Conditions: Scabies
Keywords: moxidectin acaricide oral
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 22
Healthy volunteers: no

Brief summary:
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.

Detailed description:

Arms:
arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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.

Interventions: intervention 1: Moxidectin Oral Product
Intervention descriptions: intervention 1: The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required

Protocol document:
Prot_ICF_000.pdf: 
Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 1 
19 Jun 2020 
(incorporating Amendments 1 and 2) 
Clinical Study Protocol 
 
Study Title: 
A Phase II, randomized, double-blind, parallel group dose finding 
study of single oral doses of moxidectin in adults with scabies 
Sponsor: 
Medicines Development for Global Health Limited 
Investigational New Drug 
(IND) No (If applicable): 
Not applicable 
Protocol Number: 
MDGH-MOX-2001 
EudraCT Number 
2019-001775-37 
Medical Monitor: 
Jolanta Airey 
 
 
 
Protocol Version/Date: 
Current 
3 
(incorporating 
Amendments 1 
and 2) 
Date 
19 Jun 2020 
 
Prior version 
2 
(incorporating 
Amendment 1) 
Date 
26 Aug 2019 
 
CONFIDENTIALITY STATEMENT 
This study is being performed in compliance with the guidelines of Good Clinical Practice (GCP) 
and all essential documents are being archived. 
The information contained in this document, particularly unpublished data, is the property of, or 
under the control of Medicines Development for Global Health, and is provided to you in confidence 
as an Investigator, potential Investigator, or consultant, for review by you, your staff, and an 
applicable Institutional Review Board (IRB) or Independent Ethics Committee (IEC). The information 
is only to be used by you in connection with authorized clinical studies of the investigational product 
described in the protocol. You will not disclose any of the information to others without written 
authorization from Sponsor, except to the extent necessary to obtain informed consent from those 
persons to whom the drug may be administered. 




Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 3 
19 Jun 2020 
(incorporating Amendments 1 and 2) 
INVESTIGATOR STATEMENT 
 
I have read the protocol, including all appendices, and I agree that it contains all necessary details to 
conduct this study as described. I will conduct this study as outlined herein and will make a 
reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by the Sponsor. I will discuss this material with them to ensure that they are 
fully informed about the drugs and the study. 
 
  
 
 
Principal Investigator’s Name (Printed) 
 
Signature 
 
 
 
Site number 
 
Date (dd mmm yyyy) 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 4 
19 Jun 2020 
(incorporating Amendments 1 and 2) 
1 
PROTOCOL SYNOPSIS 
Protocol Number: 
MDGH-MOX-2001 
Study Title: 
 
A Phase II, randomized, double-blind, parallel group dose finding study of 
single oral doses of moxidectin in adults with scabies  
Investigational Product: 
Moxidectin 
Indication: 
Treatment of scabies due to Sarcoptes scabiei 
Development Phase: 
Phase II 
Background: 
Scabies is an ectoparasitic infection caused by the mite Sarcoptes scabiei 
variant hominis. Scabies was recently included on the World Health 
Organisation’s list of neglected tropical diseases. It most affects people living in 
tropical regions and in overcrowded conditions, which are optimal for person-
to-person transmission of infection. It is estimated that more than 200 million 
people worldwide are affected at any time. Oral ivermectin is currently the only 
oral treatment available for scabies. The recommended regimen for oral 
ivermectin is one or two 200 micrograms/kilogram (µg/kg) doses separated by 
7 to 14 days to ensure elimination of mites hatching after the initial treatment. 
Moxidectin, a macrocyclic lactone of the milbemycin class, has broad activity 
against filarial and ectoparasitic diseases. Moxidectin has been shown in 
clinical trials to be well tolerated when administered as a single dose of 
between 2 and 36 milligrams (mg). A Phase III clinical trial completed in adults 
and adolescents (aged 12 years and over) with onchocerciasis demonstrated 
that moxidectin provided superior skin microfilariae suppression compared to 
ivermectin (Mectizan®; Merck & Co., Inc.), the current standard of care for 
onchocerciasis. Moxidectin 8 mg as a single oral dose is approved by the 
United States Food and Drug Administration for the treatment of 
onchocerciasis in patients aged 12 years and over. 
Moxidectin is well-established in veterinary practice for the treatment of 
sarcoptic mange in companion animals and livestock, and was shown to be 
effective against scabies in a porcine model of the disease. In that model, a 
single oral dose of 300 µg/kg moxidectin was shown to be more efficacious 
than two oral doses of ivermectin 200 µg/kg 10 days apart at eliminating 
scabies. Moxidectin’s long terminal half-life (20 to 43 days) may enable a 
single oral dosing regimen that would provide advantages over ivermectin.  
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. 
Design: 
Parallel, double blind, multicenter, randomized, 
pharmacokinetic/pharmacodynamic study. 
Number of Subjects: 
A maximum of approximately 36 subjects will be enrolled 
Number of Centers: 
Approximately four 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 5 
19 Jun 2020 
(incorporating Amendments 1 and 2) 
Design Details and 
Dose Regimens:  
Initially, three cohorts of approximately 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.  
Once approximately three subjects have been recruited to these three dose 
cohorts, a Protocol Steering Committee will evaluate the unblinded safety and 
efficacy data and recommend: 
• 
Continuation of the study with no dose modification to the target 
sample size of 6 subjects per cohort; or, 
• 
Stopping recruitment of one of more of the current dose cohorts; 
and/or, 
• 
The addition of a 36 mg single dose cohort. 
Once the Committee has made their recommendation, randomization will 
continue into the same or revised dosing regimens with a final target sample 
size of 6 subjects per arm.  
Subjects may receive a maximum of 18 tablets comprised of moxidectin 2 mg 
tablets and matched placebo to maintain the blind. 
Protocol Steering 
Committee  
A Protocol Steering Committee will maintain oversight on emerging efficacy 
and safety data to ensure that the study meets its objective to identify a 
well-tolerated and optimally effective dose of moxidectin for scabies. 
Primary objectives: 
• 
Identify an optimal dose of moxidectin for the treatment of scabies. 
• 
Evaluate the safety of moxidectin in adults infected with scabies. 
Secondary objectives: 
• 
Characterize the plasma pharmacokinetics of moxidectin in adults 
infected with scabies. 
Exploratory objectives: 
• 
Describe the impact of moxidectin on S. scabiei, including impact on 
morphology, motility and life cycle stages. 
• 
Evaluate clinician and patient reported outcomes of treatment with 
moxidectin. 
Primary endpoints: 
• 
Efficacy will be determined by death of the mites, defined as the 
degradation (loss of internal and/or external anatomic structures) of the 
adult mite observed by reflectance confocal microscopy (RCM). Mites 
will be assessed at Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28 in 
not less than two lesions nominated pre-treatment. 
• 
Safety will be assessed by the incidence and severity of adverse event 
(AEs), physical examinations, and measurement of vital signs up to 
and including Week 12, and laboratory safety parameters up to and 
including Day 28. 
Secondary endpoints: 
• 
Key exposure metrics for moxidectin including area under the 
concentration time curve (AUC) and maximum plasma 
concentration (Cmax), will be determined by non-compartmental 
analysis of moxidectin pharmacokinetic parameters or other methods 
as appropriate, assessed up to and including Day 28.  


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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Exploratory endpoints: 
• 
At Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28, using assessment 
by RCM of burrows selected pre-treatment: 
o 
changes in adult mite motility (peristalsis and/or movement) 
over at least 30 seconds of observation; 
o 
presence, number, morphology and motility of juvenile scabies 
mites; and, 
o 
presence of eggs and scybala in burrows. 
• 
Presence and total number of mites and burrows assessed visually at 
Days 7, 14 and 28. 
• 
Changes in assessment of clinician-reported scabies symptomology, 
including extent of symptoms on body regions assessed by the 
number of anatomically-defined regions affected, number of lesions 
and severity grading of excoriations and erythema. 
• 
Changes in patient reported outcomes, measured by Numerical Rating 
Scale, 5-D Itch Scale and Dermatology Life Quality Index. 
Inclusion criteria: 
1. Aged ≥ 18 years. 
2. Provision of written informed consent.  
3. 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 
RCM. 
4. Agree to the use of reliable contraceptive measures if female or male 
partner of a female of child-bearing potential from Screening until 6 
months after treatment with study drug. 
Exclusion criteria: 
1. History of chronic or recurring dermatologic disease (other than 
scabies) that could interfere with the diagnosis and/or subsequent 
clinical assessment of scabies. 
2. 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). 
3. 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.  
4. 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. 
5. Poor venous access. 
6. Received an investigational agent within 28 days of Screening (or 5 
half-lives of the investigational agent, whichever is longer). 
7. Body Mass Index over 35 kg/m2. 
8. 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. 
9. Clinically relevant laboratory abnormalities at Screening, including: 
a. alanine aminotransferase or aspartate aminotransferase 
> 2.5 x upper limit of reference range; 
b. creatinine > 2.0 milligrams per deciliter (mg/dL); 
c. hemoglobin < 9.5 g/dL (female) or <10.5 g/dL (male); 
d. amylase > 2.0 x upper limit of reference range. 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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MDGH-MOX-2001 Protocol version 3 final 
Page 7 
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(incorporating Amendments 1 and 2) 
10. Known or suspected hypersensitivity to macrocyclic lactones or 
excipients used in the formulation of moxidectin. 
11. 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.  
12. Subjects with known or suspected Loa loa coinfection. 
13. Difficulty swallowing tablets. 
14. Pregnant or breastfeeding, or planning to become pregnant. 
15. Known or suspected alcohol or illicit substance abuse. 
16. Unwilling, unlikely or unable to comply with all protocol specified 
assessments. 
17. Previous enrolment and treatment with moxidectin in this study. 
Study product: 
Moxidectin tablets 2 mg (plain-faced) 
Reference product: 
Placebo to match moxidectin tablets, as required for blinding 
Comparator: 
None 
Duration of treatment 
per participant: 
Up to 91 days, including: 
• 
Screening: up to 7 days prior to Baseline (Day 0) 
• 
Day patient (Day 0) 
• 
Outpatient (Hour 24 to Day 28) 
• 
Safety follow up (Week 12) 
Clinical procedures / 
assessments: 
Subjects identified based on presumptive scabies diagnosis by a physician or 
healthcare worker will have the diagnosis confirmed by the study center. After 
obtaining written informed consent, the presence of mites and not less than 
two scabies lesions, each containing at least one live adult mite will be visually 
confirmed (defined as the presence of peristalsis and/or movement and 
morphology consistent with S. scabiei by RCM). If the subject has confirmed 
scabies infection, other Screening assessments will be performed (up to 
Day -1).  
Subjects will present to the clinic on the morning of Day 0 for Baseline 
assessment, randomization, treatment and post-treatment assessment 
throughout the day. They will return to the clinic for assessment at Hours 24, 
48 and 72, Days, 7, 14 and 28 and at Week 12 for safety review. For further 
details of clinical study procedures, please refer to Table 1 and Table 2. 
Specialized analyses: 
Pharmacodynamics 
RCM will be used to evaluate the presence, number and morphology of 
S. scabiei mites by stage (adults, juvenile stages) and the presence of eggs 
and scybala within a minimum of 2 scabies lesions. 
Z-stack photos of mites, eggs and scybala in each of the lesions will be 
obtained at the following time points: 
• 
Baseline (up to 60 minutes prior to dosing); 
• 
Hours 4, 8, 24, 48 and 72; and, 
• 
Days 7, 14 and 28 after dosing. 
Clinician reported outcomes, including assessment of scabies signs and 
symptoms, will be performed by the Investigator at the following time points: 
• 
Baseline (within 60 minutes prior to dosing) 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 8 
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(incorporating Amendments 1 and 2) 
• 
Days 7, 14 and 28 after dosing. 
Patient reported outcomes will be captured through the relevant questionnaires 
administered to the subject at the following time points: 
• 
Baseline (within 60 minutes prior to dosing) 
• 
Days 7, 14 and 28 after dosing.  
Pharmacokinetics 
Blood will be drawn for analysis of plasma moxidectin concentrations at the 
following time points: 
• 
Baseline (within 15 minutes prior to dosing) 
• 
Hours 2, 3, 4, 8, 24, 48 and 72 and Days 7, 14 and 28. 
NOTE: pharmacokinetic sampling and pharmacodynamic assessment should 
be conducted within a 15 minute window of each other. 
Sample size 
determination: 
No formal sample size calculations were performed for this study. Dose 
cohorts of approximately n = 6 are considered to be practical and adequate to 
provide information for the full characterization of pharmacokinetics across the 
dose range. 
Statistical analyses: 
All statistical analyses will be prospectively described in full in a statistical 
analysis plan which will be finalized prior to breaking the blind for the final 
analysis. 
Analysis of key efficacy endpoints 
The focus of the statistical analysis will be descriptive and exploratory. 
Statistical models for estimation and/or hypothesis testing to assess various 
parasitological assessments with respect to dose may be conducted 
Analysis of pharmacokinetics 
Non-compartmental analysis (NCA) or post-hoc model-based exposure 
estimates will be implemented for the calculation of pharmacokinetic 
parameters as appropriate. Pharmacokinetic parameters include: 
• 
area under the concentration time curve (AUC); and, 
• 
observed maximum plasma concentration (Cmax). 
Other pharmacokinetic parameters may be determined as appropriate. 
Analysis of pharmacokinetics/pharmacodynamics 
Key exposure metrics, including Cmax and AUC, and pharmacodynamic data 
will be pooled across the study. The relationship between efficacy endpoints 
and plasma concentrations of moxidectin will be assessed graphically using 
scatterplots or box plots, as appropriate to the pharmacodynamic endpoint. 
Pharmacokinetic/pharmacodynamic analysis techniques will be applied as 
appropriate, such as logistic regression or time-to-event modelling approaches 
where a binary pharmacodynamic outcome is desired, or nonlinear or quantile 
regression response (Emax) in the analysis of continuous pharmacodynamic 
data. 
If deemed appropriate at the conclusion of the study, an existing moxidectin 
population-pharmacokinetic model will be updated with the pharmacokinetic 
data from this study to enable formal comparison of the moxidectin 
pharmacokinetic characteristics observed within the scabies patient population 
to other populations administered moxidectin. Where appropriate, this 
refreshed population-pharmacokinetic model will then be linked to critical 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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MDGH-MOX-2001 Protocol version 3 final 
Page 9 
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(incorporating Amendments 1 and 2) 
pharmacodynamic responses observed during the study to enable selection of 
dose regimens for future clinical studies by clinical trial simulations. 
Analysis of safety 
All safety assessments, including adverse clinical laboratory test results and 
vital sign measurements will be summarized using descriptive statistics and 
presented in data listings. No inferential statistics will be performed on the 
safety data.  
Special protocol 
requirement / issues: 
The close personal contacts (including household and sexual contacts) of all 
enrolled subjects will be offered the current standard of care for treatment of 
scabies and instructed in its use. 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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(incorporating Amendments 1 and 2) 
Table 1  Overall Schedule of Assessments 
 
 
Period 1 
Period 2 
Assessment 
Screening 
(D-7 to  
D-1) 
D0 
D1 
D2 
D3 
D7 
D14 
D28 
Week 12 
Allowable assessment 
window period 
 
See Table 2 for further information on 
schedule of assessments for Day 0 to 
Day 3 of Period 1 
± 2 days 
± 2 days 
± 3 days 
± 7 days 
Informed consent 
X 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
Medical history 
X 
 
 
 
 
Physical examinationa 
X 
X 
X 
X 
X 
Confirmation of scabies 
infection with 
dermoscopy/RCMb 
X 
 
 
 
 
Vital signsc 
X 
X 
X 
X 
X 
12-lead ECGd 
X 
 
 
 
 
Height 
X 
 
 
 
 
Body weight 
X 
 
 
 
X 
Pregnancy testing 
X 
 
 
 
X 
Hematology and serum 
chemistry  
X 
X 
 
X 
 
Pharmacokinetic blood sample 
collection 
 
X 
X 
X 
 
Plasma banking 
 
X 
X 
X 
 
Mite assessment and 
photography with RCM and 
dermoscopy 
 
X 
X 
X 
 
Patient reported outcomes 
(NRS, 5-D itch scale and 
DLQI) 
 
X 
X 
X 
 
Clinician reported outcomes  
 
X 
X 
X 
 
Adverse events 
 
<------------------------------------------------------------X------------------------------------------------------------> 
Concomitant medications 
X 
<------------------------------------------------------------X------------------------------------------------------------> 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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(incorporating Amendments 1 and 2) 
Abbreviations: D, Day; M, Month; ECG, electrocardiogram; RCM, reflectance confocal microscopy; NRS, Numerical Rating Scale; DLQI, Dermatology 
Life Quality Index. 
a. A full physical examination will be performed at Screening. At all subsequent time points, a symptom-based physical examination (informed by 
concurrent conditions, signs and symptoms, and adverse events reported) will be performed. 
b. Two live adult mites must be demonstrated by RCM in at least two representative lesions for study eligibility.  
c. Vital signs (supine blood pressure, heart rate, respiratory rate, and body temperature) will be measured after the subject has rested for 
approximately 5 minutes. 
d. Standard 12-lead safety electrocardiograms will be performed after the subject has been supine for approximately 10 minutes. At each 
relevant time point, safety 12-lead ECGs will be performed before blood collection. 
If a subject discontinues from the study or is withdrawn, the investigator will notify the Sponsor and, when possible, will perform the following 
procedures: vital sign measurements; safety 12-lead ECG; symptom-directed physical examination; collection of AEs; and clinical laboratory evaluation 
(hematology and serum chemistry (up to Day 28) and pregnancy).


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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Table 2  Period 1 (Baseline to Day 3) Schedule of Assessments 
 
D0 
D1 
D2 
D3 
 
Baseline 
(pre-dose) 
 
 
 
 
 
 
 
 
Hour relative to dosing 
Up to -1 
0 
2 
3 
4 
8 
24 
48 
72 
Allowable assessment window 
period 
 
 
± 15 
mins 
± 15 
mins 
± 30 
mins 
± 1 hr 
± 4 hrs 
± 4 hrs 
± 4 hrs 
Assessment 
 
 
 
 
 
 
 
 
 
Physical examinationa 
X 
 
 
 
 
 
X 
 
X 
Scabies infection review and 
lesion selectionb 
X 
 
 
 
 
 
 
 
 
Hematology and serum chemistry 
sample collection 
 
 
 
 
 
 
 
 
 
Vital signsc 
X 
 
 
 
 
X 
X 
 
X 
Randomization, followed by Study 
drug administrationd 
 
X 
 
 
 
 
 
 
 
Pharmacokinetic blood sample 
collectione 
X 
 
X 
X 
X 
X 
X 
X 
X 
Plasma banking 
X 
 
X 
X 
X 
X 
X 
X 
X 
Mite assessment and photography 
with RCMe 
X 
 
 
 
X 
X 
X 
X 
X 
Mite assessment and photography 
with dermoscopy 
X 
 
 
 
 
 
 
 
X 
Patient reported outcomes (NRS, 
5-D itch scale and DLQI) 
X 
 
 
 
 
 
 
 
 
Clinician reported outcomes  
X 
 
 
 
 
 
 
 
 
Adverse events 
<-----------------------------------------------------------------X-----------------------------------------------------------------> 
Concomitant medications 
<----------------------------------------------------------------X------------------------------------------------------------------> 
Abbreviations: D, day; ECG, electrocardiogram; hr, hour; mins, minutes; RCM, Reflectance Confocal Microscopy; NRS, Numerical Rating Scale; DLQI, 
Dermatology Life Quality Index. 
a. A full physical examination will be performed at Screening. At all subsequent time points, a symptom-directed physical examination (informed 
by concurrent conditions, signs and symptoms, and adverse events reported) will be performed. 
b. Live mites in at least two representative lesions must be demonstrated for study eligibility. Up to four lesions will be selected and assessed 
throughout the study. 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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c. Vital signs (supine blood pressure, heart rate, respiratory rate, and oral body temperature) will be measured after the subject has rested for 
approximately 5 minutes. 
d. On Day 0, study drug administration (moxidectin) will occur after an overnight fast of at least 8 hours. Study drug will be administered with at 
least 240 milliliters of water. No food will be allowed for 2 hours after dosing; however, clear liquids can be taken ad libitum. 
e. Windows apply to pharmacokinetic sampling followed immediately by mite assessment by RCM (as required). At Baseline pharmacokinetic 
sample will be collected within 15 minutes of study drug administration. 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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2 
TABLE OF CONTENTS 
 
1 
PROTOCOL SYNOPSIS ............................................................................................................................. 4 
2 
TABLE OF CONTENTS ............................................................................................................................ 14 
3 
LIST OF ABBREVIATIONS ...................................................................................................................... 18 
4 
STUDY CONTACTS ................................................................................................................................. 20 
5 
INTRODUCTION ....................................................................................................................................... 21 
5.1 
Scabies .............................................................................................................................................. 21 
5.2 
Current Treatment and Unmet Need ................................................................................................. 21 
5.3 
Moxidectin ......................................................................................................................................... 22 
5.3.1 
Nonclinical ................................................................................................................................. 22 
5.3.2 
Clinical ....................................................................................................................................... 24 
5.4 
Rationale ........................................................................................................................................... 31 
5.4.1 
Moxidectin ................................................................................................................................. 31 
5.4.2 
Dose Selection .......................................................................................................................... 31 
5.4.3 
Study Design ............................................................................................................................. 32 
6 
OBJECTIVES AND ENDPOINTS ............................................................................................................. 34 
6.1 
Objectives .......................................................................................................................................... 34 
6.1.1 
Primary Objectives .................................................................................................................... 34 
6.1.2 
Secondary Objective ................................................................................................................. 34 
6.1.3 
Exploratory Objectives ............................................................................................................... 34 
6.2 
Endpoints ........................................................................................................................................... 34 
6.2.1 
Primary Endpoints ..................................................................................................................... 34 
6.2.2 
Secondary Endpoints ................................................................................................................ 34 
6.2.3 
Exploratory Endpoints ............................................................................................................... 34 
7 
STUDY DESIGN ........................................................................................................................................ 36 
7.1 
Study Design ..................................................................................................................................... 36 
7.2 
Dosing Regimens .............................................................................................................................. 36 
7.3 
Study Sites ........................................................................................................................................ 36 
7.4 
Estimated Duration of the Study ........................................................................................................ 36 
8 
SUBJECT POPULATION ......................................................................................................................... 37 
8.1 
Selection of Subjects ......................................................................................................................... 37 
8.2 
Inclusion Criteria ................................................................................................................................ 37 
8.3 
Exclusion Criteria ............................................................................................................................... 37 
8.4 
Other Study Eligibility Criteria Considerations .................................................................................. 38 
8.4.1 
Loa loa Co-Endemicity .............................................................................................................. 38 
8.4.2 
Contraception ............................................................................................................................ 39 
8.4.3 
Rescreening .............................................................................................................................. 39 
8.5 
Special Protocol Issues ..................................................................................................................... 39 
8.5.1 
Treatment of Contacts ............................................................................................................... 39 
9 
SCHEDULE OF ASSESSMENTS AND PROCEDURES ......................................................................... 41 
9.1 
Study Schedule of Evaluations .......................................................................................................... 41 
9.2 
Visit Windows .................................................................................................................................... 41 
9.3 
Study Procedures .............................................................................................................................. 41 
9.3.1 
Screening Visit (Day -7 to Day -1) ............................................................................................. 41 
9.3.2 
Baseline (Day 0) ........................................................................................................................ 42 
9.3.3 
On-study Clinic Visits (Hours 24, 48 and 72, and Days 7, 14 and 28) ...................................... 43 
9.3.4 
Study Conclusion (Week 12) ..................................................................................................... 43 
9.3.5 
Unscheduled Visits .................................................................................................................... 44 
9.3.6 
Early Withdrawal ........................................................................................................................ 44 
9.3.7 
Modification of Scheduled Procedures due to COVID-19 ......................................................... 44 
9.4 
Details of Scheduled Assessments ................................................................................................... 45 
9.4.1 
Demographic Data ..................................................................................................................... 45 
9.4.2 
Medical History .......................................................................................................................... 45 
9.4.3 
Physical Examination ................................................................................................................ 45 
9.4.4 
Vital Signs .................................................................................................................................. 45 


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9.4.5 
Electrocardiograms .................................................................................................................... 46 
9.4.6 
Biological Samples .................................................................................................................... 46 
9.4.7 
Parasitology Assessments of the Scabies Mite......................................................................... 48 
9.4.8 
Clinical Assessments ................................................................................................................. 48 
10 
INVESTIGATIONAL MEDICINAL PRODUCT ...................................................................................... 50 
10.1 
Randomization Process..................................................................................................................... 50 
10.2 
Blinding .............................................................................................................................................. 50 
10.3 
Method of Unblinding......................................................................................................................... 50 
10.3.1 
Medical Emergency ................................................................................................................... 50 
10.3.2 
End of Study .............................................................................................................................. 51 
10.4 
Investigational Products .................................................................................................................... 51 
10.4.1 
Supply ........................................................................................................................................ 51 
10.4.2 
Packaging and Labelling ........................................................................................................... 51 
10.4.3 
Storage and Handling ................................................................................................................ 52 
10.4.4 
Dosage and Administration of Test Drugs ................................................................................. 52 
10.4.5 
Dispensing and Accountability .................................................................................................. 52 
11 
CONCURRENT MEDICATIONS AND TREATMENTS ........................................................................ 53 
11.1 
Special Dietary Requirements ........................................................................................................... 53 
11.2 
Concurrent Medications and Treatments .......................................................................................... 53 
11.2.1 
Prior to Study Entry ................................................................................................................... 53 
11.2.2 
During the Study Dosing Period ................................................................................................ 53 
11.2.3 
Rescue Therapy ........................................................................................................................ 53 
12 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ........................................................................ 54 
12.1 
Safety Parameters ............................................................................................................................. 54 
12.2 
Adverse Events ................................................................................................................................. 54 
12.2.1 
Assessment of Adverse Events ................................................................................................. 54 
12.2.2 
Adverse Event Reporting Period ............................................................................................... 55 
12.3 
Serious Adverse Events .................................................................................................................... 55 
12.3.1 
Serious Adverse Event Definition .............................................................................................. 55 
12.3.2 
Clarification of Serious Adverse Events .................................................................................... 56 
12.3.3 
Serious Adverse Event Reporting Requirements ...................................................................... 56 
12.4 
Follow up of Serious and Non-Serious Adverse Events ................................................................... 57 
12.5 
Additional Considerations for Reporting Adverse Events ................................................................. 57 
12.5.1 
Diagnosis Versus Signs and Symptoms ................................................................................... 57 
12.5.2 
Pre-existing Conditions .............................................................................................................. 57 
12.5.3 
Elective or Pre-Planned Surgeries or Procedures: ................................................................... 57 
12.5.4 
Overdose Reporting .................................................................................................................. 57 
12.5.5 
Clinical Laboratory Abnormalities and Other Abnormal Assessments ...................................... 57 
12.6 
Guidance for Dose Modification or Discontinuation of Treatment ..................................................... 58 
12.7 
Warnings and Precautions ................................................................................................................ 58 
12.8 
Risks for Women of Childbearing Potential or During Pregnancy .................................................... 58 
12.9 
Procedures to be Followed in the Event of Pregnancy ..................................................................... 58 
13 
PROTOCOL STEERING COMMITTEE ................................................................................................ 59 
14 
SUBJECT COMPLETION/WITHDRAWAL .......................................................................................... 60 
14.1 
Subject Completion ........................................................................................................................... 60 
14.2 
Criteria for Premature Withdrawal from Treatment or the Study ....................................................... 60 
14.3 
Withdrawal of Subjects from Study Product ...................................................................................... 60 
14.4 
Withdrawal of Subjects from the Study ............................................................................................. 60 
14.5 
Replacement of Withdrawn Subjects ................................................................................................ 60 
14.6 
Premature Termination of the Study ................................................................................................. 60 
15 
STATISTICAL ANALYSIS .................................................................................................................... 62 
15.1 
Statistical Methods ............................................................................................................................ 62 
15.2 
Hypothesis ......................................................................................................................................... 62 
15.3 
Sample Size Determination ............................................................................................................... 62 
15.4 
Analysis Sets ..................................................................................................................................... 63 
15.4.1 
Full Analysis Set ........................................................................................................................ 63 
15.4.2 
Per Protocol Analysis Set .......................................................................................................... 63 
15.4.3 
Safety Analysis Set .................................................................................................................... 63 


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15.4.4 
Pharmacokinetic Analysis Set ................................................................................................... 63 
15.4.5 
Pharmacokinetic/Pharmacodynamic Analysis Set .................................................................... 63 
15.5 
Analysis Periods and Interim Analysis .............................................................................................. 63 
15.5.1 
Protocol Steering Committee Data Review ............................................................................... 63 
15.5.2 
Final Analysis ............................................................................................................................ 63 
15.6 
Study Endpoints ................................................................................................................................ 64 
15.6.1 
Key Efficacy Endpoints .............................................................................................................. 64 
15.6.2 
Key Pharmacokinetic Endpoints ................................................................................................ 64 
15.6.3 
Exploratory Endpoints ............................................................................................................... 65 
15.6.4 
Safety Endpoints ....................................................................................................................... 65 
15.7 
General Analytic Methods ................................................................................................................. 65 
15.7.1 
Overview .................................................................................................................................... 65 
15.7.2 
Subject Disposition, Demographic and Medical History ............................................................ 65 
15.7.3 
Analysis of Key Efficacy Endpoints ........................................................................................... 65 
15.7.4 
Analysis of Pharmacokinetics .................................................................................................... 66 
15.7.5 
Analysis of Pharmacokinetics/Pharmacodynamics ................................................................... 66 
15.7.6 
Analysis of Safety ...................................................................................................................... 67 
15.7.7 
Other Efficacy Analysis .............................................................................................................. 67 
15.7.8 
Exploratory Analyses ................................................................................................................. 67 
15.7.9 
Handling of Missing Data ........................................................................................................... 67 
16 
GENERAL STUDY ADMINISTRATION ............................................................................................... 68 
16.1 
Ethical Aspects .................................................................................................................................. 68 
16.1.1 
Local Regulations/Declaration of Helsinki ................................................................................. 68 
16.1.2 
Informed Consent ...................................................................................................................... 68 
16.1.3 
Institutional Review Boards or Ethics Committees .................................................................... 68 
16.1.4 
Conditions for Modifying the Protocol ........................................................................................ 68 
16.1.5 
Conditions for Terminating the Study ........................................................................................ 69 
16.2 
Study Documentation, Case Report Forms and Record Keeping .................................................... 69 
16.2.1 
Investigator’s files/Retention of Documents .............................................................................. 69 
16.2.2 
Background Data ....................................................................................................................... 70 
16.2.3 
Audits and Inspections .............................................................................................................. 70 
16.2.4 
Case Report Forms ................................................................................................................... 70 
16.3 
Monitoring the Study .......................................................................................................................... 70 
16.4 
Confidentiality of Trial Documents and Subject Records .................................................................. 71 
16.5 
Publication of Data and Protection of Trade Secrets ........................................................................ 71 
16.6 
Anticipated Subject Accrual and Duration of the Study ..................................................................... 71 
17 
REFERENCES ...................................................................................................................................... 72 
18 
APPENDICES ....................................................................................................................................... 74 
18.1 
Toxicity Grading Scale....................................................................................................................... 74 
18.2 
Model Patient Information Sheet and Consent Form ........................................................................ 78 
18.3 
Summary of Protocol Amendments ................................................................................................... 93 
18.3.1 
Protocol version 2 (incorporating Amendment 1), dated 26 Aug 2019 ..................................... 93 
18.3.2 
Protocol version 3 (incorporating Amendments 1 and 2), dated 19 Jun 2020 .......................... 94 
 
List of Figures 
Figure 1  Map of Estimated Prevalence of Eye Worm History in Africa ............................................................ 39 
 


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List of Tables 
Table 1  Overall Schedule of Assessments ...................................................................................................... 10 
Table 2  Period 1 (Baseline to Day 3) Schedule of Assessments ..................................................................... 12 
Table 3  Number of Subjects per Dose Regimen in Healthy Volunteer Studies ............................................... 25 
Table 4  Number of Treatment-Emergent Adverse Events Reported to Day 22 in Study 1008 ....................... 26 
Table 5  Number of Subjects (%) with Treatment-Emergent Adverse Events in Study 1008 to Week 12 ....... 26 
Table 6  Adverse Reactions Occurring in > 10% of Moxidectin-treated Patients with Onchocerciasis in 
ONCBL60801 (Phase III) .................................................................................................................................. 29 
Table 7  Number (%) of Subjects Reporting Treatment-Emergent Serious Adverse Events (ONCBL60801) . 29 
Table 8  Hematology and Serum Chemistry Tests ........................................................................................... 47 
Table 9  Moxidectin Tablet Components ........................................................................................................... 51 
Table 10  Grading of Adverse Events ............................................................................................................... 54 
Table 11  Assessment of Relationship of Adverse Events to Investigational Medicinal Product ..................... 55 
Table 12  Amendment 1 Administrative Protocol Amendments ........................................................................ 93 
Table 13  Amendment 1 Formal Protocol Amendments ................................................................................... 93 
Table 14  Amendment 2 Administrative Protocol Amendments ........................................................................ 94 
Table 15  Amendment 2 Formal Protocol Amendments ................................................................................... 95 
 


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3 
LIST OF ABBREVIATIONS  
Abbreviation 
Definition 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUC0-last 
AUC from time 0 extrapolated to the last observed 
concentration 
AUC0-inf 
AUC from time 0 extrapolated to infinity 
AUC0-t 
AUC from time 0 extrapolated to time t 
BCRP1/ABCG2 
breast cancer resistance protein 
bpm 
beats per minute 
CL/F 
apparent plasma clearance 
Cmax  
maximum observed plasma concentration 
cm 
centimeter 
CRF 
case report form 
CRO 
contract research organization 
CSR 
clinical study report 
CV 
cardiovascular 
CYP 
cytochrome 
°C 
degrees Celsius  
DALY 
disability-adjusted life year 
dL 
deciliter 
DSMB 
Data Safety Monitoring Board 
ECG 
electrocardiogram 
FAS 
full analysis set 
FDA 
United States Food and Drug Administration  
g 
gram 
GCP 
good clinical practice 
GEE 
generalized estimating equation 
GLMMs 
generalized linear mixed models 
hERG 
human éther-a-go-go 
ICH 
International Conference on Harmonization 
IEC 
Independent ethics committee 
IMP 
investigational medicinal product 
IRB 
Institutional review board 
kg 
kilogram 
L 
liters 
MDGH 
Medicines Development for Global Health 
MED 
minimum effective dose 
mg 
milligram 
mL/h 
milliliters per hour 
mmHg 
millimeters of mercury 
NCA 
non-compartmental analysis 
NTD 
neglected tropical disease 
OED 
optimal effective dose 
PK 
pharmacokinetics 
PD 
pharmacodynamics 
PKAS 
pharmacokinetic analysis set 
PKPDAS 
Pharmacokinetic/Pharmacodynamic Analysis Set 
PPAS 
per protocol analysis set 
RCM 
Vivascope 3000® Reflectance Confocal Microscope 
SAE 
serious adverse event 
SfAS 
safety analysis set 
SAP 
statistical analysis plan 
SD 
standard deviation 


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SOP 
standard operating procedure 
SRM 
study reference manual 
S. scabiei 
Sarcoptes scabiei 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t½  
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time of maximum observed plasma concentration 
µg 
microgram 
Vd 
apparent volume of distribution 
WHO 
World Health Organization 


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4 
STUDY CONTACTS 
Please refer to the Study Reference Manual (SRM) for full study contacts. 
 


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5 
INTRODUCTION 
5.1 
Scabies 
Scabies is a skin disease caused by infestation with the human ectoparasite Sarcoptes scabiei 
variant hominis. Scabies is a common dermatological condition, estimated to affect between 100 and 
300 million people per year and around 200 million people worldwide at any time (GBD 2015 
Disease and Injury Incidence and Prevalence Collaborators 2016). Globally, scabies was responsible 
for 0.21% of all disability-adjusted life years (DALYs) from all conditions studied in the most recent 
Global Burden of Diseases study (Karimkhani, et al. 2017). The highest incidence of the disease 
occurs in tropical climates in socioeconomically disadvantaged populations, the main risk factors for 
infestation being poverty and overcrowding (Romani, et al. 2015b). The World Health Organization 
(WHO) Scientific and Technical Advisory Group, at its meeting in March 2017, included scabies on 
its list of neglected tropical diseases (NTD) (Strategic and Technical Advisory Group for Neglected 
Tropical Diseases 2017). Scabies was considered to meet all the criteria for classification as an NTD 
as it i) disproportionately affects populations living in poverty and causes important morbidity and 
mortality; ii) primarily affects populations living in tropical and sub-tropical areas; iii) is 
immediately amenable to broad control, elimination or eradication, and iv) is relatively neglected by 
research.  
Scabies infestation is contagious, usually spread by direct skin-to-skin contact and occasionally via 
exposure to bed-linen or clothing of an infected person, which occurs more commonly in cases of 
hyperinfestation. Transmission between close contacts and in institutional settings such as nursing 
homes or prisons is common.  
The adult female mite burrows into the top layer of the skin (stratum corneum) where it lays eggs 
that hatch and develop into adults within approximately 2 weeks. The burrow is a pathognomonic 
sign of scabies but may not always be visible. Scabies is characterized by the development of an 
intensely itchy rash caused by an allergic reaction to the presence of mite antigens and feces in the 
skin. In a first infestation symptoms may take 4 to 6 weeks to manifest, but may appear after only a 
few days in second or subsequent infestations. The itch is often reported to be worse at night. The 
rash is papular in nature and typically, although not exclusively, occurs in locations that correspond 
to sites of predilection for infestation such as on the finger webs, wrists, flexures and genitalia. The 
mite burden in typical scabies infestations is thought to be 10 to 15, though hyperinfestation with 
hundreds of mites has been reported (Chosidow 2006, Currie and McCarthy 2014). Crusted scabies, 
the most severe form of the disease, occurs when the susceptible host is infected with millions of 
mites and hyperkeratotic skin crusts form, potentially due to an inability to immunologically control 
the infestation (Davis, et al. 2013).  
A presumptive diagnosis of scabies is be made based on itch characteristics, clinical presentation of 
scabies lesions (including burrows and rash) in sites of predilection and suggestive history such as 
presence of a close contact with scabies or similar itch (Engelman, et al. 2018). A definitive 
diagnosis can be made using non-invasive microscopy (most commonly low-magnification 
dermoscopy) of suspected infestation sites or microscopic examination of skin scrapings to identify 
mites, eggs and/or fecal pellets (Engelman, et al. 2018). Reflectance confocal microscopy (RCM), a 
newer imaging technique using laser scanning to examine the top 300 to 500 µm of skin, can also be 
used to diagnose scabies (Cinotti, et al. 2015, Cinotti, et al. 2016, Micali, et al. 2016).  
5.2 
Current Treatment and Unmet Need 
Treatment either with a topical acaricide or oral treatment with ivermectin is the current standard of 
care for scabies (Rosumeck, et al. 2018). Topical treatments, such as permethrin 5% cream and 


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benzyl benzoate 10 to 25% lotion, are the mainstay of treatment and must be applied to all areas of 
the skin from head to toe and left on overnight before washing off. A second application may be 
necessary within 7 days of the first application if there are signs that the infestation persists, such as 
lesions that persist or new lesions. Although effective when applied in compliance with the 
prescribing information, these treatments have limited patient acceptability and compliance is often 
poor. Oral treatment with ivermectin tablets 200 μg/kg is approved in only a few countries and 
limited to second line treatment in the case of Australia. As ivermectin is not ovicidal, 
administration of a second dose within 7 to 14 days to ensure that mites from hatching eggs are also 
eliminated is recommended. Although current topical and oral treatments are effective when used as 
prescribed, acceptability of topical treatment and the need to treat more than once are barriers to 
optimal disease control. The necessity to treat the close contacts of scabies patients represents 
another barrier to disease control as failure to treat may otherwise contribute to re-infestation of the 
patient. 
The inability to effectively treat scabies contributes to considerable economic burden and health 
disparities in endemic regions (Worth, et al. 2012a, Worth, et al. 2012b). The direct effects of the 
itch that is characteristic of the disease include loss of sleep, school and work absences and 
psychological distress. Scabies infestation has also been associated with numerous serious 
complications, including secondary bacterial skin infestations (impetigo) due to 
Staphylococcus aureus and Streptococcus pyogenes. These skin infestations may result in potentially 
life-threatening Staphylococcus aureus bacteremia or subsequent post-streptococcal sequelae such 
as glomerulonephritis, rheumatic fever or rheumatic heart disease. Recent studies have shown that 
mass drug administration with ivermectin or permethrin, without additional antibacterial therapy, led 
to parallel reductions in both scabies and impetigo prevalence in endemic populations (Marks, et al. 
2018, Romani, et al. 2015c). 
5.3 
Moxidectin 
This section presents a brief summary of the known preclinical and clinical profile of moxidectin. A 
detailed description of the chemistry, pharmacology, efficacy and safety of moxidectin is provided 
in the Investigator’s Brochure. Moxidectin has not been fully characterized in scabies patients and is 
unapproved for scabies in any jurisdiction. Moxidectin 8 mg per oral (single dose) has been 
approved for use in the treatment of onchocerciasis by the United States Food and Drug 
Administration (FDA). 
The current approved prescribing information for use of moxidectin tablets for onchocerciasis is 
available at Drugs@FDA (www.fda.gov/drugsatfda). Additional information is available in the 
Investigator’s Brochure.  
5.3.1 
Nonclinical 
5.3.1.1 Pharmacology 
Glutamate-gated chloride channels present in arthropods and nematodes are the primary biological 
target of moxidectin. Moxidectin also acts on gamma-aminobutyric acid-gated channels.  
The activity of moxidectin against S. scabiei has been evaluated in vitro, in a porcine model of 
human scabies and several other natural S. scabiei infestations in animals such as dogs, cattle, sheep 
and goats. The precise mechanism of action in S. scabiei is not known, though a ligand-gated 
chloride channel capable of activation by ivermectin has been described in S. scabiei, suggesting the 
macrocyclic lactones may exert their efficacy in arachnids in a similar manner to other invertebrates.  


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5.3.1.2 Safety Pharmacology 
The safety pharmacology of moxidectin has been assessed in vitro using the human ether-a-go-go 
(hERG) channel assay and a range of human biological receptors (NovaScreen). In vivo studies were 
conducted in rodent and non-rodent species using the rat for neurofunctional and pulmonary 
assessment and the dog for cardiovascular safety. These studies have shown minor effects on 
neurofunctional and respiratory parameters, and a mild reduction in heart rate in dogs relative to 
controls. For more information, please refer to the Investigator’s Brochure. 
5.3.1.3 Toxicology 
The toxicology profile of moxidectin is characterized by low acute toxicity, consisting mostly of 
transient central nervous system-related clinical signs. Decreased body weight and/or body weight 
gain were also common findings, which were attributed to reduced consumption of food. In single 
and repeat dose toxicity studies with moxidectin, transient central nervous system signs were 
reported in mice, rats and dogs. There was no target organ toxicity in any of the studies based on 
evaluation by gross necropsy, clinical and anatomic pathology. Moxidectin was not genotoxic and 
showed no carcinogenic potential in lifetime mouse and rat bioassays. Moxidectin resulted in 
increased incidence of malformations in rats at maternally toxic doses, but not in rabbits, and 
decreased pup survival during the lactation period in one and three generation pre- and post-natal rat 
studies.  
There are adequate nonclinical safety margins determined in oral acute (single-dose) safety 
pharmacology and chronic (repeat-dose) toxicology studies in relation to the use of moxidectin 
doses in humans up to a maximum of 36 mg. These margins were determined to be greater than one 
for the majority of studies, regardless of whether margins were calculated with dose or exposure 
parameters. Consistent with these safety margins, existing safety data from the clinical trials 
conducted to date do not suggest any dose-limiting toxicities following administration of single oral 
moxidectin doses up to and including 36 mg (Section 5.3.2.2). 
For more information, please refer to the Investigator’s Brochure. 
5.3.1.4 Absorption, Distribution, Metabolism and Excretion 
The pharmacokinetics of moxidectin in rats and dogs were characterized by oral absorption, low 
plasma clearance, and a high volume of distribution, leading to a long terminal elimination half-life 
(t½). The distribution of moxidectin is governed primarily by its high degree of lipophilicity; in rats, 
moxidectin was shown to be distributed to and reside predominantly in fat, including the 
subcutaneous layer which acts as a reservoir for moxidectin. Moxidectin is minimally metabolized 
in vivo. Moxidectin has also been shown to be a weak substrate of breast cancer resistance protein 
(BCRP1/ABCG2). Moxidectin produced weak or no inhibition of seven major human cytochrome 
(CYP) P450 enzymes in vitro but did induce CYP3A4 mRNA and activity in vitro. However, a 
subsequent clinical study showed that moxidectin was not a CYP3A4 inducer in vivo 
(Section 5.3.2.1). 
In rat studies, moxidectin is likely cleared by a combination of biliary excretion of unchanged drug 
and oxidative metabolism. For more information, please refer to the Investigator’s Brochure. 


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5.3.2 
Clinical 
The moxidectin clinical program encompasses eight completed single oral dose trials spanning 
Phases I to III and involving a total of 1904 subjects.  
In six completed Phase I studies, 244 healthy volunteers received moxidectin at doses of 3 to 36 mg 
and 16 healthy volunteers received placebo. The studies were: 
• A single-ascending dose, placebo-controlled, double-masked, safety, tolerability, and 
pharmacokinetic study of orally administered moxidectin in normal volunteers 
(3110A1-100-EU). 
• A study of the relative bioavailability of a tablet and a liquid formulation of moxidectin in 
healthy subjects (3110A1-101-EU). 
• An open-label, single-dose study to evaluate the excretion of moxidectin into the breast milk 
of lactating, non-breastfeeding women (3110A1-1002-EU). 
• An open-label, single-dose, 4-period, sequential study to determine the effect of moxidectin 
on CYP3A4 activity in healthy subjects using midazolam as a probe substrate 
(3110A1-1004-EU). 
• An open-label, randomized, single-dose, parallel-group study to determine the effect of a 
high-fat meal on the relative bioavailability and pharmacokinetics of a single dose of 
moxidectin administered orally to healthy subjects (3110A1-1005-EU). 
• A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the 
potential effect of a single oral dose of moxidectin on the cardiac QT interval of healthy 
volunteers (MDGH-MOX-1008). 
In one Phase II and one Phase III study enrolling subjects with onchocerciasis, 1105 subjects 
received moxidectin at doses of 2 mg to 8 mg while 539 received ivermectin at the standard-of-care 
dose of 150 μg/kg. The studies were:  
• A randomized, single-ascending-dose, ivermectin-controlled, double-blind, safety, 
tolerability, pharmacokinetic, and efficacy study of orally administered moxidectin in 
subjects with Onchocerca volvulus infection (3110A1-200-GH; Phase II) 
• A single dose, ivermectin-controlled, double blind, efficacy, safety, and tolerability study of 
orally administered moxidectin in subjects infected with Onchocerca volvulus 
(ONCBL60801; Phase III) 
The safety and efficacy of moxidectin has not been evaluated in patients with S. scabiei infestation. 
5.3.2.1 Clinical Pharmacology 
Moxidectin displays linear, dose-proportional pharmacokinetics. Following a single oral moxidectin 
dose (ranging from 3 mg to 36 mg, tablet or solution) administered to fasting healthy volunteers, the 
non-compartmentally-derived apparent moxidectin plasma clearance (CL/F) ranged from 1785 to 
3506 mL/h and the mean t½ ranged from 485 to 1139 hours (approximately 20 to 47 days). 
Moxidectin was rapidly absorbed; the median time of maximum observed plasma concentration 
(tmax) in a fasted state was 3 to 4 hours post-dose. Moxidectin has a large apparent volume of 
distribution, and rapid decline of moxidectin concentrations occurred within 48 hours of dose 
administration in all studies, and, thereafter, plasma concentrations declined slowly in accordance 
with the long t½. Population pharmacokinetic analyses showed that the long t½ was governed by 
tissue distribution rate-limited elimination. 


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There was no clinically relevant effects of age, gender, race, weight, renal function or hepatic 
function on the pharmacokinetics of moxidectin from a population-pharmacokinetic model. 
Moxidectin absorption is resilient to the effects of food. Administration of moxidectin in a fed state 
modestly slows absorption and increases bioavailability, although not to a clinically relevant extent. 
Moxidectin does not induce or inhibit clinically relevant drug-drug interactions and it is unlikely to 
be a victim of drug-drug interactions via concomitant medications. 
Moxidectin is minimally metabolized and primarily excreted unchanged in the feces. Renal 
clearance of moxidectin and its metabolites is low. Moxidectin was observed in the breast milk of 
lactating women after single dose administration at a relative infant dose of less than 10% of the 
maternal dose. 
5.3.2.2 Clinical Safety and Efficacy 
5.3.2.2.1 
Overview of Safety in Healthy Volunteers 
Safety data are available from 6 studies in healthy adult volunteers. Moxidectin was well tolerated 
when given as a single dose of between 3 and 36 mg to healthy volunteers (Table 3). There was no 
treatment or dose related relationship in the incidence, nature and severity of adverse events (AEs) 
identified. There were no clinically relevant or treatment-related changes in laboratory parameters, 
physical examination findings, vital signs or electrocardiograms (ECGs)/cardiac function. In 
placebo-controlled studies, moxidectin had a safety profile similar to placebo. No subject withdrew 
due to an AE and there were no serious adverse events (SAEs) or deaths. 
Table 3  Number of Subjects per Dose Regimen in Healthy Volunteer Studies 
Regimen 
Fed/Fasted 
Formulation 
Study 
Total 
100 
101  
1002  
1004a 
1005  
1008 
Placebo 
Not applicable 
Not applicable 
6 
 
 
 
 
10 
16 
3 mg 
Fasted 
Liquid 
5 
 
 
 
 
 
5 
4 mg 
Fasted 
Tablet 
 
 
 
 
 
10 
10 
8 mg 
Fasted 
Tablet 
 
 
 
 
27 
10 
37 
8 mg 
Fed 
Tablet 
 
 
12 
38 
27 
 
77 
9 mg 
Fasted 
Liquid 
5 
 
 
 
 
 
5 
9 mg 
Fed 
Liquid 
6 
 
 
 
 
 
6 
10 mg 
Fasted 
Liquid 
 
29 
 
 
 
 
29 
10 mg 
Fasted 
Tablet 
 
29 
 
 
 
 
29 
16 mg 
Fasted 
Tablet 
 
 
 
 
 
10 
10 
18 mg 
Fasted 
Liquid 
5 
 
 
 
 
 
5 
24 mg 
Fasted 
Tablet 
 
 
 
 
 
10 
10 
36 mg 
Fasted 
Liquid 
5 
 
 
 
 
 
5 
36 mg 
Fasted 
Tablet 
 
 
 
 
 
10 
10 
36 mg 
Fed 
Liquid 
5 
 
 
 
 
 
5 
Total 
37 
58 
12 
38 
54 
60 
259 
Abbreviations: 100: Study 3110A1-100-EU, 101: Study 3110A1-101-EU, 1002: Study 3110A1-1002-EU, 
1004: Study 3110A1-1004-EU, 1005: Study 3110A1-1005-EU, 1008: Study MDGH-MOX-1008 
a One subject was enrolled and dosed with midazolam alone prior to withdrawal from the study and is not 
included. 
One hundred and fourteen (114) healthy volunteers have been administered single moxidectin doses 
in excess of the dose approved for the treatment of onchocerciasis (an 8 mg single dose). Of these, 
20 subjects have received a single dose of 36 mg moxidectin in two clinical studies, 
Study 3110A1-100-EU and Study MDGH-MOX-1008. In both studies, which were placebo-
controlled, moxidectin had a similar safety profile to placebo. There was no dose-response 


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relationship identified between the dose of moxidectin administered and frequency and nature of 
AEs, no dose-limiting toxicities and no SAEs or deaths in either study. 
MDGH-MOX-1008 was a randomized, placebo-controlled, double-blind, parallel-group study 
designed to evaluate the potential impact of moxidectin on the QT interval in healthy adult 
volunteers. Moxidectin was administered at doses between 4 and 36 mg as tablets under fasted 
conditions. The primary safety evaluation period was Day 1 to Day 22 but subjects received follow-
up evaluations at Weeks 8 and 12 due to the long half-life of moxidectin. Safety laboratory analyses 
were undertaken and AEs were reported throughout. An overview of treatment-emergent AEs 
reported during the primary safety period to Day 22 is provided in Table 4. 
Table 4  Number of Treatment-Emergent Adverse Events Reported to Day 22 in Study 1008 
Regimen  
(Number 
enrolled) 
Treatment Emergent Adverse Events 
(Number of Subjects) 
All AE 
Related AE 
Severe AE 
Withdrawn  
due to AE 
SAE 
Placebo (n=10) 
2 (1) 
2 
0 
0 
0 
4 mg (n=10) 
3 (3) 
1 
0 
0 
0 
8 mg (n=10) 
3 (3) 
2 
0 
0 
0 
16 mg (n=10) 
1 (1) 
0 
0 
0 
0 
24 mg (n=10) 
0 
0 
0 
0 
0 
36 mg (n=10) 
3 (2) 
0 
0 
0 
0 
Total (n=60) 
12 (10) 
5 
0 
0 
0 
A further two treatment-emergent AEs were reported to Week 12. Neither AE was considered by the 
Investigator to be related to treatment. Table 5 summarizes AEs reported by all subjects to Week 12. 
Each AE was reported by no more than one subject at any dose level. There was no dose-response 
relationship identified across the dose groups and moxidectin had a similar safety profile to placebo. 
Table 5  Number of Subjects (%) with Treatment-Emergent Adverse Events in Study 1008 to Week 12 
Preferred Term 
Treatment 
Total 
 
n=60 
MOX 
(4 mg) 
n=10 
MOX 
(8 mg) 
n=10 
MOX 
(16 mg) 
n=10 
MOX 
(24 mg) 
n=10 
MOX 
(36 mg) 
n=10 
Placebo 
 
n=10 
Eye irritation 
0 
1 (10.0) 
0 
0 
0 
0 
1 (1.7) 
Abdominal 
discomfort 
0 
0 
0 
0 
0 
1 (10.0) 
1 (1.7) 
Diarrhea 
1 (10.0) 
0 
0 
0 
0 
0 
1 (1.7) 
Medical device site 
reaction 
1 (10.0) 
0 
0 
0 
0 
0 
1 (1.7) 
Aspartate 
aminotransferase 
increased 
0 
0 
1 (10.0) 
0 
0 
0 
1 (1.7) 
Elevated total 
bilirubin 
0 
0 
0 
0 
1 (10.0) 
0 
1 (1.7) 
Blood cholesterol 
increased 
1 (10.0) 
0 
0 
0 
0 
0 
1 (1.7) 
Neck pain 
0 
0 
0 
0 
1 (10.0) 
0 
1 (1.7) 
Arthralgia (hip pain) 
1 (10.0) 
0 
0 
0 
0 
0 
1 (1.7) 
Pain in extremity 
0 
0 
0 
0 
1 (10.0) 
0 
1 (1.7) 
Dizziness 
0 
0 
0 
0 
0 
1 (10.0) 
1 (1.7) 
Headache 
0 
1 (10.0) 
0 
0 
0 
0 
1 (1.7) 


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Preferred Term 
Treatment 
Total 
 
n=60 
MOX 
(4 mg) 
n=10 
MOX 
(8 mg) 
n=10 
MOX 
(16 mg) 
n=10 
MOX 
(24 mg) 
n=10 
MOX 
(36 mg) 
n=10 
Placebo 
 
n=10 
Nasal congestion 
0 
1 (10.0) 
0 
0 
0 
0 
1 (1.7) 
Oropharyngeal pain 
0 
0 
0 
0 
1 (10.0) 
0 
1 (1.7) 
TOTAL 
4 (40.0) 
3 (30.0) 
1 (10.0) 
0 
4 (40.0) 
2 (20.0) 
14 (26.7) 
All AEs were considered Grade 1 (mild) in severity except for arthralgia (Grade 2, moderate) which 
occurred in Subject 1037 (moxidectin 4 mg) in the period between Day 22 and Week 12. All AEs 
were transient. The Investigator considered the following AEs to be at least possibly related to study 
drug: abdominal discomfort (Subject 1038, placebo), diarrhea (Subject 1037, moxidectin 4 mg), 
dizziness (Subject 1038, placebo), headache (Subject 1053, moxidectin 8 mg), and nasal congestion 
(Subject 1031, moxidectin 8 mg). 
There were no patterns of clinically relevant changes in any clinical laboratory values, vital signs, or 
physical examination findings in any group. Single events of raised AST and total bilirubin were 
reported in Subject 1041 (moxidectin 16 mg) at Day 22 and Subject 1047 (moxidectin 36 mg) at 
Week 12, respectively. Neither event was considered to be related to study drug by the Investigator. 
Moxidectin had no statistically or clinically significant effect on QT interval at any dose level, 
including the maximum 36 mg dose. There were also no clinically significant effects of moxidectin 
at any dose on HR, PR and QRS intervals or abnormal diagnostic statements. 
3110A1-100-EU was a single-ascending dose, placebo controlled, double blind, safety, tolerability, 
and pharmacokinetic study of single oral doses between 3 and 36 mg. Moxidectin was administered 
as an oral solution under fed and fasted conditions.  
Like MDGH-MOX-1008, there was no trend for an increase in the incidence or type of AEs, or 
clinically relevant laboratory abnormalities with increasing dose of moxidectin. There were no 
Grade 4 AEs or laboratory abnormalities and only one Grade 3 AE (enteritis, verbatim “food 
poisoning”) experienced by Subject 501 in the 36 mg moxidectin fasted group. The event occurred 
57 days after administration of test article and resolved the following day. It was considered by the 
Investigator to be unrelated to treatment. 
Modestly increased exposure to moxidectin has been observed in liquid presentations compared with 
tablets and when moxidectin is given with food. Moxidectin administered in the tablet form under a 
fasted state, as proposed in MDGH-MOX-2001, should ensure that exposure is less than or equal to 
existing clinical experience, which includes administration of 36 mg following a high-fat meal as a 
liquid solution. 
Adverse event and laboratory findings reported for each of the completed Phase I studies are further 
summarized in the Investigator’s Brochure. 
5.3.2.2.2 
Overview of Safety in Patients with Onchocerciasis 
The safety of moxidectin has been evaluated in patients with onchocerciasis. Signs and symptoms 
associated with microfilarial death, sometimes referred to as the “Mazzotti reaction” were 
commonly observed. These reactions are caused by an immunologically-mediated reaction to the 
death of microfilariae and manifest as pruritus, headache, pyrexia, rash, urticaria, hypotension 
(including symptomatic orthostatic hypotension and dizziness), tachycardia, edema, 
lymphadenopathy, arthralgia, myalgia, chills, paresthesia and asthenia. Ophthalmological 
manifestations include conjunctivitis, eye pain, eye pruritus, eyelid swelling, blurred vision, 


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photophobia, changes in visual acuity, hyperemia, ocular discomfort and watery eyes. These adverse 
reactions generally occur and resolve in the first week post-treatment. 
In the two studies conducted in onchocerciasis patients (3110A1-200-GH and ONCBL60801), the 
profile of AEs reported for moxidectin was similar to the profile in ivermectin recipients. In these 
studies, the most commonly occurring events were pruritus, edema, headache, hypotension and 
compensatory tachycardia, rash and urticaria, myalgia, arthralgia, pyrexia and chills, 
lymphadenopathy, paresthesia and asthenia (Table 6). These events were transient and self-limiting, 
generally occurring and resolving within the first week of treatment. In general, there was a transient 
(first 48 hours) increase in the number of moxidectin subjects reporting efficacy-associated AEs 
compared to ivermectin. There was not an increased need for medical or therapeutic intervention for 
management of efficacy-related events with moxidectin when compared to ivermectin. Given that 
the spectrum of symptoms and severity were similar, the guidance to patients and physicians are 
otherwise unchanged compared to ivermectin for onchocerciasis patients. 


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Table 6  Adverse Reactions Occurring in > 10% of Moxidectin-treated Patients with Onchocerciasis in 
ONCBL60801 (Phase III) 
Adverse Reaction 
Moxidectin 
N = 978 
n (%) 
Ivermectin 
N = 494 
n (%) 
Eosinophilia 
721 (74) 
390 (79) 
Pruritus 
640 (65) 
268 (54) 
Musculoskeletal pain a 
623 (64) 
257 (52) 
Headache 
566 (58) 
267 (54) 
Lymphocytopenia* 
470 (48) 
215 (44) 
Tachycardia b 
382 (39) 
148(30) 
  Orthostatic tachycardia c 
333 (34) 
130 (26) 
  Non-orthostatic tachycardia d 
179 (18) 
57 (12) 
Rash e 
358 (37) 
103 (21) 
Abdominal pain f 
305 (31) 
173 (35) 
Hypotension g 
289 (30) 
125 (25) 
  Orthostatic hypotension h 
212 (22) 
81 (16) 
Pyrexia/Chills 
268 (27) 
88 (18) 
Leukocytosis 
240 (25) 
125 (25) 
Influenza like illness 
226 (23) 
102 (21) 
Neutropenia** 
197 (20) 
112 (23) 
Cough 
168 (17) 
88 (18) 
Lymph node pain 
129 (13) 
28 (6) 
Dizziness 
121 (12) 
44 (9) 
Diarrhea/Gastroenteritis/Enteritis 
144 (15) 
84 (17) 
Hyponatremia 
112 (12) 
65 (13) 
Peripheral swelling 
107 (11) 
30 (6) 
a Includes “myalgia”, “arthralgia”, “musculoskeletal pain”, “pain” and “back pain” 
b Includes “orthostatic heart rate increased”, “postural orthostatic tachycardia syndrome”, “heart rate 
increased” and “sinus tachycardia” 
c Includes “orthostatic heart rate increased” and “postural orthostatic tachycardia syndrome” 
d Includes “heart rate increased”, “tachycardia”, and “sinus tachycardia” 
e Includes “rash,” “papular rash” and “urticaria” 
f Includes “abdominal pain”, “abdominal pain upper” and “abdominal pain lower” 
g Includes “orthostatic hypotension”, “blood pressure orthostatic decreased”, “blood pressure decreased”, 
“mean arterial pressure decreased”, “hypotension” 
h Includes “orthostatic hypotension”, and “blood pressure orthostatic decreased” 
*Lymphocytopenia is defined as absolute lymphocyte count less than 1 x 109/L 
**Neutropenia is defined as absolute neutrophil count less than 1 x 109/L 
There was no pattern indicating a temporal association with treatment or with body system of SAEs 
occurring in either the 3110A1-200-GH or the ONCBL60801 studies. In both studies, there were no 
SAEs regarded by the investigator (or Sponsor) as being treatment-related. Treatment-emergent 
SAEs (occurring during the first 180 days post-dose) are shown in Table 7. 
Table 7  Number (%) of Subjects Reporting Treatment-Emergent Serious Adverse Events 
(ONCBL60801) 
Preferred Term 
Moxidectin 
n=978  
n (%) 
Ivermectin 
n=494  
n (%) 
No. subjects with ≥ 1 treatment emergent serious 
adverse event 
39 (4.0) 
18 (3.6)* 
No. of treatment emergent serious adverse events 
52 
25 
Malaria 
15 (1.5) 
9 (1.8) 
Gastroenteritis 
2 (0.2) 
0 


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Preferred Term 
Moxidectin 
n=978  
n (%) 
Ivermectin 
n=494  
n (%) 
Respiratory tract infection 
0 
2 (0.4) 
Diarrhea 
1 (0.1) 
3 (0.6) 
Loss of consciousness 
2 (0.2) 
0 
Enteritis 
2 (0.2) 
0 
Gastritis 
2 (0.2) 
1 (0.2) 
Abdominal abscess 
0 
1 (0.2) 
Abscess limb 
1 (0.1) 
0 
Cellulitis 
1 (0.1) 
0 
Fungal skin infection 
1 (0.1) 
0 
Peritonitis 
1 (0.1) 
0 
Pneumonia 
1 (0.1) 
1 (0.2) 
Sepsis 
0 
1 (0.2) 
Shigella infection 
1 (0.1) 
0 
Abdominal pain 
1 (0.1) 
0 
Abdominal pain lower 
1 (0.1) 
0 
Abdominal pain upper 
0 
1 (0.2) 
Hematemesis 
1 (0.1) 
0 
Alcohol poisoning 
1 (0.1) 
0 
Clavicle fracture 
1 (0.1) 
0 
Contusion 
0 
1 (0.2) 
Head injury 
1 (0.1) 
0 
Limb injury 
1 (0.1) 
0 
Snake bite 
1 (0.1) 
0 
Splenic rupture 
1 (0.1) 
0 
Diabetic ketoacidotic hyperglycemic coma 
0 
1 (0.2) 
Hemiplegia 
1 (0.1) 
0 
Meningism 
0 
1 (0.2) 
Cardiac arrest 
1 (0.1) 
0 
Cardiac failure congestive 
1 (0.1) 
0 
Chills 
0 
1 (0.2) 
Influenza like illness 
0 
1 (0.2) 
Asthma 
1 (0.1) 
0 
Cough 
0 
1 (0.2) 
Macular hole 
1 (0.1) 
0 
Hepatitis chronic active 
1 (0.1) 
0 
Dehydration 
1 (0.1) 
0 
Rheumatic disorder 
1 (0.1) 
0 
Dysmenorrhea 
1 (0.1) 
0 
Skin ulcer 
1 (0.1) 
0 
* This includes a pre-treatment hospitalization for respiratory tract infection included as a result of missing 
date information  
5.3.2.2.3 
Safety and Efficacy in Scabies 
This is the first study of moxidectin in patients with S. scabiei infestation. 


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5.4 
Rationale  
This study aims to provide proof of concept that a single dose of moxidectin is effective in treating 
the scabies parasite in humans and to enable the determination of an optimal dose of moxidectin for 
treatment of scabies for further investigation. This study also aims to assess the safety of orally 
administered single moxidectin doses in adults with scabies.  
5.4.1 
Moxidectin 
Poor adherence to topical and oral regimens prescribed for the treatment of scabies are a significant 
barrier to optimal treatment outcomes. Topical treatments, applied head to toe by the infected person 
and to all their close contacts, are generally effective. However, successful treatment is limited by 
poor compliance and low patient acceptability due to limited ease of use and side effects (e.g. 
irritation, eczematisation). Ivermectin (200 µg/kg per oral) is the only oral treatment currently 
available with two doses (separated by one to two weeks) the accepted regimen. Two doses are 
required to avoid recurrence of infestation as ivermectin not ovicidal and its relatively short plasma 
half-life of approximately 18 hours is insufficient to clear any mites that hatch subsequent to 
treatment.  
Moxidectin is well-established in veterinary practice for the treatment of S. scabiei infestation in 
companion animals such as dogs, and livestock such as cattle, sheep and goats (Fourie, et al. 2006, 
Fthenakis, et al. 2000, Giadinis, et al. 2011, Losson and Lonneux 1993). Moxidectin also has the 
potential advantage of longer exposures that may abrogate the need for a second dose and enable a 
once only, oral dosing paradigm in humans. Comparison of moxidectin and ivermectin 
pharmacokinetics in the porcine scabies model indicates that moxidectin has enhanced persistence in 
blood and skin compared to ivermectin, providing exposures that may cover the entire mite life-
cycle (Bernigaud, et al. 2016). 
5.4.2 
Dose Selection 
The minimal and optimal effective doses (MED and OED) of moxidectin to treat human scabies are 
not known. Previous clinical studies have examined the safety of single moxidectin doses up to 
36 mg, which were well-tolerated in healthy volunteers (Section 5.3.2.2.1). Taking the available 
clinical data into account as well as existing moxidectin exposure margins, model-based estimations 
of human moxidectin pharmacokinetic and pharmacokinetic data from the porcine scabies model, 
the range of doses to potentially be evaluated in the current trial will include single oral doses of 
moxidectin up to a maximum of 36 mg. A single oral dose was selected as the long terminal half-life 
(t1/2) of moxidectin is expected to provide adequate exposure coverage for the entire life cycle of the 
scabies mite and eliminate hatching mites. 
The lowest dose (2 mg per oral) was chosen as this dose was shown to be effective at eliminating 
microfilariae in onchocerciasis patients. The efficacy of the 2 mg moxidectin dose in onchocerciasis 
provides evidence of its activity in the skin, a target organ of both onchocerciasis microfilariae and 
scabies mites. Twenty mg per oral was initially selected as the upper dose for this study as it is 
similar on a weight for weight basis to the dose shown to be effective against S. scabiei in the 
porcine model of scabies. In this model, scabies-infected pigs were administered 300 µg/kg 
moxidectin per oral, equivalent to a 21 mg dose in a 70 kg human. Although the 20 mg dose may be 
effective in humans, to robustly determine the OED, additional doses up to a maximum of 36 mg 
may need to be evaluated. As described in Section 5.3.2.2.1, 36 mg was well tolerated in previous 
clinical studies and is within the established clinical and nonclinical safety margins for moxidectin. 


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5.4.3 
Study Design 
This study is a multicenter, randomized, double-blind, parallel group, 
pharmacokinetic/pharmacodynamic dose finding study of single oral doses of moxidectin in adults 
with scabies. 
In previous clinical studies, there was no evidence of clinically relevant safety findings after 
administration of moxidectin at single oral dosages of up to 36 mg to healthy adult subjects. The 
safety of moxidectin in adults with scabies has not previously been evaluated. However, as the 
adverse reactions seen in onchocerciasis patients are due to host immune responses to dying 
O. volvulus microfilariae it is anticipated that the safety profile of moxidectin in scabies patient will 
be similar to that seen in healthy volunteer studies. Therefore, a parallel design has been selected as 
the doses proposed for evaluation in this study will not exceed the doses previously studied. No 
subject will receive more than a single oral dose of moxidectin. Only adult subjects will participate 
in this study as there are limited data on the pediatric use of moxidectin, which has only been 
administered to adolescents 12 years and older. 
In this protocol, scabies infestation is defined as a minimum of two lesions, each lesion containing at 
least one live adult S. scabiei mite distinguishable by a trained operator using a Vivascope® 3000 
RCM. RCM is a non-invasive imaging technique that enables visualization of the upper 300 µm of 
the skin (from upper epidermis to superficial dermis) using a laser light source. Although RCM is in 
widespread use for the diagnosis of skin malignancies such as melanoma, its clinical applications 
also extend to infectious diseases of the skin such as scabies (Cinotti, et al. 2015). RCM has been 
selected over more conventional techniques such as skin scraping or dermoscopy as it permits 
repeated and detailed visualization of the scabies mite. Unlike dermoscopy, adult and juvenile mites, 
eggs and scybala can be distinguished by RCM (Cinotti, et al. 2016). RCM can be used to assess the 
impact of treatment as it permits differentiation of live and dead mites on the basis of parasite 
morphology and movement. Treatment of scabies patients using permethrin 5% cream resulted in 
loss of anatomical structures, peristalsis function and movement of the mite within the burrow 
(D. Tilakaratne, unpublished). Further, unlike skin scraping, which results in the physical removal of 
mites from the affected individual, RCM permits repeat in vivo visualization of the impact of 
treatment on the scabies mite. 
Time-matched, repeat RCM assessments examining mite viability and measurement of moxidectin 
plasma concentrations will be used to describe the moxidectin exposure-response in scabies-infected 
patients. The pharmacokinetic and RCM sampling schedule has been designed to minimize the in-
stay period for each patient by taking into account existing moxidectin pharmacokinetic data and 
population-pharmacokinetic model, which will enable robust estimations of individual exposure 
estimations. Increased moxidectin exposure has been observed when moxidectin is given with food, 
so subjects will be administered moxidectin fasting to minimize variability of moxidectin 
pharmacokinetics. Dose cohorts of approximately 3 to 6 subjects will receive moxidectin doses of 2, 
8, or 20 mg. A dose of 36 mg may be added, depending on the pharmacodynamic response observed 
in the study. The target sample size of the additional dose cohort will be approximately 6 subjects. 
As pharmacokinetic and pharmacodynamic data will be pooled across the dose cohorts, this design 
will result in a broad range of individual subject pharmacokinetic exposure profiles. This is 
considered an adequate range to allow examination of pharmacokinetic/pharmacodynamic 
relationships and determine the therapeutic exposure required to effectively treat scabies infestation.  
Dose cohorts of approximately 6 subjects were also considered to be practical for recruitment of the 
study. Multiple centers are planned as the prevalence of scabies in countries such as Australia and 
France is generally considered to be low (approximately 1%) with higher prevalence observed in 


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socio-economically disadvantaged or vulnerable populations such as Australian Aboriginal and 
Torres Strait Islander people (La Vincente, et al. 2009) or refugees and the homeless in 
Europe (Arnaud, et al. 2016, Beeres, et al. 2018). Scabies is also a disease that occurs less frequently 
in adults than in children (Kearns, et al. 2013, Romani, et al. 2015a). The additional assessments 
required in this protocol (including RCM) are also likely to preclude recruitment of sufficient 
subjects in a single reference hospital.  
Moxidectin efficacy will be determined through a series of RCM assessments conducted over 28 
days with a further safety assessment at 12 weeks due to moxidectin’s long t1/2. This first 28-day 
period will also allow for exploratory assessment of clinical signs and symptoms following 
resolution of infestation. Scabies symptoms result from a sensitization of the host to mite antigens 
and are known to persist for several days or weeks after treatment. Twenty-eight days is considered 
a minimum period for the resolution of all symptoms after the infestation has been cleared, and is 
consistent with other studies in scabies and FDA guidance for the development of permethrin 5% 
formulations for the treatment of scabies (United States Food and Drug Administration 2017). 
Comprehensive clinical assessments will be conducted as variation in diagnostic criteria, 
examination techniques and clinical experience has limited the development of consensus criteria for 
the assessment of treatment response in scabies to date. 
 


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6 
OBJECTIVES AND ENDPOINTS 
6.1 
Objectives  
6.1.1 
Primary Objectives  
The primary objectives of the study are to: 
• Identify an optimal dose of moxidectin for the treatment of scabies. 
• Evaluate the safety of moxidectin in adults infected with scabies. 
6.1.2 
Secondary Objective 
The secondary objective of the study is to characterize the plasma pharmacokinetic of moxidectin in 
adults infected with scabies. 
6.1.3 
Exploratory Objectives 
The exploratory objectives of the study are to: 
• Describe the impact of moxidectin on S. scabiei, including impact on morphology, motility 
and life cycle stages. 
• Evaluate clinician and patient reported outcomes of treatment with moxidectin. 
6.2 
Endpoints  
6.2.1 
Primary Endpoints 
The primary endpoints of the study are: 
• Efficacy will be determined by death of the mites, defined as the degradation (loss of internal 
and/or external anatomic structures) of the adult mite observed by RCM. Mites will be 
assessed at Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28 in not less than two lesions 
nominated pre-treatment.  
• Safety will be assessed by the incidence and severity of AEs, physical examinations, and 
measurement of vital signs up to and including Week 12, and laboratory safety parameters 
up to and including Day 28. 
6.2.2 
Secondary Endpoints 
Key exposure metrics for moxidectin including area under the concentration time curve (AUC) and 
maximum plasma concentration (Cmax), will be determined by non-compartmental analysis of 
moxidectin pharmacokinetic parameters or other methods as appropriate, assessed up to and 
including Day 28. 
6.2.3 
Exploratory Endpoints 
The exploratory endpoints of the study are: 
• At Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28, using assessment by RCM of burrows 
selected pre-treatment: 
o Changes in adult mite motility (peristalsis and/or movement) over at least 30 seconds 
of observation. 
o Presence, number, morphology and motility of juvenile scabies mites. 
o Presence of eggs and scybala in burrows  
• Presence and total number of mites and burrows assessed visually at Days 7, 14 and 28. 


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• Changes in assessment of clinician-reported scabies symptomology, including extent of 
symptoms on body regions assessed by the number of anatomically-defined regions affected, 
number of lesions and severity grading of excoriations and erythema. 
• Changes in patient reported outcomes, measured by Numerical Rating Scale, 5-D Itch Scale 
and Dermatology Life Quality Index. 


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7 
STUDY DESIGN 
7.1 
Study Design 
This is a randomized, double-blind, multicenter, parallel group, dose finding study of a single oral 
dose of moxidectin in adults with scabies.  
7.2 
Dosing Regimens 
Initially, subjects will be randomized with a target allocation ratio of 1:1:1 to one of the following 
single dose treatment regimens: 
• Moxidectin 2 mg  
• Moxidectin 8 mg  
• Moxidectin 20 mg  
Once approximately three subjects have been recruited to these three dose cohorts and completed 
their Day 14 visit, a Protocol Steering Committee (see Section 13) will evaluate the unblinded safety 
and efficacy data and recommend: 
• Continuation of the study with no dose modification to the target sample size of 6 subjects 
per cohort; or, 
• Stopping recruitment of one of more of the current dose cohorts; and/or, 
• The addition of a 36 mg single dose cohort. 
Once the Committee has made their recommendation, randomization will continue into the same or 
revised dosing regimens with a final target sample size of 6 subjects per cohort. It is anticipated that 
a maximum of 36 subjects will be included in the study. 
7.3 
Study Sites 
This is a multicenter study. 
7.4 
Estimated Duration of the Study 
The study is expected to take approximately 18 months to complete. The on-study period per subject 
is 13 weeks, consisting of one week for Screening and 12 weeks post-treatment.  


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8 
SUBJECT POPULATION 
8.1 
Selection of Subjects 
The nature of the study and the potential risks will be explained to all candidates. Written informed 
consent will be obtained from each subject prior to performing Screening procedures. 
Subjects who meet all of the inclusion and none of the exclusion criteria described in Sections 8.2 
and 8.3 will be eligible for randomization. Once randomized, subjects will be considered enrolled 
and will receive treatment with moxidectin. Once randomized, subjects will not be permitted to be 
re-randomized or given a second course of treatment. 
Inclusion and exclusion criteria are to be assessed at the Screening assessment, unless otherwise 
indicated.  
8.2 
Inclusion Criteria 
A subject must meet all of the following inclusion criteria: 
1. Aged ≥ 18 years. 
2. Provision of written informed consent.  
3. 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 RCM. 
4. Agree to the use of reliable contraceptive measures if female or male partner of a female of 
child-bearing potential from Screening until 6 months after treatment with study drug 
(Section 8.4.2).  
8.3 
Exclusion Criteria 
A subject will be excluded from the study if they meet any of the following criteria: 
1. History of chronic or recurring dermatologic disease (other than scabies) that could interfere 
with the diagnosis and/or subsequent clinical assessment of scabies. 
2. 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). 
3. 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.  
4. 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. 
5. Poor venous access. 
6. Received an investigational agent within 28 days of Screening (or 5 half-lives of the 
investigational agent, whichever is longer). 
7. Body Mass Index over 35 kg/m2. 
8. Clinically relevant abnormal findings in vital signs, 12-lead ECG, or physical examination at 
Screening and/or Baseline in the opinion of the Investigator. 
9. Clinically relevant laboratory abnormalities at Screening, including: 
a. alanine aminotransferase or aspartate aminotransferase > 2.5 x upper limit of 
reference range; 
b. creatinine > 2.0 milligrams per deciliter (mg/dL); 
c. hemoglobin < 9.5 g/dL (female) or <10.5 g/dL (male); 


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d. amylase > 2.0 x upper limit of reference range. 
10. Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the 
formulation of moxidectin. 
11. Use of systemic steroids within 14 days of Screening, 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.  
12. Subjects with known or suspected Loa loa coinfection. 
13. Difficulty swallowing tablets. 
14. Pregnant or breastfeeding, or planning to become pregnant. 
15. Known or suspected alcohol or illicit substance abuse. 
16. Unwilling, unlikely or unable to comply with all protocol specified assessments. 
17. Previous enrolment and treatment with moxidectin in this study. 
8.4 
Other Study Eligibility Criteria Considerations 
In order to assess any potential impact on subject eligibility with regard to safety, the Investigator 
must refer to the relevant document(s) for detailed information regarding warnings, precautions, 
contraindications, AEs, and other significant data pertaining to the study product(s) being used in 
this study. Such documents may include the Investigator’s Brochure (IB) and the Prescribing 
Information.  
8.4.1 
Loa loa Co-Endemicity 
Patients with Loa loa may develop a serious or even fatal encephalopathy following treatment with 
macrocyclic lactones, including moxidectin. Moxidectin has not been studied in patients infected 
with Loa loa. It is recommended that individuals who have had exposure to Loa loa-endemic areas 
undergo diagnostic screening for loaisis prior to treatment with moxidectin. Loa loa parasites are 
found in West and Central Africa, including Cameroon, Democratic Republic of the Congo, Gabon, 
and Nigeria (Figure 1). 


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Figure 1  Map of Estimated Prevalence of Eye Worm History in Africa 
 
Source: World Health Organization/African Programme for Onchocerciasis Control. Online at: 
http://www.who.int/apoc/raploa/en/ accessed 07 Sep 2018. 
8.4.2 
Contraception 
All women of child-bearing potential (defined as sexually mature women who have had menses 
within the preceding 24 months and have not undergone hysterectomy, bilateral oophorectomy or 
tubal ligation) must have a negative pregnancy test at Screening. Pregnancy testing may be 
performed by analysis of serum or urine and should be confirmed at Baseline prior to study drug 
administration. Pregnancy testing will be repeated at Week 12. 
Women of child-bearing potential must agree not to attempt to become pregnant. If participating in 
sexual activity that could lead to pregnancy, women of child-bearing potential and male partners of 
women of child-bearing potential must agree to use a reliable method of contraception during the 
study and for the 6 months following study drug administration. 
Women who are not of reproductive potential (who have been postmenopausal for at least 
24 consecutive months or have undergone hysterectomy, bilateral oophorectomy or tubal ligation) 
are not required to use contraception. 
8.4.3 
Rescreening 
Subjects who are determined to be ineligible for the study on the basis of laboratory abnormalities 
may be re-screened for eligibility once. All other subjects may only be rescreened once discussed 
and agreed with the Sponsor. 
8.5 
Special Protocol Issues 
8.5.1 
Treatment of Contacts 
As untreated contacts may be a source of scabies re-infestation, all close personal contacts of 
enrolled subjects, including household, family and sexual contacts, will be offered the approved 
current standard of care scabies treatment. 


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The participant must be counselled to avoid contact with any treatments taken by their close 
personal contacts. 


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9 
SCHEDULE OF ASSESSMENTS AND PROCEDURES 
9.1 
Study Schedule of Evaluations 
The schedule of assessments is presented in Table 1 and Table 2. 
9.2 
Visit Windows 
Screening must be conducted after informed consent has been given, in the window of Day -7 to 
Day -1. 
All visit days are calculated from Day 0, which is the date of the Baseline (pre-dose) assessments 
and study drug administration. Hours are calculated based on the time of administration of 
moxidectin.  
Windows for each study assessment are: 
• ± 15 minutes for Hours 2 and 3, 
• ± 30 minutes for Hour 4, 
• ± 1 hour for Hour 8, 
• ± 4 hours for Hours 24, 48 and 72, 
• ± 2 days for Days 7 and 14,  
• ± 3 days for Day 28, 
• ± 7 days for Week 12. 
9.3 
Study Procedures 
The study procedures to be conducted are listed below. Further detail on the study procedures is 
provided in Section 9.4. Any deviation from protocol procedures must be noted in the source 
documents and the Sponsor is to be notified.  
All laboratory tests on blood and urine samples will be performed at the selected laboratory. Refer to 
the SRM and/or central laboratory instruction manuals for information on sample collection and 
shipment of all required study samples  
Additional visits and/or assessments may be conducted as clinically indicated. 
9.3.1 
Screening Visit (Day -7 to Day -1) 
Subjects will be screened up to 7 days prior to randomization to determine eligibility for 
participation in the study. Screening assessments may be conducted on different days if required. 
The following procedures will be performed and documented during Screening: 
• Obtain written informed consent prior to any study related procedures (see Section 16.1.2). 
• Parasitological assessment including confirmation of the presence of at least 2 lesions with 
live adult S. scabiei mites for assessment throughout the study by RCM (see Section 9.4.7). 
• Medical history (see Section 9.4.2). 
• A complete physical examination (see Section 9.4.3) including: 
o assessment of all appropriate body systems to determine study eligibility; 
o measurement of height and weight. 
• Vital signs while in the supine position (see Section 9.4.4) 
• A 12-lead ECG (see Section 9.4.5) 
• Concurrent medication assessment (see Section 11) 
• Blood samples drawn for hematology and clinical chemistry (see Section 9.4.6.1)  
• Pregnancy test for women of childbearing potential (see Section 9.4.6.2) 


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Results of all Screening tests must be available and reviewed prior to the subject’s Baseline visit. 
Subjects meeting all the inclusion criteria and none of the exclusion criteria will return to the clinic 
within 7 days of commencement of Screening for randomization into the study.  
Subjects will be required to fast overnight (from midnight) prior to the Baseline visit (Day 0). Water 
may be consumed ad libitum. 
9.3.2 
Baseline (Day 0) 
9.3.2.1 Pre-Treatment 
Subjects will return to the clinic for final eligibility confirmation through the following assessments: 
• Targeted physical examination (see Section 9.4.3). 
• Parasitological assessment (see Section 9.4.7), which includes: 
o selection of at least 2 (but not more than 4) lesions with live adult S. scabiei mites for 
assessment throughout the study by RCM; and  
o photographs of the selected live adult S. scabiei mites using a dermatoscope and RCM.  
• Concurrent medication assessment (see Section 11). 
• For women of childbearing potential, confirmation of a negative pregnancy test (see 
Section 9.4.6.2). 
Subjects meeting all of the inclusion and none of the exclusion criteria will be randomized to a 
treatment group and then have the following performed:  
• Vital signs (see Section 9.4.4) 
• Cannulation for collection of blood samples (see Section 9.4.6.3) for:  
o pharmacokinetic assessments;  
o plasma storage; 
o if Screening was conducted more than 72 hours before Baseline, blood samples 
should also be collected for hematology and clinical chemistry (see Section 9.4.6.1) 
• Assessment of clinical signs of scabies infestation, which includes: 
o mapping, counting and grading of scabies inflammatory and non-inflammatory 
lesions (see Section 9.4.8.1); and 
o administration of patient reported outcome questionnaires including the Numerical 
Rating Scale itch score, 5-D itch score and Dermatology Life Quality Index (see 
Section 9.4.8.2) 
• Adverse event assessment (see Section 12) 
9.3.2.2 Dosing 
Study drug will be administered observed by site staff with water as described in Section 10.4.4. The 
time of dosing (Hour 0) will be recorded in the Case Report Form (CRF). 
9.3.2.3 Post-dose (Hours 2, 3, 4 and 8) 
Subject will remain in the clinic for 8 hours following treatment. In addition to monitoring the 
subject throughout, the following will be performed on Hours 2 (± 15 minutes), 3 (± 15 minutes), 
4 (± 30 minutes), and 8 (± 1 hour) and recorded in the CRF:  
• Continuous adverse event assessment (see Section 12). 
• Continuous recording of concurrent medications (see Section 11). 
• A modified physical examination as clinically indicated (see Section 9.4.3). 


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• Blood samples for pharmacokinetic assessment at Hours 2, 3, 4 and 8 post-dosing (see 
Section 9.4.6.3). 
• Parasitological assessment (see Section 9.4.7): assessment of the viability and photographs 
of the selected scabies mites will be taken with the RCM at Hours 4 (± 15 minutes of 
pharmacokinetic blood sampling) and 8 (± 15 minutes of pharmacokinetic blood sampling) 
• Vital signs assessment at Hour 8 (see Section 9.4.4). 
Food may be offered from two hours post-dosing. Clear liquids may be provided ad libitum.  
Upon completion of the assessments and if the investigator is satisfied that the subject is well, the 
subject should be discharged from the clinic at Hour 8. 
9.3.3 
On-study Clinic Visits (Hours 24, 48 and 72, and Days 7, 14 and 28) 
Subjects will return to the clinic for assessments on Hours 24 (± 4 hours), 48 (± 4 hours) and 72 (± 4 
hours), and Days 7 (± 2 days), 14 (± 2 days) and 28 (± 3 days). The following assessments will be 
performed and documented as indicated on the CRF: 
• Adverse event assessment at each visit (see Section 12). 
• Recording of concurrent medications at each visit (see Section 11). 
• A modified physical examination at Hour 24 and 72, and Days 7, 14 and 28, and as clinically 
indicated at other times (see Section 9.4.3). 
• Vital signs assessment at Hour 24 and 72, and Days 7, 14 and 28 (see Section 9.4.4). 
• Blood samples for: 
o pharmacokinetic assessment and plasma banking at each visit (see Section 9.4.6.3); 
o hematology and clinical chemistry to be performed at Day 7 and Day 28 (see 
Section 9.4.6.1). 
• Parasitology (see Section 9.4.7) assessments which include: 
o assessment of the viability and photographs of the selected scabies mites will be 
taken with RCM within 15 minutes of pharmacokinetic blood sampling at Hours 24, 
48 and 72, and Day 7, 14 and 28; 
o photographs by dermatoscope at Hour 72 and Day 7, 14 and 28; 
o subjects with viable mites from Day 14 may be offered standard of care (see 
Section 11.2.3). 
• Assessment of clinical signs of scabies infestation at Day 7, 14 and 28, which includes: 
o mapping, counting and grading of scabies inflammatory and non-inflammatory 
lesions (see Section 9.4.8.1); 
o administration of patient reported outcome questionnaires including the Numerical 
Rating Scale itch score, 5-D itch score and Dermatology Life Quality Index (see 
Section 9.4.8.2). 
9.3.4 
Study Conclusion (Week 12) 
At Week 12, the subject will return to the clinic for the following assessments: 
• Adverse event assessment (see Section 12). 
• Recording of concurrent medications (see Section 11). 
• A modified physical examination including body weight (see Section 9.4.3). 
• Vital signs assessment (see Section 9.4.4). 
• For women of childbearing potential, confirmation of a negative pregnancy test (see 
Section 9.4.6.2). 


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9.3.5 
Unscheduled Visits 
If the subject returns to the clinic outside of the standard visit schedule, in addition to providing the 
required clinical care, for their presenting condition, the following should be performed: 
• Adverse event assessment (see Section 12). 
• Recording of concurrent medications (see Section 11). 
• A modified physical examination (see Section 9.4.3). 
• Vital signs assessment (see Section 9.4.4). 
9.3.6 
Early Withdrawal 
Subjects should be encouraged to stay in the study for until the end of study visit at Week 12. 
Should a subject decide to withdraw from the study (see Section 14), all efforts will be made to 
complete the following study procedures as thoroughly as possible: 
• Adverse event assessment (see Section 12). 
• Recording of concurrent medications (see Section 11). 
• A modified physical examination (see Section 9.4.3). 
• Vital signs assessment (see Section 9.4.4). 
• For women of childbearing potential, confirmation of a negative pregnancy test (see 
Section 9.4.6.2). 
• Blood samples for: 
o hematology and clinical chemistry (see Section 9.4.6.1) 
o plasma for banking (see Section 9.4.6.3) 
 
If withdrawal occurs prior to the Day 28 visit, all efforts will be made to complete the following 
additional study procedures: 
• Blood samples for pharmacokinetic assessment (see Section 9.4.6.3) 
• Parasitology (see Section 9.4.7) assessments, which include: 
o photographs of the live adult scabies mites will be taken with RCM within 15 
minutes of pharmacokinetic blood sampling; 
o photographs by dermatoscope. 
• Assessment of clinical signs of scabies infestation at Day 7, 14 and 28, which includes: 
o mapping, counting and grading of scabies inflammatory and non-inflammatory 
lesions (see Section 9.4.8.1); 
o administration of patient reported outcome questionnaires including the Numerical 
Rating Scale itch score, 5-D itch score and Dermatology Life Quality Index (see 
Section 9.4.8.2). 
9.3.7 
Modification of Scheduled Procedures due to COVID-19 
The safety and wellbeing of research subjects and the study team is paramount. Adherence to 
official public health guidance, government or site governance directives issued in response to the 
COVID-19 pandemic should take precedence over the procedures in this protocol. 
Subjects should be informed of the importance of notifying the study team in advance if they are 
experiencing one or more symptoms suggestive of SARS-CoV-2 infection or other infectious 
disease that includes respiratory symptoms, or have been in close contact with someone who is 
known to have contracted SARS-CoV-2. The Principal Investigator or delegate may advise the 
subject to present to the relevant health service for further investigation. 


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Subjects who are unwilling or unable to attend clinic visits or complete other trial activities due to 
the pandemic may be asked to comply with study procedures. However, subjects are entitled to 
withdraw from the study at any time or for any reason and their decision is to be respected.  
The majority of assessments in this protocol require physical attendance at the clinic. Exceptions 
may be made at the Investigator’s discretion for assessments that are able to be conducted remotely 
(such as Week 12). If subjects become unable to undertake protocol required assessments due to 
self-isolation or have been advised to stay away from the clinic, resulting protocol deviations should 
be documented to enable appropriate evaluation for the study.  
If biospecimens are collected from subjects known to be actively infected with COVID-19, this 
information should be noted in the documentation that accompanies any sample transfer activities. 
In addition to the provisions outlined in Section 14, subjects with missing key efficacy assessments 
due to COVID-19 may be replaced. 
9.4 
Details of Scheduled Assessments 
9.4.1 
Demographic Data 
Demographic data will be recorded in the clinic notes and CRF at Screening and include sex, 
ethnicity and date of birth. 
9.4.2 
Medical History 
The medical history will be recorded in the clinic notes and CRF at Screening and include any 
diagnosed medical conditions and/or recurrent medical conditions, or significant medical or surgical 
history. It will include a review of all major body systems including the skin. 
Any worsening of Baseline conditions detected during medical history review must be recorded on 
source documents as well as in the AE section of the CRF. 
9.4.3 
Physical Examination 
A complete physical examination (including head, ears, nose, throat, lungs, lymph nodes, heart, 
abdomen and skin) will be conducted at Screening to determine study eligibility and recorded in the 
clinic notes and CRF.  
A symptom-based physical examination will be conducted at visits conducted after Screening, 
according to prior findings and informed by concurrent conditions, signs and symptoms, and AEs 
reported. A full physical examination is recommended if, in the opinion of the Investigator, any 
clinical changes are suggested by the subject's interim clinical history. These data should be 
recorded in the clinic notes. Any new abnormalities or worsening of Baseline conditions detected 
during physical examinations must be recorded on source documents as well as in the AE section of 
the CRF.  
Body weight (kilograms [kg], without shoes) and height (centimeters [cm], without shoes) will be 
measured at Screening and recorded in the clinic notes and CRF. 
9.4.4 
Vital Signs 
When multiple procedures occur at the same time point, the vital sign measurements will be 
obtained first, followed by the 12-lead ECG conducted at the scheduled time point, followed by 
blood collection. 
Vital signs will be measured after the subject has been semi-supine for 5 minutes: 


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• Oral/aural body temperature (degrees Celsius [°C]) 
• Respiratory rate (breaths per minute) 
• Pulse rate (beats per minute [bpm]) 
• Blood pressure (millimeters of mercury [mmHg]) 
Vital signs should also be measured at other times if deemed clinically appropriate. These data will 
be recorded in the clinic notes and CRF. 
9.4.5 
Electrocardiograms 
12-lead ECG will be performed in triplicate over approximately 10 minutes after the subject has 
been supine for approximately 10 minutes at Screening. ECGs will be performed before blood 
collection. Repeat measurements will be performed if there are any clinical abnormalities observed 
or artifacts are present. All ECG recordings will be reviewed by the Investigator or nominee and 
retained in the clinic notes.  
9.4.6 
Biological Samples 
Safety laboratory parameters, pharmacokinetic samples and plasma banking samples are required 
throughout the study.  
The first 8 hours after dosing requires sequential blood samples to be collected in order to 
appropriately characterize moxidectin pharmacokinetics. An intravascular catheter should be used to 
facilitate venous access and use of an effective topical anesthetic for application to the skin for 
sample collection. 
9.4.6.1 Safety Laboratory Tests 
All safety laboratory tests will be conducted at the nominated laboratory. Refer to the SRM for 
detailed instructions on sample collection, handling and processing. 
Blood samples for hematology and serum chemistry will be collected at Screening, Baseline (before 
dosing, if Screening samples were collected more than 72 hours before Baseline), Day 7 and 
Day 28. It is expected that a copy of these data will be directly transferred to the Sponsor rather than 
require transcription into the CRF.  
Samples will be collected for the safety laboratory tests shown in Table 8. 


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Table 8  Hematology and Serum Chemistry Tests 
Hematology 
 
Hemoglobin 
Hematocrit 
Red blood cell (RBC) and RBC morphology (if abnormal) 
White blood cell and differential white blood cell count 
Platelet count 
Mean corpuscular volume  
Mean corpuscular hemoglobin concentration 
Serum clinical chemistry 
 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Bicarbonate 
Bilirubin, total and direct 
Blood urea nitrogen or urea 
Calcium 
Chloride 
Creatinine, estimated creatinine clearance 
Creatine phosphokinase 
Gamma glutamyltransferase 
Glucose 
Lactate dehydrogenase 
Phosphorus 
Potassium 
Serum amylase 
Sodium 
Total protein 
Uric acid 
9.4.6.2 Pregnancy Testing 
A pregnancy test will be performed for all women of childbearing potential at Screening, Baseline 
and Week 12 using a blood or urine sample. A negative pregnancy test result is required prior to 
IMP administration. 
9.4.6.3 Pharmacokinetic Samples and Samples for Plasma Banking 
Plasma for determining the pharmacokinetics of moxidectin will be collected at Baseline (pre-dose), 
Hours 2, 3, 4, 8, 24, 48 and 72 Hours, and at Days 7, 14 and 28. All samples (except those taken at 
Hours 2 and 3) will coincide with an RCM assessment (see Section 9.4.7) and will be collected as 
close to the scheduled time point as possible. Collection of pharmacokinetic samples and RCM 
assessments should be performed within a 15-minute window. 
A portion of blood samples collected for pharmacokinetic analysis will be banked for the 
development of tests to characterize biomarkers of scabies infestation. As a neglected disease, there 
have been no assays developed for the diagnosis of scabies infection and/or monitoring of efficacy 
outcomes of treatment. Such an assay would greatly improve the diagnosis and management of this 
disease. For this purpose, plasma will be prepared from blood samples and divided into two aliquots 
stored at -20°C or -80°C conditions. Details of the collection, processing, storage and shipping of 
pharmacokinetic samples and samples for banking are further detailed in the SRM. 
9.4.6.4 Handling and Processing of Biological Specimens 
Blood and urine specimens collected during the trial may contain harmful pathogens. All personnel 
involved in collecting and handling biological specimens should follow appropriate precautionary 
procedures for handling biohazardous materials as currently recommended by the national 


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regulatory authority. The processing of all biological specimens will be in accordance with relevant 
institutional Standard Operating Procedures (SOPs).  
Further details of the handling of blood samples can be found in the SRM. 
9.4.7 
Parasitology Assessments of the Scabies Mite 
 
In vivo assessments will be conducted on a minimum of 2 and a maximum of 4 live adult scabies 
mites, each within a distinct lesion. These assessments will be conducted using the 
Vivascope 3000® RCM. Some RCM assessments will be paired with high magnification 
dermatoscope assessments: 
• RCM and dermoscopy: Baseline, and Hour 72, and Days 7, 14 and 28. 
• RCM alone: Screening, and Hours 4, 8, 24 and 48. 
By RCM, live adult scabies mites are defined by an inhomogenous (i.e. with internal structures 
discernable) ovoid refractive body. Short legs may be visible and vital functions such as peristalsis 
or movement within the burrow may be observable. Dermoscopy may be used to identify the 
location of mites before assessment by RCM. The lesions selected for assessment should be 
delineated to facilitate follow up, for example directly on the skin or using appropriate methods to 
map their location.  
Once the assessable mites have been identified, optical sections will be captured using the RCM. 
Videos may also be captured as appropriate. Photographs at a minimum 10x magnification should 
be captured at the specified time points with a dermatoscope. Following image acquisition, the RCM 
and/or dermatoscope should be appropriately decontaminated.  
These data will be recorded in the CRF. The full procedure for RCM and dermatoscope handling 
and image acquisition is detailed in the SRM.  
9.4.8 
Clinical Assessments 
9.4.8.1 Clinician Reported Outcomes 
Subjects will be assessed for the clinical signs and symptoms of scabies infestation at Baseline, 
Day 7, 14 and 28. Signs and symptoms include visible mites, burrows, inflammatory lesions such as 
papules, vesicles and/or nodules, and non-inflammatory lesions such as excoriations and erythema.  
The procedure for reporting signs and symptoms is outlined below: 
• Signs and symptoms of scabies infestation will be mapped according to pre-specified 
anatomical body regions.  
• Regions showing signs and symptoms of scabies infestation should be photographed where 
possible. All efforts should be made to maintain photography conditions (e.g. lighting, 
distance and position) at each visit. 
• If present, mites and burrows, observed using dermoscopy, and inflammatory lesions will be 
counted by affected region. 
• Excoriations will be noted if present 
• If present, the severity of erythema will be graded. 
These data will be recorded in the clinic notes and CRF. Signs and symptoms of scabies that worsen 
or emerge after commencement of treatment should also be reported as AEs in the CRF. 
Complete details of these study procedures are available in the SRM. 


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9.4.8.2 Patient Reported Outcomes 
The subject will be asked to complete the following questionnaires: 
• Numerical Rating Scale for itch; 
• 5-D itch scale; 
• Dermatology Life Quality Index. 
These questionnaires will be administered at Baseline pre-dose and on Day 7, 14 and 28. Responses 
will be transcribed to the CRF. Details of these questionnaires are available in the SRM.  


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10 
INVESTIGATIONAL MEDICINAL PRODUCT 
10.1 Randomization Process 
Potential subjects who provide written informed consent will be sequentially assigned a Screening 
Number prefixed by “S” (e.g. S001).  
For each site, a randomization scheme with equal allocation to each of the initial three moxidectin 
treatment groups will be prepared in advance by an unblinded statistician otherwise independent of 
study conduct using a computer-generated system according to relevant SOPs. Treatment packs will 
be prepared according to the randomization scheme. 
Randomization will take place before dosing on Day 0, with equal random assignment to one of the 
following treatments: 
• Treatment 1: moxidectin 2 mg  
• Treatment 2: moxidectin 8 mg  
• Treatment 3: moxidectin 20 mg  
Randomization to treatment will be accomplished by sequential assignment of treatment numbers, 
corresponding to the pre-packaged individual drug supplies provided.  
Following review of safety and efficacy data by the Protocol Steering Committee (see Section 13 for 
more information), one or more dose cohort(s) may be discontinued and/or a new 36 mg dose cohort 
added. If required, the randomization plan will be revised to maintain the final target sample size of 
6 subjects per cohort.  
The study may switch from a stratified randomization by site to a central randomization scheme for 
logistical reasons. This approach would allow greater control over the number of subjects 
randomized to each dose cohort across all sites. However, random allocation of treatment 
assignment will be preserved in all cases.  
Further details on the randomization procedure, and treatment dispensing and accountability is 
provided in the SRM. 
10.2 Blinding 
Neither the subjects, staff administering the study drug nor Sponsor staff directly involved in the 
conduct of the study will know the dose of study drug being administered. To maintain the blind, 
each subject will receive the same number of tablets, regardless of dose, in pre-packed bottles. Each 
bottle will contain moxidectin 2 mg tablets and placebo tablets as required to maintain the blind. The 
placebo tablets will be matched in appearance to the active study drug and will contain the same 
excipients as moxidectin tablets, but will not contain moxidectin. 
A maximum of 18 tablets may be required to blind the doses. Investigational product will be 
packaged to permit this in line with Section 10.4.  
The Protocol Steering Committee will be unblinded. No member of the Committee will be directly 
involved in the day-to-day conduct of the study. 
10.3 Method of Unblinding 
10.3.1 Medical Emergency 
No open key to the random code will be available to the study centers and Sponsor. Sealed code 
break envelopes will be held by the clinical site, medical monitor and/or Sponsor. In an emergency, 
the Investigator or other study team member may need to break the treatment code immediately, or 


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as quickly as possible if this is in the best interest of the trial subject. The breaking of the blind 
should only occur where knowledge of the study medication treatment will affect the subject’s 
clinical management. The Medical Monitor should be consulted prior to the breaking of the blind. 
If the code is broken the envelope must be signed and dated by the individual who broke the code, 
and information entered into the subject’s source documents, explaining the reason and date that it 
was opened, identity of the person who authorized the code break, and documenting the identity of 
the study product allocated to the subject. This must be countersigned by the Investigator. 
10.3.2 End of Study 
The randomization code will be broken by the blinded Study Statistician once data entry has been 
completed, the database locked, and the per-protocol population for analysis established. Sponsor 
will provide written permission to the Study Statistician prior to the breaking of the randomization 
code. 
10.4 Investigational Products 
10.4.1 Supply 
Moxidectin will be supplied by the Sponsor as 100 mg uncoated, oval-shaped tablets containing the 
components listed in Table 9. Moxidectin tablets contain 2 mg moxidectin. 
Table 9  Moxidectin Tablet Components 
Component  
Quality Reference 
Function  
Micronized moxidectin  
United States Pharmacopeia 
Active ingredient  
Microcrystalline cellulose  
National Formulary 
Diluent  
Lactose, anhydrous  
National Formulary 
Diluent  
Sodium lauryl sulfate  
National Formulary 
Surfactant  
Colloidal silicon dioxide  
National Formulary 
Glidant  
Croscarmellose sodium  
National Formulary 
Disintegrant  
Magnesium stearate  
National Formulary 
Lubricant  
Nitrogen  
National Formulary 
Processing aid  
Placebo tablets will be matched in appearance to the active study drug and will contain the same 
excipients but will not contain moxidectin. 
10.4.2 Packaging and Labelling 
Moxidectin will be supplied to the site packaged in high density polyethylene bottles. Moxidectin 
will be shipped to site after receipt of required documentation of study approval and in accordance 
with applicable regulatory requirements.  
Product labelling will be in accordance with local regulations and requirements and will include at a 
minimum: 
• Sponsor name  
• Protocol number  
• Product name or drug code 
• Dose or product strength 
• Route of administration 
• Lot number 
• Directions for use 
• Expiry date or retest date (on outer packaging) 
• ‘For Clinical Trial Use Only’  


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• Subject Number 
Any specific cautionary statements will be included according to local law. 
10.4.3 Storage and Handling 
Moxidectin tablets and placebo to match must be stored at controlled room temperature (25°C) and 
protected from light and moisture. Tablets must not be frozen. Temperature excursions are permitted 
up to 30°C for up to 12 months.  
Only participants enrolled in the study may receive investigational products. Prior to dispensing, 
moxidectin supplies will be stored securely under the appropriate conditions at the clinical trial site 
in a secure area with access limited to authorized staff, and according to relevant regulations. 
The Investigator or authorized designee will ensure that the IMP is safely and securely stored in 
compliance with Good Laboratory Practice storage requirements. The Investigator is responsible for 
ensuring that the IMP is dispensed in accordance with the protocol and only to participants enrolled 
in the study. Authorized study personnel will dispense moxidectin. 
10.4.4 Dosage and Administration of Test Drugs 
Subjects may receive a maximum of 18 tablets for oral administration comprised of moxidectin 
2 mg tablets and matched placebo to maintain the blind and accommodate the 36 mg dose. 
Administration will be observed by clinic staff to ensure compliance. 
This pill burden is considered reasonable for this phase of study. Each moxidectin 2 mg and placebo 
to match tablet is 100 mg total weight and < 1 cm in length. Eighteen (18) tablets were administered 
without issue in MDGH-MOX-1008, where 60 healthy volunteers received 18 moxidectin 2 mg 
and/or matched placebo tablets per oral of the current formulation. No acceptability or compliance 
issues were reported in this study and all subjects were able to (and observed to) swallow the 18 
tablets.  
The dose of moxidectin will be administered on Day 0 after fasting from at least midnight and 
preferably overnight. Subjects will be required to swallow moxidectin with water. Subjects must 
continue to fast for 2 hours post-dose. Clear liquids may be consumed ad libitum. 
10.4.5 Dispensing and Accountability 
All IMP supplied is only for use in this clinical study and should not be used for any other purpose. 
The Investigator or designee is responsible for maintaining accurate records for all study 
medications dispensed and returned. The inventory and dispensing logs must be available for 
inspection by the study monitor. Study product supplies, including partially used or empty bottles 
must be accounted for by the Investigator or designee and verified by the study monitor and returned 
to the drug repository for destruction at the end of the study. 
When requested in writing by the Sponsor, unused study medication supplies may be destroyed by 
the Investigator provided such disposition can be performed safely. Records shall be maintained by 
the Investigator or any such alternate disposition of the study medication. These records must show 
the identification and quantity of each unit disposed of, the method of destruction (taking into 
account the requirements of local law), and the person who disposed of the test substance. Such 
records shall be submitted to the Sponsor. 


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11 
CONCURRENT MEDICATIONS AND TREATMENTS 
At each study visit or contact, the Investigator should question the subject about any medication 
taken. Concomitant therapies should be brought to the attention of the Investigator. Any such 
medications will be recorded on the CRF. Any changes in doses or introduction of new medications 
during the course of the study will also be recorded. 
If the medication is related to the occurrence of an AE, ensure that details are recorded in the CRF. 
11.1 Special Dietary Requirements 
There are no special dietary requirements. 
11.2 Concurrent Medications and Treatments  
11.2.1 Prior to Study Entry 
Refer to Exclusion Criteria in Section 8.3. 
11.2.2 During the Study Dosing Period 
Every effort should be made to keep concurrent medications for chronic or ongoing medical issues 
stable throughout the study period. 
All concurrent medications, including vitamin supplements and herbal remedies, must be recorded 
in the appropriate section of the CRF. All changes in medication will be noted. If the reason for use 
meets the definition of an AE, the AE will be recorded in the source documents for that subject and 
on the appropriate page of the CRF. 
Except as specified in Section 11.2.3, subjects may not receive treatment with any scabicide, 
including ivermectin, permethrin, benzyl benzoate, lindane, crotamiton, malathion or tea tree oil at 
any time up to and including Week 12.  
Scabies symptoms including pruritus may persist for several weeks after successful treatment of the 
infestation. Subjects should not receive supportive therapies to manage their scabies symptoms or 
treatment with other anti-parasitic treatments (in addition to those listed above) up to and including 
Day 28. Should the subject report scabies symptoms that are intolerable, oral antihistamines may be 
used at the discretion of the Investigator. 
Topical steroids and topical preparations containing zinc, calamine, tar or salicylic acid (including 
medicated emollients) are prohibited after Screening up to and including Day 28. 
Unmedicated emollient creams are permitted at any time. 
11.2.3 Rescue Therapy 
If subjects are shown to be either newly or persistently infected with confirmed scabies mites by 
RCM on or at any time from Day 14, standard of care may be offered. Rescue therapy may not be 
offered in the absence of scabies mites or based on symptomology only.  


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12 
ADVERSE EVENTS AND TOXICITY MANAGEMENT 
12.1 Safety Parameters 
Safety assessments will include physical examination, AEs, vital signs and clinical laboratory tests. 
12.2 Adverse Events 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered an Investigational Product (whether it is the experimental product or control) and 
which does not necessarily have a causal relationship with the Investigational Product. An AE can 
therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with 
the use of a medicinal product, whether or not considered related to the medicinal product. 
Pre-existing events that increase in frequency or severity or change in nature during or as a 
consequence of use of a drug in human clinical trials will also be considered as an AE. AEs may 
also include pre- or post-treatment complications that occur as a result of protocol-mandated 
procedures (e.g. invasive procedures such as biopsies). 
Any AE (i.e. a new event or an exacerbation of a pre-existing condition) with an onset date after 
informed consent up to the last day on study (including the follow-up, off study medication period 
of the study), should be recorded as an AE on the appropriate CRF page(s). 
An AE does not include: 
• 
medical or surgical procedures (e.g. surgery, endoscopy, tooth extraction, transfusion); the 
condition that leads to the procedure is an AE; 
• 
pre-existing diseases or conditions present or detected prior to start of study product 
administration, that do not worsen; 
• 
situations where an untoward medical occurrence has not occurred (e.g. hospitalization for 
elective surgery, social and/or convenience admissions); 
• 
overdose of either study product or concomitant medication without any signs or symptoms 
unless the subject is hospitalized for observation. 
12.2.1 Assessment of Adverse Events 
All AEs will be assessed by the Investigator and recorded on the appropriate CRF page, including 
the date of onset and resolution, severity, relationship to study product, outcome and action taken 
with study medication. Each AE will be graded for severity using the FDA Guidance for Industry: 
Toxicity Grading Scale for Healthy Adult and Adolescent volunteers Enrolled in Preventive Vaccine 
Clinical Trials in Appendix 18.1. For the purpose of monitoring toxicities, the Baseline value is 
defined as the last value prior to the administration of IMP.  
For AEs not specifically identified in the grading table, the grades presented in Table 10 should be 
applied 
Table 10  Grading of Adverse Events 
Grade 
Severity 
Comments 
1 
Mild 
Mild symptoms causing no or minimal interference with usual social & functional 
activities with intervention not indicated 
2 
Moderate 
Moderate symptoms causing greater than minimal interference with usual social 
& functional activities with intervention indicated 
3 
Severe 
Severe symptoms causing inability to perform usual social & 
functional activities with intervention or hospitalization indicated 


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Grade 
Severity 
Comments 
4 
Life-
threatening 
Potentially life-threatening symptoms causing inability to perform basic self-care 
functions with intervention indicated to prevent permanent impairment, 
persistent disability, or death 
The relationship to IMP therapy should be assessed using the definitions presented in Table 11. 
Table 11  Assessment of Relationship of Adverse Events to Investigational Medicinal Product 
Causality 
Comment 
Unrelated 
AE is clearly due to extraneous causes (e.g. underlying disease, environment, known 
effect of another drug) 
Unlikely 
The temporal association between the AE and study drug is such that study drug is not 
likely to have any reasonable association with the AE 
Possible 
The AE could have been produced by the subject’s clinical state or study drug 
Probable 
The AE follows a reasonable temporal sequence from the time of study drug 
administration, abates upon discontinuation of the study drug and cannot be reasonably 
explained by the known characteristics of the subject’s clinical state 
Definite 
The AE follows a reasonable temporal sequence from the time of study drug 
administration, abates upon discontinuation of the study drug and/or reappears when 
study drug is re-introduced 
These criteria in addition to good clinical judgment should be used as a guide for determining the 
causal assessment. If it is felt that the event is not related to study product, then an alternative 
explanation should be provided. 
12.2.2 Adverse Event Reporting Period 
All AEs, regardless of severity, causality or seriousness must be reported from the date of informed 
consent until the end of the study or 28 days after the last dose of study medication, whichever is 
later. However, any AE that the Investigator believes is at least possibly related to study medication 
should be reported regardless of time elapsed from the final dose. 
12.3 Serious Adverse Events 
12.3.1 Serious Adverse Event Definition 
A serious adverse event (SAE) is defined as follows: 
Any adverse drug experience occurring at any dose that results in any of the following outcomes: 
• 
death; 
• 
life-threatening situation (subject is at immediate risk of death); 
• 
inpatient hospitalization or prolongation of existing hospitalization (excluding those for study 
therapy or placement of an indwelling catheter, unless associated with other serious events); 
• 
persistent or significant disability/incapacity; 
• 
congenital anomaly/birth defect in the offspring of a subject who received study product; 
Important medical events that may not result in death, be immediately life-threatening, or require 
hospitalization, may be considered a SAE when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such events are: 
• 
blood dyscrasias or convulsions that do not result in hospitalization; 
• 
development of drug dependency or drug abuse. 


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12.3.2 Clarification of Serious Adverse Events 
• Death is an outcome of an AE, and not an AE in itself. In reports of death due to “Disease 
Progression”, where no other information is provided, the death will be assumed to have 
resulted from progression of the disease being treated with the study product(s). 
• All deaths, regardless of cause, must be reported to the Sponsor for subjects on study and for 
deaths occurring within 30 days of last study product dose or within 30 days of last study 
evaluation, whichever is longer. 
• “Occurring at any dose” does not imply that the subject is receiving study product at the time 
of the event. Dosing may have been given as treatment cycles or interrupted temporarily 
prior to the onset of the SAE, but may have contributed to the event. 
• “Life-threatening” means that the subject was at immediate risk of death from the event as it 
occurred. This does not include an event that might have led to death, if it had occurred with 
greater severity. 
• Complications that occur during hospitalizations are AEs. If a complication prolongs 
hospitalization, it is a SAE. 
• “In-patient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons, for any length of time. This may or may not be overnight. It does not 
include presentation and care within an emergency department. 
• The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE and/or SAE and not the individual signs/symptoms. 
12.3.3 Serious Adverse Event Reporting Requirements 
12.3.3.1 
All Serious Adverse Events 
The Sponsor has requirements for expedited reporting of SAEs meeting specific requirements to 
worldwide regulatory authorities; therefore, all appropriate parties must be notified immediately 
regarding the occurrence of any SAE that occurs during the study. The procedures for reporting all 
SAEs, regardless of whether the Investigator believes that the experience is related to study drug, are 
as follows: 
1) Complete the “Serious Adverse Event Report Form”  
2) Send the completed “Serious Adverse Event Report Form” to the Sponsor Safety Desk 
within 24 hours of the Investigator’s knowledge of the 
event.  
3) For fatal or life-threatening events, also submit copies of hospital case reports, autopsy 
reports, and other documents when requested and applicable 
Additional detail on reporting SAEs is included in the SRM. 
The Sponsor may request additional information from the Investigator to ensure the timely 
completion of accurate safety reports. 
The Investigator must take all therapeutic measures necessary for resolution of the SAE. Any 
medications necessary for treatment of the SAE must be recorded onto the concurrent medication 
section of the subject’s CRF. 
12.3.3.2 
Investigator Reporting Requirements for Serious Adverse Events 
An SAE may qualify for reporting to regulatory authorities if the SAE is considered to have a 
possible causal relationship to the study product and is unexpected (Suspected Unexpected Serious 


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Adverse Reaction [SUSAR]) based upon the current Investigator’s Brochure. In this case for multi-
center studies, all Investigators will receive a formal notification describing the SAE. 
Where this is required by local regulatory authorities, and in accordance with the local institutional 
policy, the Investigator should notify (in writing) the local Independent Ethics Committee (IEC) of 
SAEs as soon as is practical. 
12.4 Follow up of Serious and Non-Serious Adverse Events 
Follow-up of serious and non-serious AEs will continue through the last day on study (including the 
follow-up, off study medication period of the study), until the Investigator determines that the 
subject’s condition is stable, or up to 30 days after the last dose of Study Product, whichever is 
longer. The Sponsor may request that certain AEs be followed until resolution. 
12.5 Additional Considerations for Reporting Adverse Events 
12.5.1 Diagnosis Versus Signs and Symptoms 
Each AE will be recorded to represent a single diagnosis. Accompanying signs (including abnormal 
laboratory values or ECG findings) or symptoms will NOT be recorded as additional AEs. If a 
diagnosis is unknown, sign(s) or symptom(s) will be recorded as an AE(s).  
12.5.2 Pre-existing Conditions 
Pre-existing conditions (present before the start of the AE collection period) are considered 
concurrent medical conditions and will NOT be recorded as AEs. However, if the subject 
experiences a worsening (severity or frequency) or complication of such a concurrent condition, the 
worsening or complication will be recorded as an AE. The Investigator will ensure that the AE term 
recorded captures the change in the condition (e.g., “worsening of…”). 
12.5.3 Elective or Pre-Planned Surgeries or Procedures: 
Procedures (surgeries or therapies) that were planned before the start of AE collection are not 
considered AEs. However, if a pre-planned procedure is performed early (e.g. as an emergency) due 
to a worsening of the pre-existing condition, the worsening of the condition will be captured as an 
AE. Elective procedures planned or performed where there is no change in the subject’s medical 
condition will not be recorded as AEs, but will be documented in the subject’s source documents. 
12.5.4 Overdose Reporting 
Cases of study drug overdose without manifested side effects are NOT considered AEs. 
12.5.5 Clinical Laboratory Abnormalities and Other Abnormal Assessments  
All laboratory values must be reviewed by the Investigator or medically qualified designee as soon 
as practical after the data are available. 
Any laboratory values outside the reference range will be evaluated for clinical significance. 
Laboratory abnormalities that occur without related clinical symptoms and signs should generally 
not be recorded as AE unless they represent a clinically significant event. Where possible, the 
overall diagnosis rather than the laboratory abnormality should be recorded on the AE CRF. This 
will avoid duplication of laboratory abnormalities in both the AE and laboratory reports. Abnormal 
laboratory results that are of clinical significance should be reviewed by the Medical Monitor. 
Any laboratory test result that meets the criteria for a SAE (refer to Section 12.3) should be recorded 
as an AE, the AE page of the CRF completed and a SAE form also completed in order for the 


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sponsor to collect additional information about that abnormality, including information regarding 
relationship to study product or other causes, any action taken and resolution. 
12.6 Guidance for Dose Modification or Discontinuation of Treatment 
Dose modification or discontinuation of treatment are not applicable in this single dose study. 
12.7 Warnings and Precautions 
For information regarding precautions and AEs with the investigational drug, the Investigator is 
referred to the Investigator’s Brochure and Prescribing Information for moxidectin. 
12.8 Risks for Women of Childbearing Potential or During Pregnancy 
The risks of treatment with moxidectin during pregnancy have not been evaluated. Women of child-
bearing potential must agree not to attempt to become pregnant. If participating in sexual activity 
that could lead to pregnancy, women of child-bearing potential and male partners of women of 
child-bearing potential must agree to use a reliable method of contraception during the study and for 
the 6 months following study drug administration. 
12.9 Procedures to be Followed in the Event of Pregnancy 
The subject must be instructed to inform the Investigator immediately if she becomes pregnant 
during the study period or if his partner becomes pregnant. The Investigator should report all 
pregnancies to the Sponsor or designee within 24 hours of becoming aware of the pregnancy. 
Pregnancies should be reported using Clinical Pregnancy Notification Form provided by the Sponsor 
for reporting the occurrence and outcome of pregnancies in subject enrolled in the study. 
The subject should be monitored until the end of the pregnancy and the outcome of the pregnancy 
should be reported to the Sponsor. 


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13 
PROTOCOL STEERING COMMITTEE 
The Protocol Steering Committee will ensure the study meets its objectives to identify a well-
tolerated and optimally effective dose of moxidectin for scabies. The Committee will be comprised 
of up to two external experts, up to two Sponsor representatives not directly involved in 
management of the study, and a statistician. 
The Committee will review relevant accumulated unblinded safety and efficacy data for all 
randomized subjects collected through to the review cutoff date. The data review cutoff date will 
correspond to the date when the first 3 subjects in each of the 3 initial treatment arms have 
completed their Day 14 study evaluation. Study recruitment may be paused during the review 
period. 
Based on a review of the available data, the Committee will recommend one or more of the 
following actions:  
• Continuation of the study with no dose modification to the target sample size of 6 subjects 
per cohort; or, 
• Stopping recruitment of one of more of the current dose cohorts; and/or, 
• The addition of a 36 mg dose cohort. 
Should design modifications be recommended, the study will maintain the randomized allocation of 
subjects to the remaining/additional treatment cohorts, to a target sample size of 6 subjects. 
The decision-making process of the Committee will be guided by: 
• The mortality rate of adult scabies mites, or the time-to-death of adult scabies mites. 
Subject-level review may also be considered. 
• Safety outcomes, such as the frequency, nature and severity of adverse events, and 
withdrawal rates. 
• Pharmacokinetic data may be reviewed if available. 
The Committee will not reveal the results of their data review or, barring any unanticipated safety 
issues, any decisions or recommendations to Investigators, study personnel, or Sponsor personnel 
involved in the management of day-to-day study activities (Section 10.2).  
Minutes of the Protocol Steering Committee meetings as well as the interim data reviewed will be 
documented but remain confidential until the study’s conclusion. Additional unblinded  reviews and 
possible dose modification recommendations may also be undertaken by the Committee at any time 
at, or in lieu of the data review described above, at the request of the Sponsor.  
Further details can be found in the Protocol Steering Committee Charter. 
 


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14 
SUBJECT COMPLETION/WITHDRAWAL 
14.1 Subject Completion 
A subject will be deemed to have completed the study once all trial procedures have been 
conducted. Any AEs or SAEs still ongoing at the time of the Exit Evaluation will be followed in 
accordance with Section 12. 
14.2 Criteria for Premature Withdrawal from Treatment or the Study 
Subjects have the right to withdraw from the study at any time for any reason. The Investigator must 
make every reasonable effort to keep each subject in the study except where termination or 
withdrawal is for reasons of safety. The Investigator also has the right to withdraw patients from 
treatment or the study in the event of concurrent illness, AEs, pregnancy, treatment failure after a 
prescribed procedure, protocol violations, administrative reasons or other reasons. The reasons for 
withdrawal of the subject must be recorded on the CRF. 
It is understood by all concerned that an excessive rate of withdrawals from the study can render the 
study difficult to interpret. Unnecessary withdrawal of subjects from the study should be avoided. 
14.3 Withdrawal of Subjects from Study Product 
Treatment withdrawal is not relevant in this single dose study. 
If a subject is unable to swallow all required tablets and take the full dose of IMP, they should 
remain on-study and be followed up according to the protocol.  
14.4 Withdrawal of Subjects from the Study 
Should a subject decide to withdraw from the study, all efforts will be made to complete the study 
procedures as thoroughly as possible. 
If possible, the reason for withdrawal should be determined. The reason for withdrawal should be 
established by the Investigator through phone contact, a personal visit or by contacting a responsible 
relative. The reason for withdrawal should be included in a complete final evaluation which should 
be conducted at the time of the subject withdrawal. If applicable, where possible, subjects should be 
followed until ongoing AEs have been resolved or abnormal laboratory tests have returned to 
normal. 
14.5 Replacement of Withdrawn Subjects 
Any subjects who discontinues in a clinical study of their own volition or by the Investigator are 
defined as “withdrawals”. Replacement subjects may be enrolled into the study at the request of the 
Sponsor. They will receive the same treatment allocation as the withdrawn subject by use of a 
matching replacement subject number pre-assigned for each subject. This is to ensure that blinding 
is maintained. Further details are provided in the Study Reference Manual.  
14.6 Premature Termination of the Study 
The study will be completed as planned unless the following criteria are met: 
• New information regarding the safety or efficacy of the study drug that indicates a change in 
the risk/benefit profile of the IMP, such that the risks and benefits of the study are no longer 
acceptable to study subjects. 
• Significant violation of good clinical practice (GCP) that compromises the ability to achieve 
the primary study objective or compromises subject safety. 


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Conduct of the study at an investigational site may be terminated if the Investigator or site staff are 
found in significant violation of GCP, the protocol or other contractual agreements, or are unable to 
ensure adequate performance of the study. 
In the event that the Sponsor elects to terminate the study or an investigational site, an early 
termination procedure will be provided by the Sponsor, which will be followed by the 
investigational site(s) during the course of termination. 


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15 
STATISTICAL ANALYSIS 
15.1 Statistical Methods 
The study is a randomized, double-blind, proof-of-concept trial designed to describe the association 
between single moxidectin doses and various parasitological outcomes observed over a 28-day 
follow-up period. Subjects will continue to be followed for safety to Week 12. Following Screening, 
eligible consenting subjects will be randomized to one of the 3 initial moxidectin dose groups, 2, 8, 
or 20 mg. The randomization will be stratified by site and within each site subjects will be 
randomized using a 1:1:1 allocation ratio. After review of the accumulating data by the Protocol 
Steering Committee, the randomization scheme may be modified to accommodate the addition or 
deletion of doses such that the final target sample size of 6 subjects per dose retained/added after the 
unblinded data review is accommodated. The primary objective of this proof-of-concept study is to 
identify an optimal dose of moxidectin for further study.  
The target sample size, n = 6 per completed dose group, was selected to be practical and an adequate 
sample size for full characterization of pharmacokinetic profile across the dose ranges studied.  
Sample size was not based on formal power considerations with respect to statistical hypothesis 
testing, and as such, the focus of the statistical analysis will be descriptive and exploratory. 
Nonetheless, statistical models for estimation and hypothesis testing to assess various parasitological 
assessments with respect to dose may be conducted. It is recognized that the sample size may not 
adequately support more complex models. When this is the case it will be noted. Given the 
exploratory nature of the study, no adjustment for multiple comparisons or Protocol Steering 
Committee data reviews will be made. Given the small sample size per dose group, descriptive 
analyses per site may be difficult to interpret.    
For most analyses, the unit of analysis will be the subject; however, some analyses may be 
conducted where the unit of analysis may be the individual scabies mite. When this is the case, the 
unit of analysis will be clearly identified. Analyses using the individual scabies mite as the unit of 
analysis will address the potential lack of independence between mites belonging to the same 
subject.  
General statistical methods of analysis are described below with more detailed descriptions to be 
provided in the Statistical Analysis Plan (SAP). The SAP will be finalized prior to breaking the 
blind for the final analysis. Any changes to the statistical analysis plan made after the blind break 
will be identified in the clinical study report (CSR). 
15.2 Hypothesis 
Study data will be analyzed in a descriptive manner with the objective of describing an exposure-
response association between the moxidectin dose groups and parasitological outcomes and/or 
observing a single exposure or dose that appears to have the “best” parasitological effect while 
maintaining an acceptable safety profile. 
15.3 Sample Size Determination 
The sample size chosen for this study, approximately 6 subjects per dose group, was selected to be 
practical and an adequate sample size for full characterization of pharmacokinetics profile across the 
dose ranges studied. Sample size was not based on formal power considerations with respect to 
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15.4 Analysis Sets 
15.4.1 Full Analysis Set 
The Full Analysis Set (FAS) is defined as all randomized subjects receiving at least one dose of 
study drug with observed data for the particular analysis undertaken. Subjects in the FAS analysis 
set will be analyzed according to the dose group to which they were randomized. In general, the 
FAS will be used for selective analyses such as sensitivity analyses. 
15.4.2 Per Protocol Analysis Set 
The Per Protocol Analysis Set (PPAS) will include all subjects exposed to study drug without any 
major protocol deviations that could confound the assessment and/or interpretation of the analytic 
results. The identification of these protocol deviations will be identified by the study team prior to 
breaking the study blind. Subjects in the PPAS will be analyzed according to the actual treatment 
received regardless of their randomized dose group. In general, PPAS subjects with missing data for 
a specific analysis will be excluded from that analysis. It is not anticipated that missing data will be 
imputed. As this is a proof-of-concept study, the PPAS will be the primary analysis set used to 
assess parasitological outcomes as well as clinical signs and symptoms endpoints. Replacement 
subjects will be included in the PPAS if they meet the PPAS requirements. 
15.4.3 Safety Analysis Set 
The Safety Analysis Set (SfAS) will include all subjects exposed to study drug. Subjects will be 
analyzed according to the actual dose of study drug received regardless of their randomized dose 
group. Unless otherwise noted, the SfAS will be used for all safety analyses. 
15.4.4 Pharmacokinetic Analysis Set 
The Pharmacokinetic Analysis Set (PKAS) will include all subjects who received at least one dose 
of moxidectin and provide an adequate number of blood samples for the determination of plasma 
pharmacokinetic parameters using the methods described in Section 15.7.4.  
15.4.5 Pharmacokinetic/Pharmacodynamic Analysis Set 
The Pharmacokinetic/Pharmacodynamic Analysis Set (PKPDAS) will include all subjects who 
received at least one dose of moxidectin and provide blood samples for the determination of plasma 
pharmacokinetic parameters matched with RCM assessments of parasitological outcomes.  
15.5 Analysis Periods and Interim Analysis 
15.5.1 Protocol Steering Committee Data Review 
No formal interim analysis is planned. The Protocol Steering Committee will review unblinded 
safety and efficacy data as described in Section 13 and with the ability to make dose modification 
recommendations. The analyses to be conducted during these interim reviews may entail review of 
individual subject line listings and/or aggregate data. Since the study is exploratory and not powered 
to conduct hypothesis testing, no adjustments to the type I error rate will be implemented. Further 
details will be provided in the SAP and Protocol Steering Committee Charter. 
15.5.2 Final Analysis 
For purposes of final statistical analysis, this study is divided into two study periods:  
• Period 1: Commences at Screening and will finish on Day 28. The study blind will be 
maintained during this study period. After the last subject has completed the study through 
Period 1, the blind will be broken and the data from Period 1 will be analyzed. 


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• Period 2: Runs from Day 29 to Week 12. Data from Period 2 will be analyzed after all 
subjects have completed the study through Week 12. Data for some subjects may be 
collected during Period 2 after the blind has been broken and the Period 1 study results 
known. The Period 2 data will be provided in an additional safety supplement. Although the 
blind will be broken after the last subject completes Period 1, the individual treatment 
assignment will not be communicated to the subject, investigator, or site personnel until the 
last subject has completed Period 2.  
Efficacy and safety data obtained for subjects randomized to all doses, including doses that may 
have been discontinued or added based on the recommendation from the Protocol Steering 
Committee, will be included in the final analysis. Further details of analysis will be provided in the 
SAP. 
15.6 Study Endpoints 
15.6.1 Key Efficacy Endpoints 
The primary efficacy endpoint of the study will be determined by the death of adult scabies mites, 
with death defined as the degradation (homogenization of internal structures and/or external 
anatomic structures, and increased reflectance) of the adult mite observed by RCM. Mites will be 
assessed at Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28 in not less than two lesions nominated 
pre-treatment. The average proportion (crude mortality rate) of dead adult scabies mites per subject 
will be calculated as the number of dead adult scabies mites from among the live adult scabies mites 
identified at Baseline for each individual subject calculated at each time point measured. The 
proportion of subjects with 100% dead adult scabies mites from among the live adult scabies mites 
identified at Baseline calculated at each time point measured will also be reported. 
The following are examples of key efficacy endpoints defined at the individual mite level of 
analysis:  
• The mortality rate for adult scabies mites from among those identified at Baseline, calculated 
at each time point measured. 
• The time-to-death of adult scabies mites from among those identified at Baseline. 
15.6.2 Key Pharmacokinetic Endpoints 
Exposure metrics of moxidectin will be determined by non-compartmental analysis of key 
moxidectin pharmacokinetic parameters or other methods as appropriate assessed up to and 
including Day 28. 
Specific pharmacokinetic parameters for moxidectin in plasma will include: 
• AUC0-last: AUC from time 0 extrapolated to the last observed concentration  
• AUC0-inf: AUC from time 0 extrapolated to infinity  
• AUC0-t: AUC from time 0 extrapolated to time t (where t = 24, 48, 72 Hours, Day 7, 14 
and 28) 
• Cmax: maximum observed plasma concentration 
• Tmax: time to maximum observed plasma concentration 
• t1/2: terminal elimination half-life 
Additional pharmacokinetic parameters, including apparent clearance (CL), apparent volume of 
distribution (Vd), and others may be determined as appropriate. The pharmacokinetic parameters 
will be expressed in units adjusted for molecular weight where appropriate. 


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15.6.3 Exploratory Endpoints 
The exploratory endpoints of the study are: 
• At Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28, using assessment by RCM of burrows 
identified at Baseline: 
o changes in adult mite motility (peristalsis and/or movement) over at least 30 seconds 
of observation; 
o presence, number, morphology and motility of juvenile scabies mites; 
o presence of eggs and scybala in burrows  
• Presence and number of total mites and burrows assessed visually at Days 7, 14 and 28. 
• Changes in assessment of clinician-reported scabies symptomology, including extent of 
symptoms on body regions assessed by the number of anatomically-defined regions affected, 
number of lesions and severity grading of excoriations and erythema. 
• Changes in patient reported outcomes, measured by Numerical Rating Scale, 5-D Itch Scale 
and Dermatology Life Quality Index. 
• Clinical cure rates at Days 7, 14 and 28. Clinical cure is defined as resolution of all scabies 
signs and symptoms present at Baseline, no new scabies signs and symptoms and no 
evidence of mites by dermoscopy. 
15.6.4 Safety Endpoints 
• Incidence and severity of treatment emergent adverse events (TEAEs) 
• Incidence of serious TEAEs 
• Incidence of TEAEs leading to study withdrawal and/or death 
• Changes from baseline in laboratory assessments, vital signs, and physical exams 
15.7 General Analytic Methods 
15.7.1 Overview 
The focus of the statistical analysis will be descriptive and exploratory. Statistical models for 
estimation and/or hypothesis testing to assess various parasitological assessments with respect to 
dose may be conducted; however, it is recognized that the sample size may not adequately support 
more complex models that may be utilized to account for the clustering of scabies mites within 
subjects. When this is the case it will be noted. Given the exploratory nature of the study, no 
adjustment for multiple comparisons will be made.  
Detailed methods will be provided in the SAP. 
15.7.2 Subject Disposition, Demographic and Medical History 
Tables of summary data reflecting subject disposition including the number of subjects randomized, 
the number of subjects receiving study drug, the number of subjects in each analysis set, and the 
number of subjects withdrawing early including the reasons for early withdrawal will be tabulated 
by dose group and overall. 
Summaries of baseline demographic data and medical history, and baseline infection status will also 
be provided. 
15.7.3 Analysis of Key Efficacy Endpoints 
Continuous key efficacy endpoints will be summarized via the mean, standard deviation (SD), 
median, minimum, maximum, and the number of subjects with observed data by dose group and 
overall. Categorical key efficacy endpoints will be summarized via the number and percent 


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(proportion) of subjects within each category. Where feasible, 95% confidence intervals will also be 
provided. Summary measures where the mite is the unit of analysis will be identified. Due to the 
possible lack of independence between scabies mites observed within the same subject, where 
possible, “robust” standard errors and/or estimates resulting from models accounting for the 
clustering will be presented along with any unadjusted estimates.  
For the key efficacy endpoints, the PPAS will be used as the primary analysis set. If the FAS differs 
from the PPAS, sensitivity analyses using the FAS may also be conducted to assess differences 
between the two analysis sets. 
For continuous subject level endpoints such as the average proportion of dead adult scabies mites 
per subject, pairwise comparisons between dose groups may be conducted using an unpaired t-test 
or nonparametric Wilcoxon Rank-Sum Test if the assumptions of the t-test do not appear to hold. 
Binary endpoints at the subject level such as clinical cure rates may be examined via logistic 
regression models or chi-square tests with estimates of the relative risk and their associated 95% 
confidence intervals. Where appropriate exact methods will be employed. 
Point estimates and confidence intervals for the mortality rates when the scabies mite is the unit of 
analysis will be estimated using a logistic regression model with “robust” standard errors. 
Additionally, the analysis of these data using a Generalized Linear Mixed Models (GLMMs) with 
random intercepts or a Generalized Estimating Equation (GEE) model may be employed. The time-
to-death for an individual scabies mite may be analyzed using a frailty survival model.  
Because of the small sample sizes, it is recognized that convergence or estimation issues may arise 
for some of more complex exploratory models that may be conducted. 
 Further details will be provided in the SAP. 
15.7.4 Analysis of Pharmacokinetics 
Non-compartmental analysis (NCA), using Phoenix WinNonlin version 6.4, or post-hoc model-
based exposure estimates will be implemented for the calculation of pharmacokinetic parameters as 
appropriate. The Cmax will be excluded from all estimations of elimination rate constants for NCA. 
The elimination rate constant will be estimated if a given subject has more than 2 concentration 
values in the terminal portion of the curve and R square greater than 0.95. Computed 
pharmacokinetic parameters for moxidectin in plasma will be summarized and listed by treatment 
group, including mean, geometric mean, SD, median, and range, as appropriate. 
15.7.5 Analysis of Pharmacokinetics/Pharmacodynamics 
Exposure metrics, including Cmax and AUC, and pharmacodynamic data will be pooled across the 
study. The relationship between efficacy endpoints and plasma concentrations of moxidectin for all 
subjects in the PKPDAS will be assessed graphically using scatterplots or box plots, as appropriate 
to the pharmacodynamic endpoint. pharmacokinetic/pharmacodynamic analysis techniques will be 
applied as appropriate. For example, logistic regression or time-to-event modelling approaches may 
be applied to examine pharmacokinetic/pharmacodynamic where a binary pharmacodynamic 
outcome variable is desired. Alternatively, analysis of continuous pharmacodynamic data may use 
nonlinear or quantile regression response (Emax). 
If deemed appropriate at the conclusion of the study, an existing moxidectin population-
pharmacokinetic model will be updated with the pharmacokinetic data from this study to enable 
formal comparison of the moxidectin pharmacokinetic characteristics observed within the scabies 
patient population to other populations administered moxidectin. Where appropriate, this refreshed 


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population-pharmacokinetic model will then be linked to critical pharmacodynamic responses 
observed during the study to enable selection of dose regimens for future clinical studies by clinical 
trial simulations. 
15.7.6 Analysis of Safety 
15.7.6.1 
Treatment Emergent Adverse Events 
Subject incidence of treatment emergent adverse events (TEAEs) will be summarized by dose group 
and overall using the SfAS. Events will be categorized by body system and preferred term. AEs will 
also be summarized by severity, investigator assessment of relationship to study drug, serious 
events, and events leading to withdrawal or death. Line listings of all TEAEs will be provided. 
15.7.6.2 
Laboratory Assessments 
Summary statistics at each time point and changes from Baseline will be provided by dose group 
and overall for laboratory assessments. For continuous assessments, means, SDs, medians, 
minimums and maximums will be provided. For categorical assessments, the number and percent of 
subjects in each category will be provided. Shift tables may also be calculated. All laboratory 
assessments will be included in line listings. Further details will be provided in the SAP. 
15.7.6.3 
Vital Signs and Physical Exams 
The analysis of vital signs and physical exams will be similar to laboratory assessments. 
15.7.7 Other Efficacy Analysis 
Other efficacy analyses will be documented as part of the SAP. 
15.7.8  Exploratory Analyses 
The general analysis of the exploratory endpoints will follow similar analyses to those outlined 
above for the key efficacy endpoints. Further details will be provided in the SAP along with the 
scoring methodology for patient-reported outcome instruments. 
15.7.9 Handling of Missing Data 
In general, data will not be imputed except for the imputation of partial start and stop dates for AEs 
and concomitant medications. If an AE or medication cannot be identified as a TEAE or a 
concomitant medication because of a missing or partial date, the dates will be imputed using a pre-
specified algorithm for the purpose of making the assignment. 
Description of missing data and the potential impact on study results and interpretation particularly 
as it relates to key safety or efficacy assessments may be made with special attention to missing data 
associated with COVID-19. 
Details will be provided in the SAP. 
 


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16 
GENERAL STUDY ADMINISTRATION 
16.1 Ethical Aspects 
16.1.1 Local Regulations/Declaration of Helsinki 
The Investigator will ensure that this study is conducted in full conformance with the protocol, the 
latest version of the Declaration of Helsinki (and its amendments), and with the requirements of 
national drug and data protection laws of the countries in which the research is conducted. 
The Sponsor and the Investigators will ensure strict adherence to the provisions of GCP and all 
applicable and national regulations. The International Conference on Harmonization (ICH) 
guidelines will apply at a minimum. 
16.1.2 Informed Consent 
A model informed consent form template is provided in Appendix 18.2 for the preparation of the 
informed consent document to be used at sites. The written informed consent document should be 
prepared in the language(s) of the potential subject population. 
It is the responsibility of the Investigator to obtain written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives and potential 
hazards of the study prior to undertaking any study related procedures. The Investigator must also 
explain to the subject that they are completely free to refuse to enter the study or to withdraw from it 
at any time for any reason. The Investigator must use an Institutional Review Board (IRB) or IEC-
approved consent form for documenting written informed consent. 
16.1.3 Institutional Review Boards or Ethics Committees 
This protocol and any accompanying material provided to the subject (such as subject information 
sheets or descriptions of the study used to obtain informed consent), will be submitted to an IEC. 
Approval from the committee must be obtained before starting the study, and should be documented 
in a letter to the Investigator specifying the protocol number and version and the date on which the 
committee met and granted the approval. 
Any modifications made to the protocol after receipt of IEC approval must also be submitted to the 
committee in accordance with institutional procedures and regulatory requirements. 
When no local review board exists, the Investigator is expected to identify an appropriate review 
board for submission. 
16.1.4 Conditions for Modifying the Protocol 
Protocol modifications to ongoing studies which could potentially adversely affect the safety of 
participating subjects or which alter the scope of the investigation, the scientific quality of the study, 
the experimental design, dosages, duration of therapy, assessment variables, the number of subjects 
treated or subject selection criteria, may be made only after issue of a protocol amendment by the 
Sponsor and approval at the site. No prospective protocol waivers will be permitted in the study. 
Protocol modifications (amendments) must be prepared by a representative of the Sponsor and 
initially reviewed and approved by the responsible Medical Monitor and (when applicable) the 
Statistician. 
All protocol modifications must be submitted to the IEC in accordance with local requirements. 
Approval must be obtained before changes can be implemented. 


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In the event of an emergency, the Investigator may institute any medical procedures deemed 
appropriate. However, all such procedures must be promptly reported to the Sponsor, the Medical 
Monitor and the IEC. 
A protocol deviation is defined as any change from the Sponsor and IEC-approved protocol, 
regardless of whether it has been prospectively approved by the Sponsor or IEC. Protocol deviations 
that avoid or reduce an immediate hazard to trial subjects do not require prior approval. 
Administrative changes of the protocol are defined as minor corrections and/or clarifications that 
have no effect on the way the study is to be conducted, or on the safety of the subjects. These 
administrative changes will be agreed upon by the Sponsor and the Investigator, and will be 
documented in a memorandum. The Investigator will then notify the IEC of such administrative 
changes. 
16.1.5 Conditions for Terminating the Study 
Both the Sponsor and the Investigator reserve the right to terminate the study at any time. Should 
this be necessary, the procedures will be arranged on an individual study basis after review and 
consultation by both parties. In terminating the study, the Sponsor and the Investigator will assure 
that adequate consideration is given to the protection of the subject’s interests. 
16.2 Study Documentation, Case Report Forms and Record Keeping 
16.2.1 Investigator’s files/Retention of Documents 
The Investigator must maintain adequate and accurate records to enable the conduct of the study to 
be fully documented and the study data to be subsequently verified. These documents should be 
classified into two separate categories: (1) Investigator’s Site File, and (2) subject clinical source 
documents. 
The Investigator’s Site File will contain the protocol/amendments, CRFs and Query Forms, IEC and 
governmental approval with correspondence, informed consent, drug records, staff curriculum vitae 
and authorization forms and other appropriate documents and correspondence. 
Subject clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the CRFs) would include subject hospital/clinic records, 
physician’s and nurse’s notes, appointment book, original laboratory reports, ECG, 
electroencephalogram, X-ray, pathology and special assessment reports, consultant letters, screening 
and enrolment log, etc. All clinical study documents must be retained by the Investigator until at 
least 2 years after the last approval of a marketing application in an ICH region (i.e. USA, Europe, 
or Japan) and until there are no pending or contemplated marketing applications in an ICH region; or 
if no application is filed or if the application is not approved for such indication, until 2 years after 
the investigation is discontinued and regulatory authorities have been notified. The Investigator must 
notify the Sponsor prior to destroying any clinical study records. 
Should the Investigator wish to assign the study records to another party or move them to another 
location, the Sponsor must be notified in advance. 
If the Investigator cannot guarantee this archiving requirement at the study site for any or all of the 
documents, special arrangements must be made between the Investigator and the Sponsor to store 
these in a sealed container(s) outside of the site so that they can be returned sealed to the 
Investigator in case of a regulatory audit. Where source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the site. 


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16.2.2 Background Data 
The Investigator shall supply the Sponsor, on request, with any required background data from the 
study documentation or clinic records. This is particularly important when CRF are illegible or when 
errors in data transcription are suspected. In case of special problems and/or governmental queries or 
requests for audit inspections, it is also necessary to have access to the complete study records, 
provided that subject confidentiality is protected. 
16.2.3 Audits and Inspections 
The Investigator should understand that source documents for this trial should be made available to 
appropriately qualified personnel from the Sponsor or its representative or to regulatory authority or 
health authority inspectors after appropriate notification. The verification of the CRF data may be by 
direct inspection of source documents (where permitted by law) or through an interview technique. 
16.2.4 Case Report Forms 
CRFs (paper or electronic format) must be completed for each subject enrolled, and signed by the 
Principal Investigator or co-Investigator. This also applies to records for those subjects who fail to 
complete the study. If a subject withdraws from the study, the reason must be noted on the CRF. The 
CRF is essentially a data entry form and should not constitute the original, or source document. 
Data collection and entry into the CRF will be completed by authorized study site personnel 
designated by the Investigator. Appropriate training will be completed with the Investigator and all 
authorized study site personnel prior to the study being initiated and any data being entered into the 
CRF for any study participants. 
All data must be entered in English. The CRFs should always reflect the latest observations on the 
participants participating in the trial and are to be completed as soon as possible after the 
participant’s visit. The Investigator must verify that all data entries in the CRFs are accurate and 
correct. If some assessments are not done, or if certain information is not available or not applicable 
or unknown, this should be indicated in the CRF. 
The CRFs and the protocol are confidential. The CRFs remain the property of the Sponsor at all 
times. 
16.3 Monitoring the Study 
Before the start of the trial, a representative of the Sponsor or designee will contact the 
investigational site to ensure facilities are adequate and discuss responsibilities with the site staff 
with regards to following the protocol and regulatory and ethical requirements. 
During the trial, a representative from the Sponsor or its designee will regularly visit the site to 
monitor and confirm protocol, regulatory and ethical adherence, confirm data accuracy and provide 
information and support as needed. 
In accordance with ICH GCP guidelines, the study monitor must have direct access to the 
Investigator’s source documentation in order to verify the data recorded in the CRFs for consistency. 
It is understood that the responsible monitor, as the Sponsor representative, will contact and visit the 
Investigator regularly and that he/she will be allowed, on request, to inspect the various records of 
the trial (CRFs and other pertinent data) provided that subject confidentiality is maintained in accord 
with local requirements. 
It will be the monitor’s responsibility to inspect the CRFs at regular intervals throughout the study, 
to verify the adherence to the protocol and the completeness, consistency and accuracy of the data 


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being entered on them. Where local regulations permit, the monitor should have access to laboratory 
test reports and other subject records needed to verify the entries on the CRF. The Investigator 
agrees to cooperate with the monitor to ensure that any problems detected in the course of these 
monitoring visits are resolved. 
16.4 Confidentiality of Trial Documents and Subject Records 
The Investigator must assure the subjects’ anonymity will be maintained and that their identities are 
protected from unauthorized parties. On CRFs or other documents submitted to the Sponsor, 
subjects should not be identified by their names, but by the subject’s initials and an identification 
code. The Investigator should keep a subject enrolment log showing codes, names and addresses. 
Documents not for submission to the Sponsor (e.g. subject’s written consent forms), should be 
maintained by the Investigator in strict confidence. 
All information concerning the study treatment and the Sponsor and its operation, such as patent 
applications, formulae, manufacturing processes, basic scientific data and material not previously 
published are considered confidential and shall remain the sole property of the Sponsor. The 
Investigator agrees to use this information only in accomplishing the study and will not use it for 
any other purposes without written consent from the Sponsor. 
16.5 Publication of Data and Protection of Trade Secrets 
In accord with standard editorial and ethical practice, the Sponsor will support publication of 
multicenter trials only in their entirety and not as individual center data. 
The Sponsor will list the study on a public database listing of clinical trials, for example, 
www.clinical trials.gov. 
The results of this study may be published or presented at scientific meetings. If this is envisaged, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor prior to submission. 
This allows the Sponsor to protect proprietary information and to provide comments based on 
information from other studies that may not yet be available to the Investigator. 
Any formal publication of the study in which input of the Sponsor personnel exceeded that of 
conventional monitoring will be considered as a joint publication by the Investigator and the 
appropriate the Sponsor personnel. Authorship will be determined by mutual agreement prior to the 
completion of the study. 
16.6 Anticipated Subject Accrual and Duration of the Study 
The anticipated patient accrual will be agreed at the site initiation visit. The Investigator should 
continually compare the actual and expected accrual rates, and make every effort to ensure that they 
are as closely matched as possible. If the Investigator anticipates major problems with recruitment, 
or delay in the expected completion date, he/she should discuss this with the Sponsor as early as 
possible. 
 


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17 
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Negl Trop Dis 2018, 12 (5), e0006549. 
Fourie, L. J.; Heine, J.; Horak, I. G., The efficacy of an imidacloprid/moxidectin combination 
against naturally acquired Sarcoptes scabiei infestations on dogs. Aust Vet J 2006, 84 (1-2), 17-21. 
Fthenakis, G. C.; Papadopoulos, E.; Himonas, C.; Leontides, L.; Kritas, S.; Papatsas, J., Efficacy of 
moxidectin against sarcoptic mange and effects on milk yield of ewes and growth of lambs. Vet 
Parasitol 2000, 87 (2-3), 207-16. 
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, Global, regional, and 
national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–
2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016, 388, 1545–
602. 
Giadinis, N. D.; Farmaki, R.; Papaioannou, N.; Papadopoulos, E.; Karatzias, H.; Koutinas, A. F., 
Moxidectin efficacy in a goat herd with chronic and generalized sarcoptic mange. Vet Med Int 2011, 
2011, 476348. 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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Karimkhani, C.; Colombara, D. V.; Drucker, A. M.; Norton, S. A.; Hay, R.; Engelman, D.; Steer, 
A.; Whitfeld, M.; Naghavi, M.; Dellavalle, R. P., The global burden of scabies: a cross-sectional 
analysis from the Global Burden of Disease Study 2015. The Lancet Infectious Diseases 2017. 
Kearns, T.; Clucas, D.; Connors, C.; Currie, B. J.; Carapetis, J. R.; Andrews, R. M., Clinic 
attendances during the first 12 months of life for Aboriginal children in five remote communities of 
northern Australia. PLoS One 2013, 8 (3), e58231. 
La Vincente, S.; Kearns, T.; Connors, C.; Cameron, S.; Carapetis, J.; Andrews, R., Community 
management of endemic scabies in remote aboriginal communities of northern Australia: low 
treatment uptake and high ongoing acquisition. PLoS Negl Trop Dis 2009, 3 (5), e444. 
Losson, B.; Lonneux, J. F., Field efficacy of injectable moxidectin in cattle naturally infested with 
Chorioptes bovis and Sarcoptes scabiei. Vet Parasitol 1993, 51 (1-2), 113-21. 
Marks, M.; Toloka, H.; Baker, C.; Kositz, C.; Asugeni, J.; Puiahi, E.; Asugeni, R.; Azzopardi, K.; 
Diau, J.; Kaldor, J. M.; Romani, L.; Redman-MacLaren, M.; MacLaren, D.; Solomon, A. W.; 
Mabey, D. C. W.; Steer, A. C., Randomised trial of community treatment with azithromycin and 
ivermectin mass drug administration for control of scabies and impetigo. Clin Infect Dis 2018. 
Micali, G.; Lacarrubba, F.; Verzi, A. E.; Chosidow, O.; Schwartz, R. A., Scabies: Advances in 
Noninvasive Diagnosis. PLoS Negl Trop Dis 2016, 10 (6), e0004691. 
Romani, L.; Koroivueta, J.; Steer, A. C.; Kama, M.; Kaldor, J. M.; Wand, H.; Hamid, M.; Whitfeld, 
M. J., Scabies and impetigo prevalence and risk factors in Fiji: a national survey. PLoS Negl Trop 
Dis 2015a, 9 (3), e0003452. 
Romani, L.; Steer, A. C.; Whitfeld, M. J.; Kaldor, J. M., Prevalence of scabies and impetigo 
worldwide: a systematic review. Lancet Infect Dis 2015b, 15 (8), 960-7. 
Romani, L.; Whitfeld, M. J.; Koroivueta, J.; Kama, M.; Wand, H.; Tikoduadua, L.; Tuicakau, M.; 
Koroi, A.; Andrews, R.; Kaldor, J. M.; Steer, A. C., Mass Drug Administration for Scabies Control 
in a Population with Endemic Disease. N Engl J Med 2015c, 373 (24), 2305-13. 
Rosumeck, S.; Nast, A.; Dressler, C., Ivermectin and permethrin for treating scabies. Cochrane 
Database Syst Rev 2018, 4, CD012994. 
Strategic and Technical Advisory Group for Neglected Tropical Diseases Report of the Tenth 
Meeting of the WHO Strategic and Technical Advisory Group for Neglected Tropical Diseases; 
World Health Organization: Geneva, Switzerland, 2017. 
United States Food and Drug Administration, Draft guidance on Permethrin. Drugs, O. o. G., Ed. 
2017. 
Worth, C.; Heukelbach, J.; Fengler, G.; Walter, B.; Liesenfeld, O.; Feldmeier, H., Impaired quality 
of life in adults and children with scabies from an impoverished community in Brazil. Int J 
Dermatol 2012a, 51 (3), 275-82. 
Worth, C.; Heukelbach, J.; Fengler, G.; Walter, B.; Liesenfeld, O.; Hengge, U.; Feldmeier, H., 
Acute morbidity associated with scabies and other ectoparasitoses rapidly improves after treatment 
with ivermectin. Pediatr Dermatol 2012b, 29 (4), 430-6. 
 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
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MDGH-MOX-2001 Protocol version 3 final 
Page 74 
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(incorporating Amendments 1 and 2) 
18 
APPENDICES 
18.1 Toxicity Grading Scale 
The FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
volunteers Enrolled in Preventive Vaccine Clinical Trials is available from: 
https://www.fda.gov/downloads/BiologicsBloodVaccines/ucm091977 
Tables from the guidance are presented for reference.  
A. Tables for Clinical Abnormalities 
Local Reaction to 
Injectable Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not 
interfere 
with activity 
Repeated use of non-
narcotic pain reliever 
> 24 hours or 
interferes with activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
Erythema/Redness * 
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Necrosis or exfoliative 
dermatitis 
Induration/Swelling ** 2.5 – 5 cm and 
does not 
interfere with 
activity 
5.1 – 10 cm or 
interferes with activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
* In addition to grading the measured local reaction at the greatest single diameter, the measurement should 
be recorded as a continuous variable. 
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
 
Vital Signs * 
Mild (Grade 1) 
Moderate(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fever (°C) ** 
(°F) ** 
38.0 – 38.4 
100.4 – 101.1 
38.5 – 38.9 
101.2 – 102.0 
39.0 – 40 
102.1 – 104 
> 40 
> 104 
Tachycardia - beats 
per minute 
101 – 115 
116 – 130 
> 130 
ER visit or 
hospitalization for 
arrhythmia 
Bradycardia - beats 
per minute*** 
50 – 54 
45 – 49 
< 45 
ER visit or 
hospitalization for 
arrhythmia 
Hypertension 
(systolic) - mmHg 
141 – 150 
151 – 155 
> 155 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypertension 
(diastolic) - mmHg 
91 – 95 
96 – 100 
> 100 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypotension (systolic) 
– mmHg 
85 – 89 
80 – 84 
< 80 
ER visit or 
hospitalization for 
hypotensive shock 
Respiratory Rate – 
breaths per minute 
17 – 20 
21 – 25 
> 25 
Intubation 


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* Subject should be at rest for all vital sign measurements. 
** Oral temperature; no recent hot or cold beverages or smoking. 
*** When resting heart rate is between 60 – 100 beats per minute.  Use clinical judgement when 
characterizing bradycardia among some healthy subject populations, for example, conditioned athletes. 
 
Systemic (General) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Nausea/vomiting 
No interference 
with activity or 1 
– 2 episodes/24 
hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily 
activity, requires 
outpatient IV 
hydration 
ER visit or 
hospitalization for 
hypotensive shock 
Diarrhea 
2 – 3 loose stools 
or < 400 g/24 
hours 
4 – 5 stools or 400 – 
800 g/24 hours 
6 or more watery 
stools or 
> 800 g/24 hours 
or requires 
outpatient IV 
hydration 
ER visit or 
hospitalization 
Headache 
No interference 
with activity 
Repeated use of 
non-narcotic pain 
reliever > 24 hours or 
some interference with
activity 
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity 
ER visit or 
hospitalization 
Fatigue 
No interference 
with activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
Myalgia 
No interference 
with activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
 
Systemic Illness 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Illness or clinical 
adverse event (as 
defined according to
applicable 
regulations) 
No interference 
with activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily 
activity and 
requires medical 
intervention 
ER visit or 
hospitalization 
 
B. Tables for Laboratory Abnormalities 
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Sodium – Hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
< 125 
Sodium – Hypernatremia mEq/L 
144 – 145 
146 – 147 
148 – 150 
> 150 
Potassium – Hyperkalemia mEq/L 
5.1 – 5.2 
5.3 – 5.4 
5.5 – 5.6 
> 5.6 
Potassium – Hypokalemia mEq/L 
3.5 – 3.6 
3.3 – 3.4 
3.1 – 3.2 
< 3.1 
Glucose – Hypoglycemia mg/dL 
65 – 69 
55 – 64 
45 – 54 
< 45 
Glucose – Hyperglycemia 
Fasting – mg/dL 
Random – mg/dL 
100 – 110 
110 – 125 
111 – 125 
126 – 200 
>125 
>200 
Insulin requirements 
or hyperosmolar 
coma 
Blood Urea Nitrogen 
BUN mg/dL 
23 – 26 
27 – 31 
> 31 
Requires dialysis 


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(incorporating Amendments 1 and 2) 
Serum * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
> 2.5 or requires 
dialysis 
Calcium – hypocalcemia mg/dL 
8.0 – 8.4 
7.5 – 7.9 
7.0 – 7.4 
< 7.0 
Calcium – hypercalcemia mg/dL 
10.5 – 11.0 
11.1 – 11.5 
11.6 – 12.0 
> 12.0 
Magnesium – hypomagnesemia mg/dL 
1.3 – 1.5 
1.1 – 1.2 
0.9 – 1.0 
< 0.9 
Phosphorous – hypophosphatemia 
mg/dL 
2.3 – 2.5 
2.0 – 2.2 
1.6 – 1.9 
< 1.6 
CPK – mg/dL 
1.25 – 1.5 x 
ULN*** 
1.6 – 3.0 x 
ULN 
3.1 –10 x 
ULN 
> 10 x ULN 
Albumin – Hypoalbuminemia g/dL 
2.8 – 3.1 
2.5 – 2.7 
< 2.5 
-- 
Total Protein – Hypoproteinemia g/dL 
5.5 – 6.0 
5.0 – 5.4 
< 5.0 
-- 
Alkaline phosphate – 
increase by factor 
1.1 – 2.0 x 
ULN 
2.1 – 3.0 x 
ULN 
3.1 – 10 x 
ULN 
> 10 x ULN 
Liver Function Tests –ALT, AST 
increase by factor 
1.1 – 2.5 x 
ULN 
2.6 – 5.0 x 
ULN 
5.1 – 10 x 
ULN 
> 10 x ULN 
Bilirubin – when accompanied 
by any increase in Liver Function Test 
increase by factor 
1.1 – 1.25 x 
ULN 
1.26 – 1.5 x 
ULN 
1.51 – 1.75 x 
ULN 
> 1.75 x ULN 
Bilirubin – when Liver Function Test 
is normal; increase by factor 
1.1 – 1.5 x 
ULN 
1.6 – 2.0 x 
ULN 
2.0 – 3.0 x 
ULN 
> 3.0 x ULN 
Cholesterol 
201 – 210 
211 – 225 
> 226 
--- 
Pancreatic enzymes – amylase, lipase 
1.1 – 1.5 x 
ULN 
1.6 – 2.0 x 
ULN 
2.1 – 5.0 x 
ULN 
> 5.0 x ULN 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional 
normal parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of 
the laboratory abnormalities as Potentially Life Threatening (Grade 4).  For example. a low sodium value that 
falls within a grade 3 parameter (125-129 mE/L) should be recorded as a grade 4 hyponatremia event if the 
subject had a new seizure associated with the low sodium value. 
***ULN” is the upper limit of the normal range. 
Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hemoglobin (Female) - g/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Hemoglobin (Female) 
change from baseline value -  g/dL 
Any decrease – 
1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (Male) - g/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Hemoglobin (Male) 
change from baseline value – gm/dL 
Any decrease – 
1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC Increase - cell/mm3 
10,800 – 15,000 15,001 – 
20,000 
20,001 – 25, 
000 
> 25,000 
WBC Decrease - cell/mm3 
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 < 1,000 
Lymphocytes Decrease - cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3 
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased - cell/mm3 
125,000 – 
140,000 
100,000 – 
124,000 
25,000 – 
99,000 
< 25,000 
PT – increase by factor 
(prothrombin time) 
1.0 – 1.10 x 
ULN** 
1.11 – 1.20 x 
ULN 
1.21 – 1.25 x 
ULN 
> 1.25 ULN 
PTT – increase by factor 
(partial thromboplastin time) 
1.0 – 1.2 x ULN 
1.21 – 1.4 x 
ULN 
1.41 – 1.5 x 
ULN 
> 1.5 x ULN 
Fibrinogen increase - mg/dL 
400 – 500 
501 – 600 
> 600 
-- 
Fibrinogen decrease - mg/dL 
150 – 200 
125 – 149 
100 – 124 
< 100 or associated 


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CONFIDENTIAL 
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(incorporating Amendments 1 and 2) 
Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
with gross bleeding 
or disseminated 
intravascular 
coagulation (DIC) 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional 
normal parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
** “ULN” is the upper limit of the normal range. 
 
Urine * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Protein 
Trace 
1+ 
2+ 
Hospitalization or 
dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization for 
hyperglycemia 
Blood (microscopic) – 
red blood cells per high power field 
(rbc/hpf) 
1 - 10 
11 – 50 
> 50 and/or 
gross blood 
Hospitalization or 
packed red blood 
cells (PRBC) 
transfusion 
* The laboratory values provided in the tables serve as guidelines and are dependent upon institutional 
normal parameters.  Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 78 
19 Jun 2020 
(incorporating Amendments 1 and 2) 
18.2 Model Patient Information Sheet and Consent Form 
Title 
A Phase II, randomized, double-blind, parallel group dose finding 
study of single oral doses of moxidectin in adults with scabies 
Protocol Number 
MDGH-MOX-2001 
EudraCT Number (if required) 
[Insert EudraCT Number] 
Study Sponsor 
Medicines Development Limited (trading as Medicines 
Development for Global Health) 
Coordinating Principal 
Investigator/ Principal 
Investigator 
[Insert Investigator Name] 
Associate Investigator(s) 
(if required by institution) 
[Associate Investigator(s)] 
Study Site 
[Site name] 
 
This Participant Informed Consent Form has two parts: 
• Information Sheet (to share information about the research with you) 
• Consent Form (for signatures if you agree to take part) 
 
You will be given a copy of this Participant Information Sheet and Consent Form to 
keep. 
 
 
Participant Information Sheet 
 
PART 1 WHAT DOES MY PARTICIPATION INVOLVE? 
1. INTRODUCTION 
You are invited to take part in this research study because you are aged 18 years or over and your 
doctor has diagnosed you with scabies infection. The research study is testing a new experimental 
medicine called moxidectin for the treatment of scabies.  
This Participant Information Sheet and Consent Form tells you about the research study. It explains 
the treatment and tests involved. This will help you decide if you want to take part in the research. 
Participation in this research is voluntary. If you don’t wish to take part, you don’t have to. You will 
still receive the best possible care. 
Please read this information carefully. Ask questions about anything that you don’t understand or 
want to know more about. Before deciding whether or not to take part, you might want to talk about 
it with a relative, friend or your local doctor. 
If you decide you want to take part in the research, you will be asked to sign the Consent Form. By 
signing it you are telling us that you: 
• Understand what you have read 
• Consent to taking part in the research study 


Sponsor: Medicines Development for Global Health  
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• Consent to having the tests and treatments that are described 
• Consent to the use of your personal and health information as described 
2. WHAT IS SCABIES? 
Scabies is an infection of the skin. It is caused by tiny mites that burrow just under the surface of the 
skin and can cause itch, rash and skin sores. Scabies can be found all over the world: the World 
Health Organization has estimated that approximately 130 million people worldwide currently have 
scabies. Anyone can get scabies. You can become infected with the scabies mite from any infected 
people you have had contact with or from clothing and other surfaces. 
3. WHAT ARE THE CURRENT TREATMENTS FOR SCABIES? 
Scabies is treated with a cream that contains a medicine called permethrin (as appropriate to the site: 
Lyclear®/Topiscab®). Permethrin cream is applied to the skin from head to toe, left on over-night 
and washed off the next morning. The cream works well but if it is not applied thoroughly, some 
people can continue to have scabies. Scabies is also treated with another medicine available in tablet 
form called ivermectin. This is taken by mouth and is also very effective, but a second treatment is 
needed about one or two weeks after the first to kill all the mites.  
4. WHY ARE YOU BEING ASKED TO PARTICIPATE IN THIS STUDY? 
You are being asked to take part in what is called a Phase 2 clinical trial. We are doing this research 
study to find out if moxidectin can be used to treat scabies and also to find the best dose of 
moxidectin to treat it. 
5. WHAT IS MOXIDECTIN? 
Moxidectin is an experimental medicine and has not been approved for treatment of scabies 
anywhere in the world. However, it is believed that moxidectin may be useful as it is used in many 
countries to treat the scabies mite that infects animals.  
Moxidectin is from a class of drugs called “macrocyclic lactones” which includes ivermectin, the 
treatment for scabies mentioned before. Moxidectin 8 mg as a single dose has been approved by the 
United States Food and Drug Administration for the treatment of river blindness (also known as 
onchocerciasis), a disease found in Africa and Latin America caused by a parasitic worm.  
6. WHERE IS THIS STUDY BEING CONDUCTED AND HOW MANY PEOPLE ARE 
TAKING PART? 
This study is being conducted at approximately 4 hospitals in France and Australia. Up to 
approximately 36 people are going to take part. 
7. WHO IS BEING ASKED TO TAKE PART? 
People aged 18 years old and above who are known or suspected to have scabies are being asked to 
take part in this research study.  
8. DO I HAVE TO TAKE PART IN THIS RESEARCH STUDY? 
No. Your participation in the study is voluntary and it is up to you to decide whether or not to take 
part. If you decide to take part and later change your mind, you are free to withdraw at any time. This 
will not affect your future treatment, or your relationship with your local doctor or the study doctor 
or other staff at the clinic. Your study doctor will discuss available treatment options with you before 
you decide to take part in this research study. You can also discuss the options with your local doctor 
and anyone else you choose.  


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9. HOW DO I KNOW IF I CAN TAKE PART? 
Your doctor and the clinic team will check if you are eligible to take part in the study, also known as 
screening. You will be asked questions about your health and previous treatments by the doctor 
and/or study team, who will also examine you and take blood tests to see if you are eligible to take 
part. Your doctor will explain all results and let you know if you are eligible. If not, they will discuss 
your alternative treatment options with you.  
10. WHAT ARE THE TREATMENTS IN THE STUDY? 
Because we don’t know which dose of moxidectin is best to treat scabies, this study compares 
different doses of moxidectin. If you agree to participate and are eligible for the study, you will be 
allocated by chance (called “randomization”) to receive either 2 mg, 8 mg or 20 mg moxidectin as a 
single dose. You have an equal chance of receiving any one of these three doses. During this 
research study, a committee of experts not directly involved in the study will review all the available 
information to see whether or not the doses are working. The committee could suggest that we make 
no changes to the study, or that we change the study by removing one of the original three doses 
and/or adding an extra dose. If they choose to add a dose, a 36 mg single dose of moxidectin may be 
included. About 6 people will be included in each group so your chance of being allocated to a group 
might be adjusted to allow for that. Results from the participants in each dose group will be 
compared to choose the dose of moxidectin that works the best to treat scabies.  
This is a double-blind study, which means that neither you, your doctor/clinical staff, nor the staff 
from Medicines Development for Global Health will know which dose you are receiving. However, 
if an emergency occurred and your study doctor needed to do so, he/she can find out which treatment 
you are receiving.  
Moxidectin will be given to you as tablets that you swallow. Because the study is blinded, everyone 
will be required to take the same number of tablets. The maximum number of tablets you could 
receive is 18 tablets. You will only take the tablets once. Moxidectin tablets contains 2 mg of 
moxidectin so you might take a mixture of moxidectin and placebo tablets. A placebo is a dummy 
tablet with no active ingredients. It looks like the real thing but is not. This is to make sure the dose 
is hidden.  
This research study has been designed to make sure the researchers interpret the results in a fair way.  
11. WHAT DOES TAKING PART IN THIS RESEARCH STUDY INVOLVE? 
If you wish to take part, you will be asked to provide written consent to take part before any study 
assessments are performed. You should take your time, feel no pressure to take part, and ask any 
questions you would like to. You should also feel free to discuss this study with anyone of your 
choosing.  
Once you have consented to take part, you will be checked for eligibility. Screening may take up to 7 
days. If you are eligible, study assessments will take place over 12 weeks. During that time, you will 
be asked to come to the clinic 8 times. On the day you receive treatment, you will stay in the clinic 
for approximately 9 hours (called Day 0). You will then come back to the clinic each day for the next 
three days (Days 1, 2 and 3) for approximately 2 hours each time. You will then come back to the 
clinic on Days 7, 14 and 28, and Week 12 for approximately 1 to 2 hours. The visits and assessments 
are being done to answer the research questions and are not usually done to manage scabies 
infection.  
Two different pieces of equipment will be used to look at the scabies mite in your skin:  


Sponsor: Medicines Development for Global Health  
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(incorporating Amendments 1 and 2) 
• Looking at the location of the scabies infection with a low-power hand-held microscope 
called a “dermatoscope”, which allows the doctor to see the scabies mite and your skin in 
more detail. This will be used once on the day you receive treatment, then once 3, 7, 14 and 
28 days after you receive treatment. Photographs of the scabies mite will be taken with this 
microscope. 
• Use of a higher powered microscope called a “reflectance confocal microscope”. This 
microscope allows the doctor to look into the skin at the scabies mite using a safe, low power 
laser. Using this microscope causes no pain. This will be performed twice on the day you 
receive your treatment, once daily for the next three days, then once 7, 14 and 28 days after 
treatment. Photographs of the scabies mite will be taken using this microscope. 
The study doctor will also map where scabies symptoms occur on your body and take close up 
photographs of the body areas where there is a scabies infection. Scabies symptoms can include rash, 
redness and scratch marks. This will be done before treatment and 7, 14 and 28 days after treatment. 
These photographs will be carefully taken to make sure you cannot be identified. If you have scabies 
mite infection on your groin, breasts and/or face, photographs here are optional: you will be asked by 
your doctor if you consent to have photos taken of these locations and you may decline to have these 
photos taken at any time.  
You will also be required to give blood. The blood is taken to measure the amount of moxidectin in 
your blood, to monitor the safety markers in your blood, and to collect plasma for potential 
development of a test to diagnose scabies. On the first day of treatment blood will be taken several 
times. To make this easier, the study team will insert a temporary access called a cannula (a thin 
plastic tube placed in a vein in your arm). You will also give blood once daily for the next three days, 
then once 7, 14 and 28 days after treatment. About 125 mL (or about half a cup) of blood will be 
collected over the whole study. In comparison, a standard blood donation is about 470 mL. 
You will be asked to complete several questionnaires about your symptoms and how these affect 
your daily life. This will take place before treatment and 7, 14 and 28 days after treatment. If you 
need it, an interpreter can assist you with answering these questionnaires. 
More details of each assessment are provided below.  
Screening (up to 7 days before study drug dosing) 
Estimated duration: 3 hours 
The study doctor or study team members will explain the aims of the study including the risks and 
benefits involved and the fact that your participation is voluntary. If you decide to be assessed for 
inclusion in the study, you will be asked to provide written informed consent by signing the Consent 
Form at the end of this document. 
The study doctor will discuss the eligibility criteria with you, and then confirm that you have scabies 
by examining your skin with a dermatoscope and reflectance confocal microscope. If you have 
scabies and the minimum number of visible scabies mites required to participate, the study doctor 
will do a physical exam and measure your blood pressure, temperature, heart rate, breathing rate, 
height and weight. The study doctor will also conduct an electrocardiogram to measure the activity 
of your heart. You will be asked questions about your medical history, your current health and any 
medicines you are taking, including herbal preparations and vitamins. Blood samples will be 
collected using a needle and syringe (about 12 mL or about 3 teaspoons of blood) and prepared for 
testing for hematology and clinical chemistry (tests of general health and wellbeing also known as 
‘safety blood tests’). If you are a female participant, a pregnancy test will be conducted.  


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Your eligibility for the trial is dependent on the number of scabies mites in your skin and the results 
of these eligibility assessments. If you are not eligible to take part, you will be offered the current 
standard of care treatment for scabies. Your doctor or study team member will let you know if you 
are eligible for the study and discuss these options with you.  
Day 0 
Estimated duration: 9 hours 
Before treatment 
You will be asked to stop eating and drinking from midnight the night before you come to the clinic 
and until 2 hours after you have taken your treatment. This means you will not be allowed to eat any 
foods or drink, including alcohol, coffee, tea and other drinks. However, you can drink as much 
water as you would like. Two hours after you have taken your allocated treatment, you will be served 
breakfast at the clinic. 
At this visit, the study doctor will examine you and measure your blood pressure, temperature, heart 
rate and breathing rate. You will be asked questions about your health and use of medicines since the 
previous visit. Blood samples will be collected using a needle and syringe (about 8 mL or about 2 
teaspoons of blood) or using a cannula and prepared for testing the quantity of moxidectin in your 
blood and storage of a sample. 
The study doctor will examine your skin with the dermatoscope and reflectance confocal 
microscope. The study doctor will select at least two but no more than four areas on your skin that 
contain scabies mites that will be examined at each visit. The study doctor will perform an 
assessment of your symptoms, which will involve looking at your whole body (including groin and 
nipple region, with your permission) and making a record of the location of symptoms. Photos will 
be taken of the regions showing signs and symptoms of scabies such as rash or scratch marks. 
You will be asked to complete three questionnaires designed to measure how itchy you are and the 
impact scabies has had on your life. 
After treatment 
You will be required to stay in the clinic for a further 8 hours. Four more blood samples to test for 
the quantity of moxidectin will be taken (about 32 mL or about 8 teaspoons of blood). Once the last 
sample is taken, the cannula (if used) will be removed. The study doctor will do two more 
examinations with the reflectance confocal microscope of the areas containing scabies mites they 
chose before treatment. Your blood pressure, temperature, heart rate and breathing rate will also be 
measured once during this time. After the last blood sample and microscope assessment is 
performed, you may leave the clinic. 
Day 1 (24 hours), 2 (48 hours), 3 (72 hours), 7, 14 and 28. 
Estimated duration: 2 hours each visit 
You will need to come back to the clinic at these times. At these visits, you will be asked questions 
about your health and use of medicines since the previous visit. 
• At each visit, you will be asked questions about how you feel and your use of medicines since 
the previous visit. 
• The study doctor may examine you and will measure your blood pressure, temperature, heart 
rate and breathing rate. 


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• Blood samples will be also taken to test for the quantity of moxidectin and to measure safety 
markers in your blood. Over all these visits, about 75 mL of blood will be taken (about 20 
teaspoons). 
• The study doctor will examine the areas of your skin selected before treatment with the 
reflectance confocal microscope. On Day 3, this exam will also use the dermatoscope. In 
addition, on Days 7, 14 and 28 only, the study doctor will perform an assessment of your 
symptoms, which will involve looking at your whole body (including groin and nipple region 
with your permission) and making a record of the location of symptoms. Photos will be taken 
of the regions showing signs and symptoms of scabies such as rash or scratch marks.  
• Also on Days 7, 14 and 28 only, you will be asked to complete three questionnaires designed 
to measure how itchy you are and the impact scabies has had on your life. 
Week 12 
Estimated duration: 1 hour 
You will be asked to come back 12 weeks after treatment for a final follow up visit. You will be 
asked questions about your health and use of medicines since the previous visit. The study doctor 
will perform a symptom-based physical examination and measure your blood pressure, temperature, 
heart rate, breathing rate and weight. If you are a female participant, a pregnancy test will be 
conducted. 
12. COSTS AND COMPENSATION 
There are no cost to you for taking part in this research study. All medication, tests and medical care 
that are part of the research study will be provided to you free of charge. The Sponsor, Medicines 
Development for Global Health, will pay for this. 
If you are eligible for the study, and you take the treatment and complete the study, you will be 
compensated up to $XXXX [dependent on the site]. If you withdraw before the end of the study, you 
will be compensated as follows [pro-rated payments description]. Your costs for reasonable travel, 
parking, meals and other expenses will also be paid back to you. 
If your screening results show that you are not eligible for the study or you withdraw prior to taking 
the study tablets, you will receive no payment. If you wish to withdraw from the study before 
completion, or if the study doctor decides that it is in your best interests to withdraw from the study, 
the amount of the payment will be adjusted based on how long you took part and which visits you 
completed. 
13. IF WE FIND A MEDICAL CONDITION OF WHICH YOU WERE UNAWARE 
If during the course of the study the study team uncovers a medical condition of which you were 
unaware, we will refer you to your primary care doctor for follow up and advice on next steps. 
14. YOUR RESPONSIBILITIES AND RESTRICTIONS 
It is desirable that your local doctor be advised of your decision to take part in this research study. If 
you have a local doctor, your study doctor will notify them of your taking part unless you object to 
this. 
You will need to attend the clinic at the times and on the study days outlined above. 
You should notify the study team in advance of your visits if you are experiencing symptoms that 
suggest a COVID-19 infection, or if you know you have been in contact with someone with 
COVID-19. You may be required to follow site-specific instructions to manage the risk of 


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COVID-19 spread, including wearing a mask and maintaining an appropriate level of social distance 
from other patients and clinic staff. 
If you choose to take part in this study, you must observe the following restrictions: 
Medicines 
Whilst you are taking part in this research study, you may not be able to take some or all of the 
medications or treatments you have been taking for scabies or for other reasons. Your study doctor 
should also explain to you which treatments or medications need to be stopped for the time you are 
involved in the research study. 
In most cases you can take your regular medication. There are some exceptions: 
• For the duration of the study, you must tell the study doctor or study staff about any 
medicines that you may be taking, including prescription or over-the-counter medications, 
vitamins or herbal remedies, acupuncture or other alternative treatments. You should also tell 
your study doctor about any changes to these during your participation in the research study. 
• You must not take any other treatments for scabies during the course of the study. 
• You must not take any other treatments for parasites during the course of the study. 
• You must not take any antihistamines during the study.  
• You must not use any medicated topical lotions (or similar) during the study. These lotions 
include any that contain zinc, tar, calamine or salicylic acid. 
Contraception  
If you or your partner are able to become pregnant you must agree to use reliable contraception 
during the course of the research study and for a period of 3 months after completion of the study 
visits (24 weeks total). You should discuss methods of effective contraception with your study 
doctor. 
Blood Donation 
You must not donate blood or plasma during the study. 
Assessment Sites 
You must try to avoid scratching your skin at the places where you are infected with scabies, 
especially where your study doctor has chosen to examine these areas using the reflectance confocal 
microscope. The study doctor will show you these at the beginning of the study. 
15. WHAT ARE THE POSSIBLE BENEFITS OF TAKING PART? 
This is a research study. Therefore, it is not known if moxidectin will be useful in treating your 
scabies infection. We cannot guarantee or promise that you will receive any benefits from this 
research; however, possible benefits may include: 
• You will have a medical visit which will include a physical examination, vital signs 
measurements and blood tests to determine your current state of health with respect to study 
criteria. 
• The study doctor will closely follow up whether treatment gets rid of the scabies mite. If it 
does not, you will be offered other treatments as soon as possible, and you will be offered a 
clinic recall 1 week after to check this alternative treatment has worked. 
• If you choose, you will have support to ensure your home is free of scabies mites. This may 
include cleaning services to help with washing sheets, towels and clothing used in the days 


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before treatment, placing mattresses, pillows and blankets in the sun and thoroughly 
vacuuming the house and furniture. 
• Treatment will be offered to the members of your household and other close contacts at no 
additional cost. Treatment of your close contacts will help reduce the risk that you become 
infected again. 
• Information found during this study may be helpful in developing future treatment options for 
scabies. 
16. WHAT ARE THE POSSIBLE RISKS AND DISADVANTAGES OF TAKING PART? 
Side effects 
Almost all medicines cause side effects. You may have none, some or all of the effects listed below, 
and they may be mild, moderate or severe. If you have any of these side effects, or are worried about 
them, please speak with your study doctor. 
Your safety will be closely monitored throughout the study and your study doctor will also be 
looking for side effects of treatment. Tell your study doctor immediately about any new or unusual 
symptoms that you get. Many side effects are temporary. However, sometimes side effects can be 
serious, long lasting or permanent. There may be side effects that the researchers do not expect or do 
not know about and that may be serious. Your study doctor will discuss the best way of managing 
any side effects with you. 
Moxidectin is a new medicine and therefore all side effects are not known. Common side effects of 
moxidectin reported in healthy volunteers and onchocerciasis patients are listed below. In most 
cases, side effects were mild, went away on their own and lasted less than a week. No person who 
has received moxidectin has withdrawn from any clinical study due to side effects.  
This list is not a complete list of possible side effects. Side effects may occur almost immediately 
after the drug is administered, or days later. Side effects that are unknown at this time may occur. As 
information becomes available, you will be told of any newly identified risks that may affect your 
willingness to participate in the study. Your doctor will provide further information about the events 
below. 
Side effects in healthy volunteers 
Moxidectin has been given to 260 healthy volunteers at doses between 3 mg and 36 mg. The most 
common side effects, reported by 3% of participants or more were: 
• Headache 
• Rhinitis (stuffy nose) 
• Flu like symptoms 
• An upset stomach (nausea and diarrhea) 
• Dizziness 
Most of these side effects were mild. 
Side effects in patients with onchocerciasis (a parasitic worm infection present in African 
and Latin American regions) 
The most common side effects reported in patients with onchocerciasis were those often seen when 
they receive a treatment for onchocerciasis. These side effects are due to allergic reactions caused by 
the worms dying in the skin and eyes as a result of treatment and are unlikely to be the same for 
people with scabies.  


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Side effects that occurred in more than 10% of onchocerciasis patients were: 
• Changes to the proportions of white blood cells, including increases in the number of cells 
called eosinophils and decreases in the number of cells called lymphocytes and neutrophils 
• Pruritus (itching) 
• Pain (including muscle pain, joint pain, general body pain, abdominal pain and lymph node 
pain) 
• Headache 
• Tachycardia (an increased heart rate, including when people went from laying down to 
standing) 
• Rash 
• Hypotension (reduced blood pressure, including when people went from laying down to 
standing). 
• About 5% of patients reported feeling dizzy or light-headed and needed support during a test 
where they lay down for 5 minutes and then stood up. This was most common 1-2 days after 
treatment and went away when they lay down again.  
• Fever and chills 
• Influenza (flu) like illness 
• Cough 
• Dizziness 
• An upset stomach, including diarrhea, gastroenteritis and enteritis 
• Reduced concentration of salt in the blood 
• Swelling of the limbs 
Some onchocerciasis patients had side effects in their eyes, including pain and/or discomfort, itching, 
blurry vision, red eyes and conjunctivitis (a bacterial infection of the eye). Between 1% and 8% of 
patients with onchocerciasis treated with moxidectin experienced these side effects. 
Between 1% to 3% of onchocerciasis patients had changes to their liver function tests, including 
increases in some liver enzymes called AST, ALT and GGT and a product called bilirubin. Most of 
the increases were temporary. 
There is a risk that patients who are infected with a parasite called Loa loa develop serious or even 
fatal brain injury after taking moxidectin. Loa loa is only found in certain parts of West and Central 
Africa including Cameroon, Democratic Republic of Congo, Gabon and Nigeria. If you have been to 
any of these areas you should tell the study doctor as you may need a test to confirm it is safe for you 
to take part in this study. 
Side effects in patients with scabies 
Moxidectin has not been given to people with scabies. However, one of the most common side 
effects of other treatments for scabies is a temporary worsening of itch over one to two weeks. This 
has been reported following treatment with permethrin and ivermectin. 
Blood tests 
Having blood taken may cause some discomfort, bruising, minor infection at the needle site or 
bleeding. If this happens, it can be easily treated. There is also a small risk of a fainting episode, 
which can occur as a reaction to having blood drawn. 
Pregnancy 


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The effects of moxidectin on the unborn child and on the newborn baby are not known. Because of 
this, it is important that research study participants are not pregnant or breast-feeding and do not 
become pregnant during the course of the research study. You must not participate in the research if 
you are pregnant or trying to become pregnant, or breast-feeding. If you are female and having a 
child is a possibility, you will be required to undergo a pregnancy test prior to commencing the 
research study and at the end of the study. If you are male, you should not father a child or donate 
sperm for at least 6 months after the dose of study medication. 
Both male and female participants must agree to use reliable contraception during the course of 
the research and for a period of 6 months after you have taken the study medication. You should 
discuss methods of reliable contraception with your study doctor. 
If you are a female participant and you do become pregnant whilst participating in the research 
study, you should advise your study doctor immediately. Your study doctor will withdraw you from 
the research study and advise on further medical attention should this be necessary. You must not 
continue in the research if you become pregnant. 
If you are a male participant, you should advise your study doctor if you father a child while 
participating in the research study. Your study doctor will advise on medical attention for your 
partner should this be necessary. 
17. WHAT WILL HAPPEN TO MY TEST SAMPLES? 
By consenting to take part in this study, you also consent to the collection, storage and use of your 
blood samples. This is a mandatory part of the study. During the course of the study blood samples 
will be taken on 12 occasions. The total volume of blood taken for the entire study will be about 
125 mL (about half a cup). In comparison, one standard blood donation is 470 mL. Your blood 
samples are anonymous and will only be labelled with your unique study number (but not your 
name).  
Collected blood samples will be used to check your general health at screening and throughout the 
study. Your blood samples will also be used to prepare plasma (the clear liquid that carries red and 
white blood cells) to measure the quantity of moxidectin in your blood throughout the study. 
Samples of your plasma obtained for the purpose of this research study will be transferred to an 
analytical laboratory working on behalf of the study Sponsor to measure moxidectin in your blood. 
This laboratory may be located in another country to the clinic where you are assessed.  
Your blood samples will not be sold by the Sponsor or any third party contractors. A sample of your 
plasma will also be used to look for markers of scabies infection for development of tests that could 
help with diagnosis of the disease. Examples of such tests include looking for biomarkers of an 
immune response to the scabies mite (called an antibody test). Development of such a test would 
make it easier for doctors to correctly diagnose scabies because it is a disease that can be confused 
with others. Your stored samples will be used or destroyed no later than 2 years after the completion 
of the study. Your samples will not be used for any genetic testing.  
18. WHAT IF NEW INFORMATION ARISES DURING THIS RESEARCH STUDY? 
Sometimes during the course of a research study, new information becomes available about the 
treatment that is being studied. If this happens, your study doctor will tell you about it and discuss 
with you whether you want to continue in the research study. If you decide to withdraw, your study 
doctor will make arrangements for your regular health care to continue. If you decide to continue in 
the research study you will be asked to sign an updated consent form. 


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Also, on receiving new information, your study doctor might consider it to be in your best interests 
to withdraw you from the research study. If this happens, he/she will explain the reasons and arrange 
for your regular health care to continue. 
19. WHAT IF I WITHDRAW FROM THIS RESEARCH STUDY? 
You can withdrew from this research study at any time. If you decide to withdraw from the study, 
please notify a member of the research team before you withdraw. This notice will allow that person 
or the research supervisor to discuss any health risks or special requirements linked to withdrawing. 
You may be withdrawn from the study if the doctors feel it is best for you or if you do not comply 
with the requirements of the study. 
If you do withdraw your consent during the research study, the study doctor and relevant study staff 
will not collect additional personal information from you, although personal information already 
collected will be retained to ensure that the results of the research study can be measured properly 
and to comply with local and international law. You should be aware that data collected by the 
Sponsor up to the time you withdraw will form part of the research study results. If you do not want 
them to do this, you must tell them before you join the research study. 
20. COULD THIS RESEARCH STUDY BE STOPPED UNEXPECTEDLY? 
Yes, this is possible. This research study may be stopped unexpectedly for a variety of reasons which 
may include unacceptable side effects, or for reasons made in the commercial interests of the 
sponsor, or by local regulatory/health authorities.  
21. WHAT HAPPENS WHEN THE RESEARCH STUDY ENDS? 
At the final study visit 12 weeks after treatment, you will be asked about any symptoms that might 
suggest a new scabies infection. If you do show signs of infection, you will be offered [the standard 
of care], and instructed how to use it by the study doctor. You will not receive further doses of 
moxidectin after your first treatment. You will also be asked about your health and any medications 
you have taken since the last visit. 
Once all the participants have completed treatment in the study, the treatment blind will be broken. 
This means that the treatment each participant was taking and the results of the testing done can be 
analyzed together. The results of the analysis will be published.  
PART 2 HOW IS THE RESEARCH STUDY BEING CONDUCTED? 
1. WHAT WILL HAPPEN TO INFORMATION ABOUT ME? 
By signing the consent form you consent to the study doctor and relevant research staff collecting 
and using personal information about you for the research study. Any information obtained in 
connection with this research study that can identify you will remain confidential and will not be 
made publicly available. Your information cannot be used for any purposes except those clearly 
indicated within this consent form and will only be used for the purpose of this research study.  
As applicable for EU GDPR regulations: 
Any data transferred to destinations outside the European Economic Area (EEA) will be protected in 
a manner that is consistent with how personal data is protected in the EEA. Your rights to access, 
change or move your information are limited, as we need to manage your information in specific 
ways in order for the research to be reliable and accurate. If you withdraw from the study, we will 
keep the information about you that we have already obtained. To safeguard your rights, we will use 
the minimum personally-identifiable information possible. We will only retain your personal data for 


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as long as necessary to fulfil the purpose for which it was collected or to comply with legal or 
regulatory requirements. 
Your health records and any information obtained during the research study are subject to inspection 
(for the purpose of checking that the study is conducted correctly and to ensure the accuracy of the 
study information ) by relevant regulatory authorities, including the US Food and Drug 
Administration (FDA), the European Medicines Agency (EMA) and the Australian Therapeutic 
Goods Administration (TGA), and authorized representatives of the Sponsor, Medicines 
Development for Global Health, the institution relevant to this Participant Information Sheet, [Name 
of institution], or as required by law. These people are all required to maintain confidentiality by the 
nature of their work, or are bound by confidentiality agreements.  
While participating in this study, the study doctor will replace your name with a special code that 
identifies you. This code, along with your study information, will be used by the study sponsor, 
Medicines Development for Global Health and their representatives, for the study purposes 
mentioned above and to help establish whether the study drug is safe and effective. Study 
Information, your study code, and samples collected as part of this study will be included in secure 
electronic trial systems. By signing the Consent Form, you authorize release of, or access to, this 
confidential information to the relevant study personnel and regulatory authorities as noted above. 
It is anticipated that the results of this research study will be published and/or presented in a variety 
of forums. In any publication and/or presentation, information will be provided in such a way that 
you cannot be identified, except with your permission. 
Information about your participation in this research study may be recorded in your health records. 
In accordance with relevant [country] privacy and other relevant laws, you have the right to request 
access to your information collected and stored by the research team. You also have the right to 
request that any information with which you disagree be corrected. Please contact the study team 
member named at the end of this document if you would like to access your information. 
A description of this clinical trial may be available on http://www.clinicaltrials.gov, as required by 
US laws. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this website at any time. 
2. COMPLAINTS AND COMPENSATION 
In cases of trial related injury or if you require any more information concerning the trial and your 
rights and obligations as a clinical trials subject you should contact the study doctor. Any complaint 
about the way you have been dealt with during the study or any possible harm you might suffer will 
be addressed. 
Complaints 
If you have a concern about any aspect of this study, you should ask to speak with the study doctor 
who will do their best to answer your questions. If you remain unhappy and wish to complain 
formally, you can do this through the [site complaint procedure]. Details can be obtained from the 
hospital. 
Harm 
If you suffer any injuries or complications as a result of this research study, you should contact the 
study team as soon as possible and you will be assisted with arranging appropriate medical treatment. 
The Sponsor adheres to [local guidelines] for an injury resulting from participation in a company 


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sponsored study which provides for medical treatments and/or compensation in the event of injury as 
a result of your participation in this trial in compliance with local applicable laws and regulations. 
Provided the study medication was administered in accordance with the study protocol, you will be 
covered by the Sponsor’s insurance. 
3. WHO IS ORGANIZING AND FUNDING THE RESEARCH? 
This research study is being conducted by [Investigator name] and sponsored by Medicines 
Development for Global Health. The research is being funded by Medicines Development for Global 
Health. 
Medicines Development for Global Health may benefit financially from this research study if, for 
example, the study assists Medicines for Global Health to obtain approval for moxidectin as a new 
treatment for scabies. 
By taking part in this research study you agree that samples of your blood or tissue (or data generated 
from analysis of these materials) may be provided to Medicines Development for Global Health. 
You will not benefit financially from your involvement in this research study even if, for example, 
your samples (or knowledge acquired from analysis of your samples) prove to be of commercial 
value to Medicines Development for Global Health. In addition, if knowledge acquired through this 
research leads to discoveries that are of commercial value to Medicines Development for Global 
Health, the study doctors or their institutions, there will be no financial benefit to you or your family 
from these discoveries. 
The Sponsor of this study will pay the research unit for conducting the study. No member of the 
research team will receive a personal financial benefit from your involvement in this research study 
(other than their ordinary wages). 
4. WHO HAS REVIEWED THE RESEARCH STUDY? 
All research involving humans is reviewed and approved by an independent group of people called 
an Independent Ethics Committee (IEC), also known as [local ethics committee name – Human 
Research Ethics Committee (HREC) or Comité de Protection de Personnes (CPP)]. The Committee 
consists of a number of medical staff (hospital consultants, GPs, nurses and pharmacists) and lay 
members whose expertise is not in the field of medicine. 
This study has also been reviewed and approved by the local agency responsible for the standards of 
safety, quality and performance of medicines. 
This research will be conducted in accordance with the International Council for Harmonization 
Guideline for Good Clinical Practice version E6(R2), which is an international ethical and scientific 
quality standard developed to protect the interests of people who agree to participate in clinical 
studies. This research will also be conducted in accordance with any local standards that govern the 
conduct of clinical trials. 
This clinical trial is being conducted under the regulatory requirements of [local regulatory agency - 
the Australian Therapeutic Goods Administration or L'Agence nationale de sécurité du médicament 
et des produits de santé].   
5. FURTHER INFORMATION AND WHO TO CONTACT 
The person you may need to contact will depend on the nature of your query.  


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If you want any further information concerning this study or if you have any medical problems 
which may be related to your involvement in the study (for example, any side effects), you can 
contact the principal study doctor on [phone number] or any of the following people: 
Clinical contact person (available 24 hours) 
Name 
[Name] 
Position 
[Position] 
Telephone 
[Phone number] 
Email 
[Email address] 
For matters relating to research at the site at which you are participating, the details of the local site 
complaints person are: 
Complaints contact person 
Name 
[Name] 
Position 
[Position] 
Telephone 
[Phone number] 
Email 
[Email address] 
If you have any complaints about any aspect of the study, the way it is being conducted or any 
questions about being a research participant in general, then you may contact: 
Reviewing Independent Ethics Committee (IEC) approving this research and IEC 
Executive Officer details 
Reviewing IEC name 
[Name of IEC] 
IEC Executive Officer 
[Name] 
Telephone 
[IEC Executive Officer Phone number] 
Email 
[IEC Executive Officer Email address] 
Local IEC Office contact (Single Site -Research Governance Officer) 
Name 
[Name] 
Position 
[Position] 
Telephone 
[Phone number] 
Email 
[Email address] 


Sponsor: Medicines Development for Global Health  
Protocol Number: MDGH-MOX-2001 
 
CONFIDENTIAL 
MDGH-MOX-2001 Protocol version 3 final 
Page 92 
19 Jun 2020 
(incorporating Amendments 1 and 2) 
CONSENT FORM 
Title 
A Phase II, randomized, double-blind, parallel group dose finding 
study of single oral doses of moxidectin in adults with scabies 
Protocol Number 
MDGH-MOX-2001 
EudraCT Number (if required) 
[Insert EudraCT Number] 
Study Sponsor 
Medicines Development Limited (trading as Medicines 
Development for Global Health) 
Coordinating Principal 
Investigator/ Principal Investigator 
[Insert Investigator Name] 
Declaration by Participant 
I have read the Participant Information Sheet or someone has read it to me in a language that I 
understand. 
I understand the purposes, procedures and risks of the research described in the study. 
I voluntarily consent to the storage and use of blood and tissue samples taken from me for use, as 
described in the relevant section of the Participant Information Sheet, for: 
• 
This specific research study 
• 
Other research that is closely related to this research study 
• 
Any future research. 
I voluntarily give permission for my doctors, other health professionals, hospitals or laboratories 
outside this hospital to release information to [Name of Institution] concerning my disease and 
treatment for the purposes of this study. I understand that such information will remain confidential.  
I have had an opportunity to ask questions and I am satisfied with the answers I have received. 
I freely agree to participate in this research study as described and understand that I am free to 
withdraw at any time during the study without affecting my future health care.  
I understand that I will be given a signed copy of this document to keep. 
 
 
 
 
 
 
Name of Participant 
(to be completed by participant) 
 
Date (DD MMM YYYY) 
(to be completed by participant) 
 
Signature 
Declaration by Study Doctor/Senior Researcher† 
I have given a verbal explanation of the research study, its procedures and risks and I believe that the 
participant has understood that explanation. 
 
 
 
 
 
 
Name of Study Doctor† 
 
Date (DD MMM YYYY) 
 
Signature 
† A senior member of the research team must provide the explanation of, and information 
concerning, the research study.  
Note: All parties signing the consent section must date their own signature.











































SAP_001.pdf: 
Veristat International study no: MNT18001 
Medicines Development for Global Health study no: 
MDGH-MOX-2001 
Date: 16FEB2022 
Version: Final 1.0 
ST/form/010/11 
Page 1 of 27 
 
 
 
 
 
 
 
A Phase II, randomized, double-blind, parallel group dose 
finding study of single oral doses of moxidectin in adults 
with scabies 
 
Medicines Development for Global Health Study No: 
MDGH-MOX-2001 
Veristat International Ltd Study No: MNT18001 
 
 
Statistical Analysis Plan 
 
 
Version: Final 1.0 
Date: 16 February 2022 
 
 
 
 
For Veristat International Ltd – Lead Statistician 
 
 
 
 
For Medicines Development for Global Health 
 


Veristat International study no: MNT18001 
Medicines Development for Global Health study no: 
MDGH-MOX-2001 
Date: 16FEB2022 
Version: Final 1.0 
ST/form/010/11 
Page 2 of 27 
 
 
 
 
 
Contents 
1 
Introduction .......................................................................................................................................................... 4 
2 
Study Objectives and Design ........................................................................................................................... 4 
Study Objectives ............................................................................................................................................ 4 
Study Endpoints ............................................................................................................................................. 4 
Study Design .................................................................................................................................................. 5 
Visit Structure ................................................................................................................................................. 6 
3 
Sample Size ........................................................................................................................................................ 6 
4 
Randomisation..................................................................................................................................................... 6 
5 
Interim analysis ................................................................................................................................................... 6 
Protocol Steering Committee Review ....................................................................................................... 6 
Final Analysis ................................................................................................................................................. 7 
6 
Analysis Plan ...................................................................................................................................................... 8 
General ............................................................................................................................................................ 8 
General Derivations ...................................................................................................................................... 8 
Analysis Sets ................................................................................................................................................. 9 
6.3.1 
Definitions .................................................................................................................................................... 9 
6.3.2 
Assignment ............................................................................................................................................... 10 
Data Presentations ..................................................................................................................................... 11 
Disposition of Subjects .............................................................................................................................. 11 
Protocol Deviations .................................................................................................................................... 12 
Baseline and Demographic Characteristics ............................................................................................ 12 
6.7.1 
Demography ............................................................................................................................................. 12 
6.7.2 
Medical History ........................................................................................................................................ 12 
Prior and Concomitant Medications ........................................................................................................ 12 
6.8.1 
Rescue Medication ................................................................................................................................. 13 
Administration of Study Drug and Exposure .......................................................................................... 13 
Efficacy Evaluation ..................................................................................................................................... 14 
6.10.1 
Primary Endpoint .................................................................................................................................... 14 
6.10.1.1 Primary Variable...................................................................................................................................... 14 
6.10.1.2 Primary Endpoints .................................................................................................................................. 14 
6.10.1.3 Mite Status Derivation, Imputation and Missing Data ...................................................................... 15 
6.10.1.4 General Considerations.......................................................................................................................... 16 
6.10.1.5 Summaries ............................................................................................................................................... 16 
6.10.1.6 Sensitivity Analysis ................................................................................................................................. 17 
6.10.1.7 Post-hoc Analysis ................................................................................................................................... 18 
6.10.2 
Secondary Endpoints ..............................................................................................................................18 
6.10.3 
Exploratory Endpoints .............................................................................................................................18 
6.10.3.1 RCM Assessment ................................................................................................................................... 18 
6.10.3.2 Clinician Reported Scabies Signs and Symptoms ............................................................................ 20 
6.10.3.3 Patient Reported Outcomes ................................................................................................................. 22 
6.10.3.4 Clinical Cure Rate ................................................................................................................................... 23 
Multiplicity ......................................................................................................................................................24 
Pharmacokinetics ........................................................................................................................................ 24 
Pharmacodynamics .................................................................................................................................... 24 
Safety Evaluation ........................................................................................................................................ 24 
6.14.1 
Adverse Events ........................................................................................................................................ 25 
6.14.2 
Clinical Laboratory Evaluation .............................................................................................................. 26 
6.14.3 
Vital Signs .................................................................................................................................................26 
6.14.4 
Electrocardiography ................................................................................................................................. 26 
6.14.5 
Physical Examination ..............................................................................................................................26 
6.14.6 
Pregnancy Test ........................................................................................................................................ 26 
Changes from the Protocol Planned Analysis ....................................................................................... 26 


Veristat International study no: MNT18001 
Medicines Development for Global Health study no: 
MDGH-MOX-2001 
Date: 16FEB2022 
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LIST OF ABBREVIATIONS 
 
 
AE 
Adverse Event 
AUC 
Area Under the Concentration time curve 
BMI 
Body Mass Index 
Cmax 
Maximum Observed Plasma Concentration 
CI 
Confidence Interval 
DMP 
Data Management Plan 
DLQI 
Dermatology Life Quality Index 
eCRF 
Electronic Case Report Form 
FAS 
Full Analysis Set 
KM 
Kaplan Meier 
MDGH 
Medicines Development for Global Health 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRS 
Numerical Rating Scale 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PKAP 
Pharmacometric Analysis Plan 
PKAS 
Pharmacokinetic Analysis Set 
PKPDAS 
Pharmacokinetic/Pharmacodynamic Analysis Set 
PPAS 
Per Protocol Analysis Set 
PSC 
Protocol Steering Committee 
PT 
Preferred Term 
RCM 
Reflectance confocal microscopy 
SfAS 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SI 
International System of Units 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
WHO Drug 
World Health Organization Drug Dictionary 


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Medicines Development for Global Health study no: 
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Date: 16FEB2022 
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1 
INTRODUCTION 
This document details the statistical analysis of the data that will be performed for the 
Medicines Development for Global Health (MDGH) Protocol MDGH-MOX-2001: A 
Phase II, randomized, double-blind, parallel group dose finding study of single oral 
doses of moxidectin in adults with scabies. 
The proposed analysis is based on the contents of Version 3 of the protocol (dated 
19 June 2020). In the event of future amendments to the protocol, this Statistical 
Analysis Plan (SAP) may be modified to account for changes relevant to the statistical 
analysis. 
The table, listing and figure shells are supplied in a separate document. 
A separate Pharmacometric Analysis Plan (PKAP) will detail the derivation of 
pharmacokinetic (PK) parameters and associated analyses which are not covered by 
this SAP. 
 
2 
STUDY OBJECTIVES AND DESIGN 
Study Objectives 
The primary objectives of the study are to: 
• Identify an optimal dose of moxidectin for the treatment of scabies; 
• Evaluate the safety of moxidectin in adults infected with scabies. 
The secondary objective of the study is to characterize the plasma pharmacokinetics 
of moxidectin in adults infected with scabies. 
The exploratory objectives of the study are to: 
• Describe the impact of moxidectin on S. scabiei, including impact on 
morphology, motility and life cycle stages; 
• Evaluate clinician and patient reported outcomes of treatment with moxidectin. 
Study Endpoints 
The primary endpoints of the study are as follows: 
• Efficacy will be determined by death of the mites, defined as the degradation 
(loss of internal and/or external anatomic structures) of the adult mite observed 
by reflectance confocal microscopy (RCM). Mites will be assessed at Hours 4, 
8, 24, 48 and 72 and Days 7, 14 and 28 in not less than two lesions nominated 
pre-treatment. 
• Safety will be assessed by the incidence and severity of adverse events (AEs), 
physical examinations, and measurement of vital signs up to and including 
Week 12, and laboratory safety parameters up to and including Day 28. 
The secondary endpoints are the key exposure metrics for moxidectin including area 
under the concentration time curve (AUC) and maximum plasma concentration (Cmax), 
which 
will 
be 
determined 
by 
non-compartmental 
analysis 
of 
moxidectin 
pharmacokinetic parameters or other methods as appropriate, assessed up to and 
including Day 28. 


Veristat International study no: MNT18001 
Medicines Development for Global Health study no: 
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Date: 16FEB2022 
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The exploratory endpoints are: 
• At Hours 4, 8, 24, 48 and 72 and Days 7, 14 and 28, using assessment by RCM 
of burrows selected pre-treatment: 
o Changes in adult mite motility (peristalsis and/or movement) over at least 
30 seconds of observation; 
o Presence, number, morphology and motility of juvenile scabies mites; 
o Presence of eggs and scybala in burrows. 
• Presence and total number of mites and burrows assessed visually at Days 7, 
14 and 28. 
• Changes in assessment of clinician-reported scabies symptomology, including 
extent of symptoms on body regions assessed by the number of 
anatomically-defined regions affected, number of lesions and severity grading 
of excoriations and erythema. 
• Changes in patient reported outcomes, measured by Numerical Rating Scale, 
5-D Itch Scale and Dermatology Life Quality Index. 
• Clinical cure rates at Days 7, 14 and 28. Clinical cure is defined as resolution 
of all scabies signs and symptoms present at Baseline, no new scabies signs 
and symptoms and no evidence of mites by dermoscopy. 
 
Study Design 
This is a randomized, double-blind, multicenter, parallel group, dose finding study of a 
single oral dose of moxidectin in adults with scabies. Initially, subjects will be 
randomized with a target allocation ratio of 1:1:1 to one of the following single dose 
treatment regimens: 
• Treatment 1: Moxidectin 2 mg; 
• Treatment 2: Moxidectin 8 mg; 
• Treatment 3: Moxidectin 20 mg. 
Once approximately three subjects have been recruited to these three dose groups 
and completed their Day 14 visit, a Protocol Steering Committee (PSC) will evaluate 
the unblinded safety and efficacy data and recommend: 
• Continuation of the study with no dose modification to the target sample size 
of 6 subjects per dose group; or, 
• Stopping recruitment of one of more of the current dose groups; and/or, 
• The addition of a 36 mg single dose group. 
Once the Committee has made their recommendation, randomization will continue into 
the same or revised dosing regimens with a final target sample size of 6 subjects per 
dose group. It is anticipated that a maximum of 36 subjects will be included in the 
study. 
The on-study period per subject will be 13 weeks, consisting of up to one week for 
Screening and 12 weeks post-treatment. 


Veristat International study no: MNT18001 
Medicines Development for Global Health study no: 
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The study is planned to be conducted in Australia and France in approximately four 
centers. 
 
Visit Structure 
The visit structure and scheduled assessments are detailed in Table 1, Table 2 and 
Section 9 of the protocol. 
 
3 
SAMPLE SIZE 
The sample size chosen for this study, approximately 6 subjects per dose group, was 
selected to be practical and an adequate sample size for full characterization of PK 
profile across the dose ranges studied. Sample size was not based on formal power 
considerations with respect to statistical hypothesis testing. 
 
4 
RANDOMISATION 
Potential subjects who provide written informed consent will be sequentially assigned 
a Screening Number prefixed by “S” (e.g. S001). 
Initially for each site, a randomization scheme with equal allocation to each of the initial 
three moxidectin dose groups will be prepared. Treatment packs will be prepared 
according to the randomization scheme. 
Randomization will take place before dosing on Day 0. 
Following review of safety and efficacy data by the PSC, one or more dose group(s) 
may be discontinued and/or a new 36 mg dose group added. If required, the 
randomization plan will be revised to maintain the final target sample size of 6 subjects 
per dose group. The study will switch from a stratified randomization by site to a central 
randomization scheme for logistical reasons. However, random allocation of treatment 
assignment will be preserved in all cases. 
 
5 
INTERIM ANALYSIS 
Protocol Steering Committee Review 
No formal interim analysis is planned for this study. 
The PSC will review relevant accumulated unblinded safety and efficacy data for all 
randomized subjects collected through to the review cutoff date. The review cutoff date 
will correspond to the date when approximately 3 subjects in each of the initial 
3 treatment arms have completed their Day 14 evaluation. Based on a review of the 
available data, the Committee will recommend one or more of the actions described 
in Section 2.3. 
The decision-making process of the Committee will be guided by: 
• The mortality rate of adult scabies mites, or the time-to-death of adult scabies 
mites. Subject-level review may also be considered. 
• Safety outcomes, such as the frequency, nature and severity of adverse events, 
and withdrawal rates. 


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Medicines Development for Global Health study no: 
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• Pharmacokinetic data may be reviewed if available. 
The Committee will not reveal the results of their data review or, barring any 
unanticipated safety issues, any decisions or recommendations to Investigators, study 
personnel, or Sponsor personnel involved in the management of day-to-day study 
activities. 
Additional unblinded reviews and possible dose modification recommendations may 
also be undertaken by the Committee at any time at, or in lieu of the data review 
described above, at the request of the Sponsor. The analyses to be conducted during 
these interim reviews may entail review of individual subject line listings and/or 
aggregate data. 
Since the study is exploratory and not powered to conduct hypothesis testing, no 
adjustments to the type I error rate for PSC data reviews will be implemented. 
Further details can be found in the Protocol Steering Committee Charter. 
 
Final Analysis 
The study comprises two periods for the purposes of final statistical analysis as 
follows: 
• Period 1: Commences at Screening and will finish on Day 28. The study blind 
will be maintained during this study period. After the last subject has completed 
the study through Period 1, the blind will be broken and the unblinded data from 
Period 1 will be analyzed. This analysis will be referred to as the Day 28 
analysis throughout the SAP. 
• Period 2: Runs from Day 29 to Week 12. Data from Period 2 will be analyzed 
after all subjects have completed the study through Week 12. Data for some 
subjects may be collected during Period 2 after the blind has been broken and 
the Period 1 study results known. The Period 2 data will be provided in an 
additional safety supplement. The safety supplement will be referred to as the 
Week 12 analysis throughout the SAP. 
Although the blind will be broken after the last subject has completed their Day 28 visit 
or withdrawn (Period 1) for all other study personnel, the individual treatment 
assignment will not be communicated to the subject, Investigators, site personnel or 
the clinical operations team until the last subject has completed their Week 12 visit or 
withdrawn (Period 2). 
The Day 28 analysis will consist of all efficacy and safety outputs as described in this 
SAP. Data for this analysis will be cut to exclude any assessment data entered after 
Day 28 for each subject (even if the subject has progressed beyond this point at the 
time of the analysis). PK analyses will also be completed at Day 28 and further details 
can be found in the PKAP. 
The Week 12 analysis is a safety supplement and as such will include a rerun of 
selected outputs only where additional information was captured during Period 2 (i.e. 
including all data from study start up to the end of the study for these outputs). These 
additional data will include protocol deviations, disposition (including completions and 
withdrawals), adverse events, concomitant medications, physical examinations, vital 
signs (including weight) and pregnancy testing. Note that although additional data on 
post-baseline physical examination assessment times will be included in this rerun, 
these are not presented in the physical examinations listing and so the listing will not 


Veristat International study no: MNT18001 
Medicines Development for Global Health study no: 
MDGH-MOX-2001 
Date: 16FEB2022 
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be reproduced. In addition, it is possible that the additional concomitant medication 
data includes rescue medications taken after the Day 28 assessment. These will be 
included in the rerun of concomitant medication outputs. However, the analysis table 
summarizing rescue medications will not be rerun unless deemed useful post hoc. 
The outputs to be repeated at Week 12 are detailed separately in the list ‘MDGH-MOX- 
2001 (MNT18001) Week 12 Outputs’. 
Efficacy and safety data obtained for subjects randomized to all doses, including doses 
that may have been discontinued or added based on the recommendation from the 
PSC, will be included in the final analysis and presented in the outputs. 
 
6 
ANALYSIS PLAN 
General 
Summary statistics for continuous variables will consist of number of non-missing 
observations (n), mean, standard deviation (SD), minimum, median and maximum, 
unless specified otherwise. The precision of these variables is defined in the table, 
figure and listing shells document. 
For categorical variables the number and percentage of subjects in each category will 
be presented. Unless otherwise stated, this will be based on the number of non- 
missing observations apart from disposition of subjects, baseline and demographic 
characteristics, medical history, prior and concomitant medications and adverse 
events where the percentage will be based on the number of subjects in the analysis 
set. 
It is acknowledged that the sample size was not based on formal power considerations 
with respect to statistical hypothesis testing, and as such, the focus of the statistical 
analysis will be descriptive and exploratory. Although p-values may be calculated they 
should be interpreted as exploratory rather than confirmatory given the small sample 
size, lack of multiplicity adjustment, and exploratory nature of the hypotheses they may 
be testing. Where statistical testing is performed, this will assume a two-tailed 5% 
overall significance level, unless otherwise stated. Any comparisons between the dose 
groups will be reported with 95% confidence intervals for the difference. 
It is noted that particular attention may need to be given to the impact on key safety or 
efficacy assessments as a result of missing data associated with COVID-19. The 
amount of missing data will be monitored prior to database lock and, if deemed 
beneficial, a formal assessment of the impact on key assessments may be conducted. 
If this suggests that further investigation is beneficial, additional summaries and/or 
analyses of missing data may be added post hoc. This may also include additional 
sensitivity analyses using different approaches for handling of missing data if deemed 
worthwhile (see Sections 6.10.1.6 and 6.10.3.4 for more detail in relation to the primary 
endpoints and clinical cure rate exploratory endpoint). 
General Derivations 
This section provides details of general derivations. Derivations specific to a parameter 
of interest are detailed within the specific SAP sections. 


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Medicines Development for Global Health study no: 
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• Definition of study day 
Throughout this SAP any references to ‘Day XX’ refer to the pre-specified visits 
defined in the protocol (where the study drug administration visit is Day 0). 
Data listings by visit will additionally present the duration from the administration 
of study drug in days, referred to as ‘Study Day XX’. Study Day will be 
calculated relative to the date of administration of study drug in whole days. 
Thus, assessments completed on the day of study drug administration (‘Day 0’ 
visit) will be assigned a Study Day value of 1. 
• Definition of Baseline 
Baseline is defined as the last non-missing value (including scheduled and 
unscheduled assessments) prior to the subject receiving study drug. 
• Incomplete dates 
For calculation purposes, incomplete dates will be completed using a worst 
case approach. For example, assuming the earliest or latest possible date given 
all available information to ensure a worst case applies for each respective 
case. Further details are provided in the relevant sections as required. 
• Non-numeric values 
In the case where a variable is recorded as “> x”, “≥ x”, “< x” or “≤ x”, then for 
analysis purposes a value of x will be taken. Where a range of values is quoted, 
the midpoint of the range will be taken. 
• Site pooling for statistical analyses 
No analysis by center or country will be performed due to the small sample size 
of the study. Subjects from all centers will be pooled for summaries and 
analyses. 
• Methods for handling withdrawals and missing data 
In general, data will not be imputed unless otherwise stated in relevant sections. 
• Definition of planned dose and actual dose received 
Planned dose of study drug is defined as the dose group to which the subject 
was randomized and will be determined by the randomization list. Actual dose 
received is defined as the actual dose of study drug received regardless of 
randomized dose group. This will be determined once the blind has been 
broken using details provided by MDGH and/or captured on the electronic Case 
Report Form (eCRF) regarding actual doses received by subjects. 
 
Analysis Sets 
6.3.1 
Definitions 
The Enrolled Set includes all subjects who were randomized irrespective of whether 
they received the study drug. 
The Full Analysis Set (FAS) will include all randomized subjects receiving at least 
one dose of study drug. Subjects in the FAS will be analyzed according to the dose 
group to which they were randomized. In general, the FAS will only be used for 
selective analyses such as sensitivity analyses. 


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Medicines Development for Global Health study no: 
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The Per-Protocol Analysis Set (PPAS) will include all subjects exposed to study drug 
without any major protocol deviations that could confound the assessment and/or 
interpretation of the analytic results. Protocol deviations will be identified by the study 
team prior to breaking the study blind at the Day 28 analysis. Subjects in the PPAS 
will be analyzed according to the actual dose of study drug received regardless of their 
randomized dose group. In general, PPAS subjects with missing data for a specific 
analysis will be excluded from that analysis. However, imputation may be applied 
where considered appropriate. Details regarding any such imputation are given in the 
relevant sections of this SAP. As this is a proof-of-concept study, the PPAS will be the 
primary analysis set used to assess parasitological outcomes as well as clinical signs 
and symptom endpoints. Replacement subjects will be included in the PPAS if they 
meet the PPAS requirements. 
All protocol deviations will be assessed and documented on a case-by-case basis prior 
to the database lock for Day 28 analysis, and major deviations considered having a 
serious impact on the efficacy results will lead to the relevant subject being excluded 
from the PPAS. Some categories of major protocol deviations that might be considered 
as having a serious impact on the efficacy results include but are not limited to: 
• Subjects failing any eligibility criteria. 
• Any subjects with treatment administration errors. 
• Significant non-compliance with specified study visit windows. 
This is a non-exhaustive list and protocol deviations other than those specified above 
may be identified. 
The Safety Analysis Set (SfAS) will include all subjects exposed to study drug. 
Subjects will be analyzed according to the actual dose of study drug received 
regardless of their randomized dose group. Unless otherwise noted, the SfAS will be 
used for all safety analyses. 
The 
Pharmacokinetic 
Analysis 
Set 
(PKAS) 
and 
the 
Pharmacokinetic/Pharmacodynamic Analysis Set (PKPDAS) will be defined in the 
PKAP together with the use of these populations for analysis of PK data and the 
relationship between efficacy endpoints and plasma concentrations of moxidectin. 
6.3.2 
Assignment 
The Analysis Set Planning form indicates which analysis sets require individual subject 
assignments to be listed for Sponsor review and agreement prior to final analysis, as 
well as the timing of the reviews. Where the analysis set definitions are considered 
sufficient to determine the subjects included, it will not be considered necessary to 
complete listing and Sponsor review of the analysis set assignments and this will be 
indicated in the Analysis Set Planning form. Where analysis sets do require review of 
individual subject assignments, this will be completed and agreed prior to breaking the 
blind for the Day 28 analysis, once all relevant study data are available. Subject 
assignment to the PKAS and PKPDAS will be completed as part of the analysis 
detailed in the PKAP and will not be included in the activities covered by this SAP. 
It is assumed that the analysis sets for the Week 12 analysis will remain as agreed for 
the Day 28 analysis. New protocol deviations occurring after Day 28 will be 
categorized as major/minor for the presentation of the deviations only. As protocol 
deviations occurring after Day 28 will have no impact on the efficacy analyses, they 


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will not be considered to impact the PPAS assignments or necessitate a review of 
these. Therefore, no update of the PPAS will occur after the Day 28 analysis. 
 
Data Presentations 
Data will be summarized in tabular form by dose group in order of ascending dose 
(‘Moxidectin 2 mg’, ‘Moxidectin 8 mg’, ‘Moxidectin 20 mg’, ‘Moxidectin 36 mg’ (if 
required)) and overall subjects. 
Only scheduled post-Baseline assessments will be tabulated. Post-Baseline 
repeat/unscheduled assessments will not be tabulated, although they will be listed. 
Data collected under the ‘Period 1 Day 28 or Early Withdrawal’ visit in the eCRF will 
be mapped to either ‘Day 28’ for subjects who complete the study up to and including 
the Day 28 assessment, or ‘Early Withdrawal’ for subjects who withdraw early and 
prior to completing the Day 28 assessment. The mapped visits will be used for all data 
presentations and analyses. Data presentations by visit will present ‘Early Withdrawal’ 
after all other visits. 
Listings will be sorted by dose group, subject number and date/time of assessment. 
Dose groups will be presented in order of ascending dose. 
Tables, figures and listings will be prepared using the following analysis sets: 
 
 
Analysis Set 
Tables 
Figures 
Listings 
Enrolled 
Analysis sets 
Study completion/withdrawal 
Medical history 
Demography 
All non-safety 
SfAS 
Prior/concomitant medications 
Rescue medication analyses 
Safety 
All safety 
PPAS 
Efficacy summaries1 
Efficacy analyses1 
Efficacy1 
1. Where the difference between the PPAS and FAS is ≥1 subject, summaries 
and analyses of the primary efficacy endpoints may be repeated for the FAS 
post-hoc if deemed worthwhile to support the findings of the study. Selected 
exploratory efficacy endpoint summaries and analyses may also be repeated 
post-hoc, as indicated in the relevant sections of this SAP, but generally will be 
based on the PPAS only. 
 
Disposition of Subjects 
The number of subjects in the enrolled set, the number and percentage of subjects 
included in the FAS, PPAS and SfAS who were continuing the study (Day 28 
summary) or completed the study (Week 12 summary), and who prematurely 
discontinued the study, will be summarized. The number and percentage of subjects 
will be summarized by their reasons for withdrawal from the study. 


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Study completion/withdrawal data will be listed. A separate listing will also present 
eligibility for each of the analysis sets along with reasons for exclusion and the protocol 
version participants were enrolled under. 
 
Protocol Deviations 
Prior to database lock and blind break for the Day 28 analysis, MDGH will review the 
individual deviations and classify them as major or minor. Subjects with deviations 
that are determined to impact the interpretation of the results will be excluded from the 
PPAS. 
Additional deviations occurring during Period 2 (after the Day 28 database lock but 
prior to database lock at Week 12) will also be reviewed and classified by MDGH as 
major or minor. No reclassification of deviations occurring during Period 1 will take 
place at the review of Period 2 deviations. 
Details of all protocol deviations (deviation start and end dates, deviation category, 
specific details and classification of major or minor) will be listed. 
 
Baseline and Demographic Characteristics 
6.7.1 
Demography 
Demographic characteristics (age, sex and race) and body measurements (height, 
weight and Body Mass Index (BMI)) collected at Screening will be summarized. 
Age will be the collected age captured in the eCRF. Where age is missing on the eCRF 
it will derived from the year of birth as Year of Screening Visit – Year of Birth. 
BMI will be derived from (weight (kg)/height (m)²). 
All subject demographic data including informed consent date will be listed. 
6.7.2 
Medical History 
Medical history events will be coded using the latest Medical Dictionary for Regulatory 
Activities (MedDRA) version in place at the time of analysis and documented in the 
Data Management Plan (DMP). The version used will be indicated in the data 
summaries and listings. If updates to later versions are required during the study, this 
will be reflected in the DMP and the outputs. The number and percentage of subjects 
with medical history events will be presented by system organ class (SOC), and 
preferred term (PT), where SOC and PT will be presented in decreasing frequency of 
the total number of subjects with medical history events. All events will be listed. 
Prior and Concomitant Medications 
Medications will be coded using the latest World Health Organization Drug dictionary 
(WHO Drug) version in place at the time of analysis and documented in the DMP. The 
version used will be indicated in the data summaries and listings. If updates to later 
versions are required during the study, this will be reflected in the DMP and the 
outputs. 
Prior medications are defined as those that started and ended prior to the 
administration of study drug. Medications that are ongoing at the administration of 
study drug or started after the time of administration of study drug will be deemed to 
be concomitant medications. If medication dates are incomplete and it is not clear 


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whether the medication was concomitant, the medication will be assumed to be 
concomitant. 
The number and percentage of subjects taking prior medications and the number and 
percentage of subjects taking concomitant medications will be summarized 
separately. The summaries will be presented by medication class and standardized 
medication name, where medication class and standardized medication name will be 
presented in decreasing frequency of the total number of subjects with medications. 
In summary tables, subjects taking multiple medications in the same medication class 
or having the same standardized medication recorded multiple times in the study will 
be counted only once for that specific medication class and standardized medication 
name. 
Medication data will be listed and concomitant medications will be flagged. 
6.8.1 
Rescue Medication 
Any concomitant medications deemed to be rescue medication will be indicated as 
such on the concomitant medications eCRF page. 
All rescue medications will be flagged on the listing of prior and concomitant 
medications for the enrolled set. An analysis of rescue medication taken up to and 
including the Day 28 assessment for each subject will be conducted on the SfAS to 
assess any differences between dose groups in the requirement for rescue medication 
during this time period. 
The number and percentage of subjects recording at least one concomitant medication 
identified as a rescue medication up to and including their Day 28 assessment will be 
presented by dose group for the SfAS. 
Time to receipt of first concomitant rescue medication will also be derived in hours for 
each subject recording concomitant rescue medication up to and including Day 28 as: 
(Start date and time of first concomitant rescue medication) – (Date and time of study 
drug administration). 
Descriptive statistics will be presented for the time to receipt of concomitant rescue 
medication by dose group. The summary will be presented for the subset of subjects 
in the SfAS who record concomitant rescue medication in the time up and including to 
their Day 28 assessment. 
Following review of the summaries described above, further post-hoc analyses of 
rescue medication may be conducted if considered worthwhile and there are sufficient 
subjects receiving rescue medication. Any post-hoc analyses to be performed will be 
fully defined in a SAP Addendum prior to conducting the analyses. This may include 
analysis of rescue medications taken up to Week 12 as appropriate. 
 
Administration of Study Drug and Exposure 
Details regarding date and time of study drug administration will be listed. The dose 
group the subject was randomized to and the dose group the subject received will also 
be included in this listing. 


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Efficacy Evaluation 
6.10.1 
Primary Endpoint 
6.10.1.1 
Primary Variable 
The primary efficacy endpoint of the study will be determined by the death of adult 
scabies mites at each post-Baseline RCM assessment, with death defined as the 
degradation (homogenization of internal structures and/or external anatomic 
structures, and increased reflectance) of the adult mite observed by RCM. 
A minimum of 2 and maximum of 4 live adult scabies mites, each within its own distinct 
lesion, will be identified at Baseline by RCM for each subject. Only those lesions 
confirmed by RCM to contain a live adult scabies mite at Baseline will be recorded on 
the eCRF. These identified lesions will then be further assessed by RCM at Hours 4, 
8, 24, 48 and 72 and Days 7, 14 and 28 for changes in mite morphology, movement 
and peristalsis. 
For the purposes of analysis of the primary variable, only the 2, 3 or 4 individual live 
adult mites identified at Baseline by RCM will be evaluated at post-Baseline time 
points. It is not expected that juvenile mites will mature into adults within a selected 
lesion being evaluated for the primary endpoint. If there is evidence to suggest that 
this has occurred, the data will be reviewed on a case by case basis to determine how 
this should be handled in the analysis. 
6.10.1.2 
Primary Endpoints 
Four separate endpoints will be analyzed in order to assess death of adult scabies 
mites, all of which will be considered key primary efficacy endpoints. Analysis of the 
death of adult scabies mites will be performed using the individual scabies mite as the 
unit of analysis and also the subject as the unit of analysis. 
The endpoints to be analyzed using the scabies mite as the unit of analysis will be: 
• Mortality rate for adult scabies mites at each post-Baseline RCM time point. 
Mortality rate at each time point will be calculated as the proportion of the 
total number of dead adult scabies mites from among the total number of 
live adult scabies mites identified at Baseline. 
• Time to death of adult scabies mites for those identified as live at Baseline. 
Time to death of each adult scabies mite will be calculated in hours as (Date 
and time of first RCM assessment where mite confirmed dead) – (Date and 
time of study drug administration), for mites with confirmed death during the 
study. For mites without confirmed death during the study, time to death will 
be calculated in hours as (Date and time of Day 28 RCM assessment) – 
(Date and time of study drug administration), i.e. worst case. 
The endpoints to be analyzed using subject as the unit of analysis will be: 
• Mean proportion of dead adult scabies mites per subject at each post- 
Baseline RCM time point. The proportion of dead adult scabies mites for 
each individual subject at each time point will be calculated as the number 
of dead adult scabies mites from among the live adult scabies mites 
identified at Baseline for that subject. 


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• Proportion of subjects with 100% dead adult scabies mites from among the 
live adult scabies mites identified at Baseline for that subject, at each post- 
Baseline RCM time point. 
6.10.1.3 
Mite Status Derivation, Imputation and Missing Data 
The approach for identifying live versus dead mites for the above primary endpoints is 
described below. 
At Baseline, live adult mites will be defined by the following responses to the RCM 
assessment and only those lesions satisfying both of these criteria will be recorded on 
the eCRF: 
• The response to ‘Describe the mite stages present in the lesion?’ includes 
‘Adult mites’; 
• The response to ‘Does the mite have intact morphology?’ is ‘Yes’. 
As the identification of these lesions is a requirement for randomization into the study, 
no missing data is anticipated for the assessment of live mites at Baseline. 
At post-Baseline RCM assessments, an adult mite will be considered to be dead if at 
least one of the following conditions are met, based on the responses from the RCM 
assessment of the respective selected lesion: 
• The response to ‘Does the mite have intact morphology’ is ‘No’; 
• The response to ‘Describe the mite stages present in the lesion’ does not 
include ‘Adult mites’; 
• The response to ‘Is the lesion still visible’ is ‘No’. 
These conditions are hierarchical, such that if a lesion is no longer visible it will not be 
possible to identify the mite stages present or the morphology of any mites, therefore 
the mite will be considered dead. Similarly, if the response to ‘Describe the mite stages 
present in the lesion’ does not contain ‘Adult mites’ it will not be possible to confirm 
intact morphology, therefore the mite will be considered dead. 
Due to the life cycle of the mite and the subjective nature of skin assessments, it is 
possible that responses from the post-Baseline RCM assessments suggest that a mite 
previously declared as dead could be declared as live at a future assessment. To allow 
for this, the following rules will be applied to the post-Baseline assessments. 
Regardless of these rules, the baseline assessments (i.e. of live mite) will not be 
changed. 
1. Any response of ‘Unsure’ to ‘Does the mite have intact morphology’ will be 
considered as equivalent to a status of ‘live’. 
2. One assessment with a status of ‘dead’ is required in order to declare the mite 
dead for all subsequent visits, where the death of the mite will be assumed to 
have occurred at the first visit with a status of ‘dead’. 
a. Where rescue medication has been taken (identified on the concomitant 
medications page of the eCRF), any mite death occurring after the start 
date of rescue medication will be ignored and the mite will continue to 
be considered alive. If the mite has already died prior to or on the start 
date of rescue medication, it will be considered dead for all subsequent 
visits as stated here. 


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3. Should the RCM responses indicate a status of ‘live’ at an assessment 
occurring after an assessment with a status of ‘dead’, this will be assumed to 
be a new infection and thus ignored, i.e. the mite identified at Baseline will still 
be assumed to have died. This will therefore not impact the analysis of the 
primary efficacy endpoints. 
4. Where data are missing for any of the responses required to determine the 
status of a mite and therefore the mite status cannot be established, the status 
of the mite will be assumed not to have changed from the previous non-missing 
assessment (i.e. the last observation will be carried forward). This includes 
where a subject withdraws early, in which case the last observation will be 
carried forward for all remaining visits. Where the last observation is carried 
forward, this will still be subject to the above rules 1 to 3. 
These imputation methods will be applied to all missing adult mite assessments, 
regardless of the number of lesions for which data are missing for a subject at a 
timepoint. If data are missing at the subject level (i.e. the RCM assessment is not 
completed for any lesion at a timepoint for a subject), all mites being evaluated will 
have their status imputed and therefore no subjects will be missing in the primary 
analysis summaries presented at each post-Baseline visit. 
It should be noted that the above rules may not be exhaustive. If any ambiguity 
remains in the status of the mite after applying these rules, subject data will be 
reviewed on a case-by-case basis prior to breaking the blind. 
All analyses of the dead/alive response described in the SAP for the primary endpoints 
will use the values obtained after applying the strategies for any imputation where 
there is ambiguity or missing data. Similarly references to ‘first/last time point where 
dead/alive’ refer to the first/last occurrence once these imputations have been applied. 
Following review of these analyses, post hoc sensitivity analyses may be considered 
to assess the impact of these imputations, as described in Section 6.10.1.6. 
6.10.1.4 
General Considerations 
Due to the small sample size (n = 18) which was not based on formal power 
considerations with respect to statistical hypothesis testing, no formal hypothesis 
testing will be employed. Although p-values may be calculated they should be 
interpreted as exploratory rather than confirmatory given the small sample size, lack 
of multiplicity adjustment, and exploratory nature of the hypotheses they may be 
testing. 
Instead, descriptive statistical techniques will be used to identify differences between 
the doses of moxidectin with the objective of describing an exposure-response 
association between the dose groups and parasitological outcomes, and/or observing 
a single dose that appears to have the ‘best’ parasitological effect while maintaining 
an acceptable safety profile. 
All RCM assessment data will be listed, including the derived flag for mites considered 
dead at each time point and time to death of mite. 
6.10.1.5 
Summaries 
Mortality rate for adult scabies mites 
The summary of mortality rate data will include the number and percentage of dead 
adult scabies mites, presented by dose group for each post-Baseline RCM time point. 


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The total number of live adult scabies mites identified at Baseline (and used as the 
denominator for the percentages), will also be indicated in the summary. Clopper- 
Pearson 95% CIs will be presented for all percentages where independence among 
mites within subjects is assumed. 
Time to death of adult scabies mites 
Time-to-death of adult scabies mites (hours) for each mite identified as live at Baseline 
is defined as: 
(Date and time of first RCM assessment where mite confirmed dead) – (Date and time 
of study drug administration). 
The time-to-death of adult scabies mites will be interval censored. For those mites with 
confirmed death during the study, the beginning of the interval will be the 
administration of study drug and the end of the interval will be the first RCM 
assessment where the mite is confirmed dead. For mites without confirmed death 
during the study, or still alive prior to or on the start date of any rescue medication 
exposure, the time-to-death will be right censored where the beginning of the interval 
will be the administration of study drug and the end of the interval will be the Day 28 
RCM assessment (i.e. worst case), calculated in hours as: 
(Date and time of Day 28 RCM assessment) – (Date and time of study drug 
administration). 
Descriptive statistics will be presented for the time-to-death of adult scabies mites by 
dose group. This will include a summary excluding mites without confirmed death 
during the study (or still alive prior to or on the start date of any rescue medication 
exposure), as well as a separate summary including mites without confirmed death 
during the study or still alive prior to or on the start date of any rescue medication 
exposure, with the time to death censored as described above. A separate summary 
will present for each dose group, the number of mites identified as alive at Baseline, 
and the number and percentage of dead mites at the end of the study along with the 
Clopper-Pearson 95% CI for the percentage where independence among mites within 
subjects is assumed. The number and percentage of mites that are censored will also 
be summarized, along with Kaplan Meier (KM) estimates for the 25th, 50th and 
75th percentiles of time to mite death and corresponding 95% CIs. The time-to-death 
of adult scabies mites will also be presented graphically using a KM plot. 
Proportion of dead adult scabies mites per subject 
The proportion of dead adult scabies mites per subject (calculated from among the 
live adult scabies mites identified at Baseline for the subject) will be summarized via 
descriptive statistics including the mean proportion, presented by dose group for each 
post-Baseline RCM time point. 
Proportion of subjects with 100% dead adult scabies mites 
The number and percentage of subjects with 100% dead adult scabies mites from 
among the live adult scabies mites identified at Baseline for that subject will be 
presented, together with the Clopper-Pearson 95% CI for the percentage, by dose 
group for each post-Baseline RCM time point. 
6.10.1.6 
Sensitivity Analysis 
Per Section 6.4, the primary analyses may be repeated on the FAS post hoc if deemed 
worthwhile to assess any impact to the conclusions made. 


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Further sensitivity analyses, for example using different missing data or imputation 
approaches, may be considered post-hoc. This may include a completers analysis, 
repeating selected primary endpoint analyses without imputation of mite status due to 
missing data. Sensitivity analyses may also be added to assess the impact of 
imputations due to rescue medication or apparent new infections. 
6.10.1.7 
Post-hoc Analysis 
Where deemed appropriate following review of the summaries described above, post- 
hoc analyses for one or more of the primary endpoints may be considered in order to 
further evaluate any differences between dose groups. 
Any post-hoc analyses to be performed will be fully defined in a SAP Addendum prior 
to conducting the analyses, including details on the models to be applied, the 
hypotheses to be tested and the presentation of the results. 
6.10.2 
Secondary Endpoints 
PK and PD are described in further detail in Section 6.12 and Section 6.13 of this SAP. 
6.10.3 
Exploratory Endpoints 
All exploratory endpoints will be analyzed and summarized using the PPAS as the 
primary analysis set. Per Section 6.4, selected exploratory endpoints may be repeated 
on the FAS post-hoc if deemed worthwhile to assess any impact to the conclusions 
made. Where this is the case, the following endpoints will be repeated: 
• Presence and number of total mites and burrows assessed visually at Days 
7, 14 and 28 (see Section 6.10.3.1). 
• Changes in assessment of clinician-reported scabies symptomology (see 
Section 6.10.3.2). 
• Clinical cure rate (see Section 6.10.3.4). 
The exploratory endpoints will be assessed using descriptive summaries. However, if 
deemed of interest following review of the summaries, further analyses of these 
endpoints may be considered post-hoc. 
With the exception of clinical cure rate, data are included in all exploratory endpoint 
summaries irrespective of any exposure to rescue medication. The impact of rescue 
medication on data used in the summaries for clinical cure rate are detailed further 
Section 6.10.3.4. 
6.10.3.1 
RCM Assessment 
Changes in Adult Mite Motility 
The presence and changes in adult mite motility (movement and peristalsis) over time 
will be assessed in an exploratory manner using descriptive summaries, and with the 
adult scabies mite as the unit of analysis. 
The proportion of adult mites with and without movement respectively will be 
calculated at each RCM time point as the total number of adult scabies mites with and 
without movement from among the total number of live adult scabies mites recorded 
at Baseline. 
The proportion of adult mites with and without peristalsis respectively will be calculated 
at each RCM time point as the total number of adult scabies mites with and without 


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peristalsis from among the total number of live adult scabies mites recorded at 
Baseline. 
A summary will present for each dose group and RCM time point: the total number 
and percentage of lesions assessed across all subjects, the total number and 
percentage of adult scabies mites with each possible morphology response (intact/not 
intact/unsure), and the total number and percentage of adult scabies mites 
with/without movement and with/without peristalsis respectively. The denominator for 
all percentages will be the total number of live adult scabies mites recorded at Baseline 
across all subjects. The number of subjects with at least one missing or incomplete 
lesion assessment at each RCM time point will also be summarized, as well as the 
number of subjects who have been administered rescue medication prior to each 
respective RCM time point. 
There will be no imputation of missing or inconsistent data prior to the summary of the 
morphology, movement and peristalsis responses. Missing responses (due to the 
subject missing the complete RCM assessment or missing the individual lesion 
assessment) will be included under a ‘Missing’ category for each respective summary. 
Where an adult mite is recorded as no longer present or where a lesion is recorded as 
no longer visible, responses will be assumed as follows: ‘not intact’ for morphology, 
‘without movement’ and ‘without peristalsis’ for motility. 
Presence, Number, Morphology and Motility of Juvenile Mites 
The presence and characteristics of juvenile mites observed over time will be 
assessed in an exploratory manner using descriptive summaries. 
The total number of juvenile mites across all subjects, the total number and percentage 
of lesions across all subjects that were assessed and the total number and percentage 
of lesions across all subjects where any juvenile mites were observed will be 
presented by dose group and RCM time point. The table will also present the total 
number and percentage of lesions across all subjects with each of the responses to 
whether any juvenile mite has intact morphology (intact/not intact/unsure), as well as 
the total number and percentage of lesions across all subjects where any juvenile mite 
does/does not exhibit movement or peristalsis respectively, by dose group and RCM 
time point. The denominator for all percentages will be the total number of lesions 
identified at Baseline across all subjects. 
There will be no imputation of missing or inconsistent data prior to the summary of the 
juvenile mite responses. Missing responses (due to the subject missing the complete 
RCM assessment or missing the individual lesion assessment) will be included under 
a ‘Missing’ category for each respective summary. Where juvenile mites are recorded 
as no longer present or where a lesion is recorded as no longer visible, responses will 
be assumed as follows: ‘not intact’ for morphology, ‘without movement’ and ‘without 
peristalsis’ for motility. 
Mite Stages Visible by RCM 
The presence of adult mites, juvenile mites, eggs and scybala observed over time will 
be assessed in an exploratory manner using descriptive summaries. 
A summary will present the number and percentage of subjects with at least one lesion 
identified as having presence of each of the following respectively, by dose group and 
RCM time point: adult mites, juvenile mites, eggs, scybala. The table will additionally 
present the number and percentage of subjects recording presence of any one of 


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these options in at least one lesion, by dose group and RCM time point. The 
denominator for all percentages will be the number of subjects in the population for 
the respective dose group. 
There will be no imputation of missing or inconsistent data for individual lesions prior 
to summary of the responses for mite stages present. Presence of a mite stage will be 
determined from all non-missing lesion assessments at the respective time point for 
the subject, including lesions assessed as no longer visible (assumed to have no mite 
stages present). The summary may therefore include subjects with missing lesion 
assessments where at least one assessment is non-missing. Subjects with completely 
missing RCM assessment data for all lesions at a time point will be included under a 
‘Missing’ category for the respective summary. 
6.10.3.2 
Clinician Reported Scabies Signs and Symptoms 
Subjects will be assessed for the clinical signs and symptoms of scabies infestation at 
Baseline, Day 7, 14 and 28. The following exploratory endpoints will be assessed 
using this data: 
• Presence and number of total mites and burrows assessed visually at Days 7, 
14 and 28. 
• Changes in assessment of clinician-reported scabies symptomology, including 
extent of symptoms on body regions assessed by the number of anatomically- 
defined regions affected, number of lesions and severity grading of excoriations 
and erythema. 
The clinician reported scabies signs and symptoms endpoints will be assessed in an 
exploratory manner using descriptive summaries. 
Summaries will be presented for the number of subjects exhibiting each of the 
parasitological and clinical features, as well as those with new signs and symptoms, 
across all regions assessed for the subject by dose group and visit. These summaries 
will include the number and percentage of subjects with any: 
• Mites; 
• Burrows; 
• Any parasitological features (mites or burrows); 
• Lesions; 
• Nodules; 
• Excoriations (overall and by grade of excoriation); 
• Erythema (overall and by grade of erythema); 
• Any clinical features (lesions, nodules, excoriations or erythema); 
• Any parasitological or clinical features (mites, burrows, lesions, nodules, 
excoriations or erythema); 
• New mites relative to previous visit; 
• New burrows relative to previous visit; 
• New lesions relative to previous visit (including ‘Yes’ or ‘Unsure’); 


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• Region status at post-Baseline visits (‘New region’, ‘Region clear from previous 
assessment’). 
The denominator for all percentages will be the number of subjects in the dose group 
with a non-missing assessment for at least one region at the respective visit and this 
will also be presented in the summaries. If a region is assessed as clear from previous 
assessment, it will be assumed to have no parasitological or clinical features present. 
If a region is new compared to the previous assessment, all mites, burrows or lesions 
detected at that region will be assumed to be new. 
In addition to the above, the number of anatomical regions affected per subject will be 
summarized using descriptive statistics. This summary will exclude any regions 
recorded as clear from previous assessment. 
A further summary table will present the number and percentage of subjects recording 
each of the following lesion number categories by anatomical region, dose group and 
visit: 
• 0 lesions; 
• 1-10 lesions; 
• 11-20 lesions; 
• 21-30 lesions; 
• 31-40 lesions; 
• 41-50 lesions; 
• >50 lesions; 
• Total subjects with any lesions. 
The denominator for all percentages will be the number of subjects with a non-missing 
assessment for the respective region, visit and dose group and this will also be 
presented in the summary. If a region is assessed as clear from previous assessment, 
it will be assumed to have zero lesions present. Only regions with at least 1 subject 
presenting with at least 1 lesion at any visit will be presented. Regions where no 
lesions are present for any subject at any visit will not be presented. 
Further summaries will also be presented for the following: 
• Number of mites per subject across all anatomical regions, by dose group and 
visit. 
• Number of burrows per subject across all anatomical regions, by dose group 
and visit. 
Descriptive statistics for these summaries will include all subjects with a non-missing 
assessment for at least one region for the dose group and visit. If a region is assessed 
as clear from previous assessment, it will be assumed to have zero mites or burrows 
present respectively. 
All scabies signs and symptoms data will be listed. 


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6.10.3.3 
Patient Reported Outcomes 
Numerical Rating Scale (NRS) 
The NRS is a commonly used unidimensional scale which will be used as a measure 
of itch intensity. Subjects will complete the NRS at Baseline and Days 7, 14 and 28. A 
recall period of 24 hours will be used during which subjects will be asked to rate their 
average itch intensity (overall score) over those 24 hours and the itch intensity during 
the worst moment (peak score) of those 24 hours. For both of these questions, the 
subject will select a whole number from 0 to 10 corresponding to their itch intensity, 
where 0 is no itch and 10 is the worst itch imaginable. 
Scores will be categorized mild, moderate and severe where mild is a score between 
1 and 3 inclusive, moderate is a score between 4 and 6 inclusive and severe is a score 
between 7 and 10 inclusive. A score of 0 will be assigned a category of ‘none’ for the 
summaries and listings. 
Descriptive statistics will be presented for both the overall score and the peak score 
observed values by dose group and visit. In addition, the number and percentage of 
subjects 
recording 
overall 
and 
peak 
scores 
within 
each 
severity 
band 
(none/mild/moderate/severe) will be presented by dose group and visit. Finally, the 
number and percentage of subjects recording a decrease from Baseline of ≥4 points 
in the overall and peak scores respectively will be presented by dose group for each 
post-Baseline visit, together with the number and percentage of subjects recording this 
decrease at any time post-Baseline. The denominator for all percentages will be the 
number of subjects with a non-missing score for the respective dose group and visit. 
The denominator for the summary of subjects recording a decrease of ≥4 points at any 
time post-Baseline will be the number of subjects with at least one non-missing post- 
Baseline score for the respective dose group and visit. The values used as the 
denominator will be included in the summary. 
All NRS data will be listed including the observed score for each of the overall score 
and the peak score at each visit. 
5-D Itch Scale 
The 5-D Itch Scale measures five dimensions (duration, degree, direction, disability 
and distribution) of the impact of itching on the subject. The questionnaire consists of 
five items relating directly to each of the five dimensions. Subjects will complete the 
5-D Itch Scale at Baseline and Days 7, 14 and 28. A recall period of one week will be 
used. 
Questions 1 to 3 will be answered using a five-point Likert scale. These questions are 
scored according to the value selected by the subject i.e. the lowest duration, degree 
or direction response is scored a 1 and the highest duration, degree or direction is 
scored a 5. 
Question 4 is subdivided into four further subcategories of sleep, leisure/social, 
housework/errands and work/school also answered using a five-point Likert scale. The 
highest scoring response to these four sub-questions is taken as the score for 
question 4. The subcategories of leisure/social, housework/errands and work/school 
can be answered with an additional category of N/A, however as the highest score of 
the four subcategories is used for this question, and N/A is not an option for sleep, the 
overall score remains in the range of 1 to 5. 


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Question 5 requires the subject to indicate the areas in which they have experienced 
itching in the previous one week period. The number of body parts selected is then 
attributed the following scores: 0-2 body parts = 1, 3-5 body parts = 2, 6-10 body parts 
= 3, 11-13 body parts = 4 and 14-16 body parts = 5. 
The overall score is calculated as the summation of the scores of Questions 1 to 3, 
the highest score of Question 4 and the collated score of Question 5. The overall score 
ranges from 5 to 25 where higher scores indicate an increased itch related impact. 
Overall scores will be categorized mild, moderate and severe where mild is a score 
between 5 and 11 inclusive, moderate is a score between 12 and 17 inclusive and 
severe is a score between 18 and 25 inclusive. 
Descriptive statistics will be presented for the overall 5-D Itch Scale score observed 
values over time, as well as summaries of subjects by severity band and subjects with 
a decrease from Baseline of ≥4 points as described for the NRS scores above. 
All 5-D Itch Scale data will be listed including the observed score for each question 
and sub-question and the overall score at each visit. 
Dermatology Life Quality Index (DLQI) 
The DLQI is a 10-item questionnaire to assess health-related quality of life. Subjects 
will complete the DLQI at Baseline and Days 7, 14 and 28. 
For questions 1 to 6 and 8 to 10, the following responses are required: “not at all,” “a 
little,” “a lot,” or “very much”. The scoring for each of these questions is as follows: 
Very much = 3, a lot/quite a lot = 2, a little = 1, not at all = 0, not relevant = 0, question 
unanswered = 0. 
For question 7, if the answer is yes = 3, if no and no further information provided = 0, 
if no and the further question is asked then the responses are as follows: A lot = 2; a 
little = 1; Not at all, N/A or incomplete = 0. 
The overall DLQI score is calculated as the total score over all items and ranges from 
0 to 30 where higher scores indicate greater health-related quality of life impairment. 
The overall DLQI score will also be categorized as mild, moderate and severe where 
mild is a score between 0 and 5 inclusive, moderate is a score between 6 and 10 
inclusive and severe is a score between 11 and 30 inclusive. 
Descriptive statistics will be presented for the overall DLQI score observed values over 
time, as well as summaries of subjects by severity band and subjects with a decrease 
from Baseline of ≥4 points as described for the NRS scores above. 
All DLQI data will be listed including the observed score for each question as well as 
the overall score at each visit. 
6.10.3.4 
Clinical Cure Rate 
Clinical cure rate is defined as resolution of all scabies signs and symptoms present 
at Baseline, no new scabies signs and symptoms and no evidence of mites by 
dermoscopy. 
Clinical cure rate will be assessed at Days 7, 14 and 28. At each of these visits, a 
subject will be considered a responder, as determined by the clinician reported scabies 
signs and symptoms, if region status is ‘Region clear from previous assessment’, for 
each anatomical region assessed at that visit. 


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For each subject, imputation of missing assessments will be applied as follows. Where 
the scabies signs and symptoms assessment has been completed for a visit but this 
includes a missing assessment for a region previously assessed at an earlier time 
point, the region status will be imputed using the most recent previous assessment for 
the respective region (last observation carried forward). However, if the scabies signs 
and symptoms assessment has not been completed for a visit, or the assessments for 
all regions previously assessed are missing, no imputation will be applied and the 
subject will be excluded from the denominator for clinical cure rate at that visit. 
Where rescue medication has been taken (identified on the concomitant medications 
page of the eCRF), any assessment indicating clinical cure response subsequent to 
the start date of rescue medication will be ignored and the subject will be considered 
a non-responder. Visit responses identified at any visit prior to or on the start date of 
rescue medication for the subject will be unaffected. 
The number and percentage of responders, together with the Clopper-Pearson 95% 
CI for the percentage, will be presented for each dose group at each post-Baseline 
visit. The denominator for all percentages will be the number of subjects with a non- 
missing scabies signs and symptoms assessment for the respective dose group and 
visit and this will also be presented in the summary. 
A flag will be added to the listing of scabies signs and symptoms data to indicate 
subjects identified as responders at each time point. 
Following review of the above summaries, additional post hoc analyses may be 
considered, for example sensitivity analyses repeating the above clinical cure rate 
summary without imputation for missing assessments or the use of rescue medication. 
Any post-hoc analyses to be performed will be fully defined in a SAP Addendum prior 
to conducting the analyses. 
 
Multiplicity 
Given the exploratory nature of the study, no adjustment for multiple comparisons will 
be made. 
 
Pharmacokinetics 
Plasma for determining the pharmacokinetics of moxidectin will be collected at 
Baseline (pre-dose), Hours 2, 3, 4, 8, 24, 48 and 72, and at Days 7, 14 and 28. 
A separate PKAP will describe the reporting of PK concentrations as well as the 
derivation and reporting of PK parameters. 
 
Pharmacodynamics 
Details will be included in the separate PKAP regarding analysis of the relationship 
between efficacy endpoints and plasma concentrations of moxidectin. 
 
Safety Evaluation 
The primary safety endpoint is the assessment of incidence and severity of AEs, 
physical examinations, and measurement of vital signs up to and including Week 12, 
and laboratory safety parameters up to and including Day 28. 
Details regarding the evaluation of this data are given in the following respective 
sections. 


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6.14.1 
Adverse Events 
Adverse events (AEs) will be coded using the latest MedDRA dictionary version in 
place at the time of analysis and documented in the DMP. The version used will be 
indicated in the data summaries and listings. If updates to later versions are required 
during the study, this will be reflected in the DMP and the outputs. 
A treatment-emergent adverse event (TEAE) is defined as an AE that started on or 
after the start of the administration study drug or worsened after study drug exposure. 
If adverse event dates are incomplete and it is not clear whether the adverse event 
was treatment-emergent, it will be assumed to be treatment-emergent. 
A study drug-related TEAE is defined as a TEAE that is possibly, probably or definitely 
related to the study drug. If the TEAE has a missing relationship it is assumed to be 
related to the study drug for analysis purposes. 
Each AE will be graded for severity using the FDA Guidance for Industry: Toxicity 
Grading Scale for Healthy Adult and Adolescent volunteers Enrolled in Preventive 
Vaccine Clinical Trials. Details regarding this grading are given in Appendix 18.1 of 
the protocol. For AEs not specifically identified in this grading table, Section 12.2.1 
Table 10 of the protocol will be used to apply the severity grades. 
A summary table will present the following: 
• TEAEs (number of events and number of subjects); 
• Serious TEAEs (number of events and number of subjects); 
• Serious study drug-related TEAEs (number of events and number of subjects); 
• TEAEs by severity grade (Grade 1 – 4) (number of events and number of 
subjects); 
• TEAEs by relationship to study drug (Unrelated, Unlikely, Possible, Probably, 
Definite) and the pooled study drug related category (Related/Unrelated) 
(number of events and number of subjects); 
• TEAEs leading to withdrawal from study (number of subjects only); 
• TEAEs leading to death (number of subjects only). 
In the above summaries, if a subject experienced more than one TEAE, the subject 
will be counted once using the most related event for the “by relationship to study drug” 
and “study drug-related” summaries and at the worst severity for the “by severity 
grade” summary. 
The following tables will be presented: 
• TEAEs by System Organ Class (SOC) and Preferred Term (PT); 
• TEAEs by PT; 
• TEAEs by SOC, PT and severity grade; 
For all of the above, SOC and PT will be presented in decreasing frequency of the 
total number of subjects with TEAEs. 
Further details of the above three tables are given below: 
1. If a subject experienced more than one TEAE, the subject will be counted once 
for each SOC and once for each PT. 


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2. If a subject experienced more than one TEAE the subject will be counted once 
for each PT. 
3. If a subject experienced more than one TEAE, the subject will be counted once 
for each SOC and once for each PT at the worst severity grade. 
Adverse event data will be listed in full and this will also include a treatment emergent 
flag, the time of onset and cessation of event relative to dosing of study drug and 
duration of AE. 
6.14.2 
Clinical Laboratory Evaluation 
All laboratory values will be converted to the International System of Units (SI) for the 
purposes of summary and listing. 
Observed values and change from Baseline in hematology and biochemistry 
assessments will be summarized descriptively over time by dose group. 
Hematology and biochemistry data will be listed separately including change from 
Baseline, flagging all out of range values. Toxicity grades will be derived, where 
possible, for each hematology and biochemistry result as described in Section 18.1 of 
the protocol and these derived grades will be included in the listings. Parameters will 
be presented in the same order as the eCRF. 
6.14.3 
Vital Signs 
Vital sign observed values will be summarized over time by parameter (unit) and dose 
group. 
Weight, collected at Baseline and Week 12, will be included in the vital signs 
summaries and listing. 
Oral and aural body temperature measurements will be summarized and listed as 
separate parameters within the outputs. 
All vital sign data will be listed. 
6.14.4 
Electrocardiography 
Electrocardiography data will not be collected in the eCRF and will not be summarized 
or listed. 
6.14.5 
Physical Examination 
Individual subject physical examination data will be listed for the full assessment 
carried out at screening. For subsequent assessments, any findings will be 
documented as AEs and the assessment timings will not be listed. 
6.14.6 
Pregnancy Test 
Pregnancy test details and results will be listed. 
 
Changes from the Protocol Planned Analysis 
• The definition of the FAS has been amended to remove the statement regarding 
the requirement for ‘observed data for the particular analysis undertaken’. 
Instead, the inclusion/exclusion of subjects with missing data in analyses and 
summaries of the relevant endpoints on the FAS is addressed via the methods 
for handling missing data, as described in the respective sections of this SAP. 


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In addition, some imputation of missing data has been incorporated with respect 
to analysis and summary of the primary endpoint, rather than exclusion of any 
subjects with missing observations. These changes were considered more 
appropriate to ensure closer adherence to the intent to treat principle as well as 
to ensure clarity regarding the subjects included in the population and in each 
respective analysis. 
• The exploratory endpoint ‘presence of eggs and scybala in burrows’ has been 
addressed via the summary of ‘mite stages visible by RCM’.