Candidiasis, Vulvovaginal, Vulvovaginitis, Yeast Infection, Yeast Infection Vaginal
Conditions
Brief summary
This is a multi-center, randomized study to evaluate the safety, tolerability, and efficacy of 200 mg CAMB and 400 mg CAMB compared with a single 150 mg dose of fluconazole in the treatment of moderate to severe VVC.
Detailed description
This is a multi-center, randomized study to evaluate the safety, tolerability, and efficacy of 200 mg CAMB and 400 mg CAMB compared with a single 150 mg dose of fluconazole in the treatment of moderate to severe VVC. Approximately 75 women with moderate to severe VVC will be randomized to 1 of 3 treatment groups (200 mg CAMB, 400 mg CAMB, or fluconazole) to achieve approximately 25 subjects in each group. The primary objective of this study is to evaluate the safety of 200 mg and 400 mg doses of oral CAMB for 5 days compared with a single 150 mg dose of oral fluconazole in subjects with moderate to severe VVC. The secondary efficacy objectives of this study included the clinical cure rate, mycology eradication and responder outcome. Tertiary objectives include pharmacokinetics.
Interventions
lipid-crystal nano-particle formulation amphotericin B
DRUGFluconazole
Sponsors
Matinas BioPharma Nanotechnologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Informed consent Clinical diagnosis of moderate to severe VVC Negative pregnancy test Vaginal pH less than 4.5 Key
Exclusion criteria
Has an intolerance or hypersensitivity to any amphotericin B (AMB) product, or to azole antifungal drugs Receiving antifungal therapy unrelated to VVC or has evidence of systemic fungal infections requiring antifungal therapy Has received treatment for VVC within the past 30 days or has experienced 4 or more episodes of VVC in the past 12 months Has another cause of vulvovaginitis Has other urogenital infection(s) that would potentially alter their response to disease Has another vaginal or vulvar condition that would confound the interpretation of clinical response Has significant laboratory abnormality at screening Has any known azole-resistant Candida infection; Has any other condition the Investigator believes would interfere with the subject's ability to provide informed consent, comply with study instructions, or puts the subject at undue risk
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Outcome Assessed at Test of Cure Visit | 12 days | Number of patients determined to be a Clinical Cure (resolution of the VVC signs and symptoms that were present at baseline without further antifungal treatment); Clinical Failure (incomplete resolution of signs and symptoms of VVC that were present at baseline or new signs and symptoms have developed and require the initiation of non-study antifungal drugs); or Clinical indeterminate (insufficient data are available to determine if the subject is a cure or failure) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mycological Outcome Assessed at Test of Cure | 12 days | Number of patients with mycological eradication (vaginal swab culture negative for growth of baseline Candida species); mycological persistence (vaginal swab culture positive for growth of baseline Candida species); or mycological indeterminate (vaginal swab culture not available or the culture cannot be interpreted or is considered contaminated) |
| Overall Response | 12 Days | Number of patients with overall response at Day 12 (Test of cure visit) of composite signs and symptoms defined as overall success (achievement of both a clinical cure and microbiological eradication); overall failure (clinical failure or microbiological persistence) or overall indeterminate (insufficient data are available to determine if the patient is an overall success or failure). |
| Change in Composite Clinical Cure Score | Between randomization visit (Baseline) and Day 12 visit (Test of Cure) | The percent change from baseline to Day 12 (Test of Cure Visit) of the composite clinical cure score of signs (erythema, edema or excoriation) and symptoms (itching, burning or irritation) on a scale of 0 to 3 for each sign and symptom where 0 = none (complete absence of any sign or symptom); 1 = mild (slight); 2 = moderate (definitely present) or 3 = severe (marked/intense). The maximum score at baseline = 18 (score of 3 for each sign and symptom). The minimum score at baseline = 4 (score of 2 for at least 2 signs or symptoms). A lower score at Day 12 represents a better outcome. The mean percent change from baseline score to Day 12 score is presented for each arm as a negative number and represents a decrease in severity of signs and symptoms. A bigger decrease represents a better outcome. |
Countries
United States
Participant flow
Recruitment details
Recruitment period November 2016 to May 2017 at 22 medical clinics in USA
Pre-assignment details
Enrolled patients were excluded from the study before assignment to groups due to abnormal laboratory test results, negative potassium hydroxide test (KOH) for vaginal yeast or vaginal pH greater than 4.5 during the screening process.
Participants by arm
| Arm | Count |
|---|---|
| CAMB 200 mg 200 mg CAMB (MAT2203) Oral Amphotericin B
Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B | 46 |
| CAMB 400 mg 400 mg CAMB (MAT2203) Oral Amphotericin B
Oral Encochleated Amphotericin B (CAMB): lipid-crystal nano-particle formulation amphotericin B | 45 |
| Fluconazole 150 mg Fluconazole Diflucan
Fluconazole | 46 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Patient discontinued study drug | 0 | 1 | 0 |
| Overall Study | Patient had yeast at Day 5 visit | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | CAMB 200 mg | CAMB 400 mg | Fluconazole 150 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 35.7 years STANDARD_DEVIATION 12.63 | 36.2 years STANDARD_DEVIATION 9.77 | 34.3 years STANDARD_DEVIATION 11.25 | 35.4 years STANDARD_DEVIATION 11.24 |
| Body Mass Index (BMI) | 30.49 kg/m2 STANDARD_DEVIATION 8.136 | 30.64 kg/m2 STANDARD_DEVIATION 8.411 | 29.50 kg/m2 STANDARD_DEVIATION 6.973 | 30.21 kg/m2 STANDARD_DEVIATION 7.819 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 14 Participants | 9 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 31 Participants | 37 Participants | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 22 Participants | 24 Participants | 58 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 23 Participants | 22 Participants | 79 Participants |
| Region of Enrollment United States | 46 participants | 45 participants | 46 participants | 137 participants |
| Sex: Female, Male Female | 46 Participants | 45 Participants | 46 Participants | 137 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 45 | 0 / 46 |
| other Total, other adverse events | 10 / 46 | 12 / 45 | 4 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 45 | 0 / 46 |
Outcome results
Primary
Clinical Outcome Assessed at Test of Cure Visit
Number of patients determined to be a Clinical Cure (resolution of the VVC signs and symptoms that were present at baseline without further antifungal treatment); Clinical Failure (incomplete resolution of signs and symptoms of VVC that were present at baseline or new signs and symptoms have developed and require the initiation of non-study antifungal drugs); or Clinical indeterminate (insufficient data are available to determine if the subject is a cure or failure)
Time frame: 12 days
Population: All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAMB 200 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Indeterminate | 0 Participants |
| CAMB 200 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Cure | 13 Participants |
| CAMB 200 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Failure | 12 Participants |
| CAMB 400 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Cure | 12 Participants |
| CAMB 400 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Failure | 8 Participants |
| CAMB 400 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Indeterminate | 2 Participants |
| Fluconazole 150 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Indeterminate | 1 Participants |
| Fluconazole 150 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Failure | 7 Participants |
| Fluconazole 150 mg | Clinical Outcome Assessed at Test of Cure Visit | Clinical Cure | 24 Participants |
Comparison: No formal sample size calculations were made. The sample size was determined empirically rather than with a specific statistical rationale and is considered sufficient to achieve the study objectives of this proof of concept study. Women with moderate to severe Vulvovaginal candidiasis were randomized in a 1:1:1 ratio to 1 of 3 treatment groups, stratified by signs and symptoms composite score of up to 12 (moderate) and greater than 13 (severe).
Secondary
Change in Composite Clinical Cure Score
The percent change from baseline to Day 12 (Test of Cure Visit) of the composite clinical cure score of signs (erythema, edema or excoriation) and symptoms (itching, burning or irritation) on a scale of 0 to 3 for each sign and symptom where 0 = none (complete absence of any sign or symptom); 1 = mild (slight); 2 = moderate (definitely present) or 3 = severe (marked/intense). The maximum score at baseline = 18 (score of 3 for each sign and symptom). The minimum score at baseline = 4 (score of 2 for at least 2 signs or symptoms). A lower score at Day 12 represents a better outcome. The mean percent change from baseline score to Day 12 score is presented for each arm as a negative number and represents a decrease in severity of signs and symptoms. A bigger decrease represents a better outcome.
Time frame: Between randomization visit (Baseline) and Day 12 visit (Test of Cure)
Population: All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CAMB 200 mg | Change in Composite Clinical Cure Score | -80.9 percent change | Standard Deviation 24.63 |
| CAMB 400 mg | Change in Composite Clinical Cure Score | -80.1 percent change | Standard Deviation 44.66 |
| Fluconazole 150 mg | Change in Composite Clinical Cure Score | -94.0 percent change | Standard Deviation 13.71 |
Secondary
Mycological Outcome Assessed at Test of Cure
Number of patients with mycological eradication (vaginal swab culture negative for growth of baseline Candida species); mycological persistence (vaginal swab culture positive for growth of baseline Candida species); or mycological indeterminate (vaginal swab culture not available or the culture cannot be interpreted or is considered contaminated)
Time frame: 12 days
Population: All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAMB 200 mg | Mycological Outcome Assessed at Test of Cure | Mycological Indeterminate | 0 Participants |
| CAMB 200 mg | Mycological Outcome Assessed at Test of Cure | Mycological Eradication | 9 Participants |
| CAMB 200 mg | Mycological Outcome Assessed at Test of Cure | Mycological Persistence | 16 Participants |
| CAMB 400 mg | Mycological Outcome Assessed at Test of Cure | Mycological Indeterminate | 2 Participants |
| CAMB 400 mg | Mycological Outcome Assessed at Test of Cure | Mycological Eradication | 7 Participants |
| CAMB 400 mg | Mycological Outcome Assessed at Test of Cure | Mycological Persistence | 13 Participants |
| Fluconazole 150 mg | Mycological Outcome Assessed at Test of Cure | Mycological Eradication | 27 Participants |
| Fluconazole 150 mg | Mycological Outcome Assessed at Test of Cure | Mycological Persistence | 4 Participants |
| Fluconazole 150 mg | Mycological Outcome Assessed at Test of Cure | Mycological Indeterminate | 1 Participants |
Secondary
Overall Response
Number of patients with overall response at Day 12 (Test of cure visit) of composite signs and symptoms defined as overall success (achievement of both a clinical cure and microbiological eradication); overall failure (clinical failure or microbiological persistence) or overall indeterminate (insufficient data are available to determine if the patient is an overall success or failure).
Time frame: 12 Days
Population: All randomized participants who had a Candida species isolated on culture of vaginal specimen at baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAMB 200 mg | Overall Response | Overall Success | 4 Participants |
| CAMB 200 mg | Overall Response | Overall Failure | 21 Participants |
| CAMB 200 mg | Overall Response | Overall Indeterminate | 0 Participants |
| CAMB 400 mg | Overall Response | Overall Indeterminate | 2 Participants |
| CAMB 400 mg | Overall Response | Overall Success | 3 Participants |
| CAMB 400 mg | Overall Response | Overall Failure | 17 Participants |
| Fluconazole 150 mg | Overall Response | Overall Failure | 9 Participants |
| Fluconazole 150 mg | Overall Response | Overall Success | 22 Participants |
| Fluconazole 150 mg | Overall Response | Overall Indeterminate | 1 Participants |