VIOLET: A Study of Oral Oteseconazole (VT-1161) for the Treatment of Patients With Recurrent Vaginal Candidiasis (Yeast Infection)
Study Details
Study Description
Brief Summary
Recurrent vulvovaginal candidiasis (RVVC), also known as recurrent yeast infections, is defined as at least 3 episodes of acute VVC in the past 12 months. Several properties of oteseconazole (VT-1161) suggest that it might be a safer and more effective treatment for RVVC than other oral antifungal medicines.
This study will evaluate the effectiveness and safety of oteseconazole (VT-1161) for the treatment of RVVC and consists of 2 parts. The first part of the study is a 2-week period for the treatment of the patient's current VVC episode with 3 150mg doses of fluconazole. The 2nd part consists of 12 weeks, when the patient will take either oteseconazole (VT-1161) 150 mg or a placebo (according to a random assignment), and then a 36-week follow-up period.
In addition, at participating sites, an amendment to the study allows US patients who complete the initial 48 weeks without experiencing a confirmed RVVC episode to continue in a 48-week observational extension period designed to evaluate the continued effectiveness of oteseconazole (VT-1161).
This study is identical to VMT-VT-1161-CL-011.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Oteseconazole (VT-1161) 150mg capsule Once daily for 7 days starting at Day 1, followed by once weekly for 11 weeks |
Drug: Oteseconazole (VT-1161)
Oteseconazole (VT-1161) 150mg capsule
|
| Placebo Comparator: Placebo capsule Once daily for 7 days starting at Day 1, followed by once weekly for 11 weeks |
Drug: Placebo
matching placebo capsule
|
Outcome Measures
Primary Outcome Measures
- Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population. [Maintenance phase (post-randomization through Week 48)]
The primary efficacy outcome measure was the percentage of subjects with 1 or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population. An acute VVC episode during the maintenance phase (considered a recurrent episode) was defined as a positive fungal culture for Candida species and a clinical signs and symptoms score of ≥3. To calculate the signs and symptoms score, each vulvovaginal sign (erythema, edema, excoriation) and symptom (itching, burning, irritation) was scored using the following scale, with a higher score indicating a worse outcome. 0 = none (complete absence of any sign or symptom), 1 = mild (slight), 2 = moderate (definitely present), 3 = severe (marked, intense)
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
3 or more episodes of acute VVC in the past 12 months
-
Positive KOH or Gram stain test
-
Total vulvovaginal signs and symptoms score of ≥3 at screening visit
-
Total vulvovaginal signs and symptoms score of <3 at baseline visit
-
Must be able to swallow pills
Key Exclusion Criteria:
-
Presence or a history of another vaginal or vulvar condition(s)
-
Evidence of major organ system disease
-
History of cervical cancer
-
Poorly controlled diabetes mellitus
-
Pregnant
-
Recent use of topical or systemic antifungal or antibacterial drugs
-
Recent use of immunosuppressive or systemic corticosteroid therapies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 31215 | Phoenix | Arizona | United States | 85032 |
| 2 | 31227 | Little Rock | Arkansas | United States | 72212 |
| 3 | 31217 | Los Angeles | California | United States | 90057 |
| 4 | 31240 | Hartford | Connecticut | United States | 06105 |
| 5 | 31204 | Homestead | Florida | United States | 33030 |
| 6 | 31233 | North Bay Village | Florida | United States | 33141 |
| 7 | 31255 | Wichita | Kansas | United States | 67226 |
| 8 | 31245 | Hagerstown | Maryland | United States | 21740 |
| 9 | 31223 | Winston-Salem | North Carolina | United States | 27103 |
| 10 | 31244 | Columbus | Ohio | United States | 43213 |
| 11 | 31229 | Columbus | Ohio | United States | 43231 |
| 12 | 31222 | Englewood | Ohio | United States | 45322 |
| 13 | 31218 | Jackson | Tennessee | United States | 38305 |
| 14 | 31232 | Frisco | Texas | United States | 75035 |
Sponsors and Collaborators
- Mycovia Pharmaceuticals Inc.
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- VMT-VT-1161-CL-012
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 425 subjects were enrolled in a 2-week Induction Phase after providing consent. During the Induction Phase, subjects received 3 sequential 150mg of fluconazole administered 72 hours apart. Subjects whose presenting acute VVC (vulvovaginal candidiasis) episode resolved during the Induction Phase (a total of 330) entered a 48-week Maintenance Phase comprised of a 12-week treatment period and a 36-week follow-up period. |
| Arm/Group Title | Oteseconazole (VT-1161) | Placebo |
|---|---|---|
| Arm/Group Description | 1 oteseconazole 150mg capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | 1 placebo capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks |
| Period Title: Overall Study | ||
| STARTED | 220 | 110 |
| COMPLETED | 191 | 91 |
| NOT COMPLETED | 29 | 19 |
Baseline Characteristics
| Arm/Group Title | Oteseconazole (VT-1161) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 1 oteseconazole 150mg capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | 1 placebo capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | Total of all reporting groups |
| Overall Participants | 218 | 108 | 326 |
| Age (years) [Median (Standard Deviation) ] | |||
| Median (Standard Deviation) [years] |
34
(9.4)
|
36
(10.8)
|
34
(9.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
218
100%
|
108
100%
|
326
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
3
2.8%
|
3
0.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
23
10.6%
|
8
7.4%
|
31
9.5%
|
| White |
193
88.5%
|
96
88.9%
|
289
88.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
0.9%
|
1
0.9%
|
3
0.9%
|
| Region of Enrollment (participants) [Number] | |||
| Belgium |
18
8.3%
|
8
7.4%
|
26
8%
|
| Czechia |
51
23.4%
|
22
20.4%
|
73
22.4%
|
| Hungary |
8
3.7%
|
3
2.8%
|
11
3.4%
|
| Romania |
44
20.2%
|
28
25.9%
|
72
22.1%
|
| Ukraine |
17
7.8%
|
9
8.3%
|
26
8%
|
| United States |
80
36.7%
|
38
35.2%
|
118
36.2%
|
Outcome Measures
| Title | Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population. |
|---|---|
| Description | The primary efficacy outcome measure was the percentage of subjects with 1 or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population. An acute VVC episode during the maintenance phase (considered a recurrent episode) was defined as a positive fungal culture for Candida species and a clinical signs and symptoms score of ≥3. To calculate the signs and symptoms score, each vulvovaginal sign (erythema, edema, excoriation) and symptom (itching, burning, irritation) was scored using the following scale, with a higher score indicating a worse outcome. 0 = none (complete absence of any sign or symptom), 1 = mild (slight), 2 = moderate (definitely present), 3 = severe (marked, intense) |
| Time Frame | Maintenance phase (post-randomization through Week 48) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on the ITT population which included all randomized subjects except the 4 excluded subjects. Missing values were imputed with multiple imputation using the following auxiliary information: region, treatment, baseline body mass index, baseline age, ethnicity, and visit. |
| Arm/Group Title | Oteseconazole (VT-1161) | Placebo |
|---|---|---|
| Arm/Group Description | 1 oteseconazole150mg capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | 1 placebo capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks |
| Measure Participants | 218 | 108 |
| Number [percentage of subjects] |
3.9
|
39.4
|
Adverse Events
| Time Frame | Day 1 through Week 48 of the study | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The safety population was defined as all randomized subjects who received at least 1 dose of investigational product (3 subjects in the oteseconazole group did not receive investigational product). Treatment-emergent adverse events were defined as adverse events that occurred after the subject received her initial dose of investigational product. | |||
| Arm/Group Title | Oteseconazole (VT-1161) | Placebo | ||
| Arm/Group Description | 1 oteseconazole 150mg capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | 1 placebo capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | ||
All Cause Mortality |
||||
| Oteseconazole (VT-1161) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/217 (0%) | 0/110 (0%) | ||
Serious Adverse Events |
||||
| Oteseconazole (VT-1161) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/217 (3.2%) | 5/110 (4.5%) | ||
| Cardiac disorders | ||||
| Myocarditis | 0/217 (0%) | 0 | 1/110 (0.9%) | 1 |
| Infections and infestations | ||||
| Cholecystitis infective | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
| Pneumonia viral | 0/217 (0%) | 0 | 1/110 (0.9%) | 1 |
| Severe acute respiratory syndrome | 0/217 (0%) | 0 | 1/110 (0.9%) | 1 |
| Sinusitis | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
| Back pain | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer female | 0/217 (0%) | 0 | 1/110 (0.9%) | 1 |
| Nervous system disorders | ||||
| Motor dysfunction | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
| Psychiatric disorders | ||||
| Depression | 0/217 (0%) | 0 | 1/110 (0.9%) | 4 |
| Reproductive system and breast disorders | ||||
| Uterine polyp | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
| Vascular disorders | ||||
| Deep vein thrombosis | 1/217 (0.5%) | 1 | 0/110 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Oteseconazole (VT-1161) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 112/217 (51.6%) | 63/110 (57.3%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 6/217 (2.8%) | 6 | 2/110 (1.8%) | 2 |
| Vomiting | 6/217 (2.8%) | 6 | 2/110 (1.8%) | 2 |
| Abdominal pain | 2/217 (0.9%) | 3 | 2/110 (1.8%) | 3 |
| Abdominal pain upper | 2/217 (0.9%) | 2 | 2/110 (1.8%) | 2 |
| Gastrooesophageal reflux disease | 1/217 (0.5%) | 1 | 2/110 (1.8%) | 2 |
| Infections and infestations | ||||
| Bacterial vaginosis | 14/217 (6.5%) | 23 | 6/110 (5.5%) | 7 |
| Nasopharyngitis | 11/217 (5.1%) | 14 | 7/110 (6.4%) | 9 |
| Urinary tract infection | 12/217 (5.5%) | 16 | 4/110 (3.6%) | 6 |
| Influenza | 6/217 (2.8%) | 7 | 3/110 (2.7%) | 3 |
| Upper respiratory tract infection | 2/217 (0.9%) | 2 | 7/110 (6.4%) | 7 |
| Cystitis | 5/217 (2.3%) | 6 | 3/110 (2.7%) | 6 |
| Sinusitis | 5/217 (2.3%) | 7 | 2/110 (1.8%) | 2 |
| Herpes simplex | 0/217 (0%) | 0 | 3/110 (2.7%) | 3 |
| Tonsillitis | 1/217 (0.5%) | 1 | 2/110 (1.8%) | 2 |
| Tooth infection | 1/217 (0.5%) | 1 | 2/110 (1.8%) | 2 |
| Vulvovaginal candidiasis | 1/217 (0.5%) | 1 | 2/110 (1.8%) | 5 |
| Vulvovaginal mycotic infection | 1/217 (0.5%) | 1 | 2/110 (1.8%) | 5 |
| Severe acute respiratory syndrome | 0/217 (0%) | 0 | 2/110 (1.8%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 5/217 (2.3%) | 5 | 3/110 (2.7%) | 3 |
| Nervous system disorders | ||||
| Headache | 18/217 (8.3%) | 27 | 7/110 (6.4%) | 7 |
| Migraine | 4/217 (1.8%) | 7 | 0/110 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Vulvovaginal pruritus | 4/217 (1.8%) | 6 | 6/110 (5.5%) | 8 |
| Vulvovaginal discomfort | 3/217 (1.4%) | 3 | 2/110 (1.8%) | 2 |
| Dysmenorrhoea | 2/217 (0.9%) | 2 | 2/110 (1.8%) | 4 |
| Vaginal discharge | 1/217 (0.5%) | 1 | 2/110 (1.8%) | 3 |
| Menstruation irregular | 0/217 (0%) | 0 | 2/110 (1.8%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Oropharyngeal pain | 2/217 (0.9%) | 2 | 3/110 (2.7%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Neither institution nor investigator can disclose information pertaining to study until sponsor issues multi-center publication. If multi-center publication is not issued within 18 months of study completion and database lock at all sites, sponsor has 30 days from receipt to review institution's and/or investigator's communication and can require removal of confidential information other than study data and/or delay release of institution's and/or investigator's communication for 60 days.
Results Point of Contact
| Name/Title | Clinical Trial Administration |
|---|---|
| Organization | Mycovia Pharmaceuticals Inc |
| Phone | 919-467-8539 |
| adminops@mycovia.com |
- VMT-VT-1161-CL-012