6 ADVERSE REACTIONS

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 the rates in the clinical trials of another drug, and may not reflect the rates observed in practice.

The data described below reflect exposure to a single 10-minute treatment of XEGLYZE in 349 subjects (6 months of age and older) with head lice infestation in randomized, double-blind, vehicle-controlled trials (Trials 1 and 2). Of these subjects, 21 were 6 months to 4 years of age, 166 subjects were 4 to 12 years of age, 57 subjects were 12 to 18 years of age, and 105 subjects were 18 years of age or older.

Table 1 provides adverse reactions that occurred in at least 1% of subjects in the XEGLYZE group and at a greater frequency than in the vehicle group.

Table 1: Adverse Reactions Occurring in ≥ 1% of the XEGLYZE Group and at a Greater Frequency than in the Vehicle Group (Trials 1 and 2)

Adverse Reactions	XEGLYZE N=349 Subjects (%)	Vehicle ** N=350** Subjects (%)
Erythema	14 (4.0)	6 (2)
Rash	11 (3.2)	8 (2.3)
Skin burning sensation	9 (2.6)	0 (0.0)
Contact dermatitis	6 (1.7)	4 (1.1)
Vomiting	6 (1.7)	2 (0.6)
Eye irritation	4 (1.2)	2 (0.6)
Hair color changes	3 (1)	0 (0.0)

During the trials, subjects were monitored for new onset of scalp erythema/edema, scalp pruritus, and eye irritation. The number and percentage of subjects who developed these local adverse reactions after treatment are presented in Table 2.

Table 2: Monitored Local Adverse Reactions with New Onset on Day 1 Post- Treatment (Trials 1 and 2)

Adverse Reactions	XEGLYZE Subjects (%)*	Vehicle Subjects (%)*
Scalp Erythema/Edema	11 (3.2)	5 (1.4)
Scalp Pruritus	2 (1.4)	1 (0.7)
Eye Irritation	6 (1.7)	5 (1.4)

• For the calculation of the percentages, the denominators are the number of subjects who did not have the monitored local adverse reaction at baseline.

14 CLINICAL STUDIES

Two identical multi-center, randomized, double-blind, vehicle-controlled trials (Trials 1 and 2) were conducted in 704 subjects 6 months of age and older with head lice infestation. All subjects received a single application of either XEGLYZE or vehicle control. For the evaluation of efficacy, the youngest subject from each household was considered to be the index subject of the household (N=216). Other enrolled infested household members received the same treatment as the youngest subject and were evaluated for all efficacy and safety parameters. Index subjects ranged from 6 months to 49 years of age (mean 7 years), and approximately 85% of the index subjects were female, and 95% of the index subjects were Caucasian.

Efficacy was assessed as the proportion of index subjects who were treated with a single 10-minute application and were free of live lice at all follow- up visits on Days 1, 7, and 14. Subjects with live lice at any time up to the final evaluation were considered treatment failures. Table 4 presents the proportion of subjects who were free of live lice at all visits Day 1 through Day 14 in Trials 1 and 2.

Table 4: Proportion of Index Subjects Free of Live Lice at All Visits Days 1 Through 14 After Treatment

	Trial 1	Trial 2
	XEGLYZE (N=53)	Vehicle (N=55)	XEGLYZE (N=55)	Vehicle (N=53)
Treatment Success	43 (81.1%)	28 (50.9%)	45 (81.8%)	25 (47.2%)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of XEGLYZE or abametapir.

Abametapir was not mutagenic or clastogenic based on the results of two in vitro genotoxicity tests (Ames test and human lymphocyte chromosomal aberration assay) and one in vivo genotoxicity test (rat micronucleus assay).

No effects on fertility have been observed in rats following repeated oral doses of up to 75 mg/kg/dayabametapir (50 times the MRHD based on Cmax comparisons).

16 HOW SUPPLIED/STORAGE AND HANDLING

XEGLYZE is a white to off-white oil in water emulsion containing 0.74% [weight by weight] abametapir and supplied in a polyvinyl chloride (PVC) safety-coated single-use round amber glass bottle affixed with a polypropylene child resistant cap (NDC # 43598-921-11) featuring a tri-foil inner liner. The container is filled to a nominal 200 g (approximately 7 oz. or 210 mL) of the lotion.

Store upright at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F and 86°F) [See USP Controlled Room Temperature].

Do not refrigerate or freeze.