6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.

In three Phase 3 clinical trials, 616 subjects were exposed to LUZU Cream, 1%: 305 with interdigital tinea pedis and 311 subjects with tinea cruris. Subjects with interdigital tinea pedis or tinea cruris applied LUZU Cream, 1% or vehicle cream once daily for 14 days or 7 days, respectively, to affected and adjacent areas. During clinical trials with LUZU Cream, 1%, the most common adverse reactions were application site reactions which occurred in less than 1% of subjects in both the LUZU and vehicle arms. Most adverse reactions were mild in severity.

6.2 Post-Marketing Experience

The following adverse reactions have been identified during postmarketing use of luliconazole cream, 1%: contact dermatitis and cellulitis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

8.1 Pregnancy

8.3 Nursing Mothers

It is not known whether luliconazole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LUZU Cream, 1% is administered to women who are breastfeeding.

8.4 Pediatric Use

The safety and effectiveness of LUZU Cream, 1% in pediatric patients have not been established. The number of pediatric subjects ≥12 years of age were too small to adequately assess safety and efficacy.

8.5 Geriatric Use

Of the total number of subjects in clinical studies of LUZU Cream, 1%, 8 percent were 65 and over, while 1.4 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

12.1 Mechanism of Action

LUZU Cream, 1% is an azole antifungal [see Clinical Pharmacology (12.4)].

12.2 Pharmacodynamics

At therapeutic doses, LUZU Cream, 1% is not expected to prolong QTc to any clinically relevant extent.

12.3 Pharmacokinetics

Luliconazole is the R enantiomer of a chiral molecule. The potential for inter-conversion between R and S enantiomers in humans has not been assessed. Information on the pharmacokinetics of luliconazole presented below refers to both R enantiomer and S enantiomer, if any, combined.

Luliconazole is >99% protein bound in plasma.

In a pharmacokinetic trial, 12 subjects with moderate to severe tinea pedis and 8 subjects with moderate to severe tinea cruris applied a mean daily amount of approximately 3.5 grams of LUZU Cream, 1% to the affected and surrounding areas once daily for 15 days. Plasma concentrations of luliconazole on Day 15 were measurable in all subjects and fluctuated little during the 24 hour interval. In subjects with tinea pedis, the mean ± SD of the maximum concentration (Cmax) was 0.40 ± 0.76 ng/mL after the first dose and 0.93 ± 1.23 ng/mL after the final dose. The mean time to reach Cmax (Tmax) was 16.9 ± 9.39 hours after the first dose and 5.8 ± 7.61 hours after the final dose. Exposure to luliconazole, as expressed by area under the concentration time curve (AUC0–24 was 6.88 ± 14.50 ng*hr/mL after the first dose and 18.74 ± 27.05 ng*hr/mL after the final dose. In subjects with tinea cruris, the mean ± SD Cmax was 4.91 ± 2.51 ng/mL after the first dose and 7.36 ± 2.66 ng/mL after the final dose. The mean Tmax was 21.0 ± 5.55 hours after the first dose and 6.5 ± 8.25 hours after the final dose. Exposure to luliconazole, as expressed by AUC0–24 was 85.1 ± 43.69 ng*hr/mL after the first dose and 121.74 ± 53.36 ng*hr/mL after the final dose.

12.4 Microbiology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies to eva luate the carcinogenic potential of LUZU Cream, 1% have not been conducted.

Luliconazole revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster lung cell chromosomal aberration assay) and one in vivo genotoxicity test (mouse bone marrow micronucleus test).

In a fertility study in rats, subcutaneous doses of 1, 5 and 25 mg/kg/day luliconazole were administered prior to and during mating and through early pregnancy. Treatment related effects on reproductive function were noted in females (decreased live embryos and decreased corpus luteum) at 5 and 25 mg/kg/day and males (decreased sperm counts) at 25 mg/kg/day. No treatment related effects on fertility or reproductive function were noted at 1 mg/kg/day (0.1× MRHD based on BSA comparisons).

14.1 Interdigital Tinea Pedis

The safety and efficacy of LUZU (luliconazole) Cream, 1% was eva luated in two randomized, double-blind, vehicle-controlled, multi-center clinical trials in 423 subjects with a clinical and culture-confirmed diagnosis of interdigital tinea pedis. Subjects were randomized to receive LUZU Cream, 1% or vehicle. Subjects applied either LUZU Cream, 1% or vehicle cream to the entire area of the forefeet including all interdigital web spaces and approximately 2.5 cm (1 in) of the surrounding area of the foot once daily for 14 days.

The mean age of the study population was 41 years; 82% were male; 53% were White and 40% were Black or African American. Signs and symptoms of tinea pedis (erythema, scaling, and pruritus), KOH exam and dermatophyte culture were assessed at baseline, end-of-treatment (Day 14), 2 and 4 weeks post-treatment.

Overall treatment success was defined as complete clearance (clinical cure and mycological cure) at 4 weeks post-treatment. LUZU Cream, 1% demonstrated completed clearance in subjects with interdigital tinea pedis. Treatment outcomes at 4 weeks post-treatment are summarized in Table 1.

14.2 Tinea Cruris

The safety and efficacy of LUZU (luliconazole) Cream, 1% was eva luated in a randomized, double-blind, vehicle-controlled, multi-center clinical trial in 256 subjects with a clinical and culture confirmed diagnosis of tinea cruris. Subjects were randomized to receive LUZU Cream, 1% or vehicle. Subjects applied either LUZU Cream, 1% or vehicle cream to the affected area and approximately 2.5 cm (1 in) of the surrounding area once daily for 7 days.

The mean age of the study population was 40 years; 83% were male; 58% were White and 34% were Black or African American. Signs and symptoms of tinea cruris (erythema, scaling, and pruritus), positive KOH exam and dermatophyte culture were assessed at baseline, end-of-treatment (Day 7), 2 and 3 weeks post-treatment.

Overall treatment success was defined as complete clearance (clinical cure and mycological cure) at 3 weeks post-treatment. LUZU Cream, 1% demonstrated completed clearance in subjects with tinea cruris. Treatment outcomes at 3 weeks post treatment are summarized in Table 2.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room temperature].