Original Research
Secnidazole Treatment of Bacterial Vaginosis
A Randomized Controlled Trial
Sharon L. Hillier, PhD, Paul Nyirjesy, MD, Arthur S. Waldbaum, MD, Jane R. Schwebke,
Franklin G. Morgan, MD, Nikki A. Adetoro, MS, PMP, and Carol J. Braun, MD
OBJECTIVE: To evaluate secnidazole as a single oral
dose treatment for bacterial vaginosis in a phase 2
randomized, double-blind, placebo-controlled study.
METHODS: In a phase 2, randomized, double-blind,
dose-ranging, placebo-controlled study, women with
bacterial vaginosis who met all Amsel criteria (discharge;
pH 4.7 or greater; 20% or greater clue cells; positive whiff
test) were randomized one to one to one at 24 U.S.
centers to 1 or 2 g secnidazole compared with placebo.
The primary endpoint was clinical cure (normalization of
discharge, amine odor, and clue cells) 21–30 days after
treatment. Secondary endpoints included microbiologic
cure, defined as a Nugent score of 0–3, and therapeutic
cure, defined as meeting criteria for both clinical and
From the University of Pittsburgh and the Magee-Womens Research Institute,
Pittsburgh, Pennsylvania; Drexel University School of Medicine, Philadelphia,
Pennsylvania; Downtown Women’s Health Care, Denver, Colorado; the Uni-
versity of Alabama at Birmingham, Birmingham, Alabama; Tidewater Clinical
Research, Inc, Virginia Beach, Virginia; and Symbiomix Therapeutics, LLC, and
SAJE Consulting LLC, Baltimore, Maryland.
Funding for this study was provided to Magee-Womens Research Institute (S.L.H.),
Drexel University (P.N.), Downtown Women’s Health Care (A.S.W.), the
University of Alabama (J.R.S.), and Tidewater Clinical Research, Inc (F.G.M.)
by Symbiomix Therapeutics, LLC, Baltimore, Maryland. Manuscript editing was
also supported by Symbiomix Therapeutics, LLC.
Presented at the 42nd Annual Meeting of the Infectious Diseases Society for
Obstetrics and Gynecology, August 6–8, 2015, Portland, Oregon.
The authors thank Maryn Padula, PhD, of Virtuoso Healthcare Communications
for assistance with manuscript editing.
Each author has indicated that he or she has met the journal’s requirements for
authorship.
Corresponding author: Sharon L. Hillier, PhD, Magee-Womens Research
Institute, 204 Craft Avenue, B511 Pittsburgh, PA 15213; email: shillier@
mail.magee.edu.
Financial Disclosure
Dr. Hillier has received compensation as a consultant for Symbiomix
Therapeutics, LLC, Perrigo, Merck, and Cepheid Diagnostics. Drs. Hillier,
Nyirjesy, Waldbaum, Schwebke, and Morgan all received grant support from
Symbiomix Therapeutics, LLC, to their respective institutions for participation in
this study. Ms. Adetoro and Dr. Braun (deceased) were employed by Symbiomix
Therapeutics, LLC, during the conduct of this study.
© 2017 by The American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0029-7844/17
VOL. 0, NO. 0, MONTH 2017
Copyright Ó by The American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
MD,
microbiologic cure. The modified intent to treat was
used for efficacy analyses and included all randomized
patients who met the enrollment criteria. Assuming
a clinical cure rate of 40% in the active groups and 15%
in the placebo group, a sample size of 52 patients per
group provided approximately 80% power to detect
a significant difference between groups (.05 level [two-
sided]) using a Cochran-Mantel-Haenszel test.
RESULTS: Between May and September 2014, 215 pa-
tients were enrolled. In the intent-to-treat population,
the clinical cure rate was 65.3% for the 2-g group, 49.3%
for the 1-g group, and 19.4% for the placebo group. The
modified intent-to-treat population included 188 women
(median age 33 years; 32% with four or more bacterial
vaginosis episodes in the previous year; 54% black) with
baseline Nugent scores 4 or greater. Clinical, microbio-
logic, and therapeutic cure rates were 67.7%, 40.3%, and
40.3% for 2 g secnidazole and 51.6%, 23.4%, and 21.9%
for 1 g secnidazole compared with 17.7%, 6.5%, and
6.5% for placebo, respectively (P,.05 for secnidazole
compared with placebo; all endpoints). Both doses were
well-tolerated.
CONCLUSION: Oral granules containing 1 and 2 g
secnidazole were superior to placebo in bacterial vagi-
nosis treatment (P,.001 for both groups). These data
support the development of secnidazole for bacterial
vaginosis treatment.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
NCT02147899.
(Obstet Gynecol 2017;0:1–8)
DOI: 10.1097/AOG.0000000000002135
T
reatments for bacterial vaginosis currently rec-
ommended by the Centers for Disease Control
and Prevention (CDC) include multidose oral and
vaginal formulations of metronidazole and clindamy-
cin.1 Alternative regimens include oral formulations
of tinidazole or clindamycin and intravaginal formu-
lations of clindamycin and metronidazole.2,3 Currently,
there are no U.S. Food and Drug Administration
OBSTETRICS & GYNECOLOGY 1
(FDA)–approved single-dose oral therapy options for
the treatment of bacterial vaginosis.
Secnidazole, a 5-nitroimidazole with a longer half-
life than metronidazole (approximately 17 compared
with approximately 8 hours), has been used for the
treatment of bacterial vaginosis, trichomoniasis, and
other indications in Europe and Asia4 but is not avail-
able in the United States. A single dose of 2 g secni-
dazole was compared with a standard 7-day regimen
of metronidazole in a European study of women with
Nugent scores 7 or greater and found similar resolu-
tion of bacterial vaginosis between the treatment
groups.5 In vitro studies demonstrated antimicrobial
properties of secnidazole against most of the bacterial
species implicated in bacterial vaginosis. Several pub-
lished clinical studies have provided both clinical and
microbiologic evidence of activity of secnidazole in
the treatment of bacterial vaginosis.5–7 Secnidazole,
like other 5-nitroimidazoles, has limited activity
against lactobacilli, the beneficial microbes important
in establishing vaginal health after treatment.
This three-arm, placebo-controlled, phase 2,
dose-ranging study of secnidazole for bacterial vagi-
nosis treatment was conducted in accordance with
FDA guidance. The objective was to evaluate the
clinical, microbiologic, and therapeutic efficacy and
safety of a single oral dose of 1 or 2 g secnidazole in
women diagnosed with bacterial vaginosis, based on
Amsel criteria and Nugent scores 4 or greater.
MATERIALS AND METHODS
The study received institutional review board approval
(Schulman Associates institutional review board,
Cincinnati, Ohio; Western institutional review board,
Puyallup and Olympia, Washington; Wayne State
University Human Investigation Committee, Detroit,
Michigan). Patients provided written informed consent
before any study procedures were performed. Patients
determined to be eligible at baseline (day 1) were
randomized one to one to one using a centralized
permuted block randomization process through the
data management center to one of the following: one
sealed bottle of granules containing 1 or 2 g secnidazole
or matching placebo granules. The sealed bottles
contained the randomization assignment, which was
generated by the study biostatistician before the start of
the study. All ingredients of the granules were the same
with the exception of the addition of a bittering agent to
the placebo granules to mimic the potential bitter taste
of secnidazole granules. All treatment was administered
orally as a single dose in approximately 4 ounces of
applesauce under fasted conditions (ie, no food 2 hours
before through 1 hour after dosing). After baseline
2 Hillier et al Single-Dose Secnidazole for Treatment of BV
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assessments, patients self-administered treatments while
at the clinic. Randomization was stratified by the
number of self-reported episodes of bacterial vaginosis,
including the current episode, in the past 12 months
(three or fewer compared with four or more) as
reported during the medical history. Patients were
contacted by telephone once between days 8 and 10
to inquire about possible adverse events and persistence
of symptoms. Patients completed a test of cure visit,
comprising assessments pertaining to primary and
secondary efficacy endpoints and the safety endpoint
between days 21 and 30 posttreatment. Patients were
free to withdraw at any time for any reason. Women
who requested alternative treatment at any time during
the study were offered standard of care bacterial
vaginosis treatment at no cost. If a patient withdrew
before the test of cure visit, an end of study visit,
comprising a test of cure assessments, was performed at
the time of withdrawal. This study was conducted in
accordance with the ethical principles of Good Clinical
Practice.8
Patients with a clinical diagnosis of bacterial
vaginosis were recruited from 24 ambulatory gyne-
cology clinics in the United States, and by design, no
single site contributed more than 16% to the study
population. The study population included nonpreg-
nant women who were 18 years of age or older, in
general good health, had agreed to abstain from
sexual activity and use of intravaginal products for 1
week after treatment, and met the four Amsel criteria
for bacterial vaginosis (discharge; pH 4.7 or greater;
20% or greater clue cells; positive whiff test). Women
were excluded if they were pregnant, bleeding at
baseline, were allergic to metronidazole, unable or
unwilling to abstain from alcohol for 3 days after
treatment, receiving concomitant antimicrobial ther-
apy (topical or oral), or received a recent course
(within previous 14 days) of antimicrobial or antifun-
gal therapy. Baseline vaginal sample slides for Nugent
scoring and laboratory tests confirming sexually
transmitted infections (STIs) were evaluated centrally;
thus, results were unavailable at the time of random-
ization. The study protocol prespecified that patients
determined to have Nugent scores less than 4 or who
tested positive for a STI after baseline assessment
were to be considered screening failures. These
patients underwent an end of study visit and were
then discontinued from the study. Accordingly, these
patients received the randomized treatment and
remained in the study until Nugent scores and
baseline laboratory tests became available to the
investigator. Baseline Nugent scores ultimately were
used as a criterion for inclusion in the modified
OBSTETRICS & GYNECOLOGY
intent-to-treat population, the primary population for
efficacy analyses (Fig. 1).
The primary efficacy endpoint was clinical cure,
based on the 1998 FDA guidance regarding evalua-
tion of treatment for bacterial vaginosis: 1) normal
vaginal discharge, 2) negative 10% potassium hydrox-
ide whiff test, and 3) clue cells less than 20% of total
epithelial cells on microscopic examination of the
vaginal wet mount using saline at the test of cure visit.
Secondary efficacy endpoints, also evaluated at this
visit, were Nugent score, with a score of 0–3 consid-
ered Lactobacillus-dominant (ie, microbiologic cure)
and a score of 4 or greater considered abnormal,
and therapeutic cure, defined as meeting the criteria
for both clinical and microbiologic cure.
Safety evaluations were based on the incidence,
intensity, and type of adverse events and changes in
patients’ physical examination findings, vital signs,
and clinical laboratory results, but the study was not
statistically powered to detect differences in safety
between groups.
Assuming a clinical cure rate of 40% in the active
groups and 15% in the placebo group, a sample size of
52 patients per group was expected to provide
approximately 80% power to detect a statistically
significant difference between either secnidazole
group and placebo at a .05 level of significance
(two-sided) using a Cochran-Mantel-Haenszel test.
To ensure at least 52 patients met the modified
intent-to-treat criteria, between 71 and 72 patients
were randomized to each treatment group for a total
of 215 patients randomized.
No interim analyses of efficacy were performed
and sponsors and investigators remained blinded until
the database was locked. The efficacy analyses were
performed on the modified intent-to-treat population,
defined as all randomized patients who met all study
selection criteria. Clinical cure at the test of cure visit
was compared between each active secnidazole dose
and placebo using a Cochran-Mantel-Haenszel statis-
tical test adjusted for stratification by bacterial vagi-
nosis recurrence. The primary comparison was
between 2 g secnidazole and placebo; comparison
between 1 g secnidazole and placebo was a secondary
analysis. The 2- and 1-g secnidazole doses were not
compared statistically. Because there was only one
primary comparison, no adjustment for multiple
comparisons was indicated. For each secnidazole dose,
an exact 95% binomial confidence interval (CI) was
calculated for the clinical cure rate. All tests were
performed at a .05 level of significance (two-sided).
Secondary efficacy endpoints were analyzed similarly.
In a prespecified analysis, primary and secondary
endpoints were also analyzed by bacterial vaginosis
strata and baseline Nugent score (4–6, 7–10). Patients
with any missing data required for assessment of pri-
mary and secondary efficacy endpoints at either the
test of cure or end of study visit as a result of treatment
failure or early discontinuation were imputed as non-
responders for clinical and therapeutic outcomes and
as abnormal for Nugent score.
Safety evaluations were based on the incidence,
intensity, and type of treatment-emergent adverse
events and changes in the patient’s physical

Fig. 1. Patient disposition. STI, sexually transmitted infection.

Hillier. Single-Dose Secnidazole for Treatment of BV. Obstet Gynecol 2017.

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examination findings, vital signs, and clinical safety
laboratory results. Safety variables were tabulated
and presented for all patients in the intent-to-treat
population, because they all received the study drug.
A treatment-emergent adverse event was defined as
any adverse event that occurred after administration
of the study drug dose through the end of the study
visit. Any event that was considered by the investiga-
tor to be study drug–related, regardless of onset time,
or any event that was present at baseline but worsened
in intensity or was subsequently was considered
treatment-related by the investigator. Investigators
were asked to report all adverse events, whether mild,
moderate, or severe. Adverse events were recorded
verbatim and then coded using preferred Medical
Dictionary for Regulatory Activities terminology.
RESULTS
A total of 215 women were enrolled at 24 research
centers in the United States between May 28 and
September 5, 2014. Reasons for exclusion included
baseline STIs (n513 women), Nugent score less than
4 (n514), and clinically significant baseline laboratory
abnormality that led to a diagnosis of chronic myeloid
leukemia (n51; Fig. 1), leaving 188 women in the
modified intent-to-treat population with 62–64
women per arm. The demographic and baseline char-
acteristics of the study population are summarized in
Table 1 and Appendix 1 (available online at http://
links.lww.com/AOG/A973). The median age of the
study population was 33 years (range 19–54 years);
more than half of the participants (54%) described
themselves as black or African American, and 39%
identified as white. A higher proportion of white pa-
tients were enrolled in the 2-g secnidazole group (51.
6%) compared with the 1-g and placebo groups (28.
1% and 38.7%, respectively), although these differen-
ces were not statistically significantly different. Other
demographics and baseline characteristics were simi-
lar across the three treatment arms.
In the intent-to-treat population, the clinical cure
rate was 65.3% for the 2-g group, 49.3% for the 1-g
group, and 19.4% for the placebo group. However, as
prespecified in the protocol, the modified intent-to-
treat group was designated the primary analysis
population, because two different criteria for exclu-
sion—baseline Nugent scores and results from baseline
laboratory testing—were only available after the pa-
tients were randomized and treated. Clinical, micro-
biologic, and therapeutic cure rates are summarized
for the modified intent-to-treat population in Table 2.
Eight women were lost to follow-up during the course
of the study and, per the prespecified protocol, were
counted as nonresponders.
The clinical cure rate was significantly higher for
the 2-g (68%) and 1-g (52%) doses of secnidazole
compared with placebo (18%) (P,.001 for both com-
parisons). A similar trend was observed with microbi-
ologic cure, which was 40% for the 2-g dose (P,.001
compared with placebo) and 23% for the 1-g dose
(P5.007 compared with placebo). As shown in
Table 2, the therapeutic cure rate was 40%, 22%,
and 7% for the 2-g secnidazole, the 1-g, and the pla-
cebo groups, respectively. A greater treatment effect
was observed with 2 g secnidazole compared with
placebo on analysis of clinical, microbiologic, and

Table 1. Demographics and Baseline Characteristics (Modified Intent-to-Treat Population) Overall and by
Treatment Group

Secnidazole 1 g Secnidazole 2 g Placebo Overall

Parameter (n564) (n562) (n562) (n5188)

Age (y) 34 (19, 49) 31 (19, 54) 33 (19, 49) 33 (19, 54)
Race
White 18 (28.1) 32 (51.6) 24 (38.7) 74 (39.4)
Black or African American 42 (65.6) 26 (41.9) 34 (54.8) 102 (54.3)
Asian 1 (1.6) 1 (1.6) 2 (3.2) 4 (2.1)
Native American or Alaska Native 1 (1.6) 1 (1.6) 0 2 (1.1)
Other 2 (3.1) 2 (3.2) 2 (3.2) 6 (3.2)
No. of BV episodes in past 12 mo 3 (1, 13) 2 (1, 12) 3 (1, 12) 3 (1, 13)
BV strata: no. of BV episodes in past 12
mo
3 or fewer 44 (68.8) 41 (66.1) 43 (69.4) 128 (68.1)
4 or more 20 (31.3) 21 (33.9) 19 (30.6) 60 (31.9)
Baseline Nugent score 9 (5, 10) 8 (4, 10) 8 (4, 10) 8 (4, 10)
BV, bacterial vaginosis.
Data are median (minimum, maximum) or n (%).

4 Hillier et al Single-Dose Secnidazole for Treatment of BV OBSTETRICS & GYNECOLOGY

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Table 2. Summary of Primary and Secondary Efficacy Results (Modified Intent-to-Treat Population) at Day
21–30 Visit by Treatment Group

Endpoint Secnidazole 1 g (n564) Secnidazole 2 g (n562) Placebo (n562)

Clinical cure
Primary endpoint* 33 (51.6) 42 (67.7) 11 (17.7)
95% exact binomial CI for responder rate 38.7–64.2 54.7–79.1 9.2–29.5
†
P ,.001 ,.001 —
Microbiologic cure
‡
Secondary endpoint 15 (23.4) 25 (40.3) 4 (6.5)
†
P .007 ,.001 —
Therapeutic cure
§
Secondary endpoint 14 (21.9) 25 (40.3) 4 (6.5)
†
P .011 ,.001 —
Data are n (%) unless otherwise specified.
* Clinical cure was defined as a patient who had all three of the following at days 21–30: normal vaginal discharge, negative potassium
hydroxide whiff test, and clue cells less than 20%.
†
P compared with placebo from a Cochran-Mantel-Haenszel test adjusted for bacterial vaginosis strata (fewer than three or more than three
episodes in the past 12 months).
‡
Microbiologic cure was defined as a Nugent score 0–3, based on centralized review, at days 21–30. Missing Nugent scores were classified
as abnormal.
§
Therapeutic cure was defined as both clinical and microbiologic cure.

therapeutic cure, regardless of the number of prior
episodes of bacterial vaginosis (three or fewer or four
or more in the past 12 months) in the modified intent-
to-treat population. The study was not powered to
determine statistical differences in a three-way strati-
fied comparison. However, with respect to the nomi-
nal a5.05 level of significance, all three outcomes
were favorable in the 2-g treatment arm in the sub-
population of patients with four or more episodes
(P,.001 for all assessments) and for the clinical cure
assessment for the 1-g treatment arm (P5.023;
Table 3). Analyses of the primary and secondary end-
points in the per-protocol population (1-g group,
n555; 2-g group, n547; placebo group, n550), which
included patients in the modified intent-to-treat pop-
ulation who had no major protocol violations, also
showed results similar to those in the modified
intent-to-treat population (clinical cure: 1 g, 52.7%,
P,.001; 2 g, 72.3%, P,.001; placebo, 20%).
The safety and tolerability of secnidazole admin-
istered in the 2- or 1-g granule form was evaluated in
all 215 randomized patients who were treated with
a single dose of the study drug (Table 4). Treatment-
emergent adverse events were reported in 19% (14/
72), 13% (9/71), and 10% (7/72) in the 2-g secnida-
zole, 1-g secnidazole, and placebo groups, respec-
tively. Infections were the most common events in
all treatment groups, but were similar in incidence
across the three treatment groups (Table 4). Vaginal
yeast infections were infrequent, occurring in seven
women, five of whom received secnidazole. All
treatment-emergent adverse events were mild or
moderate in intensity. No serious adverse events were
reported. No secnidazole dose relationship or differ-
ences from placebo were observed in physical exam-
ination, clinical laboratory, or vital sign parameters.
Furthermore, no notable differences were observed in
the mean, median, minimum, or maximum changes
from baseline in any laboratory parameter.
DISCUSSION
This study evaluated the efficacy and safety of two
doses of secnidazole. Both dose levels of secnidazole
were superior to placebo, although the study was not
powered to detect differences between the two treat-
ment groups. This study had a balanced inclusion of
women having recurrent bacterial vaginosis over the
three treatment arms. Although cure rates were lower
overall among women having recurrent bacterial
vaginosis, the 2-g secnidazole treatment was statisti-
cally superior to placebo, even among those women
having recurrent infections. A strength of the study
was the recruitment of women from across the United
States and substantial representation by African
American women.
Since this study was conducted, the FDA has
issued new draft guidance regarding drug develop-
ment for bacterial vaginosis. Interpreting the results of
this study requires an understanding of this context, in
which the FDA recommends the inclusion of a con-
current placebo arm as part of the design and that
clinical cure being defined as the resolution of three
clinical signs (discharge, amine odor, clue cells) of
bacterial vaginosis.9 Using this definition, cure rates

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Table 3. Summary of Primary and Secondary Efficacy Results (Modified Intent-to-Treat Population) at Day
21–30 Visit Stratified by Number of Episodes of Bacterial Vaginosis in the Past Year

Treatment Group
Secnidazole 1 g Secnidazole 2 g Placebo
3 or Fewer BV 4 or More BV 3 or Fewer BV 4 or More BV 3 or Fewer BV 4 or More BV
Episodes Episodes Episodes Episodes Episodes Episodes
Endpoint (n544) (n520) (n541) (n521) (n543) (n519)

Clinical cure
Primary endpoint* 26 (59.1) 7 (35.0) 30 (73.2) 12 (57.1) 10 (23.3) 1 (5.3)
95% exact 43.2–73.7 15.4–59.2 57.1–85.8 34.0–78.2 11.8–38.6 0.1–26.0
binomial CI for
responder rate
†
P ,.001 .023 ,.001 ,.001 — —
Microbiologic cure
Secondary 13 (29.5) 2 (10.0) 18 (43.9) 7 (33.3) 4 (9.3) 0
‡
endpoint
†
P .018 .162 ,.001 .006 — —
Therapeutic cure
Secondary 13 (29.5) 1 (5.0) 18 (43.9) 7 (33.3) 4 (9.3) 0
§
endpoint
†
P .018 .330 ,.001 .006 — —
BV, bacterial vaginosis.
Data are n (% cured) unless otherwise specified.
* Clinical cure was defined as a patient who had normal vaginal discharge, negative potassium hydroxide whiff test, and clue cells less than
20% at days 21–30.
†
P compared with placebo from a Cochran-Mantel-Haenszel test adjusted for BV strata (three or fewer or four or more episodes in the past
12 months).
‡
Microbiologic cure at days 21–30 was defined as a Nugent score 0–3, based on centralized review, at days 21–30. Missing Nugent scores
were classified as abnormal.
§
Therapeutic cure was defined as both clinical and microbiologic cure.

for oral 500 mg metronidazole twice daily for 7 days
have been reported to be 58%5; the 7-day clindamycin
cream treatment has provided a similar response.2 In
a multicenter, placebo-controlled randomized trial of
oral tinidazole given at either 2 g daily for 2 days or 1
g for 5 days, resolution of bacterial vaginosis as
defined by absence of three or more Amsel criteria
was reported in 46% of women who received the 2-
day regimen and in 64% of those who received the 5-
day regimen.10
Two single-dose intravaginal treatments have
been FDA-approved for treatment of bacterial vagi-
nosis. Single-dose clindamycin cream has been re-
ported to provide clinical and microbiologic cure for
64% and 57% of women, respectively, although only
47% of enrolled women were evaluable in this study.2
A single-dose 1.3% metronidazole gel has a reported
clinical cure rate of 37% and a microbiologic cure of
18% at the 21-day visit.3 In the present study, the
single-dose oral treatment with secnidazole granules
provided a clinical cure rate of 68% and a microbio-
logic cure rate of 40%, which appears to be similar to
the efficacy of the current CDC-recommended regi-
mens and similar or superior to the published data for
single-dose clindamycin2 and metronidazole3 intrava-
ginal treatments. Treatment with a single dose of oral
secnidazole yielded similar cure rates when compared
with 7 days of oral metronidazole in a European
study.5 A consistent trend across studies is the lower
microbiologic cure rate than the clinical rate, suggest-
ing the presence of microbes persist after resolution of
clinical symptoms, and lactobacilli species have not
yet recovered to levels reflective of a healthy vaginal
environment. An improved understanding of the tip-
ping point, the point at which the imbalance of vagi-
nal microbiota leads to signs and symptoms of
bacterial vaginosis, is warranted to further understand
whether differences in microbiologic cure affect risk
of recurrence.
Side effects of oral metronidazole include nausea,
a metallic taste, headaches, and gastrointestinal dis-
tress. In this study, the incidence of adverse events
was low, with only 1 of 144 women randomized to
secnidazole having nausea and only one woman
reporting a metallic taste. The low incidence of
adverse events is consistent with clinical experience

6 Hillier et al Single-Dose Secnidazole for Treatment of BV OBSTETRICS & GYNECOLOGY

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Table 4. Patient Incidence of Treatment-Emergent Adverse Events (Intent-to-Treat Population, N5215) by
Treatment Group

Adverse Events Secnidazole 1 g (n571) Secnidazole 2 g (n572) Placebo (n572)

Total no. of participants reporting 1 or more 9 (12.7) 14 (19.4) 7 (9.7)

treatment-emergent adverse event
Any treatment-emergent adverse events with
incidence 2% or greater
Infections
Yeast infections* 3 (4.2) 2 (2.8) 2 (2.8)
Upper respiratory tract infection 0 (0) 0 (0) 2 (2.8)
Treatment-related† treatment-emergent adverse
events 1% or greater
Yeast infection 0 (0) 2 (2.8) 1 (1.4)
Vulvovaginal pruritus 0 (0) 1 (1.4) 0 (0)
Chromaturia 0 (0) 1 (1.4) 0 (0)
Dysgeusia 0 (0) 1 (1.4) 0 (0)
Headache 1 (1.4) 0 (0) 0 (0)
Nausea 0 (0) 1 (1.4) 0 (0)
Alanine aminotransferase increased 0 (0) 1 (1.4) 0 (0)
Aspartate aminotransferase increased 0 (0) 1 (1.4) 0 (0)
Data are n (%).
* Investigators reported yeast infections using any of the following acceptable terms: vulvovaginal mycotic infection, Candida infection,
fungal infection, or vulvovaginal candidiasis.
†
Adverse events that were deemed by the investigator to be “possibly” or “probably” related to treatment. All treatment-related treatment-
emergent adverse events were considered mild to moderate.

with secnidazole as treatment outside the United
States where it is approved for treatment of parasitic
diseases and bacterial vaginosis with a well-
established safety profile.5–7,11,12
The 2015 CDC Sexually Transmitted Disease
Treatment Guidelines recommends treatment of bac-
terial vaginosis for all women having symptoms.1
Although the primary objective of treatment is reso-
lution of symptoms, other potential benefits of bacte-
rial vaginosis treatment include reduction in the risk
for acquiring Chlamydia trachomatis, Neisseria gonor-
rhoeae,13 Trichomonas vaginalis,14 human immunodefi-
ciency virus,15 and herpes simplex type 2.16 Recent
studies have evaluated the effect of bacterial vaginosis
treatment on acquisition of bacterial STIs with mixed
results.17,18 Schwebke18 evaluated home screening for
bacterial vaginosis to identify and treat asymptomatic
cases to reduce acquisition of chlamydial and gono-
coccal infections, but found no difference in incident
STIs. Results from a study of periodic presumptive
treatment of bacterial vaginosis and yeast vaginitis
demonstrated a reduced incidence of C trachomatis,
N gonorrhoeae, and Mycoplasma genitalium.17 Additional
research is needed to confirm the benefits of periodic
treatment of bacterial vaginosis as a strategy to reduce
incident STIs.
Results from this study support the further
development of secnidazole for the treatment of
women with bacterial vaginosis. Additional studies
comparing single-dose 2-g secnidazole oral granules
with an active comparator such as metronidazole
may be warranted to better understand how a single-
dose treatment may compare with a multidose
regimen.
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OBSTETRICS & GYNECOLOGY