaluation and follow-up care.   
4.2 
Treatment Arms and Duration of Study 
Subjects will be randomized in a 2:1 ratio to receive VT-1161 or fluconazole and placebo. 
The duration of individual subject participation will be approximately 50 weeks: including the 
2-week Induction Phase, the 11-week Maintenance Phase, and 37 weeks of follow-up. 
Assessments and procedures will be performed as outlined in  Table 1. 
Schedule 
of 
Assessments and Procedures.  Subjects who return to the clinic for a recurrent VVC episode should 
be evaluated as per the unscheduled visit noted in the Schedule of Assessment and Procedures. 
The planned study duration is approximately 18 months from Screening of the first subject until 
the last follow-up of the last subject. 
4.3 
Number of Subjects 
Approximately 360 screened and 180 randomized subjects are planned for this study.  Assuming 
a 20% discontinuation rate for the remainder of the study, approximately 144 subjects are expected 
to complete the study. 
Subjects will be enrolled at approximately 45 U.S. sites. 
4.4 
Design Justification 
One of the study goals will be to compare the efficacy of oral VT-1161 versus fluconazole in the 
treatment of acute VVC episodes in RVVC subjects.  The proposed dosing regimen will 
incorporate an Induction Phase to treat the initial acute infection with either fluconazole or VT-
1161. 


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The fluconazole dosing regimen to be employed in the Induction Phase is in alignment with the 
recommendation proposed by the Infectious Disease Society of America (IDSA) for the treatment 
of vulvovaginal candidiasis, in which fluconazole, 150 mg, is given every 72 hours for a total of 3 
doses. This is recommendation is strongly supported by IDSA and for which high-quality evidence 
is available to support its clinical effectiveness.  
VT-1161 has previously been evaluated in a Phase 2a multi-center, randomized, double-blind, 
active-controlled, parallel-group, dose-ranging study in patients with moderate-to-severe acute 
VVC (described in Section 1.2.2.2.2).  A total of 55 subjects with moderate-to-severe acute VVC 
(severity score ≥6 and a positive fungal KOH test) participated in the study across 4 dose groups:  
1) VT-1161 300 mg qd for 3 days; 2) 600 mg qd for 3 days; 3) 600 mg bid for 3 days; or 4) a single 
dose of fluconazole 150 mg followed by matching placebo.  VT-1161 was shown to safe and well 
tolerated when administered for 3 days.  There were no serious AEs reported and no TEAEs led 
to study discontinuation.  No safety signals of clinical concern were observed from the safety 
assessments. 
The efficacy of VT-1161 in the treatment of moderate-to-severe acute VVC was evaluated at the 
TOC visit in the Per Protocol population at the Day 28 test of cure TOC visit was, 87%, 86%, 86%, 
and 75% of subjects receiving the low , mid-, or high-dose VT-1161 or comparator arm of 
fluconazole, respectively, achieved an effective therapeutic cure (defined as having a total clinical 
signs and symptoms severity score of ≤1 and a negative culture for Candida species) in the Per 
Protocol population 
It is predicted based on plasma levels obtained in previous clinical studies that the proposed 
loading dose regimen of 600 mg on Day 1 and 450 mg on Day 2 will provide for clinically effective 
plasma levels  (approximately 2 µg/mL) to treat the presenting acute Candida spp. infection a 
manner that will afford comparison of the efficacy of oral VT-1161 and fluconazole in the 
treatment of an acute VVC episode in subjects with RVVC.   
Similar and higher doses of VT-1161 have been studied previously in subjects with onychomycosis 
(VMT-VT-1161-CL-005), with a maximum high dose of 600 mg once daily for 2 weeks, then 600 
mg once weekly for 22 weeks administered (see Section 1.2.2.2.3). 
The proposed VT-1161 dosing regimen for the current Phase 3 studies will also incorporate a 
150 mg once weekly maintenance dose phase for 11 weeks.  Based on the PK results from the 
Phase 2b study, it is expected that this will provide a mean plasma concentration of approximately 
2.5 µg/mL at the end of the dosing period (Week 14). 


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4.4.1 Justification for Inclusion of Adolescents in the Study 
Vulvovaginal candidiasis, and especially RVVC, is rare in pre-menarchal girls (typically pre-
adolescents less than 12 years of age) and epidemiological data is generally lacking for this 
population. 
Adolescent females (ages 12 to 17 years, inclusive) represent a menarchal population that is newly 
influenced by reproductive hormones. The changes in reproductive hormones in adolescents cause 
vast changes in tissues and may increase the susceptibility to VVC. In this population, cases of 
VVC and RVVC exist but are substantially less common than in adult females. While 75% of 
healthy women will likely experience one episode of VVC in their lifetime, and potentially 9% 
will be characterized as having recurrent disease, the prevalence of symptomatic acute VVC in 
adolescents is less than 2% of the population and there is no published data that addresses the 
incidence of RVVC in this patient population (Fidel, 2002; Blostein, 2017; Barousse, 2004). 
Presenting symptoms of VVC in menarchal adolescents are similar to those in the adult population, 
and treatment typically consists of topical antifungal preparations while oral antifungal agents are 
prescribed only in severe or complicated cases (Joishy, 2005).  The dose and administration of the 
agents used in adolescents are the same as those used in adult females with VVC and RVVC. 
The United States FDA Draft Guidance Vulvovaginal Candidiasis: Developing Drugs for 
Treatment states that while uncomplicated VVC is unlikely to occur in healthy pre-menarchal girls, 
post-menarchal adolescent girls with VVC should be included in Phase 3 trials.  Accordingly, the 
present study will follow guidance received by the United States FDA reviewers and will allow 
enrollment of subjects 12 to 17 years of age (inclusive) to collect as much information as possible 
on the treatment of the adolescent population with RVVC. 


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5 
SELECTION OF STUDY POPULATION 
The following criteria for enrollment must be followed explicitly.  A subject will not be enrolled 
unless the following inclusion/exclusion criteria are met.  The Investigator or other study site 
personnel must record in the source documents (e.g., the site’s chart) and case report form (CRF) 
that the informed consent document or assent (for those ages 12-17) was signed and dated prior to 
any study procedures.  The presence of inclusion criteria and absence of exclusion criteria will be 
verified by the Investigator in the subject’s clinic chart. 
5.1 
Inclusion Criteria 
1. Subjects must be generally healthy, non-pregnant, post-menarchal females 12 years of age and 
older as of Screening. 
2. Subjects must have a history of recurrent VVC as defined by three (3) or more patient reported 
and/or laboratory confirmed episodes of acute VVC in the past 12 months including the 
episode confirmed at Screening, with at least one episode (not including the current episode) 
documented by a positive culture, PCR, Affirm test, KOH test, or a documented Pap test in the 
prior 12 months revealing filamentous hyphae/pseudohyphae and/or budding yeast cells. 
3. Subjects must have an acute VVC infection at Screening, defined as a total signs and symptoms 
score of ≥3 and a positive KOH wet mount preparation from a vaginal smear revealing 
filamentous hyphae/pseudohyphae and/or budding yeast cells. 
4. Subjects must have a composite vulvovaginal signs and symptoms score of <3 at the Day 14 
Visit. 
5. Subjects must have a documented Pap test results at Screening or within the current standard 
of care guidelines for the appropriate age requirement, reported as either “negative for 
intraepithelial lesion or malignancy” or “ASCUS-atypical squamous cells of undetermined 
significance” (not applicable to subjects with a history of total hysterectomy). 
6. Subjects must be suitable candidates for oral therapy and be able to swallow capsules intact.  
7. Subjects must be willing and able to provide written informed consent or assent (for those ages 
12-17) and authorization for use of protected health information. 
8. Subjects must be willing and able to comply with protocol requirements, instructions, and 
protocol-stated restrictions and be likely to complete the study as planned. 
9. Subjects of non-childbearing potential must meet the requirements defined below: 


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a. Pre-menopausal with documentation of surgical sterilization (i.e., hysterectomy, 
bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy) at least 
3 months prior to study entry. 
b. Post-menopausal defined as amenorrhea for at least 12 months following cessation of 
all exogenous hormonal treatments at Screening. 
10. Subjects of childbearing potential (includes ages 12 to 17) must use 1 of the following methods 
of contraception during the study through Week 50: 
OPTION 1 - Highly effective methods that can be used alone: 
1. Copper intrauterine device used continuously and successfully 
for at least 90 days prior to first dose of study druga 
2. Levonorgestrel-releasing intrauterine system used successfully 
for at least 90 days prior to first dose of study druga 
3. Progestin implant used successfully for at least 90 days prior to 
first dose of study druga 
4. Monogamous with a vasectomized male partner (vasectomy 
performed at least 6 months prior to first dose of study drug)a 
5. Abstinenceb 
OPTION 2 – Acceptable first and second barrier methods to be used in 
combination: 
FIRST (Hormonal Contraception)a 
1. Estrogen & progestin oral contraceptives, transdermal patch or 
vaginal ring used successfully for at least 90 days prior to first 
dose of study drug 
2. Progestin only oral contraceptives or injection used successfully 
for at least 90 days prior to first dose of study drug 
SECOND (Barrier Method) 
1. Diaphragm (with spermicide) 
2. Cervical cap (with spermicide) 
3. Male condom (with or without spermicide) 
In addition to OPTIONS 1 and 2, subjects of childbearing potential (includes ages 
12-17) may also use 1 of the following methods of contraception after completing 
the Induction Phase on Study Day 1 through Week 50: 


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OPTION 3 (Day 14 – Week 50)c – Acceptable first and second barrier methods to 
be used in combination: 
FIRST (Barrier Method) 
1. Diaphragm (with spermicide) 
2. Cervical cap (with spermicide) 
SECOND (Barrier Method) 
1. Male condom (with or without spermicide) 
a Subjects who started using an intrauterine device or any of the hormonal contraceptive methods 
described above less than 3 months prior to the first dose of study medication must agree to use a 
double-barrier method (i.e., diaphragm plus spermicide or condom) through 3 months after start 
of the use of the IUD or hormonal contraceptive. Similarly, subjects that claim a monogamous 
relationship with a vasectomized male partner where the vasectomy was performed less than 6 
months prior to the first dose of study medication, must agree to use a double-barrier method (i.e., 
diaphragm plus spermicide or condom) through 6 months after the date of the vasectomy. 
b Sexual abstinence is defined as refraining from heterosexual intercourse during the entire study 
period and where this is the usual life style of the subject. Periodic abstinence (calendar, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhoea method are not considered to be acceptable methods of contraception. 
c Because of the teratogenic risk associated with repeat dosing of fluconazole, OPTION 3 
contraceptive, methods cannot be used during Screening and the Induction Phase of the study 
[from Screening (Day 1) until Day 14 of the study].  
5.2 Exclusion Criteria 
1. Subjects must not have the presence of concomitant vulvovaginitis caused by other pathogens 
(e.g., bacterial vaginosis, Trichomonas vaginalis, Chlamydia trachomatis, or Neisseria 
gonorrhoeae) at Screening visit (Day 1) visit. 
2. Subjects must not have an active HPV infection as evidenced by visible condylomas on 
vulvovaginal examination at Screening (Day 1) visits. 
3. Subjects must not have the presence or a history of another vaginal or vulvar condition(s) that 
in the Investigator’s opinion would confound the interpretation of clinical response. 
4. Subjects must not have a history of cervical cancer. 


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5. Subjects must not use any systemic (e.g., oral or injectable) corticosteroid therapy during the 
study or within 30 days prior to Screening; nor use of topical vulvar or vaginal steroids during 
the study or within 7 days prior to Screening visit. However, use of topical (no vulvar or vaginal 
steroids), inhaled, ophthalmic, collunarium/nasal, intraarticular and intralesional steroids is 
permitted.  
6. Subjects must not use any systemic (e.g., oral or injectable) or topical (applied to the vulva or 
vaginal area) antifungal, antibacterial, or antitrichomonal drugs for the treatment of bacterial 
vaginosis, trichomonas, or other concomitant urogenital infection during the study (unless 
prescribed by the Investigator) or within 7 days prior to Screening. 
7. Subjects must not be using drugs with a narrow therapeutic index that are metabolized by 
CYP3A4 and sensitive to induction of CYP3A4 during the study (carbamazepine, cyclosporine, 
fentanyl, quinidine, sirolimus and tacrolimus). 
8. Subjects must not use any vaginal estrogen replacement therapy, ospemifene, Vitamin E gel 
capsules (vaginally) or lubricants within 7 days prior to Screening. 
9. Subjects must not have a condition that would require treatment during the study with 
concomitant topical (applied to vulva and vagina) or systemic antimicrobial therapy for any 
reason. 
10. Subjects must not have received an immunosuppressive medication (e.g. cyclosporine, 
tacrolimus, methotrexate, 6 mercaptopurine, mycophenolate, etc.), or radiation therapy within 
3 months prior to Screening or have a medical condition where it would be likely that the 
subject may need to use these therapies during the study. 
11. Subjects must not have evidence of any clinically significant major organ disease or current 
clinically significant infection or any other conditions (with the exception of acute VVC) that 
may affect the clinical assessment of RVVC per Investigator judgment. 
12. Subjects must not have any comorbid condition that in the opinion of the Investigator would 
preclude the safe participation of the subject in the study or would prevent the subject from 
meeting the study requirements. 
13. Subjects must not have any condition that in the opinion of the Investigator could impact drug 
absorption (e.g. gastrectomy, Roux-en-Y gastric bypass surgery, gastric bands or staples, etc.), 
distribution, or elimination. 


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14. Subjects must not have poorly controlled diabetes mellitus (HbA1c ≥8.5% at Screening; 
performed only on known diabetics or subjects suspected to have diabetes by the investigative 
site). 
15. Subjects must not have moderate or severe hepatic and/or renal disease (defined in Appendix B 
and Appendix C). 
16. Subjects must not have a laboratory abnormality that in the opinion of the Investigator is likely 
to introduce additional risk to the subject or might interfere with data interpretation. 
The specific findings listed below are excluded at Screening (a single repeat laboratory 
evaluation is allowed for eligibility determination, except for HIV, HBsAg and antibodies to 
hepatitis C virus): 
a. Serum ALT ≥2.0x the upper limit of normal (ULN) of the reference range. 
b. Serum AST ≥2.0x the ULN of the reference range.  
c. Serum total bilirubin ≥1.5x the ULN of the reference range, unless the elevation is 
consistent with Gilbert’s Syndrome.  
d. Electrocardiographic QTc interval >470 msec as corrected by the Fridericia formula, 
or any clinically significant electrocardiographic abnormality. 
e. Positive test for antibodies to human immunodeficiency virus (HIV), hepatitis B 
surface antigen (HBsAg), or antibodies to hepatitis C virus. 
17. Subjects of childbearing potential must not be pregnant (positive pregnancy test at Screening), 
lactating, or planning to become pregnant during the study period. 
18. Subjects must not have planned surgery or other medical procedures that in the Investigator’s 
opinion would impact compliance with the protocol. 
19. Subjects must not have active substance abuse (e.g., drugs of any kind, including alcohol) or 
any other medical, psychiatric or social condition that in the Investigator’s opinion would 
preclude compliance with the protocol.   
20. Subjects must not have received VT-1161 study medication in a previous study. 


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21. Subjects must not have received any IMP in a clinical trial within 5 half-lives of that IMP prior 
to Screening (if unknown, 60 days prior to Screening). 
22. Subjects must not have a known history of intolerance or hypersensitivity to azole antifungal 
drugs (e.g., fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole), or any 
excipients of the capsule formulation. 
 


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6 INVESTIGATIONAL MEDICINAL PRODUCT 
All protocol-specific criteria for administration of study treatments must be met and documented 
prior to IMP administration. Study treatments will be administered only to eligible subjects under 
the supervision of the Investigator. 
6.1 Description of Investigational Medicinal Product 
6.1.1 VT-1161 
Active IMP will be supplied by Mycovia Pharmaceuticals (or its designee) as capsules containing 
150 mg of VT-1161. 
6.1.2 Fluconazole 
Over-encapsulated fluconazole tablets containing 150 mg of active pharmaceutical ingredient will 
be provided by Mycovia Pharmaceuticals (or its designee) for use in the randomized treatment 
assignment during the Induction Phase. 
Fluconazole tablets containing 150 mg of active pharmaceutical ingredient will be provided by the 
Investigator or Mycovia Pharmaceuticals (or its designee) for treatment of acute VVC episodes 
during the Maintenance Phase (as described in Section 7.4.2). Fluconazole will be reimbursed by 
Mycovia Pharmaceuticals. 
6.1.3 Placebo 
Two placebo products will be supplied by Mycovia Pharmaceuticals (or its designee): 
• capsules matching the appearance of VT-1161 capsules  
• capsules matching the appearance of the over-encapsulated fluconazole tablets  
6.2 Investigational Medicinal Product Labeling and Packaging 
Mycovia Pharmaceuticals (or its designee) will package the VT-1161, over-encapsulated 
fluconazole and placebo capsules.  IMP will be supplied according to applicable regulatory 
requirements.  Information pertaining to labeling and a description of the specific packaging and 
storage conditions will be supplied to the Investigator or designee.   
VT-1161, over-encapsulated fluconazole, and matching placebos will be provided in 2 bottles for 
dosing during Days 1-7 and in a single bottle for weekly dosing through Week 14 of the study. 


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6.3 Investigational Medicinal Product Storage Conditions 
IMP will be stored in a secure location at a controlled room temperature of 15°C to 25°C (59°F to 
77°F) and protected from light and moisture.  The storage of IMP will be locked with limited 
access, available to appropriate study personnel only. 
6.4 Receipt of Supplies/Handling/Storage 
Only subjects enrolled in the study may receive study treatment, and only authorized site staff may 
supply or administer study treatment. All study treatments must be stored in a secure 
environmentally controlled and monitored area in accordance with the labelled storage conditions 
with access limited to the Investigator and authorized staff. 
Further guidance and information for final disposition of unused study treatments are provided in 
the Study Procedures Manual. 
6.5 Investigational Medicinal Product Accountability 
Mycovia Pharmaceuticals will provide the Investigator with sufficient amounts of IMP.  It is the 
responsibility of the Investigator to ensure that a current record of inventory/IMP accountability is 
maintained. 
6.6 Investigational Medicinal Product Return 
Upon the completion or termination of the study, and with supporting documentation from 
Mycovia Pharmaceuticals (or designee), all unused and/or partially used IMP should be returned 
to Sponsor or its designee or destroyed at the investigational site per the site’s standard operating 
procedure (SOP) for IMP destruction.  Prior to destruction of any used or unused IMP at a site, 
Mycovia Pharmaceuticals (or designee) must review and provide written documentation that: 
1. The site SOP for IMP destruction is acceptable.  
2. The clinical site monitor has conducted and documented full accountability of the 
IMP.  


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7 TREATMENT OF SUBJECTS 
7.1 Investigational Medicinal Product Administration and Dosing Schedule  
7.1.1 Induction Phase (Screening/Randomization to Day 14) 
At Screening all subjects will be randomized to receive either: 
• 600 mg VT-1161 (4 x 150 mg capsules) on Day 1, and 450 mg VT-1161 (3 x 150 
mg capsules) on Day 2, OR 
• 3 sequential doses (every 72 hours) of over-encapsulated fluconazole 150 mg 
starting on Day 1 
The number of capsules with active pharmaceutical ingredient (VT-1161 or fluconazole) and 
inactive capsules (placebo) for each treatment arm during the Induction Phase is described in 
Table 5. 
Table 5. 
Number of Capsules Taken Per Treatment Group During Induction Phase 
Treatment 
Group 
Investigational Medicinal 
Product 
Day 1  
(# capsules) 
Day 2 
(# capsules) 
Day 4  
(# capsules) 
Day 7  
(# capsules) 
VT-1161 
VT-1161 
4 
3 
0 
0 
Placebo 
(Matching Fluconazole) 
1 
0 
1 
1 
Fluconazole 
Fluconazole 
1 
0 
1 
1 
Placebo 
(Matching VT-1161) 
4 
3 
0 
0 
  
Regarding the dosing of fluconazole in adolescent subjects (12 to 17 years of age, inclusive), 
fluconazole exposure at the planned dose is anticipated to be similar to that in adults and 
proportional to weight. AEs associated with fluconazole would also be expected to be similar in 
adolescents as in adults. There are currently no United States FDA- or European-approved doses 
or regimens of fluconazole for treatment of VVC or RVVC in adolescents. While the United States 
FDA-approved labeling for fluconazole (Diflucan, Pfizer 2017) is silent on treatment of 
adolescents with VVC, the European prescribing information for fluconazole (Diflucan® Summary 
of Product Characteristics [2017]) provides the following guidance; “If treatment is imperative in 
adolescents (from 12 to 17 years old), the posology should be the same as in the adult population.”  
Therefore, adolescent subjects (ages 12 to 17 years) enrolled in the study will receive the same 
150 mg doses of fluconazole as adult subjects. 


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7.1.2 Maintenance Phase (Day 14 to Week 14) 
Subjects returning to the site approximately 14 days after the first dose of VT-1161 or over-
encapsulated fluconazole and demonstrating resolution of the VVC infection (defined by a signs 
and symptoms score of <3) will receive either: 
• 150-mg once weekly dose of VT-1161 for 11 weeks, if initially randomized to 
receive VT-1161 or  
• a matching placebo regimen for 11 weeks, if initially randomized to receive 
fluconazole.   
Subjects will be instructed to take the doses of VT-1161 within 30 minutes after ingestion of the 
subject’s main meal (as determined by the subject), at approximately the same time of the day 
consistently throughout the study.  Subjects should consume approximately 240 mL 
(approximately 8 oz.) of water with each dose of IMP.  Subject’s Day 14 is defined as the first day 
of weekly dosing of IMP administration. 
7.2 Method of Assigning Subjects to Treatment Groups 
Each subject who completes the study Screening assessments, meets all eligibility criteria, and is 
accepted for the study will be assigned a unique sequential identification number and will receive 
the corresponding treatment according to the randomization scheme described in the Statistical 
Analysis Plan (SAP).  For more information on subject randomization, see Section 7.7. 
7.3 Dose Interruptions and Modifications 
If any subject experiences a Grade 3 AE that is considered possibly related, or related to IMP, 
dosing will be discontinued in that subject and the AE will be followed until resolution (refer to 
Section 9.2 for AE reporting).  Dosing of IMP will not be re-initiated in any subject who 
experiences a possibly related or related Grade 3 AE.  Although these subjects should stop the 
study drug, they are encouraged to return for their remaining study visits.  Elevation in laboratory 
values that do not require medical or surgical treatment or discontinuation from the study will not 
be considered AEs (Section 9.2.1). 
If any subject experiences a Grade 4 AE that is considered possibly related or related to IMP, the 
subject may be unblinded at the discretion of the Mycovia Pharmaceuticals’ Medical Monitor and 
Investigator and dosing of IMP will be discontinued, and the AE will be followed until resolution.  
Dosing of IMP will not be re-initiated in any subject who experiences a possibly related or related 
Grade 4 AE. 


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7.4 Prohibited and Permitted Medications/Non-Medications 
All medications taken 30 days prior to the Screening visit including all prescription and non-
prescription medications (e.g., herbal and/or vitamin supplements), through the End of Study 
(EOS) visit will be recorded for each subject.  
All concomitant therapies and procedures (including any surgical and diagnostic procedures) that 
were performed 72 hours prior to Screening through the EOS visit will be recorded for each 
subject. 
7.4.1 Prohibited Medications/Non-Medications 
The following prescription and over-the-counter drug products are prohibited during the study and 
will be considered a protocol deviation: 
1. Topical or oral antifungal drugs (with the exception of fluconazole when prescribed by the 
Investigator to treat a subject with a recurrent VVC episode. If subject fails to respond to 
fluconazole treatment, the Investigator may employ treatment options corresponding to us the 
site’s standard of care treatment to treat the infection upon consult with the Medical Monitor.)  
2. Topical products applied to the vulva or vagina (e.g. antibiotic, antitrichomonal, 
corticosteroids, or anti-inflammatory agents). 
3. Oral antibacterial or antitrichomonal agents for the treatment of bacterial vaginosis, 
trichomonas, or other concomitant urogenital infection unless prescribed by the Investigator.  
4. Oral or injectable corticosteroid or immunosuppressive drugs for the duration of the study.  
Use of topical (no vulvar or vaginal steroids), inhaled, ophthalmic, or intraarticular and 
intralesional steroids is permitted. 
5. Drugs with a narrow therapeutic index that are metabolized by CYP3A4 and sensitive to the 
induction of CYP3A4 (carbamazepine, cyclosporine, fentanyl, quinidine, sirolimus and 
tacrolimus). 
 
7.4.2 Permitted Medications/Non-Medications  
The Investigator may prescribe a single dose of fluconazole to treat an acute VVC recurrence 
during the Maintenance Phase, when confirmed by a positive local KOH wet mount showing 
presence of yeast and clinical signs and symptoms score of ≥3. 


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Medications to treat any AEs the subject experiences during the study are permitted.  If a subject 
is unable to comply with the excluded medications criteria (Section 7.4.1), the subject’s continued 
participation in the study will be re-evaluated by the Investigator, in consultation with Mycovia 
Pharmaceuticals’ Medical Monitor. 
7.5 Treatment Compliance 
IMP will be administered or dispensed only to eligible subjects under the supervision of the 
Investigator. 
7.6 Replacement of Study Subjects  
Any subject who receives ≥1 dose of study drug will be considered evaluable and will not be 
replaced. 
7.7 Randomization and Blinding 
A randomized design through an interactive web response system (IWRS) will be used to assign 
subjects in a 2:1 ratio to the dose regimen of VT-1161 or fluconazole and placebo.  Day 1 
(Screening) is defined as the first day of VT-1161/fluconazole administration and subsequent study 
days are defined by the number of consecutive days thereafter. 
The subjects, study Investigators and their staff, all clinical staff members within Mycovia 
Pharmaceuticals, the clinical study monitor, the study project team, and the study Medical 
Monitor(s) will remain blinded to individual treatment assignments until the completion of the 
study.  The Unblinded Statistician responsible for creating the final randomization list and the 
IWRS personnel responsible for loading the final randomization list into the IWRS will be 
unblinded to the treatments.  The bioanalytical personnel responsible for assay of VT-1161 in 
plasma samples will also be unblinded to subject treatments. 
 
 


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7.8 Conditions for Breaking the Blind 
In the event the breaking of the blind is required, the following will apply: 
• The Investigator may unblind a subject’s treatment assignment only in the case of an 
emergency (i.e., a Grade 4 AE) OR in the event of a serious medical condition when knowledge 
of the study treatment is essential for the appropriate clinical management or welfare of the 
subject as judged by the Investigator (ICH GCP 4.3.1).  If the SAE requires that an expedited 
regulatory report be sent to 1 or more regulatory agencies, a copy of the report, identifying the 
subject’s treatment assignment, may be sent to Investigators in accordance with local 
regulations. 
• The Investigator must contact the Medical Monitor or appropriate Mycovia Pharmaceuticals 
study personnel to communicate the reasons for unblinding the subject’s treatment assignment 
immediately after the unblinding occurred (ICH GCP 4.7). 
• If unblinding is required, the Mycovia Pharmaceuticals’ Medical Monitor and the Investigator 
will be provided with the treatment assigned to the subject. The Investigator must NOT 
disclose the treatment assignment to the subject and/or other study personnel including other 
site personnel, monitors, or the Sponsor’s project team; nor should there be any written or 
verbal disclosure of the code in any of the corresponding subject documents.  The treatment 
assignment of the subject is to be revealed only if that information is important to the safety of 
subjects currently in the study. 
• The date and reason for unblinding must be fully documented in the eCRF. 
7.9 Treatment After the End of the Study 
After the completion 
of 
the 
study, 
Mycovia 
Pharmaceuticals 
will follow local 
regulatory/International Conference on Harmonisation (ICH) guidelines for any follow-up 
treatment provided to subjects. The Investigator is responsible for ensuring that consideration has 
been given to the post-study care of a subject’s medical condition. 


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8 STUDY PROCEDURES  
8.1 Assessments and Procedures 
The study subjects should be seen within the timeframes noted in the Table 1. Schedule of 
Assessments and Procedures.  All study visits should be scheduled within the visit windows and 
projected from the Screening (Day 1) visit.




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a. 
All medication taken 30 days prior to Screening and all non-pharmacologic treatments received 72 hours prior to Screening will be recorded through the EOS visit. 
b. Weight only. 
c. 
Vital signs include sitting heart rate, blood pressure, temperature, and respiratory rate.  
d. Limited physical examination, i.e. vaginal speculum examination plus a symptom directed physical examination. 
e. 
Subjects participating in the intense Day 1 and Day 2 PK collection will have samples taken predose and 1, 2, 4, and 8 hours after dosing.  All subjects will have PK draws prior 
to IMP on Day 14 and Week 14 and at Week 50. 
f. 
Serum chemistry (creatinine, BUN, AST, ALT, alkaline phosphatase, total bilirubin, conjugated bilirubin, albumin, total protein, total carbon dioxide, glucose, sodium, 
potassium, chloride, calcium, and phosphorus, and creatine phosphokinase [CK], cholesterol and triglycerides). Testing for HbA1c is performed only in known or suspected 
diabetic subjects at Screening. Cultures to test for Chlamydia trachomatis and Neisseria gonorrhoeae will be taken at Screening and sent to the central lab. Testing for bacterial 
vaginosis will be done locally at Screening. An OSOM® Rapid test or similar test will be performed for Trichomonas vaginalis locally at Screening. 
g. For WOCBP, a local lab urine and central lab serum pregnancy test will be obtained at the Screening Day 1 visit. A central lab serum pregnancy test will be performed at Weeks 
14, 26, and 50. 
h. IMP is to be administered within 30 minutes after the subject’s main meal of the day (as determined by the subject) at approximately the same time of the day consistently 
throughout the study. Approximately 240 mL (approx. 8 oz.) of water is to be consumed with each dose of IMP.  
Subject will be randomized to receive either 600 mg VT-1161 (4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) on Day 2 followed by 11 weekly 
doses of 150mg VT-1161, or 3 sequential 150 mg oral doses (every 72 hours) of over-encapsulated fluconazole followed by 11 weekly doses of placebo. In the Induction Phase, 
IMP may be over-encapsulated and matching placebo capsules will be provided to maintain study blind. Subjects participating in the intense PK collection will be required to 
take the Days 1 and 2 IMP at the Investigational site.  
Remind subject to bring IMP to each visit to assess compliance.  
i. 
Only subjects participating in the intense PK will come in for the Day 2 visit. 
j. 
All procedures listed are to be completed only for unscheduled visits where a recurrent VVC episode is suspected. If the unscheduled visit is for repeat procedures (i.e., ECG, 
safety labs, etc.), only those specific procedures need to be performed, along with collection of any changes in medical treatments or medications and collection of any AEs. 


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8.1.1 Screening (Day 1) Assessments and Procedures 
The subject will be randomized and start IMP at Screening if the subject has met all preliminary 
enrollment criteria, (central lab results are not required to initiate IMP).  Proper written 
informed consent or assent (for those ages 12-17) must be obtained from all subjects prior to 
any study procedures, see Section 13.2 for more information.  Once the subject has signed the 
Institutional Review Board (IRB) approved informed consent document or assent the following 
evaluations will be performed to assess subject eligibility: 
1. Review Inclusion and Exclusion criteria. 
2. Document subject demographics, including date of birth, race, and ethnic origin.  
3. Document and review medical/medication and surgical history, including all current, 
pertinent and major past illnesses and surgical procedures.  All concomitant therapies 
or procedures (including any surgical or diagnostic procedures) that were performed 
72 hours prior to the Screening will be recorded. 
4. Review alcohol and tobacco history (previous 12 months). 
5. Record all medications, including prescription and non-prescription medications, 
herbal products, and vitamin/mineral supplements taken within 30 days prior to 
Screening.       
6. Assess height and weight to determine the body mass index. 
7. Obtain vital signs in the sitting position (blood pressure, heart rate, respiratory rate, and 
temperature). 
8. Conduct a comprehensive physical examination, including vaginal exam, as described 
in Section 9.1.3.  For proper assessment, it is best the subject is not menstruating at 
time of the visit. 
9. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7.  Subjects must be cautioned to not use any treatment (topical or systemic) for 
their infection during the Screening period. 
10. KOH wet mount test, performed locally (Section 9.1.6). 


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11. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
12. Standard 12-lead ECG will be obtained in the supine position (Section 9.1.4).    
13. Clinical chemistries, hematology, and urinalysis for study eligibility as outlined in 
Section 9 and the Schedule of Assessments and Procedures.  Cultures for testing of 
Chlamydia trachomatis and Neisseria gonorrhoeae will also be taken.  Vaginal pH will 
be determined.  Local testing will be done for Bacterial vaginosis and an OSOM® 
Rapid test or similar test will be performed locally for Trichomonas vaginalis.   
14. Testing for HBsAg, HCV, and HIV as outlined in Section 9.1.5.2 and the Schedule of 
Assessments and Procedures (results for these tests are not required for the start of the 
Induction Phase). 
15. A urine pregnancy test will be performed locally and a serum pregnancy test will be 
obtained and sent to the central laboratory for all women of childbearing potential 
(WOCBP). 
16. For subjects participating in intense PK sampling at participating sites, administer IMP 
within 30 minutes after a site-provided meal and 240 mL of water. 
17. For subjects participating in intense PK sampling at participating sites, PK samples will 
be obtained pre-dose and at 1, 2, 4, and 8 hours after dosing.  This is outlined in 
Section 10.1 and the Schedule of Assessments and Procedures. 
18. IWRS randomization of the subject to a treatment arm. 
19. Provide two bottles of IMP for Induction Phase dosing to subject along with dosing 
instructions. 
20. Remind subjects that consented to intense PK sampling to return for Day 2 visit. 
21. Remind subject that have NOT consented to intense PK sampling, to return for Day 14 
visit.   
Safety laboratory results are not required prior to start of treatment with IMP and mycology 
results will not be sent to sites. Subjects may be eligible for re-screening and the investigate 


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site is to refer to the Study Procedures Manual and contact the study clinical monitor for 
guidance. 
8.1.2 Day 2 Assessments and Procedures – Intense PK Sampling 
The subjects who have consented to intense PK sampling will return to the investigative site 
for the following evaluations: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the last visit will be recorded. 
2. Review and record any AEs.  
3. Administration of IMP within 30 minutes after a site-provided meal and 240 mL water. 
4. PK samples will be obtained pre-dose and at 1, 2, 4, and 8 hours after dosing.  This is 
outlined in Section 10.1 and the Schedule of Assessments and Procedures. 
5. Remind subject to return for Day 14 visit.   
8.1.3 Day 14 (±2 Days) Assessments and Procedures 
The subjects will return to the investigative site for the following evaluations: 
1. Confirm all Inclusion and Exclusion criteria have been met 
2. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the last visit will be recorded. 
3. Review and record any AEs.  
4. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
5. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 


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6. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects with clinical signs and symptoms score of < 3 will continue into 
Maintenance Phase and subjects with score of ≥3 will be an Induction failure, ending 
study participation. Subjects must be cautioned to not use any treatment (topical or 
systemic) for vulvovaginitis except study drug.  
7. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
8. Standard 12-lead ECG will be obtained in the supine position (Section 9.1.4).  
9. Obtain PK plasma specimen. 
10. Obtain clinical chemistries, hematology, and urinalysis as outlined in Section 9 and the 
Schedule of Assessments and Procedures.  
11. Collect and review accountability of the two IMP Induction Phase bottles with the 
subject for compliance.  
12. Dispense bottle for IMP Maintenance Phase dosing (weekly) to the subject along with 
instructions 
13. Remind subject to return for Week 8 (±7 days) visit. 
8.1.4 Week 8 (±7 Days) Assessments and Procedures 
Subjects will return to the investigative site for follow-up evaluation as follows: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. All 
concomitant therapies or procedures (including any surgical or diagnostic procedures) 
that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
4. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
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5. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
6. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
7. Obtain clinical chemistries, as outlined in Section 9.1.5.3. 
8. Review accountability of IMP Maintenance Phase bottle with the subject for 
compliance.   
9. Remind subject to return for Week 14 (±14 days) visit. 
8.1.5 Week 14 (±14 Days) Assessments and Procedures (End of Treatment) 
The subjects will return to the investigative site for the following evaluations: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain body weight. 
4. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
5. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
6. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
7. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
8. Standard 12-lead ECG will be obtained in the supine position (Section 9.1.4).  


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9. Obtain PK plasma specimen. 
10. Obtain clinical chemistries, hematology, and urinalysis as outlined in Section 9 and the 
Schedule of Assessments and Procedures.  
11. Obtain serum sample for pregnancy testing for all WOCBP. 
12. Collect and conduct final review accountability of IMP Maintenance Phase bottle with 
the subject for compliance.  
13. Remind subject to return for Week 20 (±14 days) visit. 
8.1.6 Week 20 (±14 Days) Assessments and Procedures 
The subjects will return to the investigative site for the following evaluations: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
4. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
5. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
6. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
7. Obtain clinical chemistries, as outlined in Section 9.1.5.3. 
8. Remind subject to return for Week 26 (±14 days) visit. 


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8.1.7 Week 26 (±14 Days) Assessments and Procedures 
Subjects will return to the investigative site for follow-up evaluations as follows: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain body weight. 
4. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
5. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
6. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
7. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
8. Standard 12-lead ECG will be obtained in the supine position (Section 9.1.4).  
9. Obtain clinical chemistries, hematology, and urinalysis as outlined in Section 9 and the 
Schedule of Assessments and Procedures.  
10. Obtain serum sample for pregnancy testing for all WOCBP. 
11. Remind subject to return for Week 32 (±14 days) visit. 
8.1.8 Week 32 (±14 Days) Assessments and Procedures 
Subjects will return to the investigative site for follow-up evaluations as follows: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 


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All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
4. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
5. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
6. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
7. Obtain clinical chemistries, as outlined in Section 9.1.5.3. 
8. Remind subject to return for Week 38 (±14 days) visit. 
8.1.9 Week 38 (±14 Days) Assessments and Procedures 
Subjects will return to the investigative site for follow-up evaluations as follows: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
4. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 


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5. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
6. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
7. Obtain clinical chemistries, hematology, and urinalysis as outlined in Section 9 and the 
Schedule of Assessments and Procedures.  
8. Remind subject to return for Week 44 (±14 days) visit. 
8.1.10 Week 44 (±14 Days) Assessments and Procedures 
Subjects will return to the investigative site for follow-up evaluations as follows: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
4. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
5. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
6. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
7. Obtain clinical chemistries, as outlined in Section 9.1.5.3. 
8. Remind subject to return for Week 50 (±14 days) visit. 


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8.1.11 Week 50 (±14 Days) Assessments and Procedures (End of Study) 
Subjects will return to the investigative site for follow-up evaluations as follows: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain body weight. 
4. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
5. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
6. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
7. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
8. Standard 12-lead ECG will be obtained in the supine position (Section 9.1.4).  
9. Obtain PK plasma specimen. 
10. Obtain clinical chemistries, hematology, and urinalysis as outlined in Section 9 and the 
Schedule of Assessments and Procedures.  
11. Obtain serum sample for pregnancy testing for all WOCBP. 
If the Investigator suspects the subject is experiencing a recurrent episode at a regular study 
visit, a local KOH wet mount test is to be performed to confirm whether filamentous 
hyphae/pseudohyphae and/or budding yeast cells are present. 


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8.1.12 Unscheduled Visit Assessment and Procedures 
Subjects should be encouraged to return for an unscheduled visit if they experience a 
recurrence of VVC anytime during the study.  The following evaluations are to be performed: 
1. Record all medications taken since the previous visit, including all prescription and 
non-prescription medications, herbal products, and vitamin/mineral supplements. 
All concomitant therapies or procedures (including any surgical or diagnostic 
procedures) that were performed since the previous visit.     
2. Review and record any AEs.  
3. Obtain vital signs in the sitting position, (blood pressure, heart rate, respiratory rate, 
and temperature). 
4. Limited physical examination, includes vaginal exam (as described in Section 9.1.3).  
For proper assessment, it is best the subject is not menstruating at time of the visit. 
5. Recording of clinical signs and symptoms of vulvovaginitis, as outlined in Section 
9.1.7. Subjects must be cautioned to not use any treatment (topical or systemic) for 
vulvovaginitis except study drug. 
6.  KOH wet mount test, performed locally (Section 9.1.6). 
7. Vaginal swab for culture will be obtained and sent to the central mycology laboratory 
(Section 9.1.6). 
8. Obtain clinical chemistries, as outlined in Section 9.1.5.3. 
If a subject has a recurrent acute VVC episode prior to the end of treatment at Week 14, the 
subject will continue her assigned treatment through Week 14 and will receive one dose of 
fluconazole to treat her acute VVC infection.  Throughout the Maintenance Phase, the 
Investigator is to prescribe one dose of fluconazole to treat the acute VVC episode, once 
confirmed by a positive KOH to show presence of yeast and if the clinical signs and symptoms 
score is ≥3.  If subject fails to respond to fluconazole treatment, the Investigator may employ 
treatment options corresponding to the site’s standard of care treatment to treat the infection 
upon consult with the Medical Monitor. 


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If a subject comes in for an unscheduled visit to repeat a procedure (i.e., ECG, safety labs, 
etc.), only those specific procedures need to be performed, along with collection of any changes 
in medical treatments, medications and collection of any AEs. 
If subjects experience any AEs other than a potential recurrent VVC episode they may be 
evaluated at the site at the Investigators discretion. 
8.2 Exercise 
Subjects will be encouraged, if possible, to avoid engaging in strenuous activity within 
48 hours prior to study visits.  Walking at a normal pace during these periods is acceptable. 


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9 SAFETY ASSESSMENTS 
9.1 Safety Tests and Assessments 
Safety assessments will include attention to relevant changes in the following parameters, 
which are identified as occurring after the start of IMP, regardless of whether the change is in 
an examination finding, test result, or symptom(s) reported by a subject, and regardless of 
presumed relationship to IMP (VT-1161 or fluconazole and placebo). The Investigator will 
follow all clinically significant abnormal findings after IMP treatment until resolution, return 
to baseline, or permanent documented change in medical history. 
9.1.1 Height and Weight 
Height and body weight will be collected at times specified in Table 1. Schedule of 
Assessments and Procedures. 
9.1.2 Vital Signs 
Vital signs to include body temperature, heart rate (pulse), breathing rate, and blood pressure 
will be obtained in a sitting position after resting for at least 5 minutes at times specified in 
Table 1. Schedule of Assessments and Procedures. 
9.1.3 Physical Examination 
Comprehensive Physical Examination: general appearance; head, eyes, ears, nose, and throat; 
thyroid/neck (endocrine); chest and lungs; cardiovascular system, abdomen, pelvic exam, 
musculoskeletal system, lymph nodes, extremities/skin, and neurological system will be 
performed at Screening.  Special attention should be given during the vulvovaginal 
examination to erythema, edema, and excoriation.  For proper assessment, it is best the subject 
is not menstruating at time of the study visits.   
Symptom Directed Physical Examination: A symptom directed physical exam consists of a 
very brief history of present illness. Investigators should use the symptom directed exam for 
all study visits after the Screening visit. If the subject has no present illness this should be 
documented by the Investigator or qualified designee.   
9.1.4 Electrocardiograms 
Standard 12-lead ECGs to assess heart rate, rhythm, and interval information such as PR, QRS, 
QT, and QTc will be obtained in the supine position at times specified in Table 1. Schedule of 
Assessments and Procedures. 


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9.1.5 Laboratory Determinations 
After the Screening (Day 1) visit, laboratory test values that fall outside the reference range on 
the laboratory reports and are deemed clinically significant by the Investigator may be repeated 
at the discretion of the Investigator.  Those values deemed clinically significant should be 
followed until resolution or permanent documented change in medical history.    
The following laboratory samples will be obtained at times specified in the Schedule of 
Assessments and Procedures and analyzed by the central laboratory: 
9.1.5.1 Pregnancy Testing 
All WOCBP must undergo urine and serum pregnancy testing at Screening to assess protocol 
eligibility. Serum pregnancy tests will be performed thereafter as specified in the Schedule of 
Assessments and Procedures. 
9.1.5.2 Immunology 
HIV antibody, HBsAg, anti-HCV at Screening.  Laboratory results are not required prior to 
start of IMP.  Investigators are to follow local and/or state laws in regards to parental disclosure 
of any positive pregnancy tests or reportable and treatable serologies or STDs in adolescents. 
9.1.5.3 Clinical Chemistry Panel 
Creatinine, blood urea nitrogen, AST, ALT, alkaline phosphatase, total bilirubin, conjugated 
bilirubin, albumin, total protein, total carbon dioxide, glucose, sodium, potassium, chloride, 
calcium, phosphorus, CK, cholesterol and triglycerides. Testing for HbA1c should be 
performed in known or suspected diabetic subjects at Screening. Laboratory results are not 
required prior to start of IMP. 
After the Screening (Day 1) visit, subjects may be re-tested for ALT, AST and total bilirubin 
to confirm any abnormal values and to determine if they are increasing or decreasing.  
The Investigator will also assess the subject for any associated emergent symptoms. 
9.1.5.4 Hematology 
A complete blood count with differential to include red blood cell count, total and differential 
white blood cell counts, hemoglobin, hematocrit, RBC, MCV, MCH, MCHC, RDW and 
platelet count will be performed at times specified in Table 1. Schedule of Assessments and 
Procedures.  Laboratory results are not required prior to start of IMP. 


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9.1.5.5 Urinalysis 
Testing for glucose, ketones, leukocyte esterase, nitrite, blood, pH, protein, and specific gravity 
will be performed at times specified in Table 1. Schedule of Assessments and Procedures.  
Laboratory results are not required prior to start of IMP. 
9.1.5.6 Chlamydia Trachomatis and Neisseria Gonorrhoeae 
Cultures to test for Chlamydia trachomatis and Neisseria gonorrhoeae will be taken at 
Screening.  
9.1.5.7 Trichomonas Vaginalis 
An OSOM® Rapid test or similar test will be performed for Trichomonas vaginalis locally at 
Screening.  Instructions for collecting, processing, storing, and shipping samples to the central 
laboratory are outlined in the laboratory manual. Testing for Bacterial vaginosis will be done 
locally. 
9.1.6 KOH Wet Mount Tests and Fungal Cultures 
A local KOH wet mount test will be performed locally at the Screening visit and at unscheduled 
visits where a recurrent VVC episode is suspected.  A vaginal fungal culture will be obtained 
at Screening and all subsequent visits and sent to the central mycology laboratory for fungal 
identification and susceptibility testing according to approved Clinical Laboratory Standards 
Institute methods.  Subjects should not be menstruating at time of the study visits to ensure 
proper sample collection of the vaginal fluid.  Details as to the collection of samples, shipping, 
testing methods and analysis will be delineated in a laboratory manual.  Mycology samples 
may be retained for future analysis for a period of up to 15 years, after which time the samples 
will be destroyed. 
9.1.7 Vulvovaginitis Clinical Assessment 
Vulvovaginal signs and symptoms will be evaluated at Screening and each subsequent study 
visit.  Each of the following vulvovaginal signs and symptoms will be scored and the individual 
scores combined for a maximum score of 18, using the following scale: 
a. Signs: erythema, edema, and excoriation 
b. Symptoms: itching, burning, and irritation 
 
Scoring Scale: Each score should be objectively defined on a scale of 0 to 3 as follows: 
0 = none (complete absence of any signs or symptoms) 


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1 = mild (slight) 
2 = moderate (definitely present) 
3 = severe (marked, intense) 
9.2 Adverse Event Reporting 
9.2.1 Definition of Adverse Events 
Monitoring of all AEs will be conducted throughout the study as specified in the Schedule of 
Assessments and Procedures. 
An AE is any untoward, undesired, unplanned clinical event in the form of signs, symptoms, 
disease, or laboratory or physiological observations occurring in a human participating in a 
clinical study with a Mycovia Pharmaceuticals product, regardless of causal relationship. 
A “pre-existing” condition is one that is present prior to the start of IMP administration and is 
reported as part of the subject’s medical history.  Pre-existing conditions should be reported as 
AEs only if the frequency, intensity, or character of the pre-existing condition worsens during 
the study. 
Any abnormal safety assessments, such as ECGs, radiological scans, vital sign measurements, 
that are judged by the Investigator to be clinically significant should be recorded as an AE or 
SAE provided it meets one of those definitions.  Laboratory abnormalities generally are not 
considered AEs unless they are associated with clinical signs or symptoms or require medical 
intervention.  A laboratory abnormality (e.g., a clinically significant change detected on 
clinical chemistry, hematology) that is independent from a known underlying medical 
condition and that requires medical or surgical intervention, or leads to IMP interruption or 
discontinuation, should be considered an AE. 
Clinically significant abnormal laboratory findings or other abnormal assessments that are 
associated with the disease being studied are not considered AEs unless their severity is greater 
than expected in the judgement of the Investigator.  
In addition, the following apply: 
• All AEs, including clinically significant laboratory abnormalities, will be documented 
as an AE and followed until resolution. 


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• All AEs and SAEs will be collected from the start of taking the first dose of IMP until 
the last follow-up visit of the study, at the time points specified in the Schedule of 
Assessments and Procedures. 
• Medical occurrences that begin prior to the start of IMP but after obtaining informed 
consent or assent (for those ages 12-17) should be recorded in the medical history 
section of the eCRF. 
• Investigators are not obligated to actively seek AEs or SAEs in former study subjects. 
However, if the Investigator learns of an SAE, including a death, at any time after a 
subject has been discharged from the study, and he/she considers the event reasonably 
related to the study treatment or study participation, the Investigator must promptly 
notify Mycovia Pharmaceuticals. 
9.2.2 Definition of a Serious Adverse Event 
An SAE is any AE occurring after the first administration of IMP that results in any of the 
following outcomes: 
• Deatha 
• Is a life-threatening experienceb 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability/incapacityc 
• Results in a congenital anomaly/birth defect 
• Additionally, important medical events that may not result in death, be life-threatening, 
or require hospitalization may be considered an SAE when, based upon appropriate 
medical judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent 1 of the outcomes listed above.  Example: allergic 
bronchospasm requiring intensive treatment in an emergency room or at home. 
NOTES: 
a. “Death” is an outcome and is NOT the AE.  In the event of death, the cause of death 
should be recorded as the SAE.  The only exception is “sudden death” when the 
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b. Life-threatening SAEs include any adverse drug experience, which, in the view of 
the Investigator, places the subject at immediate risk of death from the reaction as 
it occurs. It does not include a reaction that, had it occurred in a more serious form, 
might have caused death. 
c. Disability is defined as a substantial disruption in a person’s ability to conduct 
normal life functions. 
All SAEs, regardless of causal relationship, must be reported to Mycovia Pharmaceuticals 
(or designee) within 24 hours of the site’s knowledge of the event.  The initial report must be 
captured in the electronic SAE CRFs within 1 business day. 
The SAE report should provide as much of the required information as is available at the time. 
The following minimum information is required for reporting an SAE: subject identification 
number, reporting source, and an event outcome.  Supplemental information may be entered 
into the electronic SAE CRFs and should not delay the initial report.  Mycovia Pharmaceuticals 
(or designee) may contact the investigational site to solicit additional information or to follow-
up on the event. 
If there is any doubt whether the information constitutes an SAE, the information will be 
treated as an SAE for the purposes of this protocol. 
All SAEs will be followed until resolution, return to baseline (when worsening of a pre-existing 
condition is reported), or permanent documented change in medical history. 
All relevant documentation pertaining to the SAE (additional laboratory tests, consultation 
reports, discharge summaries, post-mortem reports, etc.) will be provided by the Investigator 
to Mycovia Pharmaceuticals (or designee) in a timely manner. 
9.2.3 Recording of Adverse Events  
Subjects should be instructed to report all AEs to the Investigator.  In addition, the Investigator 
should seek to elicit any clinical or objective reactions by open-ended questioning (“How have 
you been feeling?”) and, as appropriate, by examination.  All AE information obtained during 
the subject questioning should be documented in the subjects’ clinical records and entered into 
the CRF.  All clearly related signs, symptoms, and results of diagnostic procedures performed 
because of an AE should be grouped together and recorded as a single diagnosis.  
The component parts of the diagnosis may be listed for verification.  If the AE is a laboratory 
abnormality that is part of a clinical condition or syndrome, it should be recorded as the 


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syndrome or diagnosis rather than the individual laboratory abnormality.  It should also be 
documented, verbatim, directly on the laboratory report. 
To avoid vague, ambiguous, or colloquial expressions, all AEs should be recorded in standard 
medical terminology on the CRF and on the medical record rather than in the subject’s own 
words.  Each AE will also be described in terms of duration (start and stop date), severity, 
association with the IMP, action(s) taken, and outcome. 
9.2.4 Severity of Adverse Events 
All AEs and SAEs will be assessed by the Investigator or MD designee for severity, according 
to the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table, (Draft, 
November 2007) Appendix A.  For AEs involving a body system or laboratory value which is 
not addressed in the DMID Adult Toxicity Table, the most recent version of the Common 
Terminology Criteria for Adverse Events, version 4.0 published by the National Cancer 
Institute will be used. 
Where discrepancies in the ULN and lower limit of normal (LLN) laboratory ranges occur 
between those included in the DMID and those of the central laboratory that performs the 
assays, the values provided by the central laboratory will be used for assignment of severity 
grade. 
For AEs involving a body system or laboratory value not addressed in the DMID Adult 
Toxicity Table, the following general scale may be used with Investigator discretion to assign 
severity: 
• GRADE 1 Mild: An event easily tolerated by the subject; transient or mild discomfort 
(usually < 48 hours); no medical intervention/therapy required. 
• GRADE 2 Moderate: An event that may interfere with normal, everyday activities; some 
assistance may be needed; no or minimal medical intervention/therapy required. 
• GRADE 3 Severe: An event that prevented the subject from performing their normal, 
everyday activities; some assistance usually required; medical intervention/therapy 
required; hospitalizations possible. 
• GRADE 4 Life-threatening: At the time of the event the subject was at risk of death or 
the event resulted in a persistent or significant disability or incapacity. 


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• GRADE 5 Death: An event that resulted in death. 
When changes in the severity of an AE occur more frequently than once a day, the maximum 
severity for the experience that day should be noted. If the severity category changes over 
several days, then those changes should be recorded separately (with distinct onset dates). 
NOTE: An AE that is assessed as severe should not be confused with an SAE.  Severity is a 
category utilized for rating the intensity of an event (such as mild, moderate, or severe 
myocardial infarction).  However, the event itself may be of relatively minor medical 
significance, (such as a severe headache), and both AE(s) and SAE(s) can be assessed as 
severe.  An event is defined as ‘serious’ when it meets one of the pre-defined outcomes as 
described in Section 9.2.2. 
Where discrepancies in the ULN and lower limit of normal of laboratory ranges occur between 
those included in the DMID tables and those of the central laboratory that performs the assays, 
the values provided by the central laboratory will be used for assignment of severity grade. 
9.2.5 Causality Assessment 
The Investigator is obligated to assess the relationship between the IMP and the occurrence of 
each AE or SAE by using his or her best clinical judgment.  It should be clearly documented 
in the medical notes that he/she has reviewed the AE/SAE and that they are the ones providing 
the assessment of causality. Other elements to be considered, such as the history of the 
underlying disease, concomitant therapy, other risk factors, and the temporal relationship of 
the event to the IMP will be considered and investigated.  The Investigator will also consult 
the VT-1161 Investigational Brochure and the study Medical Monitor in estimating the 
relationship. 
An SAE may be recorded when the Investigator has minimal information to include in the 
initial report. However, the Investigator must always make an assessment of causality for every 
event prior to reporting the SAE report. The Investigator may change his or her opinion of the 
causality upon evaluation of follow-up information or discussions with the study Medical 
Monitor with subsequent amendment of the SAE report. Causality assessment is one of the 
criteria used to determine regulatory reporting requirements and should not be left blank. 
For each reported adverse reaction, the Investigator must assess the relationship of the event 
to the IMP using the following scale: 


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Unrelated: 
• Does not follow a known response pattern to the suspect IMP (if response pattern is 
previously known). 
• Can clearly be explained by the known characteristics of the subject’s clinical state or other 
modes of therapy administered to the subject. 
Unlikely Related: 
• The temporal sequence from administration of the IMP suggests that a relationship is 
unlikely. 
• Follows a response pattern that is unlike that of the suspect IMP (if response pattern is 
previously known). 
• Could be reasonably explained by the subject’s clinical state or other modes of therapy 
administered to the subject. 
Possibly Related: 
• Follows a reasonable temporal sequence from administration of the IMP. 
• May follow a known response pattern to the suspect IMP (if response pattern is previously 
known). 
• Could also be reasonably explained by the subject’s clinical state or other modes of therapy 
administered to the subject. 
Related: 
• Follows a reasonable temporal sequence from administration of the IMP. 
• Could not be reasonably explained by the known characteristics of the subject’s clinical 
state or any other modes of therapy administered to the subject. 
• Is confirmed by improvement on stopping or slowing administration of the IMP, if 
applicable. 


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If an assessment is not provided, the event will be treated as Possibly Related for purposes of 
regulatory reporting. 
9.2.6 Action Taken Following Adverse Events 
For each reported AE and SAE, the Investigator must document the action taken according to 
the following criteria: 
• No action taken 
• Non-pharmacologic treatment added 
• New drug therapy added 
• IMP interrupted 
• Discontinued from study 
• New or prolonged hospitalization 
9.2.7 Outcome of Adverse Events 
For each reported AE and SAE, the Investigator must document the outcome according to the 
following criteria: 
• Resolved 
• Ongoing 
• Unknown 
• Death 
The appropriate AE or SAE report page will be updated once the outcome is determined. 
The Investigator will also ensure that additional follow-up information includes any 
supplemental data that may explain causality of the event(s). 
For SAEs, new or updated information will be recorded on the originally completed SAE 
report, with all changes signed and dated by the Investigator or designee.  The updated SAE 
report will then be signed by the Investigator and resubmitted to Mycovia Pharmaceuticals (or 
designee). 


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9.2.8 Other Reportable Events 
Reports of overdose (with or without an AE), abuse, dependency, inadvertent or accidental 
exposure, pregnancy and unexpected therapeutic benefit should be forwarded to Mycovia 
Pharmaceuticals (or designee) in the same time frame as an SAE. 
Overdose occurs when a subject is administered or has taken a dose substantially greater than 
the intended or scheduled dose specified by the protocol. 
All pregnancies occurring from the time the subject takes their first dose of IMP through the 
last study visit (Week 50) must be followed for information regarding the course of pregnancy, 
delivery, and condition of the newborn.  Follow-up should be provided by the Investigator to 
Mycovia Pharmaceuticals in a timely manner. 
 


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10 PHARMACOKINETIC ASSESSMENTS  
10.1 Sample Collection and Handling 
Blood samples for determination of VT-1161 plasma concentrations will be collected at visits 
specified in Schedule of Assessments and Procedures.  Timing of samples will be with respect 
to the day and time study drug is administered. Intense PK blood draws for VT-1161 plasma 
concentrations will be obtained from consenting subjects, at participating sites, on Day 1 and 
Day 2, (predose and 1, 2, 4, and 8 hours after dosing, with ±10-minute window per timepoint).  
The date and time of each PK sample will be recorded in the CRF.  PK samples should be 
stored frozen at -20°C or colder.  Detailed shipping instructions will be provided in the lab 
manual. 
10.2 Analytical Procedures 
Plasma samples will be analyzed to determine concentrations of VT-1161 using a validated, 
specific and sensitive liquid chromatography/tandem mass spectrometry method at a 
bioanalytical laboratory designated by Mycovia Pharmaceuticals.  Pharmacokinetic samples 
may be retained for future analysis of the metabolite profile for a period of up to 15 years, after 
which time the samples will be destroyed. 
10.3 Pharmacokinetic Parameters 
For subjects in the VT-1161 treatment arm, VT-1161 concentrations will be presented by visit 
with descriptive statistics.  The PK data may be used in a cross-population PK analysis that 
may be presented in a separate report.   


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11 STUDY TERMINATION AND SUBJECT DISCONTINUATION 
11.1 Screening/Baseline Failures 
Subjects who sign and date the informed consent form or assent (for those ages 12-17) but fail 
to be randomized are defined as screen failures.  Site personnel should maintain documentation 
for all subjects who sign an informed consent or assent.  Study completion is defined as when 
the last subject has completed their last study visit. 
11.2 Subject Withdrawal or Premature Discontinuation from the Study 
The following actions must be taken in relation to a subject who fails to attend the clinic for a 
required study visit: 
• The incidence or severity of AEs in the study indicates a potential health hazard to subjects. 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible. 
• The site must counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the 
study. 
• In cases where the subject is deemed ‘lost to follow-up’, the Investigator or designee must 
make every effort to regain contact with the subject (e.g., multiple telephone calls on 
various dates/time, a certified letter to the subject’s last known mailing address, or 
equivalent methods). These contact attempts should be documented in the subject’s source 
documents. 
• Should the subject continue to be unreachable, only then will they be considered to have 
withdrawn from the study with a primary reason of “Lost to Follow-up”. 
A subject may be withdrawn due to lack of tolerability or safety concerns, including study 
drug-related AEs or development of clinically-significant study drug-related laboratory 
abnormalities.  If a subject is withdrawn from treatment, the subject must be followed clinically 
until the event is resolved or deemed stable. A subject must be discontinued from the study 
drug if ALT or/and AST is > 5 times the upper limit of normal (ULN) or ALT or/and AST is 
> 3 times the ULN and serum total bilirubin is > 2 times the ULN. 


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A subject may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioral, or administrative reasons.  
If a subject withdraws from the study, he/she may request destruction of any laboratory 
samples taken, and the Investigator must document this in the site study records and 
communicate this request to Mycovia Pharmaceuticals. 
Subject who want to discontinue from the study should be encouraged to remain in the study 
for all remaining visits through Week 50 for safety and efficacy assessments.  All subjects who 
do discontinue early from the study should have all EOS procedures performed on the day of 
discontinuation.  
If a subject is prematurely discontinued from study treatment for any reason other than 
withdrawal of consent, the Investigator (or designee) should request that the subject continues 
to participate in the study, attending all remaining visits in accordance with the Schedule of 
Assessments and Procedures. Subjects who prematurely discontinue study medication, but 
remain in the study, may be treated according to the standard local practice.  If the subject does 
not agree to remain in the study, the Investigator (or designee) must make every effort to 
perform the early withdrawal visit/EOS visit procedures. 
11.3 Subject and Study Completion 
A completed subject is one who has completed all visits, Screening through Week 50 (EOS), 
as defined in the Schedule of Assessments and Procedures. Study completion is defined as 
when the last subject has completed their last study visit. 


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11.4 Premature Study Termination 
Reasons for discontinuation of the study at the investigative site may include, but are not 
limited to, the following: 
• The incidence or severity of AEs in the study indicates a potential health hazard to subjects. 
• Subject wishes to withdraw consent for reasons other than an AE. 
• Subject non-compliance or unwillingness to comply with the procedures required by the 
protocol. 
• Investigator request to withdraw from participation. 
• Sponsor decision. 
• Serious and/or persistent non-compliance by the Investigator with the protocol, the clinical 
research agreement, the Form Food and Drug Administration 1572, or applicable 
regulatory guidelines in conducting the study. 
• Decision by the IRB/IEC to terminate or suspend approval for the investigation or the 
Investigator. 
• Investigator fraud (altered data, omitted data, or manufactured data). 
 


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12 STATISTICAL ANALYSIS  
A formal SAP will be finalized before 50% of subjects are enrolled.  The SAP will provide a 
more technical and detailed description of the proposed data analysis methods and procedures. 
Any deviation from the analyses outlined in the protocol will be described in the SAP. 
The primary statistical objectives of this study are: 
1. To determine if there is a difference in the proportions of subjects with one or more 
episodes of culture-verified acute VVC in those receiving VT-1161 compared to those 
receiving placebo; and 
2. To determine if there is a difference in the ability of VT-1161 and fluconazole to resolve 
acute episodes in RVVC subjects. 
12.1 Determination of Sample Size 
The study will enroll 180 total subjects (120 in the VT-1161 arm and 60 in the 
fluconazole/placebo arm).  For the primary efficacy endpoint determination, a sample size of 
82 subjects in the VT-1161 arm and 41 subjects in the fluconazole/placebo arm provides at 
least 90% power to detect a treatment difference between the VT-1161 treatment group and 
the fluconazole / placebo treatment group with a type 1 error rate of 0.05. (PASS 2008: Fisher's 
exact test, two-sided alpha = 0.05, and assuming 50% of placebo subjects have 
recurrence).  For the first key secondary endpoint, the proportion of subjects with resolved 
acute VVC infections (clinical signs and symptoms score of <3) at Day 14 following treatment 
with VT-1161 or fluconazole, a sample size of 120 subjects in the VT-1161 arm and 60 subjects 
in the fluconazole/placebo arm provides at least 88% power to detect non-inferiority between 
the VT-1161 treatment group and the fluconazole treatment group with a non-inferiority 
margin of 15% and a type 1 error rate of 0.05. (PASS 2008: Z-test for two independent 
proportions, one-sided alpha = 0.025, non-inferiority margin = 15%, and assuming that 90% 
of fluconazole subjects resolve their acute VVC infection).     
12.2 Analysis Populations 
ITT Population: All randomized subjects. 
Safety Population: All randomized subjects who received at least 1 dose of IMP.  
PP Population: All randomized subjects who had the following:  


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• Had no deviations to inclusion/exclusion criteria that could impact treatment 
outcome. 
• Were compliant with the assigned study treatment, defined as ≥80% compliance 
during the Induction Phase and ≥50% compliance during the weekly dosing phase. 
• Had the Week 50 visit completed within the acceptable time window (±14 days). 
• Had no major protocol violations that would impact treatment outcome. 
Modified ITT: All randomized subjects who had the following: 
• Positive KOH at Screening. 
• Positive culture at Screening. 
• Negative culture at Baseline. 
All statistical populations will be defined in the SAP.  
12.3 Missing Data 
For the efficacy analyses, missing values for the Investigator’s assessment of clinical signs and 
symptoms or the culture result will be imputed using the method of multiple imputation.  
For subjects who discontinue the study early and have missing assessments for all visits after 
discontinuation, the missing values for the expected scheduled visits will be imputed using the 
method of multiple imputation. The missing values will be imputed using the following 
auxiliary information: region, treatment, baseline BMI, baseline age, ethnicity, and visit. 
The procedure PROC MI in SAS will be used to generate 10 possible imputed datasets. 
Multiple sensitivity analyses will be performed for the primary endpoint to assess the impact 
of missing data on the results. The details of these sensitivity analyses will be outlined in the 
SAP.  
12.4 Multiple Testing 
If the comparison for the primary endpoint is significant (two-sided p-value < 0.05), then 
testing will continue for the key secondary endpoints. To control for the type I error rate at 
0.05 for multiple secondary endpoints, the hierarchical/gate-keeping method will be used.  
Each key secondary endpoint will be tested according to the hierarchy. 
 


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12.5 Demographic and Baseline Characteristic Analyses 
Subject disposition, demographics, baseline characteristics and study drug exposure will be 
summarized by treatment group. 
12.6 Efficacy Analyses  
Clinical and mycological assessments will be conducted as outlined in the Schedule of 
Assessments and Procedures. 
The primary efficacy outcome measure is the proportion of subjects with one or more culture-
verified acute VVC episodes (post-randomization through Week 50) in the ITT population, 
which will include the subjects who failed clearing their infection during the Induction Phase. 
An acute VVC episode (considered a recurrent episode) is defined as a positive culture for 
Candida species and a clinical signs and symptoms score of ≥3. The primary efficacy outcome 
will be analyzed with a chi-square test.  The Wilson-Hiferty transformation will be applied to 
the Chi-square test statistics prior to combining the 10 results using PROC MIANALYZE. 
 
 


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The key secondary efficacy outcome measures include the following: 
• The proportion of subjects with resolved acute VVC infections (clinical signs and 
symptoms score of <3) at Day 14 following treatment with VT-1161 or fluconazole. 
• The proportion of subjects with at least one culture-verified acute VVC episode 
with signs and symptoms of ≥3 during the Maintenance Phase (post Day 14 through 
Week 50). 
• Time to first recurrence of a culture-verified acute VVC episode with signs and 
symptoms score ≥3 during the Maintenance Phase (post Day 14 through Week 50). 
• The proportion of subjects with at least one positive culture for Candida during the 
Maintenance Phase. 
 
The secondary endpoint of the proportion of subjects with resolved acute VVC infections at 
Day 14 in the VT-1161 arm will be evaluated for non-inferiority versus the fluconazole arm.  
A non-inferiority margin of 15% will be used.  If the lower limit of the 95% confidence interval 
for the difference in proportions between the VT-1161 arm and the fluconazole arm is greater 
than -15% then non-inferiority will be claimed.  
Justification of the non-inferiority margin:  Fluconazole clears 80% of acute VVC 
infections.  Women can clear a VVC infection without intervention only when the infection is 
mild and even then, the complete clearance of the infection is very rare.  Thus, a conservative 
estimate for the effect of fluconazole to treat a VVC infection versus no intervention is at least 
70% (assuming 10% clear with no intervention).  Per the FDA guidance document on Non-
Inferiority Clinical Trials to Establish Effectiveness, a non-inferiority margin that is half the 
effect of the control drug should be used.  A non-inferiority margin of 15% was selected for 
this trial which is equivalent to approximately 21% of the effect of fluconazole, which is 
substantially less than the recommended use of 50% of the effect of the control drug for the 
non-inferiority margin.   
The secondary endpoints of the proportion of subjects with at least one culture-verified acute 
VVC episode during the Maintenance phase, and the proportion of subjects with at least one 
positive culture for Candida during the Maintenance phase, will be analyzed using a similar 
method as the primary efficacy outcome. The secondary endpoint of time to first recurrence 
will be analyzed using the Kaplan-Meier method. Subject’s with no recurrence will be 


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censored at their last non-missing assessment. Differences between treatment groups will be 
assessed using a log-rank test.  
Subject who want to discontinue from the study should be encouraged to remain in the study 
for all remaining visits through Week 50 for safety and efficacy assessments.  Subjects who do 
discontinue early from the study should have all Week 50/EOS assessments performed on the 
day of discontinuation.  
12.7 Safety Analyses  
To meet the safety dataset requirement, approximately 150 subjects will be screened to 
randomize approximately 180 subjects that would meet the inclusion/ exclusion criteria. 
Assuming a 20% discontinuation rate, it is expected that approximately 144 subjects will 
complete the study. 
All subjects who receive at least one dose of IMP will be included in the safety analyses. 
Subjects will be analyzed as per the treatment they receive.  The number and percentage of 
subjects having TEAEs will be tabulated by system organ class and preferred term with a 
breakdown by treatment group.  Mean changes from pre-treatment in vital signs, ECGs, and 
clinical laboratory variables will be summarized by treatment group.  
AEs will be collected from the date of the first dose of IMP through Week 50 (EOS).   Physical 
examination findings, vital signs, ECGs and safety laboratory tests (hematology and chemistry) 
will be obtained throughout the study as outlined in the Schedule of Assessments and 
Procedures.  All concomitant medications taken during the period from 30 days prior to 
Screening through the Week 50 (EOS) visit will be recorded in the CRF.  Pertinent and all 
major medical conditions will be recorded on the Medical History CRF.   
For subjects discontinuing early from the study, every effort will be made for all EOS 
procedures to be performed as outlined in the Schedule of Assessments and Procedures.  
AEs will be coded with the Medical Dictionary for Regulatory Activities (MedDRA®) version 
21 dictionary, or higher.  The number and percentage of subjects having treatment-emergent 
AEs will be tabulated by system organ class and MedDRA® preferred term with a breakdown 
by treatment group.  Mean changes from pre-treatment in vital signs, ECG, and clinical 
laboratory variables will be summarized by treatment group.  The AE profile will be 
characterized with severity and relationship to IMP.  SAEs and AEs resulting in 
discontinuation of IMP will be identified. 


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Treatment-emergent abnormal laboratory test results will be identified.  Treatment-emergent 
abnormal laboratory tests results are those in which the baseline value is within normal 
laboratory limits and at least 1 post-baseline value is outside normal laboratory limits.  Baseline 
will be defined as the last clinical laboratory result obtained before the first dose of IMP.  
Per protocol, the baseline for laboratory values should be obtained at the Screening (Day 1) 
visit.   
Change from baseline to the minimum, maximum, and final vital sign value after first dosing 
will be summarized descriptively.   
ECG measurements will include heart rate, QT interval, QTc interval, PR interval, and QRS 
interval.  Baseline for ECG measurements is defined per protocol as the value pre-dosing at 
the Day 1 (Baseline) visit.  Change from baseline will be summarized descriptively at each 
scheduled evaluation.  Subjects with clinically significant changes in ECG rhythm or 
waveform will be identified.  Subjects who meet each of the following criteria from ICH 
Guideline E14 “Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic 
Potential for Non-Antiarrhythmic Drugs” (October 2005) for QT and corrected QT intervals 
will be identified. 
• QT or Fridericia-corrected QT >450 msec 
• QT or Fridericia-corrected QT >480 msec 
• QT or Fridericia-corrected QT >500 msec 
• QT or Fridericia-corrected QT increases from baseline by at least 30 msec  
• QT or Fridericia-corrected QT increases from baseline by at least 60 msec 
12.8 Pharmacokinetic Analyses  
For subjects in the VT-1161 treatment arms, VT-1161 concentrations will be presented by visit 
with descriptive statistics.  The PK data may be used in a cross-population PK analysis that 
may be presented in a separate report. 


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13 CLINICAL STUDY ADMINISTRATION/STUDY GOVERNANCE 
CONSIDERATIONS 
13.1 Ethical Conduct of Study 
The study will be conducted in accordance with ICH Good Clinical Practice (GCP), all 
applicable subject privacy requirements, the guiding principles of the current version of the 
Declaration of Helsinki, and applicable country-specific regulatory requirements. This 
includes, but is not limited to, the following: 
• IRB/IEC review and favorable opinion/approval of the study protocol and amendments, as 
applicable, informed consent documents or assents (for those ages 12-17), and 
investigational brochure. 
• Signed informed consent form or assent to be obtained for each subject before participation 
in the study (and for amendments as applicable). 
• Investigator 
reporting 
requirements 
(e.g., 
continuing 
reviews, 
reporting 
of 
AEs/SAEs/protocol deviations to the IRB/IEC). 
• If any documents are translated, an official certificate of translation must be maintained. 
13.2 Informed Consent or Assent 
Written informed consent or assent (for those ages 12-17) must be obtained from all subjects. 
The informed consent or assent document must be signed and dated prior to the initiation of 
study-related tests and prior to administration of IMP.  The original signed informed consent 
or assent for each participating subject shall be filed with records kept by the Investigator(s).  
A copy of the informed consent or assent document must be provided to the subject.  If 
applicable, it will be provided in a certified translation of the local language. 
13.3 Quality Control (Study Monitoring) 
In accordance with applicable regulations, including GCP, the representative(s) or the 
designated clinical study monitor of Mycovia Pharmaceuticals will contact the site staff prior 
to the start of the study to review the protocol, study requirements, and their responsibilities to 
satisfy regulatory, ethical, and Mycovia Pharmaceuticals’ requirements. When reviewing the 
data collection procedures, the discussion will also include identification, agreement, and 
documentation of data items that will serve as the source document. 


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Mycovia Pharmaceuticals representative(s) or the designated clinical study monitor will 
monitor the study and site activity at regular intervals throughout the study to verify the 
following:  
• Data are authentic, accurate, and complete. 
• Safety and rights of subjects are being protected. 
• Study is conducted in accordance with the currently approved protocol and any other study 
agreements, GCP, and all applicable regulatory requirements. 
The Investigator and the head of the medical institution (where applicable) agrees to allow the 
clinical study monitor direct access to all relevant documents. 
Relevant documents or source documents are defined as the results of original observations 
and activities of a clinical investigation.  Source documents may include, but are not limited 
to, study progress notes, e-mail correspondences, computer printouts, laboratory data, and drug 
accountability records.   
13.4 Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, Mycovia 
Pharmaceuticals may conduct a quality assurance assessment and/or audit of the site records, 
and the regulatory agencies may conduct a regulatory inspection at any time during or after the 
completion of the study. In the event of an assessment, audit or inspection, the Investigator 
(and institution) must agree to grant the advisor(s), auditor(s), and inspector(s) direct access to 
all relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues, and to implement any corrective and/or 
preventative actions to address any findings/issues identified. 
13.5 Compliance with Standards of Medical Research/ Deviations 
This protocol will be conducted in accordance with the applicable ICH guidelines and GCP. 
Any instance of non-compliance with the protocol will result in a documented deviation. If a 
change is deemed necessary to protect the safety, rights or welfare of a subject, Mycovia 
Pharmaceuticals and IRB/IEC should be notified as soon as possible and preferably prior to 
introducing the deviation. Major deviations are defined as, but not limited to, the following: 
• Subjects who did not meet entry criteria. 


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• Subjects who developed withdrawal criteria during the study but were not withdrawn. 
• Subjects who received the wrong treatment or incorrect dose. 
• Subjects who were <80% IMP compliant in the Induction phase or <50% IMP compliant 
in the Maintenance Phase. 
• Subjects who received an excluded concomitant medication or treatment. 
13.6 Data Management 
Electronic case report forms (eCRFs) will be used to capture study results and data.  The study 
coordinator or other authorized site study personnel will transcribe data from source documents 
into the eCRFs.  All eCRFs will be reviewed and source verified by the clinical study monitor 
during periodic site visits, and the clinical study monitor will ensure that all data in the eCRF 
are correct and complete.  Prior to or between visits, the Medical Monitor or clinical study 
monitor may request copies of the eCRFs for preliminary medical review. Once the eCRFs are 
complete and source verified, the Investigator must sign and date all required pages, verifying 
the accuracy of all data contained within the eCRF. 
Training will be provided for the Electronic Data Capture (EDC) system.  All personnel using 
the EDC system must have the appropriate education, training, and experience, or any 
combination thereof. The Investigator will be provided with SOPs (contained in the 
Study Procedures Manual or a vendor-specific SOP) on the use of the EDC system. 
Documentation for employee education, training, and previous experience that pertains to the 
EDC system must be present in the Investigator files. 
If electronic data systems other than those provided and maintained by Mycovia 
Pharmaceuticals are used for documentation and data capture, the Investigator must ensure that 
the systems are validated and ensure regular data back-up. 
The eCRF will be signed by the Principal Investigator listed on the Food and Drug 
Administration (FDA) 1572 form.  It is the responsibility of the Principal Investigator to ensure 
the eCRFs are completed and submitted to Mycovia Pharmaceuticals (or designee) in an 
accurate and timely manner.  The processing of eCRFs will include an audit trail (to include 
changes made, reason for change, date of change, and person making change). At the 
completion of the study, the Investigator will be provided with a final copy of the eCRFs for 
their subjects.  Mycovia Pharmaceuticals will be provided with a final copy of all subject eCRF 
data for the study. 


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Management of clinical data will be performed in accordance with applicable Mycovia 
Pharmaceuticals standards and data cleaning procedures to ensure the integrity of the data (e.g., 
removing errors and inconsistencies in the data).  AEs and concomitant medications will be 
coded using MedDRA®.  Electronic CRFs (including queries and audit trails) will be retained 
by the Mycovia Pharmaceuticals and copies will be sent to the Investigator to maintain as the 
Investigator copy. 
13.7 Study and Site Closure 
Upon completion or premature discontinuation of the study, the representative (or designated 
clinical study monitor) of Mycovia Pharmaceuticals will conduct site closure activities with 
the Investigator or site staff, as appropriate, in accordance with applicable regulations 
including GCP.  Mycovia Pharmaceuticals reserves the right to temporarily suspend or 
prematurely discontinue this study at any time for reasons including, but not limited to, safety 
or ethical issues or severe non-compliance. For multicenter studies, this can occur at 1 or more 
or at all sites.  If the Sponsor determines such action is needed, Mycovia Pharmaceuticals will 
discuss the reasons for taking such action with the Investigator or head of the medical 
institution (where applicable).  When feasible, Mycovia Pharmaceuticals will provide advance 
notification to the Investigator or head of the medical institution (where applicable) of the 
impending action.  If the study is suspended or prematurely discontinued for safety reasons, 
Mycovia Pharmaceuticals will promptly inform all Investigators, heads of medical institutions 
(where applicable), and/or institutions conducting the study.  Mycovia Pharmaceuticals will 
also promptly inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.  If required by applicable 
regulations, the Investigator must inform the IRB/IEC promptly and provide the reason(s) for 
the suspension or premature discontinuation. 
13.8 Records Retention 
Following closure of the study, the Investigator must maintain all site study records (except 
for those required by local regulations to be maintained elsewhere), in a safe and secure 
location.  The records must be maintained to allow easy and timely retrieval when needed (e.g., 
for a Mycovia Pharmaceuticals audit or regulatory inspection) and must be available for review 
in conjunction with the assessment of the facility, supporting systems, and relevant site staff. 
When permitted by local laws/regulations or institutional policy, some or all of the records can 
be maintained in a format other than hard copy (e.g., microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken.  The Investigator must 
ensure that all reproductions are legible and are a true and accurate copy of the original and 


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meet accessibility and retrieval standards, including regenerating a hard copy, if required. 
Furthermore, the Investigator must ensure there is an acceptable back-up of these reproductions 
and that an acceptable quality control process exists for making these reproductions.   
Investigators are required to retain essential documents pertaining to the conduct of this study 
for at least 2 years after the last approval of a marketing application in an ICH region and until 
there are no pending or contemplated marketing applications in an ICH region or at least 
2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product, per ICH guidelines.  The minimum retention time will meet the 
strictest standard applicable to that site for the study, as dictated by any institutional 
requirements, local laws or regulations, or Mycovia Pharmaceuticals’ standards/procedures. 
The Investigator must notify Mycovia Pharmaceuticals of any changes to the archival 
arrangements, including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the Investigator is no longer associated with the site. 
13.9 Disclosure of Data 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission to national and/or international registration and supervising authorities.  If required, 
these authorities will be provided with the names of Investigators, their addresses, 
qualifications, and extent of involvement.  It is understood that the Investigator is required to 
provide Mycovia Pharmaceuticals with all study data, complete reports, and access to all study 
records. 
Data generated by this study must be available for inspection by the United States FDA and 
other regulatory authorities, by Mycovia Pharmaceuticals, and the IRB/IEC as appropriate.  
At a subject’s request, medical information may be given to his or her personal physician or 
other appropriate medical personnel responsible for his or her welfare. Subject medical 
information obtained during this study is confidential and disclosure to third parties other than 
those noted above is prohibited. 
13.10 Financial Disclosure 
The United States FDA Financial Disclosure by Clinical Investigators (21 Code of Federal 
Regulations 54) regulations require Sponsors to obtain certain financial information from 
Investigators participating in covered clinical studies; each Principal Investigator and 
Sub-Investigator is required to provide the required financial information and to promptly 
update Mycovia Pharmaceuticals with any relevant changes to their financial information 
throughout the course of the clinical study and for up to 1 year after its completion.  This rule 


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applies to all Investigators and Sub-Investigators participating in covered clinical studies to be 
submitted to the FDA in support of an application for market approval. 
13.11 Publication Policy 
The publication policy is outlined in the Clinical Trial Agreement. 
13.12 Confidentiality 
Confidentiality is outlined in the Clinical Trial Agreement. 
13.12.1 
Data 
All information about the nature of the proposed investigation provided by Mycovia 
Pharmaceuticals or the designated clinical study monitor to the Investigator (with the exception 
of information required by law or regulations to be disclosed to the IRB/IEC, the subject, or 
the appropriate regulatory authority) must be kept in confidence by the Investigator. 
13.12.2 
Subject Anonymity 
The anonymity of participating subjects must be maintained. Subjects will be identified by an 
assigned subject number on CRFs and other documents retrieved from the site or sent to the 
designated 
clinical 
study 
monitor, 
Sponsor, 
regulatory 
agencies, 
or 
central 
laboratories/reviewers.  Documents that identify the subject (e.g., the signed informed consent 
document, subject identification record) must be maintained in strict confidence by the 
Investigator, except to the extent necessary to allow auditing by the appropriate regulatory 
authority, the clinical study monitor, or Mycovia Pharmaceuticals representatives. 


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14 REFERENCES 
Barousse, M., et al. Vaginal yeast colonisation, prevalence of vaginitis, and associated local immunity 
in adolescents. Sexually Transmitted Infections, 2004;80(1):48-53. 
Bates DW and Yu DT. Clinical impact of drug-drug interactions with systemic azole antifungals.  Drugs 
Today 2003; 39: 801-813. 
Blostein, F., et al. Recurrent vulvovaginal candidiasis. Annals of Epidemiology, 2017: In press. 
Diflucan® 150 Capsules [Summary of Product Characteristics]. Pfizer Limited. Sandwich, UK.  
Accessed through http://www.medicines.org.uk/emc/medicine/1458/spc.  Last updated 19-May-2017.   
Eschenbach DA. Chronic Vulvovaginal Candidiasis. New Engl J Med 2004; 351: 851-852. 
Fidel, P., Jr. and J. Sobel. Host defense against vaginal candidiasis. Candida and candidiasis, ed. R. 
Calderone. Washington, D.C.: ASM Press. 2002, 193-209. 
Foxman B, Muraglia R, Dietz JP, et al. Prevelence of recurrent Vulvovaginal Candidiasis in 5 European 
countries and the United States:  results from an internet panel survey.  Am Soc of Colposcopy and 
Cervical Path 2013; 17(3): 340-345. 
Garvey EP, Fidel PL, Lilly EA, et al. The clinical antifungal agent VT-1161 is orally efficacious in a 
murine model of C. albicans vaginitis.  Presented at the 11th American Society for Microbiology 
Conference on Candida and Candidiasis, San Francisco, CA. Abstract #33C (2012). 
Goncalves B, Ferreira C, Alves CT, et al. Vulvovaginal candidiasis: epidemiology, microbiology and 
risk factors.  Crit Rev Microbiol 2016; 42(2): 905-927. 
Joishy, M., et al., Do we need to treat vulvovaginitis in prepubertal girls? British Medical Journal, 
2005;330(7484):186-188. 
Pfizer, 
I. 
Diflucan®, 
fluconazole 
tablet, 
<https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f694c617-3383-416c-91b6-
b94fda371204> (2017). 
Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016 (1):6. 
Sobel JD, Wiesenfeld HC, Martens M, et al. Maintenance fluconazole therapy for recurrent 
Vulvovaginal Candidiasis. New Engl J Med 2004; 351:876-883. 
Sobel JD. Vulvovaginal Candidosis.  Lancet 2007; 369:1961-1971. 
VT-1161 Investigational Brochure, v005. Durham, NC.  Mycovia Pharmaceuticals Inc. (2017). 
Yoshida Y. Cytochrome P450 of fungi: primary target for azole antifungal agents.  Curr Top Med 
Mycol 1988; 2: 388-418. 
Zarn JA, Bruschweiler BJ, Schlatter JR. Azole fungicides affect mammalian steroidogenesis by 
inhibiting sterol 14α-demethylase and aromatase.  Env Health Pers 2003; 111: 255-261. 
 
 


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APPENDICES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix A. Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity 
Table (Draft November 2007) Modified for Use in VMT-VT-1161-CL-017 
Study 
*This toxicity table is applicable for subjects ages 12-17 years of age. 
 
ABBREVIATIONS:  Abbreviations utilized in the Table: 
ULN = Upper Limit of Normal          LLN = Lower Limit of Normal 
Rx = Therapy                                      Req = Required 
Mod = Moderate                                 IV = Intravenous 
ADL = Activities of Daily Living       Dec = Decreased 
 
ESTIMATING SEVERITY GRADE 
For abnormalities NOT found elsewhere in the Toxicity Tables use the scale below to estimate 
grade of severity: 
 
GRADE 1 
Mild: 
Transient 
or 
mild 
discomfort 
(<48 
hours); 
no 
medical 
intervention/therapy required 
GRADE 2 
Moderate: Mild to moderate limitation in activity - some assistance may be 
needed; no or minimal medical intervention/therapy required 
GRADE 3 
Severe: Marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalizations possible. 
GRADE 4 
Life-threatening:  
Extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice care 
probable 
 
SERIOUS OR LIFE-THREATENING AEs 
ANY clinical event deemed by the clinician to be serious or life-threatening should be 
considered a Grade 4 event.   
 
LABORATORY RANGES 
Where discrepancies in the ULN and LLN of laboratory ranges occur between those included 
in this document and those of the laboratory that performs the assays, the values provided by 
the laboratory will be used for assignment of severity grade. 
















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Appendix B:  Grading of Renal Impairment 
 
GFR categories in CKD 
Category 
GFR 
ml/min/1.73 m2 
Terms 
G1 
     ≥90 
Normal or high 
G2 
60 – 89 
Mildly decreased* 
G3a 
45 – 59 
Mildly to moderately decreased 
G3b 
30 – 44 
Moderately to severely decreased 
G4 
15 – 29 
Severely decreased 
G5 
     <15 
Kidney failure 
Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate. 
*Relative to young adult level. 
In the absence of evidence of kidney damage, neither GFR category G1 nor G2 fulfill the criteria for 
CKD. 
 
Albuminuria categories in CKD 
Category 
ACR (mg/g) 
Terms 
A1 
      <30 
Normal to mildly increased 
A2 
30 – 300 
Moderately increased* 
A3 
     >300 
Severely increased** 
Abbreviations: ACR, albumin-to-creatinine ratio; CKD, chronic kidney disease. 
*Relative to young adult level. 
**Including nephrotic syndrome (albumin excretion ACR >2220 mg/g) 
Reference:  https://www.kidney.org/professionals/explore-your-knowledge/how-to-classify-ckd 
 
 


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Appendix C: Child-Pugh Classification of Hepatic Impairment 
 
The Child- Pugh classification is a means of assessing the severity of liver cirrhosis. 
Score 
1 
2 
3 
bilirubin (micromol/l) 
<34 
34 – 50 
>50 
albumin (g/l) 
>35 
28 – 35 
<28 
PT (s prolonged) 
<4 
4 – 6 
>6 
encephalopathy 
none 
mild 
marked 
ascites 
none 
mild 
marked 
If there is primary biliary cirrhosis or sclerosing cholangitis then bilirubin is classified as <68 =1; 
6 – 170 = 2; >170 = 3. 
The individual scores are summed and then grouped as: 
• 
<7 = A (Mild impairment) 
• 
7 – 9 = B (Moderate impairment) 
• 
>9 = C (Severe impairment) 
A C classification forecasts a survival of less than 12 months. 
From: Pugh RNH, Murray-Lyon IM, Dawson JL et al. Transection of the oesophagus for 
bleeding oesophageal varices. Br J Surg 1973;60:649-9.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix D. Protocol Amendment 1, Version 2 Summary of Protocol Changes 
 


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Section 
Change 
Reason 
Impact on Human 
Subject (risk/benefit) 
Synopsis  Added ‘.. except for HIV, 
HBsAg and antibodies to 
hepatitis C virus’ and ‘e. 
Positive test for antibodies to 
human immunodeficiency 
virus (HIV), hepatitis B 
surface antigen (HBsAg), or 
antibodies to hepatitis C 
virus.’ to Excl. # 16. 
Inadvertently left out of the 
synopsis. 
N/A 
Synopsis 
Added ‘Maintenance 
Treatment Phase’ 
Added header 
N/A 
Synopsis 
Changed ‘patients’ to ‘subjects’. 
Corrected error 
N/A 
Synopsis, 
Sect. 
7.4.1 #3 
Added ‘urogenital’. 
Add clarification on type of 
concomitant infections. 
Benefit 
Synopsis, 
Sect. 5.1 
Added ‘results’ to Incl. #5. 
Provide clarification that 
the results must be present 
at the Screening visit. 
Benefit 
Synopsis, 
Sect. 5.1 
Added ‘used continuously and 
successfully for at least 90 days 
prior to first dose of study drug’ 
to Incl #10 Option 1, #1. 
Provide guidance on length 
of time of use of 
contraceptive method 
Benefit 
Synopsis, 
Sect. 5.1 
Added ‘used successfully for at 
least 90 days prior to first dose of 
study drug’ to Incl #10 Option 1, 
#2 and #3 and Option 2, #1 and 
#2. 
Provide guidance on length 
of time of use of 
contraceptive method 
Benefit 
Synopsis, 
Sect. 5.1 
Added ‘(vasectomy performed at 
least 6 months prior to first dose 
of study drug)’ to Incl #10 
Option 1, #4. 
Provide guidance on 
contraception methods 
women with vasectomized 
male partners  
Benefit 
Synopsis, 
Sect. 5.1 
Added language and move to 
subscript a, ‘Subjects who 
started using an intrauterine 
device or any of the hormonal 
contraceptive methods described 
above less than 3 months prior to 
the first dose of study medication 
must agree to use a double-
barrier method (i.e., diaphragm 
plus spermicide or condom) 
through 3 months after start of 
the use of the IUD or hormonal 
Provide clarification on the 
birth control 
Benefit 


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contraceptive. Similarly, subjects 
that claim a monogamous 
relationship with a vasectomized 
male partner where the 
vasectomy was performed less 
than 6 months prior to the first 
dose of study medication, must 
agree to use a double-barrier 
method (i.e., diaphragm plus 
spermicide or condom) through 6 
months after the date of the 
vasectomy.’ 
Synopsis, 
Sect. 5.2 
Added ‘; nor use of topical 
vulvar or vaginal steroids during 
the study or within 7 days prior 
to Screening visit’ to Excl. #5. 
Clarification on prohibited 
use of vulvar and vaginal 
steroids and the wash out 
period. 
Benefit 
Synopsis, 
Sect. 5.2 
Added ‘collunarium/nasal’ to 
Excl. #5. 
Additional method 
permitted. 
Benefit 
Synopsis, 
Sect. 5.2 
Added ‘for the treatment of 
bacterial vaginosis, trichomonas, 
or other concomitant urogenital 
infection’ to Excl. #6. 
Provide specification on 
type of treatment. 
Benefit 
Synopsis 
Corrected from 12.5 to 15% non-
inferiority margin. 
Error correction 
N/A 
Synopsis, 
Sect. 
10.1 
Added ‘with ±10-minute window 
per timepoint’. 
Provide a time window for 
intense PK timepoints. 
N/A 
Table 1 
Changed in footnote g ‘12’ to 
‘14’ and ’24’ to ‘26’. 
Error correction 
N/A 
Table 1 
Removed ‘X’ in the table for 
Administer VT-1161 or Placebo 
at Weeks 8 and 14 
Error correction 
N/A 
Sect. 1.3 
Added ‘…approved…often’, 
changed ‘better’ to ‘improved’, 
changed ‘it’ to ‘VT-1161’, 
changed ‘Its’ to ‘The’, and added 
‘asociated with VT-1161’. 
Provided improved text in 
section. 
N/A 
Sect. 
7.1.2 
Added ‘returning to the site 
approximately 14 days after the 
first dose of VT-1161 or over-
encapsulated fluconazole and 
demonstrating resolution of the 
VVC infection (defined by a 
signs and symptoms score of 
<3)….. if initially randomized to 
receive VT-1161….. if initially 
randomized to receive 
fluconazole’. 
Provide additional 
information for qualifying 
subjects entering the 
Maintenance Phase. 
Benefit 


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Sect. 
8.1.1 
Added ‘Safety’. 
Provided clarification on 
type of laboratory results. 
N/A 
Sect. 
8.1.2 
Added ‘(±2 Days)’ 
Provide visit window for 
Day 14 
Benefit 
Sect. 
8.1.3 
Removed ‘Obtain serum sample 
for pregnancy testing for all 
WOCBP.’ 
Corrected error. 
N/A 
Sect. 
8.1.3 
Add ‘Subjects with clinical signs 
and symptoms score of < 3 will 
continue into Maintenance Phase 
and subjects with score of ≥3 
will be an Induction failure, 
ending study participation.’ 
Provided criteria for 
subjects to enter 
Maintenance Phase. 
Benefit 
Sect. 
11.2 
Added ‘The incidence or severity 
of AEs in the study indicates a 
potential health hazard to 
subjects’ and ‘A subject may be 
withdrawn due to lack of 
tolerability or safety concerns, 
including study drug-related AEs 
or development of clinically-
significant study drug-related 
laboratory abnormalities.  If a 
subject is withdrawn from 
treatment, the subject must be 
followed clinically until the 
event is resolved or deemed 
stable. A subject must be 
discontinued from the study drug 
if ALT or/and AST is > 5 ×times 
the upper limit of normal (ULN) 
or ALT or/and AST is > 3 
×times the ULN and serum total 
bilirubin is > 2.0 times the 
ULN’, and ‘Subjects who 
prematurely discontinue study 
medication, but remain in the 
study, may be treated according 
to the standard local practice.’  
Replaced ‘do so’ with ‘remain in 
the study’.   
Provide further clarification 
on subject withdrawals and 
discontinuation. 
Benefit 
Sect 11.3 
Added ‘Study completion is 
defined as when the last subject 
has completed their last study 
visit.’ 
Provided definition for 
study completion. 
N/A 

SAP_001.pdf: 
PRS COVER PAGE for STATISTICAL ANALYSIS PLAN 
 
TITLE: A Phase 3, Randomized, Double-Blind Study to Evaluate the 
Efficacy and Safety of VT-1161 Oral Capsules versus Fluconazole and 
Placebo in the Treatment of Acute Vulvovaginal Candidiasis Episodes in 
Subjects with Recurrent Vulvovaginal Candidiasis (VMT-VT-1161-CL-017) 
 
DATE: 21 December 2020 
 
CLINICALTRIALS.GOV ID: NCT03840616 
 
 






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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN REVIEW AND APPROVAL .............................................. 2 
1. 
INTRODUCTION .................................................................................................................... 5 
1.1. 
Study Overview .................................................................................................................... 5 
1.2. 
Glossary of Abbreviations ................................................................................................... 7 
2. 
OBJECTIVES ........................................................................................................................... 7 
3. 
GENERAL STATISTICAL CONSIDERATIONS ............................................................... 7 
3.1. 
Primary Study Hypotheses ................................................................................................. 7 
3.2. 
Sample size ........................................................................................................................... 8 
3.3. 
Randomization and Blinding ............................................................................................ 11 
3.4. 
Handling of data ................................................................................................................ 12 
3.4.1. Strata and Covariates ....................................................................................................... 12 
3.4.2. Examination of Subject Subsets ...................................................................................... 12 
3.4.3. Multiple Testing and Comparisons ................................................................................. 12 
3.4.4. Missing Data and Outliers ............................................................................................... 12 
3.4.5. Derived and Transformed Data ....................................................................................... 16 
3.4.6. Imputation of Incomplete Dates ...................................................................................... 16 
3.4.7. By-Study Visit Displays .................................................................................................. 17 
3.4.8. Visit Windows ................................................................................................................. 17 
3.4.9. Definitions and Terminology .......................................................................................... 17 
3.5. 
Timing of Analyses ............................................................................................................ 20 
4. 
ANALYSIS POPULATIONS ................................................................................................ 20 
4.1. 
Intent-to-treat population ................................................................................................. 20 
4.2. 
Modified Intent-to-treat population ................................................................................. 20 
4.3. 
Safety Population ............................................................................................................... 21 




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1. 
INTRODUCTION 
This document describes the statistical methods and data presentations to be used in the summary 
and planned analysis of data from Protocol VMT-VT-1161-CL-017. Background information is 
provided for the overall study design and objectives. The reader is referred to the study protocol, 
case report forms (CRFs) and randomization specification form for details of study conduct and 
data collection.  
1.1. 
STUDY OVERVIEW 
This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study.  
The study will evaluate the efficacy and safety of oral VT-1161 capsules versus fluconazole in the 
treatment of acute vulvovaginal candidiasis episodes in subjects with recurrent vulvovaginal 
candidiasis (RVVC).  In addition, the study will evaluate the efficacy of oral VT-1161 compared to 
placebo in the prevention of RVVC.  The study consists of two phases: 1) an Induction Phase for 
the treatment of the acute vulvovaginal candidiasis (VVC) episode in which subjects will be 
randomly assigned in a 2:1 ratio (VT-1161 to fluconazole) to receive either a) a 600 mg VT-1161 
dose on Day 1 and 450 mg VT-1161 dose on Day 2, or b) 3 sequential 150 mg oral doses (every 72 
hours) of over-encapsulated fluconazole, and 2) a Maintenance phase in which subjects randomized 
to receive VT-1161 in the Induction Phase will receive 150 mg VT-1161 weekly for 11 weeks and 
subjects initially randomized to over-encapsulated fluconazole in the Induction Phase will received 
placebo weekly for 11 weeks.  The maintenance phase will include follow-up for each subject 
through Week 50. 
Once subjects have provided informed consent or assent (for those ages 12-17), the investigational 
site will evaluate all subjects by completing a review of pertinent medical history, obtaining vital 
signs, height and weight, electrocardiogram (ECG) and laboratory tests, reviewing clinical signs 
and symptoms of vulvovaginitis, performing a complete physical examination including speculum 
examination of the vagina, performing a potassium hydroxide (KOH) wet mount test from a 
vaginal smear to confirm the presence of yeast, and collecting vaginal swabs to establish a baseline 
culture for identification of fungal species. Eligible subjects must have an acute VVC episode at 
Screening, defined as a total signs and symptoms score of ≥3 and a positive local KOH wet mount 
preparation from a vaginal smear revealing filamentous hyphae/pseudohyphae and/or budding 
yeast cells and must meet other initial entry criteria. 
Once eligibility is confirmed, subjects will be randomized in a 2:1 ratio (VT-1161: fluconazole) to 
enter the Induction Phase.  During the Induction Phase, the presenting acute VVC episode will be 
treated with either 600 mg VT-1161 (4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 
150 mg capsules) on Day 2, or 3 sequential 150 mg oral doses (every 72 hours) of over-
encapsulated fluconazole. Subjects will return approximately 14 days after the first dose of VT-
1161 or over-encapsulated fluconazole to determine if the acute VVC episode has resolved 
(defined by a signs and symptoms score of <3).  If the acute VVC has not resolved, the subject will 
be considered an Induction Failure and encouraged to see their physician for follow-up.  All 
subjects in which the acute VVC infection has resolved will continue into a Maintenance Phase.  
Day 1 (Screening) is defined as the first day of investigational medicinal product (IMP) 
administration and subsequent study days are defined by the number of consecutive days thereafter.  
Day 14 is defined as the first day of weekly dosing of IMP administration.  


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Vulvovaginal signs and symptoms will be evaluated at Screening and at each subsequent study 
visit.  A local mycological assessment using KOH wet mount followed by microscopy will be 
performed at Screening to determine study eligibility and at any study visit where a recurrent acute 
VVC episode is suspected. In addition, from the collected vaginal swabs, culture growth will be 
evaluated by the central mycology laboratory.  Blood samples for assay of VT-1161 plasma 
concentrations will be collected from subjects at Day 14, Weeks 14 and 50.  Intense sampling will 
be obtained from approximately 12 consenting subjects at participating sites on Day 1 and on Day 
2, at time points predose and 1, 2, 4, and 8 hours after dosing.  Subject safety will be monitored by 
the reporting of adverse events (AEs) and changes in vital signs, physical and vaginal exam 
parameters, ECGs, and safety laboratory parameters, including pregnancy tests for women of child-
bearing potential. 
 
 


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1.2. 
GLOSSARY OF ABBREVIATIONS 
AE  
adverse event 
ANCOVA 
analysis of covariance 
BMI 
body mass index 
CI 
confidence interval 
CRF 
case report form 
ECG 
electrocardiogram 
IMP 
investigational medicinal product 
ITT 
intent-to-treat 
IWRS 
interactive web response system 
KOH 
potassium hydroxide 
LS 
least squares 
mITT 
modified intent to treat 
PK 
pharmacokinetic 
PP 
per-protocol 
QTcF 
Fridericia-corrected QT interval 
SAE  
serious adverse event 
TEAEs 
treatment-emergent adverse events 
VT-1161 
IMP, oral inhibitor of fungal CYP51 
RVVC 
recurrent vulvovaginal candidiasis 
VVC 
vulvovaginal candidiasis 
2. 
OBJECTIVES 
Primary: 
x 
To evaluate the efficacy of oral VT-1161 in the prevention of culture-verified acute 
episodes of VVC through Week 50 in RVVC subjects. 
x 
To compare the efficacy of oral VT-1161 and fluconazole in the treatment of an acute 
episode in RVVC subjects. 
Secondary: 
x 
To evaluate the safety and tolerability of oral VT-1161 through Week 50. 
3. 
 GENERAL STATISTICAL CONSIDERATIONS 
3.1. 
PRIMARY STUDY HYPOTHESES 
The primary null hypothesis for this study is that the proportion of subjects with one or more 
culture-verified acute VVC episodes post randomization through Week 50, which includes 


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subjects with an unresolved VVC episode during the Induction Phase (post-randomization 
through Day 14), is the same for subjects treated with VT-1161 and those treated with placebo.  
The alternative hypothesis is that the proportion of subjects with one or more culture-verified acute 
VVC episodes post randomization through Week 50, which includes subjects with an 
unresolved VVC episode during the Induction Phase (post-randomization through Day 14), 
is different for subjects treated with VT-1161 and those treated with placebo.  A culture-verified 
acute VVC episode during the Maintenance phase (considered a recurrent episode) is defined as a 
positive culture for Candida species associated with clinical signs and symptoms score of ≥3. 
The key secondary null hypothesis for this study is that the proportion of subjects whose acute 
VVC has resolved by Day 14 is inferior (i.e. less) for subjects treated with VT-1161 compared to 
those treated with fluconazole.  The alternative hypothesis is that the proportion of subjects whose 
acute VVC has resolved by Day 14 is non-inferior for subjects treated with VT-1161 compared to 
those treated with fluconazole.  A non-inferiority margin of 15% will be used for the testing of this 
hypothesis. 
3.2. 
SAMPLE SIZE  
The study will enroll approximately180 total subjects (120 in the VT-1161 arm and 60 in the 
fluconazole/placebo arm).  For the primary efficacy endpoint determination, a sample size of 82 
active subjects and 41 fluconazole/placebo subjects provides at least 90% power to detect a 
treatment difference between the VT-1161 treatment group and the fluconazole/placebo treatment 
group in the percentage of subjects with one or more culture-verified acute VVC episodes during 
the Maintenance Phase (post randomization through Week 50). (PASS 2008: Fisher's exact test, 
two-sided alpha=0.05, and assuming 50% of fluconazole/placebo subjects have recurrence).  For 
the first key secondary endpoint, the proportion of subjects with resolved acute VVC infections 
(clinical signs and symptoms score of <3) at Day 14 following treatment with VT-1161 or 
fluconazole, a sample size of 120 subjects in the VT-1161 arm and 60 subjects in the 
fluconazole/placebo arm provides at least 88% power to detect non-inferiority between the VT-
1161 treatment group and the fluconazole treatment group with a non-inferiority margin of 15% 
and a type 1 error rate of 0.05. (PASS 2008: Z-test for two independent proportions, one-sided 
alpha = 0.025, non-inferiority margin = 15%, and assuming that 90% of fluconazole subjects 
resolve their acute VVC infection).  
For the primary endpoint, the placebo rate was based on data generated in the Phase 2b RVVC 
study; the primary efficacy outcome measure in this study was the proportion of subjects with one 
or more culture verified acute VVC episodes during the Maintenance Phase through Week 48 of 
the study in the ITT population (all randomized subjects).  Culture-verified acute VVC was defined 
as a positive fungal culture for Candida species associated with a total signs and symptoms score of 
≥ 3.  The proportion of subjects with one or more culture-verified acute VVC episodes through 
Week 48 was lower in the VT-1161 dosing regimens (0-7%) compared with the placebo group 
(52.2%).  This difference was statistically significant in all VT-1161 treatment groups compared 
with placebo (p<0.0001). When powering the VMT-VT-1161-CL-017 study, it was determined 
that a separation of at least 35% between the treatment groups would be a clinically meaningful 
separation.  Thus, the sample size was powered to detect at least a 35% separation between the 
treatment groups. 


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Treatment of RVVC Non-inferiority justification 
 Fluconazole Assumptions 
The Fluconazole clinical improvement (signs and symptoms < 2) rate at Day 14 was calculated 
using the data recently collected from the induction period of the following Mycovia studies: 
x 
VMT-VT-1161-CL-006, titled ‘A Phase 2, Randomized, Double-Blind, Placebo-
Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of VT-1161 Oral 
Tablets in the Treatment of Patients With Recurrent Vulvovaginal Candidiasis’.   
x 
VMT-VT-1161-CL-011, titled ‘A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of VT-1161 Oral Capsules in the 
Treatment of Subjects with Recurrent Vulvovaginal Candidiasis’ 
x 
VMT-VT-1161-CL-012, titled ‘A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of VT-1161 Oral Capsules in the 
Treatment of Subjects with Recurrent Vulvovaginal Candidiasis’ 
Mycovia study CL-006 enrolled 215 subjects who received fluconazole to clear an acute VVC 
infection.  At Day 14, 84.7% of subjects had clinical improvement (signs and symptoms of 0 or 1).  
Mycovia’s 2 pivotal Phase 3 studies (CL-011 and CL-012) have clinical improvement rates of 
78.1% (374 subjects) and 80.1% (366 subjects) at Day 14.  When combining the data from Phase 
2b and the 2 Phase 3 studies, the clinical improvement rate in 955 subjects at Day 14 is 80.3%.   
Placebo Assumptions 
The placebo clinical improvement rate was calculated using the results from the Scynexis Second 
Quarter 2020 Financial Results and Company Updates (https://www.globenewswire.com/news-
release/2020/08/10/2075630/0/en/SCYNEXIS-Reports-Second-Quarter-2020-Financial-Results-
and-Provides-Company-Update.html).   Scynexis reported topline results from 2 of their pivotal 
Phase 3 studies in subjects with acute VVC: 
x 
VANISH-306, titled ‘A Phase 3, Multicenter, Randomized, Double-Blind, Placebo 
Controlled Study to Evaluate the Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs 
Placebo in Subjects with Acute Vulvovaginal Candidasis.’  
x 
VANISH-303, titled ‘A Phase 3, Multicenter, Randomized, Double-Blind, Placebo 
Controlled Study to Evaluate the Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs 
Placebo in Subjects with Acute Vulvovaginal Candidasis.’ 
VANISH-306 with 84 placebo patients had clinical improvement of 54.8% at Day 10 and 
VANISH-303 with 98 patients had clinical improvement of 36.7% at Day 10.  The projected 
clinical improvement rates at Day 14, are 57.0% and 41.0%.   The projected rates for Day 14 were 
determined for each study by using the formulas for the clinical improvement lines in each study 
(VANISH-306: y = 0.56x + 49.2, VANISH-303: y = 1.087x + 25.83).  For each study, to determine 
the formula for the line for clinical improvement, the slope was derived using the Day 10 and Day 
25 clinical cure rates.  Mycovia is assuming the slope between Day 10 and Day 25 for clinical 
improvement for each study is the same as the slope between Day 10 and Day 25 for clinical cure 
for each study.   A weighted average of the Day 14 projected rates from the 2 Phase 3 studies was 
used as the expected placebo clinical improvement rate of 48.4%.  


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NI Margin Justification 
Fluconazole has a clinical improvement (signs and symptoms < 2) rate of 80.3% at Day 14. 
Placebo has a clinical improvement rate of 48.4% at Day 14.  Thus, an estimate of the effect of 
fluconazole to treat an acute VVC infection versus no intervention in subjects with RVVC is 
31.9%.  Per the FDA guidance document on Non-Inferiority Clinical Trials to Establish 
Effectiveness, a non-inferiority margin that is at most half the effect of the control drug should be 
used.  A non-inferiority margin of 15% was selected for this trial which is less than 50% of the 
effect of the control drug.  The placebo rate in the NI margin calculation is a conservative estimate 
of the placebo improvement rate in RVVC subjects since the placebo rate is from VVC subjects.  
This is a conservative estimate for the placebo improvement rate in RVVC subjects as it has been 
shown to be harder for subjects with RVVC to clear their infections.  Per the package insert for 
Fluconazole (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f694c617-3383-416c-
91b6-b94fda371204 ), for all endpoints that are in the insert (clinical cure, mycologic eradication, 
and therapeutic cure), the rates were lower in RVVC subjects than in VVC subjects.  Thus, the true 
effect of fluconazole over placebo is likely greater than 31.9%. 
Treatment of Acute VVC Non-inferiority justification 
Fluconazole Assumptions 
The Mycovia Fluconazole clinical cure rate (clinical signs and symptoms score of 0) in RVVC was 
determined by first using the data from the induction period of the following Mycovia studies: 
x 
VMT-VT-1161-CL-006, titled ‘A Phase 2, Randomized, Double-Blind, Placebo-
Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of VT-1161 Oral 
Tablets in the Treatment of Patients With Recurrent Vulvovaginal Candidiasis’.   
x 
VMT-VT-1161-CL-011, titled ‘A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of VT-1161 Oral Capsules in the 
Treatment of Subjects with Recurrent Vulvovaginal Candidiasis’ 
x 
VMT-VT-1161-CL-012, titled ‘A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of VT-1161 Oral Capsules in the 
Treatment of Subjects with Recurrent Vulvovaginal Candidiasis’ 
Mycovia study CL-006 enrolled 215 subjects who received fluconazole to clear an acute VVC 
infection.  At Day 14, 59.5% of subjects had clinical cure (signs and symptoms of 0).  Mycovia’s 2 
pivotal Phase 3 studies (CL-011 and CL-012) have clinical cure rates of 58.3% (374 subjects) and 
55.2% (366 subjects) at Day 14.  When combining the data from Phase 2b and the 2 Phase 3 
studies, the clinical improvement rate in 955 subjects is 57.4%.  The package insert for fluconazole 
notes a 57% clinical cure rate in RVVC patients and an 80% clinical cure rate in patients with acute 
VVC.  The rate observed in the 3 Mycovia studies is numerically the same as the package insert 
(57.4% vs 57%).  Thus, the clinical cure rate of 80% for subjects with acute VVC will be used in 
the NI calculation to determine the benefit of fluconazole over no intervention.   
Placebo Assumptions 
The placebo clinical cure rate was calculated using the results from the Scynexis Second Quarter 
2020 Financial Results and Company Updates (https://www.globenewswire.com/news-
release/2020/08/10/2075630/0/en/SCYNEXIS-Reports-Second-Quarter-2020-Financial-Results-


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and-Provides-Company-Update.html).   Scynexis reported topline results from 2 of their pivotal 
Phase 3 studies in subjects with an acute VVC infection: 
x 
VANISH-306, titled ‘A Phase 3, Multicenter, Randomized, Double-Blind, Placebo 
Controlled Study to Evaluate the Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs 
Placebo in Subjects with Acute Vulvovaginal Candidasis.’  
x 
VANISH-303, titled ‘A Phase 3, Multicenter, Randomized, Double-Blind, Placebo 
Controlled Study to Evaluate the Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs 
Placebo in Subjects with Acute Vulvovaginal Candidasis.’ 
VANISH-306 with 84 placebo patients had clinical cure of 44% at Day 10 and VANISH-303 with 
98 patients had clinical cure of 28.6% at Day 10.  The projected clinical cure rates at Day 14 are 
46.24% and 32.95%.   The projected rates for Day 14 were determined for each study by utilizing 
the formulas for the clinical cure lines in each study (VANISH-306: y = 0.56x + 38.4, VANISH-
303: y = 1.087x + 17.73).  For each study, the Day 10 and Day 25 clinical cure rates were used to 
determine the formula for the line for clinical cure.  A weighted average of the Day 14 projected 
rates from the 2 studies was used as the expected placebo clinical cure rate of 39.1%.   
NI Margin Justification 
Fluconazole has a clinical cure (signs and symptoms = 0) rate of 80% at Day 14 in subjects with 
acute VVC. Placebo has a clinical cure rate of 39.1% at Day 14 in subjects with acute VVC.  Thus, 
the effect of fluconazole to treat an acute VVC infection versus no intervention in subjects with 
acute VVC is 40.9%.  The effect of fluconazole to treat an acute infection versus no intervention in 
subjects with RVVC is expected to be the same as the effect in subjects with acute VVC.  A non-
inferiority margin of 15% was selected for this comparison which is less than 50% of the effect of 
the control drug. 
3.3. 
RANDOMIZATION AND BLINDING 
A total of approximately 180 eligible subjects will be randomized in a 2:1 ratio to either VT-1161 
or fluconazole/placebo based on the randomization list which will be prepared according to 
appropriate standard operating procedures. Randomization to treatment will be sequentially 
assigned to eligible subjects at the Day 1 (Screening) Visit.  
This is a double-blind study. Therefore, the subjects, study investigators and their staff, all clinical 
staff members within Mycovia, Clinical Study Monitors, and the Study Medical Monitor will 
remain blinded to individual treatment assignments until the completion of the study.  The only 
study personnel who will be unblinded to the treatments will be the Unblinded Statistician 
responsible for creating the final randomization list, the interactive web response system (IWRS) 
personnel responsible for loading the final randomization list into the IWRS system, clinical supply 
management (Vendor/Mycovia) and distribution personnel and bioanalytical personnel.  
Should the Investigator or the Study Medical Monitor need to reveal a given subject's treatment 
assignment, such as in the case of a serious adverse event (SAE) report where knowledge of the 
IMP treatment assignment may be needed to treat the subject with the SAE, the IWRS may be 
accessed to break the study blind for that subject.  The Investigator must contact and discuss with 
Mycovia’s Medical Monitor the circumstances leading to his/her decision to break the blind.  




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For scheduled visits where the investigator’s assessment of clinical signs and symptoms or the 
culture result is missing, missing values will be imputed using the method of multiple imputation.  
For subjects who discontinue the study early and have missing assessments for all visits after 
discontinuation, the missing values for the expected scheduled visits will be imputed using the 
method of multiple imputation.  The missing values will be imputed using the following auxiliary 
information: region, treatment, baseline body mass index (BMI), baseline age, ethnicity, and visit.  
Region, treatment, baseline BMI, baseline age, ethnicity, and visit are included as auxiliary 
information because it is believed that subjects with similar values for each of these parameters 
would respond similarly.   One of the benefits of using multiple imputation is that it uses a set of 
values rather than a single value which better accounts for the uncertainty about the values being 
imputed.  The procedure PROC MI in SAS will be used to generate 10 possible imputed datasets.  
Using these multiple imputation datasets, determination of meeting the primary endpoint of a 
culture-verified acute VVC episode during the Maintenance Phase will be derived.  Subjects with a 
culture-verified acute VVC episode at any point from post Day 14 through Week 50 (including 
unscheduled visits) and subjects with an unresolved VVC episode during the Induction Phase 
(post-randomization through Day 14) will be counted as having an episode when calculating the 
primary endpoint.   The multiple datasets containing the primary endpoint will be analyzed using a 
Chi-square test and the results will be combined using PROC MIANALYZE to obtain an 
inferential result.  Here is a summary of the steps that will be performed: 
1. For subjects with a missing value for clinical signs and symptoms or a missing value for 
culture result at a scheduled visit, who have an unscheduled visit (within the visit window) 
with non-missing values as outlined in Section 3.4.8, their values from the unscheduled 
visit will be used to replace scheduled visit values. 
2. Any missing values for clinical signs and symptoms or culture result for scheduled visits 
will be imputed using PROC MI.  Any unscheduled visit values that are not used to replace 
scheduled visit values, as described in Step 1, will not be used in the imputation process.  
The seed for the imputation procedure will be randomly generated and documented in the 
study files.  This will result in 10 complete datasets. 
3. The primary efficacy endpoint of culture-verified acute VVC episode will be derived using 
values from all scheduled visits from the complete datasets and all unscheduled visits that 
were not already used in Step 1.  In other words, if an unscheduled visit for a subject is 
already being used to replace a missing visit in Step 1, then it would not be used again as 
an unscheduled visit when calculating the primary endpoint.  This will result in 10 datasets 
with one record per person for the primary endpoint. 
4. The primary efficacy endpoint will be analyzed 10 times using a Chi-square test as 
outlined in Section 5.2.1.  The Wilson-Hilferty transformation will be applied to the Chi-
square test statistics prior to combining the results using PROC MIANALYZE. 
5. The results from the analysis from the 10 datasets will be combined using PROC 
MIANALYZE to produce an inferential result comparing the treatment groups. 
The following sensitivity analyses will be performed for the primary endpoint to assess the impact 
of missing/censored data on the results: 
1. The first sensitivity analysis will use Kaplan-Meier methods to estimate the proportion of 
subjects with one or more culture-verified acute VVC episodes post randomization through 


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Week 50.  The Kaplan-Meier estimate, and 95% confidence interval will be determined 
and compared to the primary result.  For this analysis, time to event and censoring will be 
calculated using the following rules: 
a. Subjects who experience a culture-verified acute VVC episode post randomization 
through Week 50 will have their time to event calculated as the time in weeks from 
post randomization to the first culture-verified acute VVC episode.   
b. Subjects who discontinue the study for any reason prior to Week 50 without 
experiencing a culture-verified acute VVC episode will be censored at the last 
nominal visit for which they have signs and symptoms and culture data.   
c. Subjects who have missing data at any point prior to Week 50, who do not 
experience a culture-verified acute VVC episode and have both non-missing signs 
and symptoms data at Week 50 and non-missing culture data at Week 50 will be 
censored at the Week 50 visit.    
2. Like the first sensitivity analysis, the second sensitivity analysis will also use Kaplan-
Meier methods to estimate the proportion of subjects with one or more culture-verified 
acute VVC episodes post randomization through Week 50.  The Kaplan-Meier estimate, 
and 95% confidence interval will be determined and compared to the primary result.  For 
this analysis, time to event and censoring will be calculated using the following rules: 
a. Subjects who experience a culture-verified acute VVC episode post randomization 
through Week 50 will have their time to event calculated as the time in weeks from 
post randomization to the first culture-verified acute VVC episode.   
b. Subjects who discontinue the study for any reason prior to Week 50 and have no 
nominal visits with missing signs and symptoms or culture data prior to 
discontinuation will be censored at the last nominal visit prior to discontinuation 
for which they have signs and symptoms and culture data.  
c. Subjects who do not experience a culture-verified acute VVC episode post 
randomization through Week 50 with missing signs and symptoms or culture data 
at any point not due to COVID-19 will be censored at the last nominal visit before 
the first visit with missing signs and symptoms and culture data not due to 
COVID-19.  Subjects who reach Week 50 without a culture-verified acute VVC 
episode and without any missing data, not due to COVID-19, will be censored at 
Week 50. Subjects who do not experience a culture-verified acute VVC episode 
post randomization through Week 50 with the only missing signs and symptoms or 
culture data due to COVID-19 will be censored at the last nominal visit for which 
they have signs and symptoms and culture data.   
3. Subjects who were censored for the second sensitivity analysis due to early discontinuation 
or missing data not due to COVID-19 will be counted as failures.  In other words, these 
subjects will be counted as having an episode.  The proportion of subjects with episodes 
will be calculated and presented along with the 95% confidence intervals.  The p-value 
from a Chi-square test comparing the 2 treatments will also be presented.  The denominator 
for the calculation of the proportion of subjects with at least one culture-verified acute 
VVC episode will be the ITT population.  


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4. A completer analysis will be performed where subjects who did not have a culture-verified 
acute VVC episode and have either missing assessments for a given visit or who 
discontinued from the study prior to Week 50 are excluded from the analysis.  The 
proportion of subjects with episodes will be calculated and presented along with the 95% 
confidence intervals.  The p-value from a Chi-square test comparing the 2 treatments will 
also be presented.   
5. The primary analysis method will be used to analyze a modified definition of the primary 
endpoint where subjects are included as having an acute VVC episode if 1) they meet the 
primary endpoint definition or 2) they have a recurrence in the absence of Investigator 
confirmed signs and symptoms and/or culture confirmation but took a medication known 
to treat VVC during the Maintenance Phase.  The p-value from a Chi-square test 
comparing the 2 treatments will also be presented.   
Sensitivity analyses will also be performed for the key secondary endpoints to assess the impact of 
censored data on the results. 
Endpoint = proportion of subjects with resolved acute VVC infections (clinical signs and 
symptoms score of < 3) at Day 14 following treatment with VT-1161 or fluconazole 
For the Day 14 assessments, subjects with a missing investigator assessment of clinical signs and 
symptoms, will have their missing values imputed using the method of multiple imputation.  The 
missing values will be imputed using the following auxiliary information: region, treatment, 
baseline BMI, baseline age, and ethnicity.  The procedure PROC MI will be used to generate 10 
possible imputed datasets.  Using these 10 multiple imputation datasets, determination of meeting 
the secondary endpoint of resolved acute VVC infection at Day 14 will be derived.  Then, these 10 
multiple imputation datasets containing the secondary endpoint of resolved acute VVC infection 
for each subject will be used to calculate the proportion of subjects who have cleared their infection 
in each treatment arm and the difference between these proportions using PROC FREQ.  PROC 
MIANALYZE will be used to combine these ten results to produce a single 95% confidence 
interval for the difference in proportions between the VT-1161 arm and the fluconazole arm. 
For the first sensitivity analysis, any subjects with missing Day 14 assessments will be counted as 
not having resolved the acute VVC infection. The 95% confidence interval for the difference in 
proportions between the VT-1161 arm and the fluconazole arm will be presented. 
For the second sensitivity analysis, subjects who did not complete the Day 14 assessment will be 
excluded from the analysis.  The 95% interval for the difference in proportions between the VT-
1161 arm and the fluconazole arm will be presented. 
 
Endpoint = proportion of subjects with at least one culture-verified acute VVC episode with 
sign and symptoms score ≥ 3 during the Maintenance Phase (post Day 14 through Week 50) 
All 5 sensitivity analyses for the primary endpoint will be applied to this secondary endpoint with 
the exception that for the sensitivity analyses of this endpoint, only data from Day 14 through 
Week 50 will be considered. 
Endpoint = time to first recurrence of a culture-verified acute VVC episode with sign and 
symptoms score ≥3 during the Maintenance Phase (post Day 14 through Week 50) 


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The primary analysis for the time to first acute VVC episode during Maintenance Phase will censor 
any subjects who do not have a culture-verified acute VVC episode at their last non-missing 
assessment for signs and symptoms and culture.  If a subject does not experience a culture-verified 
acute episode post Day 14 through Week 50, they will be censored at Week 50.   
For the sensitivity analysis, subjects who discontinue the study early during the Maintenance Phase 
will be considered to have a culture-verified acute VVC episode at the next scheduled assessment 
after their last non-missing assessment, if there is no recurrence prior to discontinuation.  The 
scheduled study day of that assessment will be used for the time to recurrence.  For subjects with a 
missing signs and symptoms or culture result not due to COVID-19 prior to discontinuation, the 
subject will be considered to have an episode at the visit with the missing assessments.  The 
scheduled study day of the missing assessment will be used for the time to recurrence. 
A second sensitivity analysis will be performed on the endpoint of time to first known treatment for 
VVC or recurrence of acute VVC during the Maintenance Phase.  Time will be calculated as: 
Earliest date between date of first culture-verified acute VVC episode and date of first 
known treatment for VVC – date of randomization + 1 
Subjects with no known treatment or no recurrence will be censored at their last non-missing 
assessment.  The analysis methods for the secondary endpoint of time to first recurrence will be 
used. 
Endpoint = proportion of subjects with at least one positive culture for Candida species 
during the Maintenance Phase  
The first 4 sensitivity analyses for the primary endpoint will be applied to this secondary endpoint 
with the exception that for the sensitivity analyses of this endpoint, only the culture data will be 
considered. 
3.4.5. Derived and Transformed Data 
There are no planned transformations of data. 
3.4.6. Imputation of Incomplete Dates 
An incomplete date is any date for which either the day, month or year is unknown, but not all 3 
fields are unknown. An incomplete date occurs when the exact date an event occurred or ended 
cannot be obtained from a subject. For many of the analyses, a complete date is necessary to 
determine if the event should be included in the analysis (i.e., if the event is treatment-emergent) or 
to establish the duration of an event.  In such cases, incomplete dates will be imputed. 
For purposes of imputation of dates for Adverse Events and concomitant medications, all events 
with an incomplete end date are assumed to be on-going at the end of the study.  
To minimize bias, the project statistician will impute dates in a systematic, reasonable manner. If 
the month/year is the same as the Day 1 month/year, then the date will be set to the date of Day 1. 
In other cases, missing days will be imputed as the day component of Day 1, missing months/years 
will be imputed as the month/year of Day 1. If the resulting imputed date is an invalid date, then 
the next valid date will be used (ex: 31FEB2019 will be 01MAR2019). 
 


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Duration will not be calculated for events with a partial start or stop date. 
3.4.7. By-Study Visit Displays 
When data are collected serially over time, individual data presentations may include by-study visit 
displays for all scheduled study visits. Visits will be presented according to the nominal visit as 
obtained from the electronic data collection system or laboratory data unless the visit is an 
unscheduled visit. Unscheduled visits will be windowed based on the Study Day at which they 
occurred as defined in section 3.4.8. An unscheduled visit will only be used if a scheduled visit is 
not available. If a subject has multiple non-missing scheduled values on the same date, then the last 
one is used, as determined by the time collected, if available.  If time is not present and the subject 
has multiple non-missing scheduled values on the same date, the ‘worst’ value will be the one 
designated as the value used. If no scheduled values are available, an unscheduled visit may be 
used. 
3.4.8. Visit Windows  
The visits will be used as nominally recorded in the electronic data collection system. Unscheduled 
visits will be windowed based on the Study Day at which they occur but will only be used if the 
scheduled visit is not available. The exception to this will be for the primary and key secondary 
endpoints where an unscheduled visit with a culture-verified acute VVC episode with signs and 
symptoms of ≥3 will result in the subject being considered as a failure.  Unscheduled visits will be 
windowed based on the table below: 
 
Table 1: Visit Windows for Early Termination and Unscheduled Visits 
Nominal Visit 
Visit Window 
Day 1 
Study Day ≤ 1 
Day 14 
Study Day 12 to 16 
Week 8 
Study Day 49 to 63 
Week 14 
Study Day 84 to 112 
Week 20 
Study Day 126 to 154 
Week 26 
Study Day 168 to 196 
Week 32 
Study Day 210 to 238 
Week 38 
Study Day 252 to 280 
Week 44 
Study Day 294 to 322 
Week 50 
Study Day 336 to 364 
3.4.9. Definitions and Terminology 
 
Baseline Value 
For purposes of analysis, the baseline value is defined as the last non-missing value obtained prior 
to initiation of IMP. 
 
Day 1  
Day 1 is defined as the date of first randomized IMP administration/dispensation.   
 


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Study Day  
Study Day is defined relative to Day 1.  Thus, the study day of an event is calculated as: 
 
Study Day = ((event date – date of Day 1) + 1) 
Study Visit 
Study Visit is the nominal visit as recorded on the CRF. 
Induction Phase 
Induction phase will include all assessments done from randomization through Day 14. 
Maintenance Phase 
Maintenance Phase will include all assessments performed from post Day 14 through Week 50 or 
early termination. 
Days on Maintenance  
Days on Maintenance is calculated as: 
 
Number of Days on Maintenance = study discontinuation date – date of first day maintenance IMP 
was taken + 1 
Last Dose of IMP 
Last Dose of Study IMP is defined as the last date that the subject received IMP as determined by 
last date of dosing as recorded on the IMP administration panel of the CRF. 
IMP Exposure (days) 
IMP Exposure is defined as the number of days from Day 1 to the date of Last Dose of IMP. 
IMP Compliance for the Induction Phase (first week of the study) 
Number of daily doses taken will be the count of days the subject received a dose on Days 1 to 7. 
For the purpose of compliance calculation, doses that are marked as “Missed/Interrupted” or 
“Discontinued VT-1161 Permanently” will not be counted as a received dose. IMP Compliance is 
calculated as:  
 
IMP Compliance = (Number of Daily Doses Taken)/ 4 
IMP Compliance for the Maintenance Phase Weekly Dosing (Day 14 through Week 12 of the 
study) 
Number of weekly doses taken will be the count of days the subject received a dose on Weeks 2 to 
12. For the purpose of compliance calculation, doses that are marked as “Missed/Interrupted” or 
“Discontinued VT-1161 Permanently” will not be counted as a received dose. IMP Compliance is 
calculated as:  
 
IMP Compliance = (Number of Weekly Doses Taken)/ 11 
 
 


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Days on Study 
Days on Study is calculated as: 
 
Number of Days on Study = study discontinuation date - informed consent date + 1 
Age 
The age is defined as the age value recorded in the electronic case report form. 
 
Change from Baseline  
Change from Baseline for a given endpoint is defined as the Study Day X Value minus the 
Baseline Value. 
Acute VVC episode in Maintenance 
Acute VVC episode in the Maintenance Phase (considered a recurrent episode) of the study is 
defined as having a total clinical signs and symptoms score ≥3 associated with a positive culture 
for Candida species. 
 
Recurrent VVC 
A history of RVVC is defined as 3 or more VVC episodes in the past 12 months.  
Treatment-emergent Laboratory Abnormalities 
A treatment-emergent laboratory abnormality is defined as a result in which the baseline value is 
within normal laboratory limits and the post-baseline value is outside normal laboratory limits. If 
the relevant baseline assessment is missing, then any post-baseline value outside normal laboratory 
limits is considered to be treatment-emergent.   
 
Treatment-emergent Laboratory Toxicity 
A treatment-emergent laboratory toxicity is defined as an increase of at least one toxicity grade 
from the baseline assessment at any post baseline visit. If the relevant baseline assessment is 
missing, then any graded abnormality (i.e., at least Grade 1) is considered to be treatment-
emergent. 
 
Adverse Event 
An AE is any untoward, undesired, unplanned clinical event in the form of signs, symptoms, 
disease, or laboratory or physiological observations occurring in a human participating in a clinical 
study with a Mycovia Pharmaceuticals, Inc. product, regardless of causal relationship. A “pre-
existing” condition is one that is present prior to the start of IMP administration and is reported as 
part of the subject’s medical history. Pre-existing conditions should be reported as AEs only if the 
frequency, intensity, or character of the pre-existing condition worsens after the start of 
IMP. 
 
Laboratory abnormalities generally are not considered AEs unless they are associated with clinical 
signs or symptoms or require medical intervention.  A laboratory abnormality (e.g., a clinically 
significant change detected on clinical chemistry, hematology, urinalysis) that is independent from 
a known underlying medical condition and that requires medical or surgical intervention, or leads 
to IMP interruption or discontinuation, must be considered an AE. 


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Treatment-Emergent Adverse Event 
Any recorded Adverse Event that occurs on or after the initiation of IMP is considered treatment-
emergent.  Additionally, it is assumed that an Adverse Event which was reported to have started on 
Day 1 without an associated onset time may have occurred after the initiation of IMP.  Hence, 
Adverse Events occurring on Day 1 are assumed to be treatment-emergent. 
Concomitant Medications 
Concomitant medications are those medications taken on or after the initiation of IMP.  This 
definition includes medications started prior to the initiation of IMP but continuing concomitantly 
with IMP.   
 
Prior Medications 
Prior medications are those medications taken prior to the initiation of IMP but stopped before 
initiation of IMP. 
 
3.5. 
TIMING OF ANALYSES 
The final analysis will be conducted once the last subject completes or discontinues the study, and 
the resulting clinical database has been cleaned, quality checked, the pre-analysis meeting has 
occurred, and the database has been locked. 
 
4. 
ANALYSIS POPULATIONS 
The populations for analysis will include Intent-to-Treat (ITT), Modified ITT (mITT), Safety, Per 
Protocol (PP), and Induction Phase PP. 
4.1. 
INTENT-TO-TREAT POPULATION  
The ITT population is defined as all randomized subjects.  
The ITT population will be the primary population for the primary and the secondary endpoints 
except for the key secondary endpoint of the proportion of subjects with resolved acute VVC 
infections (clinical signs and symptoms score of <3) at Day 14 following treatment with VT-1161 
or fluconazole. 
4.2. 
MODIFIED INTENT-TO-TREAT POPULATION  
The mITT population is defined as all randomized subjects who: 
x 
had a positive central KOH at Screening,  
x 
had a positive culture at Screening,  
x 
had a negative culture at Day 14. 
The Induction Phase mITT population is defined as all randomized subjects who: 
x 
had a positive central KOH at Screening,  
x 
had a positive culture at Screening.  


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4.3. 
SAFETY POPULATION 
The safety population is defined as all randomized subjects who receive at least 1 dose of IMP. 
4.4. 
PER-PROTOCOL POPULATION 
The PP population is defined as all randomized subjects who: 
x 
had no deviations to inclusion/exclusion criteria that could impact treatment outcome. 
x 
were compliant with the assigned study treatment, defined as ≥80% compliant during the 
Induction Phase and ≥50% compliant during the Maintenance Phase 
x 
had the Week 50 visit completed within the acceptable time window (±14 days) 
x 
had no major protocol violations that would impact treatment outcome. 
The Induction Phase PP population is defined as all randomized subjects who:  
x 
had no deviations to inclusion/exclusion criteria that could impact treatment outcome 
during the Induction Phase. 
x 
were compliant with the assigned study treatment during the Induction Phase, defined as 
≥80% compliant during the Induction Phase  
x 
had no major protocol violations that would impact treatment outcome during the 
Induction Phase 
Mycovia will review all protocol violations to determine which subjects should be removed from 
the Per Protocol populations prior to the blind being broken.  The output from this review, 
including the date(s) the meetings were held, the data reviewed, and the decisions made will be 
documented and placed into the study files. 
The Induction Phase PP population will be the primary population for the key secondary efficacy 
endpoint of the proportion of subjects with resolved acute VVC infections (clinical signs and 
symptoms score of <3) at Day 14 following treatment with VT-1161 or fluconazole. 
5. 
STATISTICAL METHODS 
Descriptive statistical methods will also be used to summarize the data from this study, with 
hypothesis testing performed for the primary and key secondary efficacy endpoints.  Unless stated 
otherwise, the term “descriptive statistics” refers to number of subjects, mean, median, standard 
deviation, minimum, and maximum for continuous data, and frequencies and percentages for 
categorical data.  For categorical variables, the denominator of percentages will be the number of 
subjects in the treatment group, except for those collected by study visit and/or scheduled time 
point, in which case the denominator of percentages will be the number of subjects with a non-
missing value at the visit and/or the scheduled time point.  












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plot of time to first recurrence of a culture-verified acute VVC during the maintenance phase will 
be generated by treatment group. 
5.3. 
SAFETY  
All safety analyses will be performed on the Safety Population. 
5.3.1. 
Adverse Events 
Adverse events will be mapped to a Medical Dictionary for Regulatory Activities version 21 or 
higher by preferred term and system organ classification. Within a study phase (induction, 
maintenance), if a subject experiences multiple events that map to a single preferred term, the 
greatest severity grade and strongest investigator assessment of relation to study medication 
observed will be assigned to the preferred term for the appropriate summaries. Should an event 
have a missing severity or relationship, it will be classified as having the highest severity and/or 
strongest relationship to study medication. The occurrence of treatment-emergent adverse events 
(TEAEs) will be summarized by treatment group using preferred terms, system organ 
classifications, and greatest severity. Separate summaries of treatment-emergent SAEs, TEAEs 
related to IMP as evaluated by the investigator, TEAEs related to IMP as evaluated by Mycovia, 
and events leading to the discontinuation of IMP will be generated. TEAEs will be summarized 
overall and by treatment group. All adverse events reported will be listed for individual subjects 
showing both verbatim and preferred terms. All adverse events that occurred prior to the initiation 
of IMP will be excluded from the tables but will be included in the listings.  
Missing onset dates will be imputed as previously outlined in Section 3.4.6 as required to 
determine TEAEs. 
5.3.2. Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization dictionary 
(Version: March 2018). Concomitant medications will be summarized by frequency of generic 
drug name. Prior and concomitant medications will be presented in a data listing.   
5.3.3. Clinical Laboratory Assessments  
Descriptive summaries of quantitative clinical laboratory results (hematology, chemistry, and 
urinalysis) and their change from baseline values will be presented by study visit and treatment 
group.  Observed values of categorical urinalysis data will be displayed with frequencies and 
percentages.  All laboratory data will be listed for individual subjects. 
 
Treatment-emergent abnormal laboratory toxicities will be identified.  These abnormalities will be 
graded according to the Division of Microbiology and Infectious Diseases Adult Toxicity Table.  If 
a laboratory value is not addressed in the Division of Microbiology and Infectious Diseases Adult 
Toxicity Table, then the most recent version of the Common Terminology Criteria for Adverse 
Events, version 4.0 published by the National Cancer Institute will be used. 
Frequency and percentage of subjects experiencing at least one treatment-emergent graded toxicity 
will be summarized by study visit and treatment group.  The number and percentage of subjects 


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having a Grade 3 or 4 treatment-emergent graded toxicity will also be presented by study visit and 
treatment. Additionally, a shift table of the number and percentage of subjects with each toxicity 
grade at baseline value to each study visit toxicity grade, as well as worst overall toxicity grade will 
be presented by treatment group. 
 
Treatment-emergent laboratory abnormalities will also be identified. The number and percentage of 
subjects having each abnormality will be presented by study visit and treatment group. 
5.3.4. Other Safety Analyses 
Descriptive summaries of vital signs and their change from baseline will be presented by study visit 
and treatment group and all vital signs will be listed.  
 
Physical examination findings will be listed. 
ECG measurements will include heart rate, QT interval, Fridericia-corrected QT interval (QTcF), 
PR interval, and QRS interval.  Change from baseline will be summarized descriptively by 
treatment group at each scheduled evaluation and all ECG data will be listed. Proportion of 
subjects with abnormal ECG interpretations will be summarized at each study visit and by 
treatment group. Proportion of subjects who meet each of the following criteria from International 
Conference on Harmonization Guideline E14 “Clinical Evaluation of QT/QTc Interval 
Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs” (October 2005) for QT 
and corrected QT intervals will be summarized across treatment groups: 
x 
QTcF >450 msec 
x 
QTcF >480 msec 
x 
QTcF >500 msec 
x 
QTcF increases from baseline by ≥30 msec 
x 
QTcF increases from baseline by ≥60 msec 
6. 
PROTOCOL VIOLATIONS 
Possible protocol deviations will be identified and displayed in a data listing and sorted by 
treatment group, subject, and study day (where applicable).  In addition, the following deviations 
may be identified and classified as a protocol violation from the database:  
x 
Missing efficacy assessments  
x 
Violations of inclusion/exclusion criteria  
x 
Non-compliance with IMP 
All protocol violations, including the ones identified by statistics, will be reviewed by the Medical 
Monitor and appropriate study team members prior to unblinding, as stated in section 4.4.  There 
will be a face-to-face meeting to discuss all subjects that have been removed from the per-protocol 
population programmatically. A document will be provided for the meeting detailing the criteria 
not met for each subject.  All protocol deviations will be listed.  Separate listings will be presented 
for subject level deviations and site level deviations. 








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Added Induction Phase 
PP mITT Population 
Added mITT Population for the acute infection 
endpoints to be consistent with the mITT 
Population definition in the FDA guidance for the 
treatment of VVC  
 
Updated planned 
populations for the 
analyses of the acute 
VVC infection 
Included analyses on the Induction Phase mITT 
population for the following acute infection 
endpoints: resolved acute VVC infection (clinical 
signs and symptoms score of < 3) at Day 14, 
clinical cure (clinical signs and symptoms score of 
0) at Day 14, and clinical signs and symptoms 
score of 0 and negative culture for Candida species 
at Day 14. 
 
Added consort diagram 
Included a consort diagram to show a visual of the 
disposition table 
 
Added listing for site 
level deviations 
Split the planned deviation listing into 2 listings, 
one for subject level deviations and one for site 
level deviations 
 


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10. 
PROGRAMMING CONVENTIONS 
x 
Page orientation, margins, and fonts: Summary tables, listings, and figures will appear in 
landscape orientation.  There should be a minimum of a 0.5” boundary on the upper (bound) 
and lower edge, and a minimum of a 0.75” boundary on the right and left edges. Output should 
be printed in Courier New with a point size of 8. Titles should be printed using Arial point size 
10. 
x 
Identification of analysis population: Every summary table and figure should clearly specify 
the analysis population being summarized. Listings will be prepared for all subjects enrolled. 
x 
Group headers: In the summary tables, the group headers will identify the summary group and 
the within-group sample size for the indicated analysis population. Of note, the header’s 
sample size does not necessarily equal the number of subjects actually summarized within any 
given summary module; some subjects in the analysis population may have missing values and 
thus may not be summarized. 
x 
Presentation of sample sizes: Summary modules should indicate, in one way or another, the 
number of subjects actually contributing to the summary statistics presented in any given 
summary module. As mentioned above, this may be less than the number of subjects in the 
analysis population. 
i In the quantitative modules describing continuous variables (and thus presenting sample 
size, means, and standard deviations), the sample size should be the number of non-
missing observations 
i For categorical variables that are presented in frequency tables, the module should present 
the total count in addition to the count in each category. Percentages should be calculated 
using this total as the denominator, and the percentage corresponding to the sum itself (that 
is, 100%) should be presented so as to indicate clearly to a reviewer the method of 
calculation. 
x 
Sorting: Listings will be sorted by summary group, subject number and date, if applicable. If a 
listing is sorted in a different manner, a footnote will indicate as such.  
x 
General formatting rules: Rounding for all variables will occur only as the last step, 
immediately prior to presentation in listings, tables, and figures. No intermediate rounding will 
be performed on derived variables. The standard rounding practice of rounding numbers 
ending in 0-4 down and numbers ending in 5-9 up will be employed.   
x 
The presentation of numerical values will adhere to the following guidelines:  
i Raw measurements will be reported to the number of significant digits as captured 
electronically or on the CRFs.   
i Standard deviations will be reported to one decimal place beyond the number of decimal 
places the original parameter is presented. 
i Means will be reported to the same number of significant digits as the parameter.  
i Calculated percentages will be reported with no decimals. 


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x 
Dates will be formatted as DDMMMYYYY. Partial dates will be presented on data listings as 
recorded on CRFs. 
x 
Time will be presented according to the 24-hour clock (HHMM). 
 




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14.2.2.2.4 
Proportion of Subjects with One or More Culture-Verified Acute VVC Episode 
During the Maintenance Phase (Post Day 14 through Week 50), PP Population 
14.2.2.2.5 
Proportion of Subjects with One or More Culture-Verified Acute VVC Episode 
During the Maintenance Phase (Post Day 14 through Week 50) – Sensitivity 
Analysis Results, ITT Population 
14.2.2.2.6 
Proportion of Subjects with One or More Culture-Verified Acute VVC Episode 
During the Maintenance Phase (Post Day 14 through Week 50) by Subgroup, ITT 
14.2.2.3.1 
Time to First Recurrence of Culture-Verified Acute VVC During the Maintenance 
Phase (Post Day 14 through Week 50), ITT Population 
14.2.2.3.3 
Time to First Recurrence of Culture-Verified Acute VVC During the Maintenance 
Phase (Post Day 14 through Week 50), mITT Population 
14.2.2.3.4 
Time to First Recurrence of Culture-Verified Acute VVC During the Maintenance 
Phase (Post Day 14 through Week 50), PP Population 
14.2.2.3.5 
Time to First Recurrence of Culture-Verified Acute VVC During the Maintenance 
Phase (Post Day 14 through Week 50) – Sensitivity Analysis Results, ITT 
Population 
14.2.2.3.6 
Time to First Recurrence of Culture-Verified Acute VVC During the Maintenance 
Phase (Post Day 14 through Week 50) by Subgroup, ITT 
14.2.2.4.1 
Proportion of Subjects with At Least One Positive Culture During the 
Maintenance Phase (Post Day 14 through Week 50), ITT Population 
14.2.2.4.3 
Proportion of Subjects with At Least One Positive Culture During the 
Maintenance Phase (Post Day 14 through Week 50), mITT Population 
14.2.2.4.4 
Proportion of Subjects with At Least One Positive Culture During the 
Maintenance Phase (Post Day 14 through Week 50), PP Population 
14.2.2.4.5 
Proportion of Subjects with At Least One Positive Culture During the 
Maintenance Phase (Post Day 14 through Week 50) – Sensitivity Analysis 
Results, ITT Population 
14.2.2.4.6 
Proportion of Subjects with At Least One Positive Culture During the 
Maintenance Phase (Post Day 14 through Week 50) by Subgroup, ITT Population 
14.2.3.1.1 
Summary of Acute VVC by Study Visit, ITT Population 
14.2.3.1.2 
Summary of Acute VVC by Study Visit, mITT Population 
14.2.3.2.1 
Summary of Culture Results by Study Visit, ITT Population 
14.2.3.2.2 
Summary of Culture Results by Study Visit, mITT Population 
14.2.3.3.1 
Summary of Signs and Symptoms Composite Score by Study Visit, ITT 
Population 
14.2.3.3.2 
Summary of Signs and Symptoms Composite Score by Study Visit, mITT 
Population 
14.2.3.4.1 
Summary of Signs by Study Visit, ITT Population 
14.2.3.4.2 
Summary of Signs by Study Visit, mITT Population 
14.2.3.5.1 
Summary of Symptoms by Study Visit, ITT Population 
14.2.3.5.2 
Summary of Symptoms by Study Visit, mITT Population 


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14.2.3.6.1 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Day 14 Through Week 26, ITT Population 
14.2.3.6.2 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Day 14 Through Week 26, mITT Population 
14.2.3.7.1 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Week 26 Through Week 50, ITT Population 
14.2.3.7.2 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Week 26 Through Week 50, mITT Population 
14.2.3.8.1 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Day 14 Through Week 14, ITT Population 
14.2.3.8.2 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Day 14 Through Week 14, mITT Population 
14.2.3.9.1 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Day 14 Through Week 38, ITT Population 
14.2.3.9.2 
Proportion of Subjects with At Least One Culture-Verified Acute VVC Episode 
from Day 14 Through Week 38, mITT Population 
14.2.3.10.1 
Proportion of Subjects with At Least One Signs and Symptoms Score ≥ 3 During 
the Maintenance Phase (Post Day 14 through Week 50), ITT Population 
14.2.3.10.2 
Proportion of Subjects with At Least One Signs and Symptoms Score ≥ 3 During 
the Maintenance Phase (Post Day 14 through Week 50), mITT Population 
14.2.3.11.1 
Summary of Number of Culture Confirmed Episodes During the Maintenance 
Phase (Post Day 14 through Week 50), ITT Population 
14.2.3.11.2 
Summary of Number of Culture Confirmed Episodes During the Maintenance 
Phase (Post Day 14 through Week 50), mITT Population 
14.2.3.12.1 
Summary of Number of Times Subject was Treated with a Known Treatment for 
VVC During the Maintenance Phase (Post Day 14 through Week 50), ITT 
Population  
14.2.3.12.2 
Summary of Number of Times Subject was Treated with a Known Treatment for 
VVC During the Maintenance Phase (Post Day 14 through Week 50), mITT 
Population 
14.2.3.13.1 
Proportion of Subjects with Clinical Signs and Symptoms Score of 0 at Day 14, 
Induction Phase PP Population 
14.2.3.13.2 
Proportion of Subjects with Clinical Signs and Symptoms Score of 0 at Day 14, 
ITT Population 
14.2.3.13.3 
Proportion of Subjects with Clinical Signs and Symptoms Score of 0 at Day 14, 
Induction Phase mITT Population 
14.2.3.14.1 
Proportion of Subjects with Clinical Signs and Symptoms Score of 0 and 
Negative Culture for Candida Species at Day 14, Induction Phase PP Population 
14.2.3.14.2 
Proportion of Subjects with Clinical Signs and Symptoms Score of 0 and 
Negative Culture for Candida Species at Day 14, ITT Population 


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14.2.3.14.3 
Proportion of Subjects with Clinical Signs and Symptoms Score of 0 and 
Negative Culture for Candida Species at Day 14, Induction Phase mITT 
Population 
 
Safety 
14.3.1.1 
Overall Summary of Adverse Events 
14.3.1.2.1 
Treatment-Emergent Adverse Events by System Organ Classification, Preferred 
Term, and Greatest Severity, Safety Population 
14.3.1.2.2 
Event Counts of Treatment-Emergent Adverse Events by System Organ 
Classification, Preferred Term, and Severity, Safety Population 
14.3.1.3 
Treatment-Emergent Adverse Events by System Organ Classification and 
 
Preferred Term, Safety Population 
14.3.1.4 
Treatment-Emergent Serious Adverse Events by System Organ Classification and 
 
Preferred Term, Safety Population 
14.3.1.5 
Treatment-Emergent Adverse Events Related to IMP by System Organ 
Classification and Preferred Term, Safety Population 
14.3.1.6 
Treatment-Emergent Adverse Events Related to IMP as evaluated by Mycovia by 
               System Organ Classification and Preferred Term, Safety Population 
14.3.1.7               Treatment-Emergent Adverse Events Leading to Discontinuation of IMP 
 
by System Organ Classification and Preferred Term, Safety Population 
14.3.4.1.1 
Summary of Hematology Results and Change from Baseline by Visit, Safety 
Population 
14.3.4.1.2 
Summary of Treatment-Emergent Abnormal Hematology by Visit, Safety
 
Population 
14.3.4.2.1 
Summary of Serum Chemistry Results and Change from Baseline by Visit, 
 
Safety Population 
14.3.4.2.2 
Summary of Treatment-Emergent Abnormal Serum Chemistry by Visit, Safety
 
Population 
14.3.4.3.1 
Summary of Urinalysis by Visit, Safety Population 
14.3.4.3.2 
Summary of Treatment-Emergent Abnormal Urinalysis by Visit, Safety
 
Population 
14.3.4.4.1 
Summary of Subjects Experiencing At least One Treatment-Emergent Graded  
 
Laboratory Toxicity by Visit, Safety Population 
14.3.4.4.2 
Shifts from Baseline for Graded Laboratory Toxicities by Visit, Safety Population 
14.3.4.4.3 
Summary of Subjects with Grade 3 or 4 Treatment-Emergent Laboratory 
 
Toxicities by Visit, Safety Population 
14.3.5.1.1  
Summary of ECG Results and Change from Baseline by Visit, Safety Population 
14.3.5.1.2 
Proportion of Subjects with Abnormal ECG Interpretations by Visit, Safety 
Population 
14.3.5.2 
Summary of Vital Signs and Change from Baseline, Safety Population 
14.3.5.3 
 
Concomitant Medications, Safety Population 


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Figures 
14.1.3.3.2 
VT-1161 Mean Plasma Concentration by Visit, ITT Population Randomized to 
VT-1161 
14.2.1.2 
Proportion of Subjects with One or More Culture-Verified Acute VVC Episodes 
by Treatment Group, ITT Population 
14.2.2.1.2 
 
Proportion of Subjects with Resolved Acute VVC Infections at Day 14 by 
Treatment Group, Induction Phase PP Population 
14.2.2.2.2 
 
Proportion of Subjects with One or More Culture-Verified Acute VVC Episodes 
During the Maintenance Phase (Post Day 14 through Week 50) by Treatment 
Group, ITT Population 
14.2.2.3.2 
 
Kaplan-Meier Time to First Recurrence of Culture-Verified Acute VVC During 
the Maintenance Phase (Post Day 14 through Week 50) by Treatment Group, ITT 
Population 
14.2.2.4.2 
 
Proportion of Subjects with At Least One Positive Culture During the 
Maintenance Phase (Post Day 14 through Week 50) by Treatment Group, ITT 
Population 
 
Data Listings 
16.2.1  
Early Termination/Study Completion 
16.2.2.1 
Subject Level Protocol Deviations 
16.2.2.2 
Site Level Protocol Deviations 
16.2.3.1 
Study Populations 
16.2.3.2 
Inclusion/Exclusion Criteria 
16.2.4.1 
Demographics 
16.2.4.2 
Medical and Surgical History 
16.2.4.3 
Recurrent VVC History 
16.2.4.4 
Substance Use 
16.2.5.1.1 
IMP Administration – Induction Phase 
16.2.5.1.2 
IMP Administration – Maintenance Phase 
16.2.5.1.3 
IMP Exposure and Compliance 
16.2.5.1.4            VT-1161 Plasma Concentration 
16.2.5.2.1 
Prior and Concomitant Medications 
16.2.5.2.2 
Concomitant Therapies and Procedures 
16.2.6.1 
Primary Efficacy and Key Secondary Efficacy Endpoints 
16.2.6.2 
Clinical Signs and Symptoms 
16.2.6.3 
KOH Results 
16.2.6.4 
Culture Assessments 
16.2.6.5 
KOH Result, Culture Result, Total Signs and Symptoms, and Culture-Verified 
Acute VVC Infection 


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16.2.7.1 
Adverse Events 
16.2.7.2.1 
Serious Adverse Events 
16.2.7.2.2 
Details for Serious Adverse Events 
16.2.7.3 
Adverse Events Leading to Discontinuation 
16.2.8.1.1  
Laboratory Tests – Hematology 
16.2.8.1.2 
Laboratory Tests – Serum Chemistry 
16.2.8.1.3 
Laboratory Tests – Urinalysis 
16.2.8.1.4 
Laboratory Tests – Immunology 
16.2.8.1.5 
Laboratory Tests – Sexually Transmitted Diseases 
16.2.8.1.6 
Pregnancy Tests 
16.2.8.2  
Vital Signs 
16.2.8.3  
Physical Examination 
16.2.8.4  
ECG 
16.2.8.5 
Comments 
 




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Statistical Analysis Plan                                                                                                                                                                                            Final Version 3 
 
 
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a. 
All medication taken 30 days prior to Screening and all non-pharmacologic treatments received 72 hours prior to Screening will be recorded through the 
EOS visit. 
b. Weight only 
c. 
Vital signs include sitting heart rate, blood pressure, temperature, and respiratory rate.  
d. Limited Physical Examination, i.e. vaginal speculum examination plus a symptom-directed physical examination 
e. 
Subjects participating in the intense Day 1 and Day 2 PK collection will have samples taken predose and 1, 2, 4, and 8 hours after dosing.  All subjects 
will have PK draws prior to IMP on Day 14 and Week 14 and at Week 50. 
f. 
Serum chemistry (creatinine, BUN, ALT, AST, alkaline phosphatase, total bilirubin, conjugated bilirubin, albumin, total protein, total carbon dioxide, 
glucose, sodium, potassium, chloride, calcium, and phosphorus, and creatine phosphokinase [CK], cholesterol, and triglycerides). Testing for HbA1c is 
performed only in known or suspected diabetic subjects at Screening. Cultures for testing for Chlamydia trachomatis and Neisseria gonorrhoeae will be 
taken at Screening and sent to the central lab. Testing for bacterial vaginosis will be done locally at Screening.  An OSOM® Rapid test or similar test 
will be performed for Trichomonas vaginalis locally at Screening. 
g. For WOCBP, a local lab urine and central lab serum pregnancy test will be obtained at the Screening Day 1 visit.  A central lab serum pregnancy test 
will be performed at Weeks 14, 26, and 50. 
h. IMP is to be administered within 30 minutes after the subject’s main meal of the day (as determined by the subject) at approximately the same time of 
the day consistently throughout the study. Approximately 240 mL (approx. 8 oz.) of water is to be consumed with each dose of IMP.  Subject will be 
randomized to receive either 600mg VT-1161 (4 x 150 mg capsules) on Day 1 and 450 mg VT-1161 (3 x 150 mg capsules) on Day 2 followed by 11 
weekly doses of 150 mg VT-1161, or 3 sequential 150 mg oral doses (every 72 hours) of over-encapsulated fluconazole followed by 11 weekly doses of 
placebo.  In the Induction Phase, IMP may be over-encapsulated and matching placebo capsules will be provided to maintain study blind.  Subjects 
participating in the intense PK collection will be required to take the Days 1 and 2 IMP at the Investigational Site.  Remind subject to bring IMP to each 
visit to assess compliance.  
i. 
Only subjects participating in the intense PK will come in for the Day 2 visit. 
j. 
All procedures listed are to be completed only for unscheduled visits where a recurrent VVC episode is suspected. If the unscheduled visit is for repeat 
procedures (i.e., ECG, safety labs, etc.), only those specific procedures need to be performed, along with collection of any changes in medical treatments 
or medications and collection of any AEs.