Phase 3 Trial to Assess the Safety and Efficacy of Natroba for the Treatment of Scabies

The primary study is a double blind, two-arm, 28-day, placebo-controlled study with approximately 120 infested "index" subjects randomized 1:1 to Natroba™ or Placebo. All members of a household (no more than 6 individuals) with a suspected "index" subject must be screened at the first visit. In this study, "index" subjects are defined as the youngest infested household member (≥4 years). If the members have an active scabies infestation and meet all other criteria, they must agree to participate in the study. Household members who do not present with scabies at the screening visit must also agree to apply the same blinded investigational product (IP) as household members who present with scabies. All household members must agree to participate in the study or none will be enrolled. Screening procedures include informed consent, medication and medical history, urine pregnancy test for females of childbearing potential, scabies assessment (visual evidence of burrows, inflammatory/non-inflammatory lesions and pruritus), microscopic examination of skin scraping, or dermatoscopy, to demonstrate the presence of mites, eggs, and/or scybala (dermatoscopy must confirm burrows), vital signs, general skin and eye assessment, randomization, CBC and serum chemistry, and IP dispensing and instruction.

After screening on Day 1, all randomized subjects in the primary population will be dispensed IP (Natroba™ or Placebo) to apply at home later the same day as a single treatment over the entire body from the neck down to the toes (including the soles of the feet) and to the scalp (if balding) or hairline, temples and forehead on the same day. Subjects less than 12 years of age should be assisted with administration by a parent, guardian or caregiver. Subjects will rub the treatment into the skin followed by a 10-minute wait period before getting dressed. Showering or bathing must not occur earlier than 6 hours after treatment and no later than at least 1 hour prior to Day 2 visit.

A separate population of 24 pediatric "non-index" subjects that do not reside in the "index" subject's household will be enrolled to assess the PK of spinosad and benzyl alcohol for 12 hours after open-label topical application on a single in-clinic visit (Day 1, or Day 2 if screening only on Day 1). There will be 12 male or female subjects 4 - 9 years of age (with a minimum of 6 male or female subjects 4 - 6 years of age) and 12 male or female subjects 10 - 16 years of age. With assistance from a caregiver, Natroba™ will be applied over entire body from the neck down to the toes (including the soles of the feet) and to the hairline, temples, and forehead. The open-label product will remain on the skin for at least 6 hours before bathing or showering. The subjects will stay in the clinic until the 12-hour procedures are completed. Blood draws will be taken at 0 hours just prior to treatment, and then at 0.5, 1.0, 3.0, 6.0 hours post-treatment and then at 12 hours post-treatment. Bathing must occur after the 6 hour blood draw but prior to the 12 hour blood draw. A ±5 minute time window will be allowed for all post-treatment blood samples. Safety will be assessed with adverse events (AEs), general skin and eye irritation assessments, pre-dose and pre-discharge laboratory evaluations, and vital signs during the 12 hours in-clinic. Following the sample collections subjects will be released from the clinic and directed to their primary care physician for follow-up. PK subjects will be provided 5% Permethrin upon discharge to dispense to household members.

In the primary population (all household members), on Day 2 (Visit 2), general skin and eye assessments will be made for possible irritation, and to confirm that all IP was left on for a minimum of 6 hours before bathing or showering. If a subject reports an adverse event assessed as related by the PI on Day 2 (Visit 2) then a follow-up visit with the investigator must be scheduled within 7 days of visit. Subjects will receive a well-being phone call on Day 14 to continue to emphasize instructions to prevent re-infestation, determine if any concomitant medications have been used, and check for adverse events. If a subject reports an adverse event assessed as related by the PI on the Day 14 well-being phone call, then a follow-up visit with the investigator must be scheduled within 7 days of phone call.

On Day 28 (Visit 3), all household members will return to the clinic for safety and efficacy assessments. The primary endpoint of complete cure will be assessed in the infested household members. If the infested subject is completely cured at Day 28, he or she will have completed the study and termination procedures will be conducted. If the subject is not completely cured at Day 28 (with Natroba™ or Placebo), the subject will receive 5% Permethrin and will be directed to their primary care physician for follow-up.

Safety assessments will be made for all household members and will include monitoring of adverse events (AEs) throughout the study, vital signs recording (Days 1 and 28), clinical laboratory analyses (Days 1 and 28), and general skin and eye irritation assessments (Days 1, 2, and 28).

The Day 28 procedures will also be completed for early termination (ET) except subjects will not receive rescue Permethrin, but will be directed to follow-up with their primary care physician.