More Information for Jublia (efinaconazole)
Who participated in the study?
The combined Phase 3 clinical trials enrolled 1651 subjects aged 18 to 75 years old randomized to treatment or Vehicle (1239 in the IDP-108 (JULBIA) group and 416 in the Vehicle group). The two Phase 3 clinical trials were designed identically and conducted simultaneously across three countries (US, Japan, and Canada); therefore, these two studies were pooled for evaluation. The baseline demographics by subgroup included in the efficacy studies are summarized in the table below.
Table 2 Baseline Demographics (Phase 3 studies Combined)
| IDP-108 N=1236
| Vehicle N=415
| Total N=1651
|
|---|---|---|---|
| Age (years) |
|
|
|
| Mean (Standard Deviation) | 51.5 (11.4) | 51.4 (11.4) | 51.4 (11.4) |
| Minimum to maximum | 18.0 to 71.0 | 18.0 to 70.0 | 18.0 to 71.0 |
| Sex, n (%) |
|
|
|
| Male | 953 (77.1) | 322 (77.6) | 1275 (77.2) |
| Female | 283 (22.9) | 93 (22.4) | 376 (22.8) |
| Ethnicity, n (%) |
|
|
|
| Hispanic/Latino | 193 (15.6) | 77 (18.6) | 270 (16.4) |
| Not Hispanic/Latino | 1042 (84.3) | 338 (81.4) | 1380 (83.6) |
| Race, n (%) |
|
|
|
| White | 947 (76.6) | 304 (73.3) | 1251 (75.8) |
| Black or African American | 70 (5.7) | 28 (6.7) | 98 (5.9) |
| American Indian/Alaskan Native | 3 (0.2) | 2 (0.5) | 5 (0.3) |
| Asian | 200 (16.2) | 69 (16.6) | 269 (16.3) |
| Native Hawaiian/Pacific Islander | 2 (0.2) | 1 (0.2) | 3 (0.2) |
| Other | 14 (1.1) | 11 (2.7) | 25 (1.5) |
| Percent of affected toenail (%) |
|
|
|
| Mean (Standard Deviation) | 36.4 (10.6) | 36.7 (10.5) | 36.5 (10.6) |
| Number of affected non-target toenails |
|
|
|
| Mean (Standard Deviation) | 2.8 (1.6)
| 2.8 (1.7) | 2.8 (1.6) |
Source: From FDA Medical Review, Table 7
How was the study designed?
The safety and efficacy of once daily use of JUBLIA for the treatment of onychomycosis of the toenail were assessed in two 52-week prospective, multi-center, randomized, double-blind clinical trials in patients 18 years and older (18 to 70 years of age) with 20% to 50% clinical involvement of the target toenail, without dermatophytomas or lunula (matrix) involvement. The trials compared 48-weeks of treatment with JUBLIA to the vehicle solution. The Complete Cure rate was assessed at Week 52 (4-weeks after completion of therapy). Complete cure was defined as 0% involvement of the target toenail (no clinical evidence of onychomycosis of the target toenail).
What are the results of the efficacy study?
The results showed that efinaconazole solution 10% (JUBLIA) was superior to the vehicle in the treatment of onychomycosis for the primary endpoint of achieving complete cure. Efinaconazole solution 10% was also superior to the vehicle for the 3 secondary endpoints at Week 52 of treatment –see Table below:
Table 3 – Primary and Secondary Efficacy Endpoints at Week 52
| Trial 1 | Trial 2 | |||
|---|---|---|---|---|
| JUBLIA N = 656 | Vehicle N = 214 | JUBLIA N = 580 | Vehicle N = 201 | |
| Complete Curea | 117 17.8% | 7 3.3% | 88 15.2% | 11 5.5% |
| Complete or Almost Complete Cureb | 173 26.4% | 15 7.0% | 136 23.4% | 15 7.5% |
| Mycologic Curec | 362 55.2% | 36 16.8% | 310 53.4% | 34 16.9% |
a Complete cure defined as 0% clinical involvement of the target toenail plus negative KOH and negative culture.
bComplete or almost complete cure defined as ≤5% affected target toenail area involved and negative KOH and culture.
c Mycologic cure defined as negative KOH and negative culture.
Source: Drug Label, Table 2
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
Subgroup analyses were conducted for sex, race and age.
- Sex: A greater trend towards efficacy was observed in women than men taking JUBLIA.
- Race: A greater trend towards efficacy was observed in Asians than Whites or Black/African Americans taking JUBLIA.
- Age: JUBLIA is similarly effective among those above and below 65 years of age.
In the Phase 3 clinical trials, the primary efficacy endpoint was evaluated by treatment group within subgroups based on median age (53>40%>
Table 4: Subset Analysis of the Primary Efficacy Endpoint (ITT Subjects Phase 3 Studies Combined)
| Gender | Males | Females | ||
|---|---|---|---|---|
| IDP-108 | Vehicle | IDP-108 | Vehicle |
| Complete Cure at Week 52 | (N=953) | (N=322) | (N=283) | (N=93) |
| Success | 134 (14.1%) | 12 (3.7%) | 71 (25.1%) | 6 (6.5%) |
| Failure | 819 (85.9%) | 310 (96.3%) | 212 (74.9%) | 87 (93.5%) |
| Age | ≥53 years | |||
| IDP-108 | Vehicle | IDP-108 | Vehicle |
| Complete Cure at Week 52 | (N=612) | (N=202) | (N=624) | (N=213) |
| Success | 112 (18.3%) | 9 (4.5%) | 93 (14.9%) | 9 (4.2%) |
| Failure | 500 (81.7%) | 193 (95.5%) | 531 (85.1%) | 204 (95.8%) |
| Ethnicity | Hispanic/Latino | Not Hispanic/Not Latino | ||
| IDP-108 | Vehicle | IDP-108 | Vehicle |
| Complete Cure at Week 52 | (N=193) | (N=77) | (N=1042) | (N=338) |
| Success | 41 (21.2%) | 0 (0.0%) | 164 (15.7%) | 18 (5.3%) |
| Failure | 152 (78.8%) | 77 (100.0%) | 878 (84.3%) | 320 (94.7%) |
Despite varying subgroup sample sizes, within the IDP-108 groups, a greater trend towards efficacy was observed in female subjects compared with male subjects (25.1% success versus 14.1% success, respectively), in Asian subjects compared with white and black/African American subjects (24.5% success versus 14.7% success and 12.9% success, respectively), and in subjects who had less than 40% affected toenail area compared with subjects who had 40% or more affected toenail area (21.5% success versus 12.0% success, respectively). Subgroup differences based on age and ethnicity were not clearly indicative of any trends.
What are the results of the safety study?
Adverse reactions reported within 48 weeks of treatment and in at least 1% of subjects treated with JUBLIA and those reported in subjects treated with the vehicle are presented in the Table below.
Table 5: Adverse Reactions Reported by at Least 1% of Subjects Treated for up to 48 Weeks
| Adverse Event, n (%) | JUBLIA N = 1227 | Vehicle N = 413 |
|---|---|---|
| Ingrown toenail | 28 (2.3%) | 3 (0.7%) |
| Application site dermatitis | 27 (2.2%) | 1 (0.2%) |
| Application site vesicles | 20 (1.6%) | 0 (0.0%) |
| Application site pain | 13 (1.1%) | 1 (0.2%) |
Source: Drug Label Section 6.1
Were there any differences in side effects of the clinical trials among sex, race and age?
Subgroup analyses were not conducted for sex and race but were evaluated for age.
- Sex: The difference in side effects by sex was not evaluated.
- Race: The difference in side effects by race was not evaluated.
- Age: No differences in side effects were observed between those above and below 65 years of age.