Dose-finding Study of Moxidectin for Treatment of Scabies

Study Overview
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Brief Summary
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The effective dose of moxidectin to treat human scabies is not known. This study aims to provide proof of concept that a single dose of moxidectin is effective in eliminating the scabies parasite in humans and to enable the determination of an optimal dose of moxidectin for treatment of scabies for further clinical studies.

Official Title
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A Phase II, Randomized, Double-blind, Parallel Group Dose Finding Study of Single Oral Doses of Moxidectin in Adults With Scabies

Conditions
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Scabies

Intervention / Treatment
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* Drug: Moxidectin Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years. Provision of written informed consent. Parasitologically confirmed active Sarcoptes scabiei infestation, defined as the presence of at least two lesions (which may include burrows), each containing at least one live (internal and/or external structures discernable) adult Sarcoptes scabiei mite observed by reflectance confocal microscopy. Agree to the use of reliable contraceptive measures if female or male partner of a female of child-bearing potential from Screening and until 6 months after treatment with study product. Exclusion Criteria: History of chronic or recurring dermatologic disease (other than scabies) that could interfere with the diagnosis and/or subsequent clinical assessment of scabies. Diagnosis of crusted/Norwegian scabies or scabies that, in the opinion of the Investigator, would require treatment with more than one standard of care (e.g. scabies requiring concurrent topical and oral treatment). Received any treatment for scabies within 7 days of Screening, including but not limited to permethrin, ivermectin, benzyl benzoate, lindane, crotamiton, malathion, and/or tea tree oil. Presence of any other clinically relevant condition, including infection, immunological disorder, malignant disease, and/or other underlying condition or circumstance at Screening or Baseline that would put the subject at increased risk from participating in the study or confound study evaluations. Poor venous access. Received an investigational agent within 28 days of Screening (or 5 half-lives of the investigational agent, whichever is longer). Body Mass Index over 35 kg/m2. Clinically relevant abnormal findings in vital signs, 12-lead electrocardiogram (ECG), or physical examination at Screening and/or Baseline in the opinion of the Investigator. Clinically relevant laboratory abnormalities at Screening, including: alanine aminotransferase or aspartate aminotransferase > 2.5 x upper limit of reference range; creatinine > 2.0 milligrams per deciliter (mg/dL); hemoglobin < 9.5 g/dL (female) or <10.5 g/dL (male); amylase > 2.0 x upper limit of reference range. Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin. Use of systemic steroids within 14 days of Screening, or history of prolonged use of systemic and/or high-dose inhaled corticosteroids, or use of topical steroids for 7 out of the 14 days prior to Screening. Subjects with known or suspected Loa loa coinfection. Difficulty swallowing tablets. Pregnant or breastfeeding, or planning to become pregnant. Known or suspected alcohol or illicit substance abuse. Unwilling, unlikely or unable to comply with all protocol specified assessments. Previous enrolment and treatment with moxidectin in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel, double blind, multicenter, randomized, pharmacokinetic/pharmacodynamic study. Three cohorts of six subjects per cohort are planned. Subjects will be randomized 1:1:1 to receive 2, 8 or 20 mg moxidectin as a single oral dose. An additional cohort of 36 mg may be initiated with a target sample size of 6 subjects.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moxidectin 2 mg<br>Moxidectin 2 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required<br>|
| Experimental: Moxidectin 8 mg<br>Moxidectin 8 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required<br>|
| Experimental: Moxidectin 20 mg<br>Moxidectin 20 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required<br>|
| Experimental: Moxidectin 36 mg<br>Moxidectin 36 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality Rate for Adult Scabies Mites | Adult scabies mite death was based on the reflectance confocal microscopy (RCM) morphology assessment of 2 live adult scabies mites nominated pre-treatment (Baseline), hence overall number of units analyzed are different from the overall number of participants. For the outcome measure, the number of adult mites assessed at each timepoint is the sum of the number of adult mites from all participants in the analysis population for each dose. Therefore, mortality was assessed in 2 mites in the 2 mg group, 6 in the 8 mg group, 8 in the 20 mg group and 14 in the 32 mg group. Adult mite death was defined as the degradation (homogenization of internal structures and/or external anatomic structures, and increased reflectance) of the adult mite observed by RCM. The number of dead mites was assessed at Hours 4, 8, 24, 48 and 72, and Days 7, 14 and 28 compared to the baseline adult mites. | 28 days | 
| Summary of Participants With Most Commonly Occurring Adverse Events by Preferred Term (Safety Analysis Set) | No formal statistical analysis of AEs was undertaken. Adverse events reported in this Section refer to treatment emergent adverse events (TEAE), defined as AEs that started, or worsened, on or after the start of the administration of Investigational Product (Moxidectin). Moxidectin was generally well tolerated, with no treatment-related SAEs reported and no treatment emergent adverse event (TEAEs) leading to study withdrawal or resulting in death. Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term. Data up to and including the Day 28 assessment for each subject. | Day 0 to Day 28 inclusive | 
| Number of Participants and Severity of Adverse Events | Number of participants with Adverse events reported in this Section refer to treatment emergent adverse events (TEAE), defined as AEs that started, or worsened, on or after the start of the administration of IP. Data up to and including the Day 28 assessment for each subject. The severity of adverse events were assessed using the Toxicity Grading Scale for Healthy Adult and Adolescent volunteers Enrolled in Preventive Vaccine Clinical Trials. | Day 0 to Day 28 inclusive | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of Moxidectin Plasma Concentrations | The final PK analysis dataset included a total of 240 evaluable PK samples from 22 subjects. All pre-dose samples were below the limit of quantitation (BQL). | Nominal time of PK sample collection was Pre-dose, 2hours (h), 3h, 4h, 8h, Day 1 (24h), Day 2 (48h), Day 3 (72h), Day 7 (168h), Day 14 (336h) and Day 28 (672h) | 
| Analysis of Moxidectin Maximum Plasma Concentrations (Cmax) | The final PK analysis dataset included a total of 240 evaluable PK samples from 22 subjects. All pre-dose samples were below the limit of quantitation (BQL). | Nominal time of PK sample collection was Pre-dose, 2hours (h), 3h, 4h, 8h, Day 1 (24h), Day 2 (48h), Day 3 (72h), Day 7 (168h), Day 14 (336h) and Day 28 (672h) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moxidectin, acaricide, oral