Onychomycosis of Toenails
Conditions
Keywords
Onychomycosis, nail fungus, toenail fungus, fungal nail, hyperkeratosis, nail infection, nail treatment, toenail infection, toenail treatment, foot dermatoses, fungal culture, onycholysis, podiatrist, podiatry, subungual, tinea unguium, antifungal, anti-fungal, dermatologist, dermatology, dermatophyte, distal subungual onychomycosis, yellow nail, thick nail, brittle nail, crumbling nail, discolored nail, weak nail
Brief summary
The purpose of this study is to determine whether AN2690 topical solution is a safe and effective treatment for onychomycosis of the toenail.
Interventions
AN2690 Topical Solution, 5%, applied once daily for 48 weeks
DRUGSolution Vehicle
AN2690 Topical Solution, Vehicle, applied once daily for 48 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of distal subungual onychomycosis affecting at least one great toenail * KOH positive at screening * Willingness not to use any other products including nail polish applied to the toenails during the study * Women of childbearing potential who are currently sexually active must agree to use contraception for the entire study period
Exclusion criteria
* Concurrent or recent use of certain topical or systemic medications without a sufficient washout period * History of any significant chronic fungal disease other than onychomycosis * Significant confounding conditions as assessed by study doctor * Participated in any other trial of an investigational drug or device within 30 days or participation in a research study concurrent with this study * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Cure (Completely Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Week 52 | No clinical evidence of onychomycosis as evidenced by normal toenail plate, no onycholysis, and no subungual hyperkeratosis, and negative KOH wet mount and negative fungal culture. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Completely Clear or Almost Clear Target Great Toenail at Week 52 | Week 52 | No clinical evidence of onychomycosis as evidenced by normal toenail plate, no onycholysis, and no subungual hyperkeratosis, or no more than minimal evidence of onychomycosis as evidenced by toenail plate dystrophic or discolored over ≤ 10% of the distal aspect, with minimally evident onycholysis and subungual hyperkeratosis. |
| Treatment Success (Completely Clear or Almost Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Week 52 | No clinical evidence of onychomycosis as evidenced by normal toenail plate, no onycholysis, and no subungual hyperkeratosis, or no more than minimal evidence of onychomycosis as evidenced by toenail plate dystrophic or discolored over ≤ 10% of the distal aspect, with minimally evident onycholysis and subungual hyperkeratosis, and negative KOH wet mount and negative fungal culture. |
| Negative Mycology of Target Great Toenail at Week 52 | Week 52 | Negative KOH and negative fungal culture. |
Countries
United States
Participant flow
Recruitment details
Subjects were screened and enrolled at thirty-four investigative centers in the United States and Mexico. The study population included men and women, 18 years of age and older who had distal subungual onychomycosis. The first subject visit occurred on December 1, 2010, and the last subject completed the Post Study Follow Up on January 8, 2013.
Pre-assignment details
Eligible subjects were randomized in a 2:1 ratio to receive AN2690 Topical Solution, 5% or Solution Vehicle to be applied once daily to all affected toenails throughout the 48-week treatment period.
Participants by arm
| Arm | Count |
|---|---|
| AN2690 Topical Solution, 5% AN2690 Topical Solution, 5%
AN2690 Topical Solution, 5%: AN2690 Topical Solution, 5%, applied once daily for 48 weeks | 399 |
| Solution Vehicle Solution Vehicle
Solution Vehicle: AN2690 Topical Solution, Vehicle, applied once daily for 48 weeks | 194 |
| Total | 593 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 18 | 5 |
| Overall Study | Non compliance | 2 | 2 |
| Overall Study | Non-specific | 7 | 3 |
| Overall Study | Withdrawal by Subject | 24 | 11 |
Baseline characteristics
| Characteristic | AN2690 Topical Solution, 5% | Total | Solution Vehicle |
|---|---|---|---|
| Age, Continuous Age | 53.6 years STANDARD_DEVIATION 12.5 | 53.5 years STANDARD_DEVIATION 12.4 | 53.4 years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 99 Participants | 153 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 300 Participants | 440 Participants | 140 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 31 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 62 Participants | 92 Participants | 30 Participants |
| Race (NIH/OMB) White | 316 Participants | 468 Participants | 152 Participants |
| Region of Enrollment Mexico | 59 participants | 89 participants | 30 participants |
| Region of Enrollment United States | 340 participants | 504 participants | 164 participants |
| Sex: Female, Male Female | 75 Participants | 111 Participants | 36 Participants |
| Sex: Female, Male Male | 324 Participants | 482 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 90 / 396 | 57 / 193 |
| serious Total, serious adverse events | 12 / 396 | 8 / 193 |
Outcome results
Primary
Complete Cure (Completely Clear Nail and Negative Mycology) of Target Great Toenail at Week 52
No clinical evidence of onychomycosis as evidenced by normal toenail plate, no onycholysis, and no subungual hyperkeratosis, and negative KOH wet mount and negative fungal culture.
Time frame: Week 52
Population: Efficacy analysis was performed using the ITT population. The last observation was carried forward (LOCF) in order to provide a value for efficacy parameters that were missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2690 Topical Solution, 5% | Complete Cure (Completely Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Success | 26 participants |
| AN2690 Topical Solution, 5% | Complete Cure (Completely Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Failure | 373 participants |
| Solution Vehicle | Complete Cure (Completely Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Success | 1 participants |
| Solution Vehicle | Complete Cure (Completely Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Failure | 193 participants |
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Completely Clear or Almost Clear Target Great Toenail at Week 52
No clinical evidence of onychomycosis as evidenced by normal toenail plate, no onycholysis, and no subungual hyperkeratosis, or no more than minimal evidence of onychomycosis as evidenced by toenail plate dystrophic or discolored over ≤ 10% of the distal aspect, with minimally evident onycholysis and subungual hyperkeratosis.
Time frame: Week 52
Population: Efficacy analysis was performed using the ITT population. The LOCF was used in order to provide a value for efficacy parameters that were missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2690 Topical Solution, 5% | Completely Clear or Almost Clear Target Great Toenail at Week 52 | Failure | 295 participants |
| AN2690 Topical Solution, 5% | Completely Clear or Almost Clear Target Great Toenail at Week 52 | Success | 104 participants |
| Solution Vehicle | Completely Clear or Almost Clear Target Great Toenail at Week 52 | Success | 18 participants |
| Solution Vehicle | Completely Clear or Almost Clear Target Great Toenail at Week 52 | Failure | 176 participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Negative Mycology of Target Great Toenail at Week 52
Negative KOH and negative fungal culture.
Time frame: Week 52
Population: Efficacy analysis was performed using the ITT population. The LOCF was used in order to provide a value for efficacy parameters that were missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2690 Topical Solution, 5% | Negative Mycology of Target Great Toenail at Week 52 | Failure | 275 participants |
| AN2690 Topical Solution, 5% | Negative Mycology of Target Great Toenail at Week 52 | Success | 124 participants |
| Solution Vehicle | Negative Mycology of Target Great Toenail at Week 52 | Failure | 180 participants |
| Solution Vehicle | Negative Mycology of Target Great Toenail at Week 52 | Success | 14 participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Treatment Success (Completely Clear or Almost Clear Nail and Negative Mycology) of Target Great Toenail at Week 52
No clinical evidence of onychomycosis as evidenced by normal toenail plate, no onycholysis, and no subungual hyperkeratosis, or no more than minimal evidence of onychomycosis as evidenced by toenail plate dystrophic or discolored over ≤ 10% of the distal aspect, with minimally evident onycholysis and subungual hyperkeratosis, and negative KOH wet mount and negative fungal culture.
Time frame: Week 52
Population: Efficacy analysis was performed using the ITT population. The LOCF was used in order to provide a value for efficacy parameters that were missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2690 Topical Solution, 5% | Treatment Success (Completely Clear or Almost Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Success | 61 participants |
| AN2690 Topical Solution, 5% | Treatment Success (Completely Clear or Almost Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Failure | 338 participants |
| Solution Vehicle | Treatment Success (Completely Clear or Almost Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Failure | 191 participants |
| Solution Vehicle | Treatment Success (Completely Clear or Almost Clear Nail and Negative Mycology) of Target Great Toenail at Week 52 | Success | 3 participants |
p-value: <0.001Cochran-Mantel-Haenszel