Drug Trials Snapshot: NUZOLVENCE
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the NUZOLVENCE Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
NUZOLVENCE (zoliflodacin)
(Nu-ZOL-vence)
Entasis Therapeutics, Inc.
Approval date: December 12, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
NUZOLVENCE is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor that is indicated for the treatment of adults and pediatric patients 12 years of age and older, weighing at least 35 kilograms (kg), with uncomplicated urogenital gonorrhea caused by the bacterium Neisseria gonorrhoeae.
How is this drug used?
NUZOLVENCE is provided as a single packet of granules to be mixed with water and taken by mouth as a single dose.
Who participated in the clinical trials?
The FDA approved NUZOLVENCE based on evidence from one phase 3 clinical trial. There were 930 adult and adolescent patients with uncomplicated gonorrhea enrolled in the trial. The trial was conducted at 16 sites in five countries including South Africa, Thailand, the United States, Netherlands, and Belgium. Among the 930 patients, the median age was 27 (range: 15 to 73 years); 88% were male; 55% were Black or African American, 31% were Asian, 12% were White, 2% were other; 3% were of Hispanic or Latino ethnicity; and 17% of patients were from the United States.
How were the trials designed?
The benefit (efficacy) and safety of NUZOLVENCE were evaluated in one clinical trial (NCT03959527; Trial 1) that included 930 patients with uncomplicated gonorrhea infection. Patients were enrolled in the trial if they had one of the following: a) signs and symptoms of urethral or cervical gonorrhea; b) confirmed N. gonorrhoeae on culture (positive culture) from a urethral or cervical sample; or c) unprotected sexual contact with an individual with a positive culture for N. gonorrhoeae. Adult and adolescent patients were chosen at random to receive either NUZOLVENCE or two comparator antibiotics. The benefit of NUZOLVENCE was measured only in patients whose clinical samples grew N. gonorrhoeae bacteria on culture before treatment (efficacy population) by comparing how many patients treated with NUZOLVENCE versus how many patients treated with comparator antibiotics had negative culture results after treatment.
How were the trials designed?
Trial 1 was a randomized, open-label, noninferiority trial that included 930 adult and adolescent patients with uncomplicated gonorrhea infection. A total of 930 patients were randomized 2:1 to receive a single 3 g oral dose of NUZOLVENCE or combination therapy with a single intramuscular (IM) 500 mg dose of ceftriaxone and a single 1 g oral dose of azithromycin.
The efficacy population included all patients who had a positive N. gonorrhoeae culture from a urogenital site at baseline and whose baseline antimicrobial susceptibility testing result showed susceptibility to ceftriaxone or azithromycin. A total of 744 patients were included in this population.
The primary efficacy endpoint was microbiological cure determined by culture results at the urogenital site at the test of cure (TOC) visit (Day 6±2 after randomization). The benefit of NUZOLVENCE was measured by comparing NUZOLVENCE versus the combined therapy with ceftriaxone and azithromycin.
DEMOGRAPHICS SNAPSHOT
The demographics and benefit (efficacy) data include patients who had a positive culture for N. gonorrhoeae from a urogenital site which was susceptible to treatment with ceftriaxone or azithromycin, the antibiotics in the comparator arm.
Figure 1 summarizes how many male and female subjects were enrolled into the efficacy population in Trial 1.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of subjects by race in the efficacy population in Trial 1.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
* Other includes: American Indian or Alaska Native (7 participants), Native Hawaiian or other Pacific Islander (2 participants), multiple races (3 participants), and other race (3 participants).
Figure 3 summarizes the percentage of subjects by age in the efficacy population in Trial 1.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of subjects by ethnicity in the efficacy population in Trial 1.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population
| Characteristic | NUZOLVENCE N=506 | Ceftriaxone and Azithromycin N=238 |
|---|---|---|
| Sex (assigned at birth), n (%) | ||
| Female | 50 (9.9) | 18 (7.6) |
| Male | 456 (90.1) | 220 (92.4) |
| Age, years | ||
| Mean (SD) | 30.3 (9.72) | 29.2 (9.41) |
| Median (min, max) | 28.0 (16.0, 73.0) | 26.0 (16.0, 67.0) |
| Age group, years, n (%) | ||
| <18 | 9 (1.8) | 1 (<1) |
| ≥18 to <65 | 495 (97.8) | 236 (99.2) |
| ≥65 | 2 (<1) | 1 (<1) |
| Race, n (%) | ||
| Black or African American | 278 (54.9) | 128 (53.8) |
| Asian | 161 (31.8) | 67 (28.2) |
| White | 57 (11.3) | 38 (16.0) |
| American Indian or Alaska Native | 6 (1.2) | 1 (<1) |
| Native Hawaiian or other Pacific Islander | 1 (<1) | 1 (<1) |
| Multiple | 1 (<1) | 2 (<1) |
| Other | 2 (<1) | 1 (<1) |
| Ethnicity, n (%) | ||
| Hispanic or Latino | 15 (3.0) | 13 (5.5) |
| Not Hispanic or Latino | 491 (97.0) | 225 (94.5) |
| Country of participation, n (%) | ||
| Belgium | 3 (<1) | 1 (<1) |
| Netherlands | 42 (8.3) | 16 (6.7) |
| Thailand | 149 (29.4) | 64 (26.9) |
| United States | 95 (18.8) | 44 (18.5) |
| South Africa | 217 (42.9) | 113 (47.5) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
In Trial 1, 90.9% of patients treated with NUZOLVENCE were cured compared to 96.2% of patients treated with comparator antibiotics, showing the efficacy of NUZOLVENCE.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes the efficacy results in the efficacy population in Trial 1. NUZOLVENCE demonstrated efficacy in the efficacy population.
Table 2. Microbiological Cure Rates at the Urogenital Site at TOC, Efficacy Population
| Paramenter | NUZOLVENCE n/N (%) | Ceftriaxone and Azithromycin n/N (%) | Difference (95% CI)a |
| Microbiological cureb | 460/506 (90.9) | 229/238 (96.2) | -5.3 (-8.7, -1.4) |
| Failure | 46/506 (9.1) | 9/238 (3.8) | |
| Bacterial persistence by culture | 15/506 (3.0) | 0 | |
| Nonassessablec | 31/506 (6.1) | 9/238 (3.8) |
Source: Adapted from NUZOLVENCE Prescribing Information
a Calculated with the Newcombe score method for the NUZOLVENCE – (ceftriaxone and azithromycin) treatment difference.
b Microbiological cure is defined as negative or indeterminate Neisseria gonorrhoeae (NG) culture at the urogenital site at the TOC visit. There were no indeterminate NG cultures at the urogenital site at TOC.
c Nonassessable outcomes were due to missed TOC visits, unobtainable specimens, or TOC visits out of window.
Abbreviations: CI, confidence interval; TOC, test of cure
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: Over 90% of patients enrolled were male; therefore, differences in how NUZOLVENCE worked between males and females could not be determined.
- Race: The observed effect of NUZOLVENCE was larger for Asian patients than Black or African American patients in this study; however, because race and geographic region were closely linked in this trial, it is difficult to determine whether the differences were due to race or location. The majority of Black or African American patients were from South Africa and the majority of Asian patients were from Thailand. The number of patients of other races was small; therefore, differences in how the drug worked in other races could not be determined.
- Age: Not applicable. Almost all patients were between 18 and 64 years of age.
- Ethnicity: Not applicable. Almost all patients identified as not Hispanic or Latino.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Microbiological Cure Rate at TOC at Urogenital Site by Subgroup, Efficacy Population
| Subgroup | NUZOLVENCE N=506 n/Ns (%) | Ceftriaxone and Azithromycin N=238 n/Ns (%) | Difference % (95% CI)a |
|---|---|---|---|
| Sex (assigned at birth) | |||
| Female | 48/50 (96.0) | 16/18 (88.9) | 7.1 (-5.3, 29.0) |
| Male | 412/456 (90.4) | 213/220 (96.8) | -6.5 (-9.9, -2.4) |
| Age group, years | |||
| <18 | 9/9 (100) | 1/1 (100) | |
| ≥18 to <65 | 449/495 (90.7) | 227/236 (96.2) | -5.5 (-8.9, -1.5) |
| ≥65 | 2/2 (100) | 1/1 (100) | |
| Race | |||
| Black or African American | 241/278 (86.7) | 125/128 (97.7) | -11.0 (-15.7, -5.4) |
| Asian | 158/161 (98.1) | 65/67 (97.0) | 1.1 (-3.0, 8.5) |
| White | 51/57 (89.5) | 34/38 (89.5) | 0 (-12.4, 14.7) |
| American Indian or Alaska Native | 6/6 (100) | 1/1 (100) | |
| Native Hawaiian or other Pacific Islander | 1/1 (100) | 1/1 (100) | |
| Multiple | 1/1 (100) | 2/2 (100) | |
| Other | 2/2 (100) | 1/1 (100) | |
| Ethnicity | |||
| Hispanic or Latino | 15/15 (100) | 12/13 (92.3) | 7.7 (-13.7, 33.3) |
| Not Hispanic or Latino | 445/491 (90.6) | 217/225 (96.4) | -5.8 (-9.2, -1.8) |
Source: Adapted from FDA Review
a 95% CI was calculated with Newcombe score method
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; SD, standard deviation; TOC, test of cure
What are the possible side effects?
Common side effects observed during Trial 1 were headache, low white blood cell count, dizziness, nausea, and diarrhea.
NUZOLVENCE was tested on animals using doses equal to or higher than the maximum dose recommended for humans for 28 days or more. Concerning findings included: 1) when pregnant mice were given NUZOLVENCE, a few of them had pups with a serious birth defect called exencephaly (when the brain develops outside the skull); 2) female mice and rats that were not given NUZOLVENCE but were mated with males who received the drug lost more embryos than normal; 3) male rats and dogs given NUZOLVENCE had decreased fertility and produced fewer sperm cells, but these changes were reversible. Because of these animal study results, the NUZOLVENCE prescribing information includes important Warnings and the following recommendations:
- Women who can get pregnant should take a pregnancy test before starting NUZOLVENCE treatment. Women should avoid the use of NUZOLVENCE during pregnancy.
- Men taking NUZOLVENCE with female partners who can get pregnant should use birth control for three months during and after treatment.
When NUZOLVENCE is prescribed, a Medication Guide will be provided to ensure that patients are aware of the Warnings and recommendations.
What are the possible side effects (results of trials used to assess safety)?
The safety population includes all patients who received at least one dose of NUZOLVENCE or comparator. Table 4 summarized the most common adverse reactions observed in the trials.
Table 4. Adverse Reactions Occurring in ≥2% of Patients With Suspected Uncomplicated Gonorrhea Infection Treated With NUZOLVENCE, Safety Population
| Adverse Reaction | NUZOLVENCE N=619 n (%) | Ceftriaxone and Azithromycin N=308 n (%) |
|---|---|---|
| Headache | 61 (10) | 15 (5) |
| Dizziness | 21 (3) | 5 (2) |
| Nausea | 16 (3) | 12 (4) |
| Diarrhea | 15 (2) | 22 (7) |
Source: NUZOLVENCE Prescribing Information
Table 5. Laboratory Abnormalities in ≥2% of Patients With Suspected Uncomplicated Gonorrhea Infection Treated With NUZOLVENCE, With Normal Baseline Values, Safety Population
| Laboratory Parameters | NUZOLVENCE N=609 n (%) | Ceftriaxone and Azithromycin N=304 n (%) |
|---|---|---|
| Neutropeniaa | 71 (12) | 43 (14) |
| <1500 to 1000 cells/µL | 56 (9) | 31 (10) |
| <1000 to 500 cells/µL | 14 (2) | 12 (4) |
| <500 cells/µL | 1 (0.2) | 0 |
| Leukopeniab | 54 (9) | 33 (11) |
| <3500 to 3000 cells/µL | 34 (6) | 20 (7) |
| <3000 to 1000 cells/µL | 20 (3) | 13 (4) |
| <1000 cells/µL | 0 | 0 |
Source: NUZOLVENCE Prescribing Information
a Neutropenia is defined as neutrophil count less than 1500 cells/µL.
b Leukopenia is defined as white blood cell count less than 3500 cells/µL.
In repeat-dose nonclinical studies resulting in exposures at or above the maximum human recommended dose (MHRD) of NUZOLVENCE, signals of embryofetal toxicity (i.e., exencephaly) in pregnant mice, increased embryonic loss in untreated female mice and rats mated with male mice and rats, respectively, and impaired fertility and decreased spermatogenesis in male rats and dogs were observed. The Prescribing Information contains Warnings regarding these nonclinical findings and recommendations for pregnancy testing in women of reproductive potential prior to NUZOLVENCE treatment as well as contraception for three months in males treated with NUZOLVENCE who have female partners of reproductive potential.
When NUZOLVENCE is prescribed, a Medication Guide will be provided to ensure that patients are aware of the Warnings and recommendations.
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar between male and female patients.
- Race: The occurrence of side effects was similar in Asian, Black or African American, and White patients. The number of patients of other races was too small to draw conclusions about other racial differences in side effects.
- Age: The number of patients younger than 18 years and older than 65 years of age was too small to draw conclusions about age differences in side effects.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 6 summarizes the differences in adverse events among subgroups observed in Trial 1.
Table 6. Adverse Events by Subgroup, Safety Population
| Characteristic | NUZOLVENCE N=619 n/Ns (%) | Ceftriaxone and Azithromycin N=308 n/Ns (%) |
|---|---|---|
| Sex | ||
| Female | 35/77 (45.5) | 20/38 (52.6) |
| Male | 252/542 (46.5) | 123/270 (45.6) |
| Age group, years | ||
| <18 | 2/12 (16.7) | 2/2 (100) |
| 18 to 64 | 284/604 (47.0) | 140/305 (45.9) |
| ≥65 | 1/3 (33.3) | 1/1 (100) |
| Age group ≥75, years | ||
| ≥75 | 0/619 (0) | 0/308 (0) |
| Race | ||
| American Indian or Alaska Native | 6/8 (75.0) | 0/1 (0) |
| Asian | 101/193 (52.3) | 52/92 (56.5) |
| Black or African American | 155/348 (44.5) | 71/164 (43.3) |
| Multiple | 0/1 (0) | 2/2 (100) |
| Native Hawaiian or other Pacific Islander | 1/2 (50.0) | 0/1 (0) |
| Other | 0/2 (0) | 0/1 (0) |
| White | 24/65 (36.9) | 18/47 (38.3) |
| Ethnicity | ||
| Hispanic or Latino | 9/18 (50.0) | 2/13 (15.4) |
| Not Hispanic or Latino | 278/601 (46.3) | 141/295 (47.8) |
| Is in United States | ||
| United States | 43/107 (40.2) | 14/51 (27.5) |
| Non-United States | 244/512 (47.7) | 129/257 (50.2) |
Source: Adapted from FDA Review
Abbreviations: N, number of subjects in treatment arm; n, number of subjects with adverse event; Ns, total number of participants for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.