ACKNOWLEDGEMENTS: Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics; Ortho Dermatologics is a division of Bausch Health US, LLC | Presented at Winter Clinical Dermatology Conference 2020 • January 17-22, 2020 • Kohala Coast, HI

SYNOPSIS

 ◾ Onychomycosis—a chronic fungal nail infection—can occur in children, 
ranging in prevalence from 0.35% – 5.5% worldwide1

 ◾ Onychomycosis has been reported to be responsible for approximately 15% 
of all nail dystrophies in children2

 ◾ Treatment of onychomycosis is challenging, and can require systemic 
antifungals for prolonged periods of time; however, parents and healthcare 
practitioners are hesitant to use long-term systemic treatments in children3

 ◾ Efinaconazole 10% topical solution (Jublia® Ortho Dermatologics, 
Bridgewater, NJ) is an azole antifungal indicated for the topical treatment of 
onychomycosis of the toenails due to Trichophyton rubrum and Trichophyton 
mentagrophytes

OBJECTIVE

 ◾ To evaluate efinaconazole 10% topical solution in pediatric patients with 
onychomycosis

METHODS

 ◾ This phase 4, multicenter, open-label study evaluated safety, 
pharmacokinetics (PK), and efficacy of efinaconazole 10% topical solution in 
pediatric patients with distal lateral subungual onychomycosis

 ◾ Efinaconazole was administered once daily for 48 weeks, with a 4-week 
posttreatment follow up at week 52

 ◾ Participants were aged 6 – 16 years with culture-positive mild-to-severe 
onychomycosis affecting ≥20% of at least 1 great toenail

 ◾ The PK subset was patients 12 – 16 years with moderate-to-severe 
onychomycosis affecting ≥50% of each great toenail and onychomycosis in 
≥4 additional toenails

 ◾ The primary objective of this study was evaluation of safety and PK

• Safety included adverse events (AEs) and serious AEs (SAEs)

• PK assessments included area under the concentration time curve from 
0 to 24 hours (AUC0 -24 ), maximum plasma concentration (Cmax ), and time to 
Cmax (Tmax ); PK parameters were assessed based on blood samples collected 
on days 28 and 29 (predose and up to 24 hours postdose)

 ◾ Efficacy assessments included mycologic cure, complete cure, and clinical 
efficacy

RESULTS

Study Population

 ◾ A total of 62 patients were enrolled in the study; of these, 12 (19.4%) 
patients did not complete the study (withdrawal by parent/guardian, n=6; 
lost to follow-up, n=5; participant request, n=1) 

Safety, Pharmacokinetics, and Efficacy of Efinaconazole 10% Topical Solution for the Treatment of Onychomycosis in 
Pediatric Patients

Pharmacokinetics 

 ◾ The final PK analysis population comprised 15 patients; 2 patients were not 
included (samples arrived thawed from facility [n=1] and statistical outlier 
[n=1])

 ◾ The concentration-time profiles for efinaconazole and the H3 metabolite 
were relatively stable, with only minor fluctuations during the 24-hour dosing 
interval (Figure 1)

 ◾ Systemic exposure to efinaconazole was low (Table 2)

 ◾ Based on mean AUC0-24 in molar amounts, exposure to the H3 metabolite 
was approximately 5-fold higher than that observed for efinaconazole (0.169 
versus 0.0327 nmol*h/mL)

FIGURE 1. Mean Efinaconazole and H3 Metabolite Plasma 
Concentration-Time Profiles After Topical Administration of 
Efinaconazole Solution on Day 28 (PK Analysis Population)

0

0.25

0.5

0.75

1.0

1.25

1.5

1.75

2.0

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Time (hours)

E�naconazole (n=15)

H3 metabolite (n=15)

0 2 4 12 24

TABLE 2. Mean Pharmacokinetic Parameters of Efinaconazole 
and H3 Metabolite After Topical Administration of Efinaconazole 
Solution on Day 28 (PK Analysis Population)

Efinaconazole  
(n=15)

H3 Metabolite  
(n=15)

Tmax , median (range), h 12.0 (0.00 – 24.5) 4.05 (0.00 – 24.5)

Cmax , mean (SD), ng/mL 0.549 (0.375) 1.65 (1.31)

AUC0-24 , mean (SD), ng*h/mL 11.4 (7.68)a 38.1 (30.4)b

an=11; bn=13. 
AUC0-24 , area under the concentration time curve from 0 to 24 hours; Cmax , maximum plasma 
concentration; SD, standard deviation; Tmax , time to maximum plasma concentration.

 ◾ Sixty participants administered ≥1 dose of study drug (safety population), 
17 of whom had PK data on days 28 and 29 (PK population) 

 ◾ In the safety population, mean age was 13.4 years (range: 6 – 16 years), 
66.7% were male, and 88.3% were white

 ◾ In the PK population, mean age was 14.1 years (range: 12 – 16 years), 
64.7% were male, and 100% were white

Safety 

 ◾ A summary of all treatment-emergent AEs (TEAEs) is shown in Table 1

 ◾ All TEAEs were mild or moderate and none led to study discontinuation 

 ◾ The only treatment-related TEAE was ingrowing nail, with 8 events in 
2 participants (Table 1)

 ◾ No treatment-related SAEs were reported

 ◾ No safety signals or trends associated with local skin reactions were 
observed

TABLE 1. Treatment-Emergent Adverse Event Summary 
(Safety Population)

Efinaconazole 
Solution  
(n=60)

Number of TEAEs, No. 99

Participants with ≥1 TEAE, n (%) 38 (63.3)

Participants with ≥1 treatment-emergent SAE, n (%) 1 (1.7)a

Most common TEAEs (>5% in safety population), n (%)

 Nasopharyngitis 18 (30.0)

 Headache 6 (10.0)

 Influenza 5 (8.3)

 Tinea pedis 4 (6.7)

 Contusion 4 (6.7)

 Nail injury 4 (6.7)

 Ingrowing nail 4 (6.7)

Treatment-related TEAE, n (%)

 Ingrowing nail 2 (3.3)

aThe SAE of pneumonia was deemed unrelated to treatment; the moderate event resolved with 
hospitalization and did not require a change in study drug application. 
SAE, serious adverse event, TEAE, treatment-emergent adverse event.

Efficacy  

 ◾ By week 52, 65.0% of patients achieved mycologic cure, with a 36.7% 
mycologic cure rate observed as early as week 12 (Figure 2)

 ◾ A total of 40.0% of patients had complete cure by week 52 (Figure 3), and 
half of patients achieved clinical efficacy by study end (Figure 4)

FIGURE 2. Mycologic Cure (Safety Population, LOCF)

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50%

75%

100%

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Study Visit (weeks)

E�naconazole 10% (n=60)

0 12 36 48 5224

0%

36.7%

70.0% 70.0%

65.0%

53.3%

Mycologic cure was defined as negative potassium hydroxide (KOH) and negative fungal culture. 
LOCF, last observation carried forward.

FIGURE 3. Complete Cure (Safety Population, LOCF)

0%

25%

50%

75%

100%

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Study Visit (weeks)

E�naconazole 10% (n=60)

0 12 36 48 5224

0% 0%

8.3%

35.0%
40.0%

0%

Complete cure was defined as 0% clinical involvement of the target toenail and mycologic cure 
(negative KOH and negative fungal culture). 
LOCF, last observation carried forward.

Lawrence F Eichenfield, MD1; Boni Elewski, MD2; Jeffrey L Sugarman, MD, PhD3; Ted Rosen, MD4; Aditya Gupta, MD, PhD5; Radhakrishnan Pillai, PhD6; Tina Lin, PharmD7
1Departments of Dermatology and Pediatrics; University of California, San Diego School of Medicine and Rady Children’s Hospital, San Diego, CA; 2University of Alabama at Birmingham School of Medicine, Birmingham, AL; 3University of California, San Francisco, CA; 4Baylor College of Medicine, Houston, TX; 
5Mediprobe Research Inc., London, ON, CAN and University of  Toronto, Toronto, ON, CAN; 6Bausch Health US, LLC*, Petaluma, CA; 7Ortho Dermatologics*, Bridgewater, NJ
*Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC.

FIGURE 4. Clinical Efficacy (Safety Population, LOCF)

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Study Visit (weeks)

E�naconazole 10% (n=60)

0 12 36 48 5224

0% 0%

18.3%

43.3%

50.0%

8.3%

Clinical efficacy was defined as affected target great toenail area <10%. 
LOCF, last observation carried forward.

CONCLUSIONS
 ◾ Efinaconazole 10% topical solution administered once daily for 
a year was well tolerated in this pediatric population

 ◾ The systemic exposure to efinaconazole in this pediatric 
population was comparable to that previously reported in 
adults (Cmax , 0.67 ng/mL; AUC0-24 , 12.15 ng*h/mL)4

 ◾ Efinaconazole was efficacious in pediatric patients, with 
improved mycologic cure (65%) and complete cure (40%) rates 
compared with adults from two 1-year studies (mycologic cure: 
53.4–55.2%; complete cure: 15.2–17.8%)4

REFERENCES
1. Gupta AK, et al. Pediatr Dermatol. 2018;35(5):552-559.
2. Rodriguez-Pazos L, et al. Mycoses. 2011;54(5):450-453.
3. Eichenfield LF, Friedlander SF. J Drugs Dermatol. 2017;16(2):105-109.
4. Prescribing Information. JUBLIA® (efinaconazole) topical solution, 10%. Ortho Dermatologics.

AUTHOR DISCLOSURES
LE has served as investigator and consultant for Ortho Dermatologics. BE has provided clinical research 
support (research funding to University) for Abbvie, Anaptys- Bio, Boehringer Ingelheim, Bristol Myers 
Squibb, Celgene, Incyte, Leo, Lilly, Merck, Menlo, Novartis, Pfizer, Regeneron Sun, Ortho 
Dermatologics, Vanda; and as consultant (received honorarium) from Boehringer Ingelheim, Celgene, 
Leo, Lilly, Menlo, Novartis, Pfizer, Sun, Ortho Dermatologics, Verrica. JS is a consultant for Ortho 
Dermatologics, Bausch Health, Regeneron, Sanofi, and Pfizer. TR has served as consultant for Ortho 
Dermatologics. AG has served as consultant, speaker, and investigator for Ortho Dermatologics. RP is 
an employee of Bausch Health US, LLC and may hold stock and/or stock options in its parent company. 
TL is an employee of Ortho Dermatologics and may hold stock and/or stock options in its parent 
company.