Clinical trial NCT04533347
Conditions: COVID 19 Disease
Keywords: mild to moderate COVID 19 disease SARS-CoV-2 infectious disease severe acute respiratory syndrome coronavirus 2
Sponsor: 60 Degrees Pharmaceuticals LLC
Start date: 2021-02-19; Completion date: 2022-06-30
Enrollment: 86 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A clinical study to assess the efficacy and safety of oral tafenoquine compared to placebo in patients with mild to moderate COVID 19 disease.

Detailed description:
The TQ 2020\_06 study is a double-blind placebo-controlled, Phase 2 clinical trial that plans to enroll approximately 275 patients with mild to moderate infection with COVID-19. Patients will undergo a brief screening period before being randomized to receive either self-administer 200 mg tafenoquine or matching placebo for 10 days. Following the treatment period, patients will have a follow up visit at study Day 28 (28 days after the first dose of study medication). The study's primary efficacy endpoint is proportion of patients with clinical recovery from COVID-19 symptoms on Day 14 in patients with mild to moderate COVID-19 disease compared with placebo.

Arms: arm 1: Tafenoquine two 100 mg oral tablets 1x/day on Days 1,2,3 and 10 arm 2: Placebo two tablets 1x/day on Days 1,2,3 and 10
Interventions: intervention 1: Tafenoquine Oral Tablet intervention 2: Placebo
Intervention descriptions: intervention 1: Patients will be randomized and will receive and self-administer 200 mg Tafenoquine or matching placebo on Days 1, 2, 3, and 10. intervention 2: Patients will be randomized and will receive and self-administer 200 mg Tafenoquine or matching placebo on Days 1, 2, 3, and 10.

Protocol documents:
Prot_SAP_000.pdf: 
60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
TQ 2020_06 
CONFIDENTIAL 
1.0/11 Aug 2020 
  60º Pharmaceuticals LLC 
Clinical Protocol
NCT04533347  
A double-blind placebo-controlled study to assess the efficacy and 
safety of oral tafenoquine versus placebo in patients with mild to 
moderate COVID-19 disease 
TQ 2020_06 
152009 
Geoff Dow, PhD 
Chief Executive Officer 
60 Degrees Pharmaceuticals 
(240) 351-1167
geoffdow@60degreespharma.com
Akila Chandrasekar, M.D. 
Peachtree BioResearch Solutions, Inc. 
4985 Lower Roswell Road 
Bldg. 100 
Marietta, GA 30068 
617-285-9779
Protocol Title: 
Protocol Number: IND   
Number: Sponsor 
Contact: 
Medical Monitor: 
Sponsor’s Chief Medical 
Officer: 
Bryan Smith, MD, FAACP 
Chief Medical Officer 
60 Degrees Pharmaceuticals 
301-807-8548
bsmith@60degreespharma.com
FOR OFFICIAL USE ONLY 
Information and data included in this document contain proprietary and confidential information, 
which is the property of 60º Pharmaceuticals. No person is authorized to make it public without 
express written permission of 60º Pharmaceuticals. These restrictions on disclosure will apply 
equally to all future information, which is indicated as proprietary and confidential. 
Page 1 of 84


60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
TQ 2020_06 
CONFIDENTIAL 
1.0/11 Aug 2020 
Signature Page 
Protocol Number: 
TQ 2020_06 
Protocol Title: 
A double-blind placebo-controlled study to assess the efficacy and safety 
of oral tafenoquine versus placebo in patients with mild to moderate 
COVID-19 disease 
The signatures below indicate approval of the protocol. 
Sponsor  
Representative: 
_________________________________________ ___________________ 
Geoffrey Dow  
 
 
 
Date 
CEO 
Page 2 of 84


60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
Investigator’s Statement of Agreement: 
 
I acknowledge possession of and have read the tafenoquine Investigator’s Brochure and this 
protocol. Having fully reviewed all the information provided, I consider it ethically justifiable to 
give the study drug to patients according to the agreed protocol. I will conduct the study in full 
accordance with this protocol and all applicable laws and regulations, including but not limited to 
current Good Clinical Practices. 
 
 
 
Investigator: 
_________________________________________ ___________________ 
 
 
 
 
 
(Signature) 
 
 
 
 
Date 
 
 
 
 
 
________________________________________ 
 
 
 
 
          (Printed Name) 
 
 
 
Page 3 of 84


60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
Table of Contents 
1 
List of Abbreviations and Definition of Terms ................................................................................................ 8 
2 
Protocol Synopsis .......................................................................................................................................... 10 
3 
Introduction .................................................................................................................................................... 15 
3.1 
COVID-19 ............................................................................................................................................. 15 
3.2 
Tafenoquine (TQ) .................................................................................................................................. 15 
3.3 
Summary of Nonclinical and Clinical Studies ...................................................................................... 16 
3.3.1 
Nonclinical Studies ........................................................................................................................... 16 
3.3.2 
Clinical Studies ................................................................................................................................. 17 
3.4 
Rationale for the Study .......................................................................................................................... 19 
4 
Study Objectives ............................................................................................................................................ 21 
4.1 
Primary .................................................................................................................................................. 21 
4.2 
Secondary .............................................................................................................................................. 21 
4.3 
Exploratory ............................................................................................................................................ 21 
5 
Study Endpoints ............................................................................................................................................. 22 
5.1 
Efficacy Endpoints ................................................................................................................................ 22 
5.1.1 
Primary .............................................................................................................................................. 22 
5.1.2 
Secondary .......................................................................................................................................... 22 
5.1.3 
Exploratory ........................................................................................................................................ 22 
5.2 
Safety Endpoints ................................................................................................................................... 22 
6 
Study Design .................................................................................................................................................. 23 
6.1 
Study Description .................................................................................................................................. 23 
6.1.1 
Study Duration Per Patient ................................................................................................................ 24 
6.1.2 
Planned Number of Sites and Patients .............................................................................................. 24 
6.1.3 
Randomization .................................................................................................................................. 24 
6.2 
Schedule of Study Assessments ............................................................................................................ 25 
6.3 
Rationale for Study Design and Selection of Dose ............................................................................... 27 
7 
Selection and Withdrawal of Patients ............................................................................................................ 28 
7.1 
Inclusion Criteria ................................................................................................................................... 28 
7.2 
Exclusion Criteria .................................................................................................................................. 28 
7.3 
Withdrawal Criteria ............................................................................................................................... 29 
8 
Study Treatments ........................................................................................................................................... 31 
8.1 
Identity of Investigational Products and Additional Products ............................................................... 31 
8.2 
Treatment(s) to be Administered ........................................................................................................... 31 
8.3 
Packaging .............................................................................................................................................. 31 
8.4 
Labeling................................................................................................................................................. 31 
8.5 
Storage and Handling Procedures ......................................................................................................... 31 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
8.6 
Drug Accountability .............................................................................................................................. 31 
8.7 
Procedures for Monitoring Patient Compliance .................................................................................... 32 
8.8 
Study Restrictions ................................................................................................................................. 32 
8.9 
Important Administration Instructions .................................................................................................. 32 
8.10 
Concomitant Medication(s)/treatment(s) .............................................................................................. 32 
8.10.1 
Permitted Concomitant Treatments (Medications and Therapies) ................................................ 33 
8.10.2 
Prohibited Concomitant Treatments (Medications and Therapies) ............................................... 33 
8.11 
Blinding ................................................................................................................................................. 33 
8.11.1 
Procedures for Maintaining and Breaking the Treatment Blind ................................................... 33 
9 
Study Procedures ........................................................................................................................................... 35 
9.1 
Recruitment of Patients ......................................................................................................................... 35 
9.2 
Screening Period ................................................................................................................................... 35 
9.2.1 
Informed Consent .............................................................................................................................. 35 
9.2.2 
Week 1/Day -4 to Day -1 – In-Clinic ................................................................................................ 35 
9.3 
Treatment Period ................................................................................................................................... 35 
9.3.1 
Week 1/Day 1 through Week 1/Day 3 (± 1 day for self-administration of study drug) – In-home .. 35 
9.3.2 
Week 1/Day 4 through Week 2/Day 9 – In-home ............................................................................. 36 
9.3.3 
Week 2/Day 10 (± 1 day) – In-home ................................................................................................. 36 
9.3.4 
Week 2/Day 11 – In-home ................................................................................................................ 36 
9.4 
Follow-up Period ................................................................................................................................... 36 
9.4.1 
Week 2/Day 12 (± 1 day) – In-clinic ................................................................................................. 36 
9.4.2 
Week 2/Day 13 to Week 4/Day 27 (± 1 day) – In-home ................................................................... 37 
9.4.3 
Week 4/Day 28 (± 1 day) – In-home ................................................................................................. 37 
9.5 
Withdrawal Early Termination Visit/ Unscheduled Visit ..................................................................... 37 
10 
Assessment of Safety ................................................................................................................................ 38 
10.1 
Adverse Events ...................................................................................................................................... 38 
10.1.1 
Definitions ..................................................................................................................................... 38 
10.1.2 
Assessing Adverse Events ............................................................................................................. 39 
10.1.3 
Reporting Adverse Events ............................................................................................................. 40 
10.2 
Pregnancy and Birth Control ................................................................................................................. 42 
10.3 
Overdose of Investigational Medicinal Product .................................................................................... 42 
10.4 
Safety Signal Detection ......................................................................................................................... 43 
10.5 
Laboratory Measurements ..................................................................................................................... 43 
10.6 
Other Measurements ............................................................................................................................. 43 
10.6.1 
Demographics ............................................................................................................................... 43 
10.6.2 
Medical History ............................................................................................................................. 43 
10.6.3 
Physical Examination .................................................................................................................... 43 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
10.6.4 
Vital Signs ..................................................................................................................................... 44 
10.6.5 
Hospitalizations ............................................................................................................................. 44 
10.6.6 
Prior and Concomitant Medications .............................................................................................. 44 
11 
Study Management and Administration .................................................................................................... 45 
11.1 
Adherence to Protocol ........................................................................................................................... 45 
11.2 
Monitoring............................................................................................................................................. 45 
11.2.1 
Definition of Source Documents ................................................................................................... 45 
11.2.2 
Source Data Verification ............................................................................................................... 46 
11.3 
Data Handling ....................................................................................................................................... 46 
11.3.1 
Case Report Forms ........................................................................................................................ 46 
11.3.2 
Database Entry and Reconciliation ............................................................................................... 47 
11.3.3 
Patient Screening and Enrollment Log/Patient Identification Code List ...................................... 47 
11.3.4 
Quality Control and Quality Assurance ........................................................................................ 47 
11.4 
Study Termination ................................................................................................................................. 47 
11.5 
Archiving and Data Retention ............................................................................................................... 48 
11.6 
Audit and Inspection ............................................................................................................................. 48 
11.7 
Good Clinical Practice .......................................................................................................................... 49 
12 
Statistical Methods .................................................................................................................................... 50 
12.1 
General Statistical Considerations ........................................................................................................ 50 
12.2 
Analysis Populations for Analyses ........................................................................................................ 50 
12.2.1 
Patient Disposition ........................................................................................................................ 50 
12.2.2 
Demography and Other Baseline Data .......................................................................................... 50 
12.2.3 
Study Medication .......................................................................................................................... 50 
12.2.4 
Prior/Concomitant Therapy ........................................................................................................... 51 
12.3 
Planned Efficacy Analyses .................................................................................................................... 51 
12.3.1 
Analysis of the Primary Efficacy Variable .................................................................................... 51 
12.3.2 
Other Efficacy Analyses ................................................................................................................ 51 
12.4 
Planned Safety Analyses ....................................................................................................................... 51 
12.4.1 
Adverse Events .............................................................................................................................. 51 
12.4.2 
Laboratory Data............................................................................................................................. 52 
12.4.3 
Physical Examination .................................................................................................................... 52 
12.4.4 
Vital Signs and Body Measurements ............................................................................................ 52 
12.5 
Planned Interim Analysis and Data Monitoring .................................................................................... 52 
12.6 
Determination of Sample Size............................................................................................................... 52 
13 
Ethics and Regulatory Requirements ........................................................................................................ 53 
13.1 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) ............................................... 53 
13.2 
Informed Consent .................................................................................................................................. 53 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
TQ 2020_06 
CONFIDENTIAL 
1.0/11 Aug 2020 
13.3 
Patient Confidentiality .......................................................................................................................... 54 
13.4 
Protocol Amendments ........................................................................................................................... 54 
13.5 
Publications ........................................................................................................................................... 54 
14 
References ................................................................................................................................................. 56 
15 
Appendices ................................................................................................................................................ 57 
15.1 
Appendix A Prescribing Information ARAKODA ............................................................................... 57 
15.2 
Appendix B: Dyspnea and Cough Severity Scales ............................................................................... 58 
15.2.1 
Rating of Perceived Dyspnea (RPD) Scale ...................................................................................84 
15.2.2 
Cough Severity Scale .................................................................................................................... 84 
List of Tables 
Table 1 
Schedule of Procedures ..................................................................................................................... 25 
List of Figures 
Figure 1 
Structure of Tafenoquine ................................................................................................................... 16 
Figure 2 
Predicted Tafenoquine Concentration-time Curves for Plasma, Lung, and Lung Unbound Following 
Administration of Tafenoquine ............................................................................................................................. 20 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation/Term 
Definition 
ACE2 
angiotensin‐converting enzyme II 
AE 
adverse event 
ALT 
alanine transaminase 
ARDS 
Acute Respiratory Distress Syndrome 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BCRP 
breast cancer resistance protein 
BUN 
blood urea nitrogen 
CDMS 
clinical data management system 
CFR 
Code of Federal Regulations 
Cmax 
maximum concentration 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CYP 
cytochrome P450 
DMC 
Data Monitoring Committee 
eCRF 
electronic case report form 
ePRO 
electronic patient-reported outcome 
FDA 
U.S. Food and Drug Administration 
G6PD 
glucose-6-phosphate-dehydrogenase 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
GMP 
Good Manufacturing Practice 
hERG 
human Ether-à-go-go-Related Gene 
IC50 
50% inhibitory concentration 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IIV 
Inter-Individual Variability 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
MAPK 
mitogen‐activated protein kinase 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
Abbreviation/Term 
Definition 
MATE-1 
multidrug and toxin extrusion 1 transporter 
MATE2-K 
multidrug and toxin extrusion 2K transporter 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
N 
sample size 
N/A 
not applicable 
NP 
Nasopharyngeal 
OAT1 
organic anion transporter 1 
OAT3 
organic anion transporter 3 
OATP1B1 
organic anion transporting polypeptide 1B1 
OATP1B3 
organic anion transporting polypeptide 1B3 
OCT2 
human organic cation transporter 2 
P-gp 
P-glycoprotein 
PRO 
patient-reported outcome 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
PXR 
pregnane-X-receptor 
RBCs 
red blood cells 
RR 
respiratory rate 
RT-PCR 
reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-Cov-2 
severe acute respiratory syndrome coronavirus 2 
SD 
standard deviation 
SOPs 
standard operating procedures 
Tmax 
time to maximum concentration 
TQ 
Tafenoquine 
WBC 
white blood cell 
 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
2 
PROTOCOL SYNOPSIS 
Protocol Title: 
A double-blind placebo-controlled study to assess the efficacy and safety of oral 
tafenoquine versus placebo in patients with mild to moderate COVID-19 disease 
Protocol Number: 
TQ 2020_06 
Sponsor: 
60º Pharmaceuticals LLC 
CRO: 
Peachtree Bioresearch Solutions, Inc. 
Study Sites: 
Multiple sites in USA or elsewhere as appropriate.  
Sites must have: 
• 
Capacity to conduct Food and Drug Administration (FDA)-authorized real-time 
polymerase chain reaction (RT-PCR) SARS-CoV-2 test and provide results 
within 48 hours 
• 
Access to point of care glucose-6-phosphate-dehydrogenase (G6PD) testing or be 
able to receive G6PD test result from an in-house or commercial laboratory 
within 48 hours  
• 
Pharmacy with capability to dispense study medication in secondary child-proof 
containers with appropriate labelling 
Study Phase: 
Phase 2 
Study Objectives: 
Primary Objective:  
The primary objective is to determine if tafenoquine (TQ) [trade names ARAKODA™ 
and KODATEF™] increases the proportion of patients with clinical recovery from 
COVID-19 symptoms on Day 12 in patients with mild to moderate COVID-19 disease 
compared with placebo.  
Clinical recovery on Day 12 is defined as: 
• 
Temperature - ≤37.7°C [oral or skin surface] 
• 
Respiratory rate ≤ 24/minute on room air 
• 
Shortness of breath - absent 
• 
Cough – mild or absent on a patient reported scale of absent, mild, moderate, 
and severe 
Secondary objectives include determining if TQ: 
• 
Increases the proportion of patients with absence of detectable SARS-CoV-2 
virus by RT-PCR at Day 12 
• 
Increases the proportion of patients with absence of clinical symptoms by 
individual symptom at Day 12 
• 
Decreases the hospitalization rate due to COVID-19 disease by Day 12 
• 
Decreases the number of medical follow-up visits by Day 12 
Study Design 
This study is a double-blind, randomized, multisite, placebo-controlled trial comparing the 
safety and efficacy of TQ with placebo in non-hospitalized patients with mild to moderate 
COVID-19 disease. Patients will undergo screening procedures from Day -4 to Day -1 
including G6PD testing, an FDA-authorized RT-PCR test (from nasopharyngeal [NP] 
swab specimens) to confirm presence or absence of SARS-CoV-2, pregnancy testing, 
hematology, blood chemistry, vital signs, O2 saturation, physical exam, and assessment for 
symptoms of COVID-19 disease including cough, shortness of breath, respiration rate, and 
temperature.  
On Day 1, eligible patients will either return to the clinic or may have a telemedicine visit. 
Continued eligibility will be reviewed, and if still eligible, patients will be randomized and 
will receive and self-administer 200 mg TQ or matching placebo on Days 1, 2, 3, and 10 
Page 10 of 84


60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
[each administration of drug will be within ± 1 day with the exception of the first dose]. If 
the Day 1 visit is a telemedicine visit, the randomized blinded study drug will be sent via 
courier to the patient. Patients will be provided an oral thermometer to check and record 
their daily temperature and a home pulse oximeter to record their daily oxygen saturation. 
Patients will also be provided with an electronic study diary (eDiary) (loaded onto a device 
of their choosing) and be required to complete the eDiary entries from Day 1 through Day 
12 [± 1 day]. Patients will record respiration rate, temperature, COVID-19 clinical signs 
including presence and severity of cough, respiration rate and shortness of breath, AEs, 
and concomitant medications in the electronic diary daily. They will also record study 
drug administrations in the diary to monitor compliance. Daily diary data will be 
automatically uploaded to the electronic data management system and will be reviewed 
daily by clinical staff. 
Patients will be contacted by telephone or videoconferencing by designated study 
personnel on a daily basis to review AEs for severity by asking an open ended question, 
check for use of concomitant medications, and if there are new or worsening signs and 
symptoms of COVID-19 disease from Day 1 through Day 11 [± 1 day]. Telemedicine 
interviews will follow a script and information will be recorded in source documents. If a 
suspected SAE or worsening of signs and symptoms of COVID-19 are reported, a study 
physician will be contacted to determine if the patient needs additional support (clinic 
visit, medication, or emergency room visit). If the patient cannot be reached, an individual 
from their emergency contact list will be contacted to determine if the patient has been 
hospitalized.  
Patients will return to clinic on Day 12 [± 1 day] for the assessments listed in Table 1. 
From Day 13 [± 1 day] through Day 28 [± 1 day], patients will be instructed to complete 
the eDiary and will have a final telemedicine call on Day 28 [± 1 day]. 
Primary Efficacy 
Endpoint: 
• Proportion of patients with clinical recovery of COVID-19 symptoms on Day 12 [± 1 
day]  
Secondary Efficacy 
Endpoints: 
• Proportion of patients with negative SARS-CoV-2 RT-PCR on Day 12 [± 1 day]  
• Hospitalization rates due to COVID-19 symptoms (excluding admittance only for 
administrative or observations purposes)  
• Number of COVID-19-related medical follow up visits [Doctor’s office or emergency 
room (ER) visit]  
• Proportion of patients with COVID-19 symptoms at Day 12 by individual symptoms  
Exploratory Efficacy 
Endpoints: 
• Time to maximum severity of COVID-19 symptoms after start of treatment  
• Time to resolution of COVID-19 symptoms including cough, fever, shortness of 
breath and elevated respiratory rate. 
• Proportion of patients clinically recovered at Day 28 [± 1 day]  
Safety Endpoints 
• Adverse events (AEs) and serious adverse events (SAEs) 
• Vital signs (respiratory rate, temperature, heart rate, blood pressure, O2 saturation) 
• New symptoms of COVID-19 disease not present at screening 
• Clinical chemistry and hematology 
Study Drug and 
Administration: 
TQ will be administered orally as 2 x 100 mg dark pink coated tablets [or matching 
placebo] on Days 1, 2, 3, and 10. Placebo will be a identically appearing tablet containing 
excipients. 
Planned 
Participants: 
Approximately 275 patients with mild to moderate infection with COVID-19 will be 
enrolled with the goal of reaching 250 patients meeting the criteria for the modified 
intention-to-treat (mITT) population.  
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
Participant 
Selection: 
Inclusion criteria: 
(1) 
Male or female, aged ≥18 years of age; 
(2) 
Laboratory confirmed infection with COVID-19 virus by an FDA-authorized 
SARS-Cov-2 RT-PCR; 
(3) 
Able and willing to give written informed consent. 
(4) 
Willing to keep an electronic diary from Study Day 1 to Day 12 [± 1 day] and 
have daily phone or videoconferences with study team personnel. 
(5) 
At least one of the following clinical symptoms of COVID-19 infection within 
the 4 days prior to and inclusive of the day of screening: 
a. 
Respiratory rate ≥ 24/min: 
b. New cough or shortness of breath that has presented within the last 4 
days; 
c. 
Fever – temperature  ≥ 37.7°C [oral or skin surface] 
(6) 
Must agree not to enroll in another study of an investigational agent prior to 
completion of Day 28 of the study. 
(7) 
Able to take ARAKODA or KODATEF according to Prescribing Information 
(8) 
Have been symptomatic no longer than 5 days when the first dose of study 
medication is administered. 
(9) 
If female, agree to use an acceptable method of birth control from the time of 
consent through 56 days after the last dose of study drug. 
Exclusion criteria: 
(1) 
Have of the contraindications for ARAKODA or KODATEF  in the 
prescribing information (Section 15.1) including: 
a. 
G6PD deficiency 
b. Breastfeeding 
c. 
Psychotic disorder or current psychotic symptoms 
d. Known hypersensitivity reaction to TQ 
(2) Evidence of severe or critical illness, defined by at least one of the following:  
a. 
Clinical signs indicative of severe systemic illness with COVID-19, such 
as respiratory rate ≥30 breaths per minute, heart rate ≥ 125 beats per 
minute, SpO2 ≤93% on room air  
b. Respiratory failure defined based on resource utilization requiring at 
least one of the following:  
i. Endotracheal intubation and mechanical ventilation, oxygen 
delivered by high flow nasal cannula (heated, humidified, 
oxygen delivered via reinforced nasal cannula at flow rates 
> 20 L/min with fraction of delivered oxygen ≥ 0.5), 
noninvasive positive pressure ventilation, extracorporeal 
membrane oxygenation (ECMO), or clinical diagnosis of 
respiratory failure (i.e., clinical need for one of the preceding 
therapies, but preceding therapies not able to be administered in 
setting of resource limitation)  
ii. Shock (defined by systolic blood pressure < 90 mmHg, or 
diastolic blood pressure <60 mmHg or requiring vasopressors)  
iii. Multi-organ dysfunction/failure  
(3) 
Any other clinically significant acute illness unrelated to COVID-19 within 
seven days prior to first study drug administration 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
(4) 
Receipt of any experimental treatment for COVID-19 (off-label, 
compassionate use, or study-related) within the 30 days prior to the time of the 
screening evaluation 
(5) 
Any excluded concomitant medication as described in the ARAKODA 
package insert [Section 15.1] 
(6) 
Any COVID-19 symptoms which, in the opinion of the investigator, is 
suggestive of possible requirement to hospitalize within 48 hours of 
enrollment 
(7) 
Positive pregnancy test 
(8) 
Have been symptomatic for more than five days when the first dose would be 
administered 
Treatment Groups: 
There will be 2 treatment groups; TQ and placebo for which at least 250 patients will be 
randomized in 1:1 ratio to treatment with clinical site as a stratification variable. 
Randomizations will continue until at least 250 patients meet the criteria for mITT. 
Screening 
Procedures: 
After signing informed consent, patients will be screened for eligibility including medical 
history, G6PD, RT-PCR for SARS-CoV-2, pregnancy testing for females of child-bearing 
potential, hematology, blood chemistry, vital signs, O2 saturation, and physical exams. The 
Screening period will be a maximum of 4 days (Days -4 to -1), and the first day of dosing 
will be Study Day 1. 
Randomization 
Procedure: 
Eligible patients will be randomized at a 1:1 ratio to receive TQ or placebo. 
Randomization will be performed through a centralized, web-based, validated system that 
automates the assignment of patients to treatment allocation. Randomization will be 
stratified by clinical site. 
Efficacy 
Assessments: 
• 
Clinical signs and symptoms of COVID-19 (clinically diagnosed and patient reported) 
including fever, shortness of breath, cough, and respiratory rate daily from Day 1 to 
Day 28 (Note, the clinical signs of COVID-19 will not be reported as AEs) 
• 
SARS-CoV-2 PCR at Day 12 ± 1 day. 
• 
Hospitalization  
Safety and 
Tolerability 
Assessments: 
Clinical: 
• 
Vital signs (blood pressure, heart rate, and O2 saturation) 
• 
AEs 
Laboratory: 
• 
Hematology: red blood cells (RBC), white blood cells (WBC) with partial 
differential (neutrophils), hematocrit, hemoglobin, platelets; C-reactive protein 
(CRP), international normalized ratio (INR), prothrombin time (PT)/ partial 
thromboplastin time (PTT)  
• 
Blood chemistry: blood urea nitrogen (BUN), creatinine, alanine transaminase 
(ALT), and aspartate aminotransferase (AST) 
• 
Pregnancy test 
Statistical Analysis: 
Analysis Populations: 
• 
The modified Intention-to-Treat (mITT) population will include all patients who 
took at least one dose of study medication and had at least one post baseline 
assessment. The mITT population will be analyzed as they are randomized, 
regardless of which treatment a patient received.  
• 
Safety population: Any patient randomized and received any dose of study drug. 
Safety population will be analyzed based on the actual treatment received. 
• 
The PP population includes all mITT patients who completed the Day 12 clinic 
visit without any major protocol deviations. Protocol deviation category (minor 
or major) will be determined prior to the database lock and unblinding. 
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Primary Efficacy Endpoint: 
The proportion of patients with clinical recovery at Day 12 will analyzed using two 
methods: a 2x2 contingency table and logistic regression. The contingency table will 
provide unadjusted estimates of the proportions of patients with clinical recovery at 
Day 12. Copper-Pearson exact 95% confidence intervals around the recovery proportion 
within each treatment group will be provided. In a logistic regression treatment group will 
be the primary independent factor, additional covariates will be included in the model if 
there are sufficient events. Patients who do not have a Day 12 visit due to hospitalization 
for COVID-19 symptoms will be considered treatment failures 
Other Efficacy Endpoints: 
Dichotomous secondary endpoints will be analyzed in the same manner as the primary 
endpoint. The number of medical follow-up visits tabulated to determine if the endpoint 
can be considered continuous or ordinal. If the data are continuous the treatment groups 
will be compared by t-test. If the frequency distribution indicates few numbers of visits 
(e.g., 0, 1, 2, and 3 visits) then the analysis will use a chi-squared test to compare treatment 
groups. 
Safety Endpoints: 
AEs will be coded using the most recent version of the Medical Dictionary of Regulatory 
Activities (MedDRA) preferred terms and will be grouped by system, organ, and class 
(SOC) designation. The incidence of new COVID-19 symptoms not present at screening 
will be reported separately from other AEs including the maximum severity and time of 
maximum severity relative to the start of investigational product. The severity, frequency, 
and relationship of AEs to investigational product will be presented by preferred term by 
SOC grouping. Listings of each individual AE including start date, stop date, severity, 
relationship, outcome, and duration will be provided. Each AE (based on preferred 
terminology) will be counted once only for a given patient. If the same AE occurred on 
multiple occasions, the highest severity and relationship to investigational product will be 
assumed. Thus, study participants are not counted multiple times in a given numerator in 
the calculation of frequencies for a specific AE. Laboratory data and vital signs will be 
reported as summary statistics and change from baseline by treatment group for the safety 
population.  
Justification of Sample Size: 
Assuming an 85% clinical recovery rate in the TQ group and a 70% clinical recovery rate 
in the placebo group, sample sizes of 125 per treatment group will achieve 80% power 
with a two-sided alpha of 0.05 by logistic regression analysis. 
Study Duration: 
Patients will participate for up to 33 days including up to 4 days for screening, a treatment 
period over 10 days with safety/efficacy follow-ups through Day 28 [± 1 day].  
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3 
INTRODUCTION 
3.1 
COVID-19 
COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome coronavirus 2 
(SARS-CoV-2). It was first identified in 2019 in Wuhan, China, and quickly spread to over 215 
countries and territories (Worldometer 2020). As of 03 July 2020, there were more than 2,730,000 
cases in the USA with more than 128,000 deaths related to the disease (CDC 2020). Worldwide, as of 
03 July 2020, there were more than 11,190,000 cases and 529,000 deaths (Worldometer 2020).  
SARS‐CoV‐2 infects lung alveolar epithelial cells using receptor‐mediated endocytosis via the 
angiotensin‐converting enzyme II (ACE2) receptor. ACE2 is expressed on Type I and type II alveolar 
epithelial cells (Jia 2005). The binding of SARS‐CoV‐2 on ACE2 causes damage to alveolar epithelial 
cells that results a series of inflammatory processes (Zhou 2020).  
The current pandemic of COVID-19 is associated pulmonary inflammation and Acute Respiratory 
Distress Syndrome (ARDS) (Zhou 2020). In symptomatic patients, the clinical manifestations of the 
disease usually start within a week of exposure, and include fever, cough, shortness of breath, nasal 
congestion, fatigue, and upper respiratory tract infections. Gastrointestinal symptoms and 
asymptomatic infections have also been reported (Xiao 2020). The infection can progress to severe 
disease with dyspnea and severe pneumonia in the second or third week of infection, as evidenced by 
decreased oxygen saturation, blood gas deviations, and chest X ray (or other imaging) changes 
indicating deterioration. Lymphopenia may be present, and inflammatory markers (C‐reactive protein 
and proinflammatory cytokines) are elevated (Velavan 2020). 
Drugs administered late in the course of the disease, when patients are hospitalized with moderate to 
severe disease, may have minimal benefit (Beigel 2020, Geleris 2020, Wang 2020). It has been 
proposed that the anti-viral activity of antimalarial drugs may have potential in the treatment of earlier 
stage disease when symptoms start to emerge by blocking the viral replication cycle. 
Hydroxychloroquine was tested in nonhospitalized adults with early symptoms of COVID-19 disease 
and was found to have modest activity in reducing symptoms of infection and well as subsequent 
hospitalizations compared with placebo, but these differences were not statistically significant (Skipper 
2020). TQ was compared with hydroxychloroquine for inhibition of SARS-CoV-2 viral replication and 
was found to be 4-fold more potent (see Section 3.4). Therefore, TQ is of interest for investigation in 
early stage disease. 
3.2 
Tafenoquine (TQ) 
Tafenoquine [2, 6-methoxy-4-methyl-5-(3-trifluoromethylphenoxy) primaquine, succinate] is an 
8-aminoquinoline, formulated as an oral tablet (100 mg). TQ is a primaquine derivative (Figure 1) with 
a long half-life of approximately 14 days (Brueckner 1998). As such, TQ is safe and effective (as a 
prophylactic drug for the prevention of plasmodial infections) with weekly administration.  
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Figure 1 
Structure of Tafenoquine 
 
Figure taken from Brueckner 1998. 
3.3 
Summary of Nonclinical and Clinical Studies 
3.3.1 Nonclinical Studies 
The key target tissue effects in repeat-dose general toxicology studies of TQ of up to 26- and 52-weeks 
duration in rats and dogs, respectively, were oxidative changes in red cell elements of blood 
(methemoglobinemia, Heinz bodies, decreased hemoglobin concentration) and findings indicative of 
phospholipidosis (foamy macrophage accumulation, lamellar inclusion bodies in alveolar macrophages 
and type II pneumonocytes, and eosinophilic material in alveoli), which were manifested principally in 
the lung. All of the principal pathological changes were fully reversible, or showed partial reversibility, 
following a 13-week drug-free recovery period in the 13-week studies. No ophthalmological changes 
have been observed in any of the nonclinical animal toxicity studies.  
Based on the phospholipidosis-related changes in the lungs, the approximate overall no observed effect 
dose was 0.5 mg/kg/day (26 weeks) in rats and 0.1 mg/kg/day (52 weeks) in dogs. In separate eight 
week toxicokinetic studies using the same doses as the repeat dose studies, the no observed effect dose 
was shown to be associated with plasma area under the curve from Week 0 to Week 1 (AUC0-1) week 
values of 6.66 μg·h/mL in rats and 6.84 μg·h/mL in dogs (sexes combined). When compared to the 
AUC in humans consequent to the anticipated clinical regimen of TQ (200 mg x 3 days followed by 
200 mg/week), systemic exposures at the no effect doses in both rat and dog were assessed as 
representing relatively small fractions (~12%) of the AUC in humans, further confirming the observed 
heightened sensitivity of the two animal species to the treatment-related phospholipidosis and 
hematological effects seen with TQ. 
In an in vitro human Ether-à-go-go-Related Gene (hERG) channel electrophysiology assay, the 
inhibitory concentration at 50% (IC50) value for inhibition of hERG tail current was determined to be 
1.1 μM (equivalent to 0.510 μg/mL), a relatively low micromolar value and approximately equivalent 
to the predicted plasma concentration at the maximum proposed dose in humans. However, there were 
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no adverse effects observed in the electrocardiographic evaluations (including QTc interval) conducted 
in the in vivo oral and intravenous cardiovascular and pulmonary safety pharmacology studies in dogs, 
and in repeat-dose oral toxicity studies in dogs of up to 52 weeks in duration, in which plasma TQ 
concentrations of ~18.4 μg/mL and greater were achieved. In addition, there were no remarkable 
effects on action potential parameters in an in vitro dog isolated Purkinje fiber assay at concentrations 
up to 10 μM. Therefore, TQ has a low potential for QTc prolongation. 
No adverse effects on fertility or embryofetal development (including at maternally toxic doses), or on 
post-natal survival, were observed in a complete battery of reproductive toxicology studies.  
Standard mutagenic tests for TQ led to the conclusion that TQ itself does not present a genotoxic risk 
to man. Refer to the Investigator’s Brochure for additional information. 
3.3.2 Clinical Studies 
Tafenoquine has been approved by the FDA for prophylaxis of malaria in adults (ArakodaTM, 60º 
Degrees Pharmaceuticals, 100 mg tablets) and for radical cure of Plasmodium vivax in persons greater 
than 16 years old (KrintafelTM, GSK, 150 mg tablets). The Australian Therapeutics Good 
Administration has also approved tefenoquine under the trade name of KodatefTM, 60º Degrees 
Pharmaceuticals, 100 mg tablets). 
3.3.2.1 Pharmacology 
Despite TQ inhibiting a variety of cytochrome P450 (CYP) enzymes in vitro (including CYP1A2, 2C9, 
2D6 and 3A4/5), subsequent clinical studies have shown a low risk of clinically relevant drug-drug 
interactions via these enzymes. No clinically significant effects on the pharmacokinetics of substrates 
of CYP1A2 (caffeine), CYP2D6 (desipramine), CYP2C9 (flurbiprofen), or CYP3A4 (midazolam) 
were observed following coadministration with TQ in healthy adult patients. Furthermore, TQ did not 
activate the human pregnane-X-receptor (PXR), using an in vitro reporter gene assay, suggesting that 
TQ is unlikely to perpetrate a drug-drug interaction as a result of induction of CYP3A4. 
Tafenoquine inhibited the in vitro transport of 14C-metformin via human organic cation transporter 2 
(OCT2), multidrug and toxin extrusion 1 transporter (MATE1), and multidrug and toxin extrusion 2K 
transporter (MATE2-K) with calculated 50% inhibitory concentration (IC50) values of 0.28, 2.0 and 
0.63 μM, respectively. Based on unbound systemic concentrations at therapeutic doses, and the IC50-
derived, there is a potential, but low risk of drug interactions with OCT/MATE substrates. 
Tafenoquine is not an inhibitor of human breast cancer resistance protein (BCRP), P-glycoprotein (P-
gp), Organic anion transporter 1/3 (OAT1 or OAT3), Organic anion transporting polypeptide 1B1/1B3 
(OATP1B1 or OATP1B3) mediated transport at clinically relevant concentrations. Tafenoquine is also 
not a substrate of human OATP1B1 or OATP1B3 at clinically relevant concentrations. It is 
inconclusive as to whether TQ is a substrate of P-gp and/or BCRP mediated transport. 
3.3.2.2 Safety Pharmacology 
The effect of TQ on the QT interval was evaluated in a study of healthy adult patients. In this study, 
patients received once daily 400 mg (2 times the approved recommended dosage) doses of TQ for 3 
days. The results suggest that the mean increase in the QTcF interval for TQ is less than 20 msec. 
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3.3.2.3 Pharmacokinetics 
In majority of the clinical studies, TQ was administered under fed conditions. Following single dose 
administration of 200 mg TQ (two 100-mg TQ tablets) in 65 healthy adult patients under fed 
conditions (a high-calorie, high-fat meal [approximately 1000 calories with 19% protein, 31% 
carbohydrate, and 50% fat]), the maximum concentration (Cmax), time to maximum concentration 
(Tmax), and AUCinf were determined to be 147 ng/mL, 14 hr, and 70 hr*µg/mL, respectively. Following 
administration of a single dose of TQ orally under fasted conditions in healthy adult patients, AUC and 
Cmax increased dose proportionally over the dose range from 100 mg to 400 mg. When healthy adult 
patients received once-weekly administrations of 200 mg TQ orally for ten weeks without a loading 
dose under fasting conditions, the mean plasma accumulation ratio of TQ was approximately 4.4. 
The apparent oral clearance of TQ is approximately 4.2 L/hr (Inter-Individual Variability [IIV]: 23.6 
%) in healthy adult patients. The mean terminal half-life following administration of TQ is 
approximately 16.5 days (range: 10.8 days to 27.3 days) in healthy adult patients. Tafenoquine is 
greater than 99.5% bound to protein in humans. The apparent volume of distribution of TQ in healthy 
adult patients is 2470 L (IIV: 24.1%). 
3.3.2.4 Efficacy 
There have been no clinical studies with TQ in the proposed indication (mild to moderate COVID-19 
infection). 
3.3.2.5 Safety 
The safety of TQ was assessed in clinical studies to support the approval of TQ for prophylaxis of 
malaria and for radical cure of Plasmodium vivax at various doses and regimens in 3,184 patients. The 
recommended TQ regimen was evaluated in 825 patients in 5 controlled clinical studies. The mean 
duration of exposure to TQ in these five clinical studies was 21 weeks (range 10-29 weeks). Three 
studies were conducted in healthy semi-immune (to malaria) volunteers in Ghana or Kenya and were 
placebo-controlled; a mefloquine arm was included in 2 clinical studies as a benchmark. An additional 
study, an active comparator (mefloquine) controlled study, was conducted in healthy soldiers deployed 
in East Timor (Timor Leste), and a placebo-controlled study was conducted in healthy volunteers in 
the United States and United Kingdom. 
Tafenoquine has been generally well-tolerated in clinical studies. The most common adverse events 
(AEs) include nausea, vomiting, abdominal pain, diarrhea, and reversible vortex keratopathy (whorl-
like patterns of corneal epithelial deposits that did not interfere with visual acuity). Gastrointestinal 
(GI) AEs occurred with a greater incidence in patients treated with TQ compared with placebo and 
appeared to increase with increasing dose. Methemoglobinemia has been commonly reported 
following dosing of TQ in all studies and is most likely secondary to TQ-induced oxidative stress 
within red blood cells (RBCs). Elevations in serum creatinine without changes in glomerular filtration 
rate have also been observed. Hypersensitivity reactions (urticaria) have been reported in two patients. 
Hemolytic anemia should be anticipated in patients with glucose-6-phosphate dehydrogenase (G6PD) 
deficiency; therefore, patients must undergo G6PD deficiency testing and only be enrolled into TQ 
studies if G6PD-normal. 
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Refer to the Investigator’s Brochure and/or prescribing information (Section 15.1) for additional 
information. 
3.4 
Rationale for the Study 
Tafenoquine inhibited SARS-CoV-2 replication and the yield of progeny virus in VERO E6 cells with 
EC50/90s for the latter endpoint of ~ 2.6/5.1 µM, and 4-fold greater potency than hydroxychloroquine 
(see Dow 2020 and the Investigator’s Brochure for details on methodology used). Time of addition 
studies (head to head concentrations of 15 µM tafenoquine and hydroxychloroquine) were suggestive 
of either a more robust effect and/or a different mode of action for tafenoquine, with TQ inhibiting 
viral replication when added early in the viral replication cycle (Dow 2020). 
Whole lung, lung unbound, and plasma concentrations were simulated following administration of the 
approved dose of TQ for malaria prophylaxis (200 mg on Days 1, 2, 3 and 10), using Certara’s Simcyp 
model for tafenoquine (see Dow 2020 and the Investigator’s Brochure for more details on methods, 
and the modeling assumptions made). Concentration time profiles over 10 and 60 days were plotted 
versus the in vitro EC50, EC90, and EC90u values, with the latter calculated after adjustment for non-
specific protein binding in the in vitro assay system (Dow 2020). As is evident from Figure 2, lung 
unbound concentrations exceed the EC90u for more than 60 days following administration of TQ. 
Therefore, it is reasonable to hypothesize that the approved dose of TQ for malaria prophylaxis might 
reduce viral load in patients with COVID-19 disease, and thereby provide clinical benefit. 
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Figure 2 
Predicted Tafenoquine Concentration-time Curves for Plasma, Lung, and Lung 
Unbound Following Administration of Tafenoquine 
10 Days 
 
60 Days 
 
Figure 2: Predicted tafenoquine concentration-time curves for plasma, lung, and lung unbound following administration of 
tafenoquine at the approved dose for malaria prophylaxis (200 mg/day for three days followed by 200 mg one week later), 
in which the pH of lung tissue was assumed to be 6. The EC50, EC90, and EC90u concentrations from the YR assay are 
indicated as horizontal lines across the figure. 
 
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4 
STUDY OBJECTIVES 
4.1 
Primary 
The primary objective is to determine if TQ increases the proportion of patients with clinical recovery 
from COVID-19 symptoms on Day 12 in patients with mild to moderate COVID-19 disease compared 
with placebo. 
Clinical recovery is defined as:  
• 
Temperature ≤ 37.7ºC [surface by infra-red or oral] 
• 
Respiratory rate ≤ 24/minute on room air 
• 
Shortness of breath is absent (Section 15.2.1) 
• 
Cough is mild or absent on a patient-reported scale of absent, mild, moderate, and severe 
(Section 15.2.2) 
4.2 
Secondary 
Secondary objectives include determining if TQ: 
• 
Increases the proportion of patients with absence of detectable SARS-CoV-2 virus by 
RT-PCR at Day 12 
• 
Increases the proportion of patients with absence of clinical symptoms by individual 
symptom at Day 12 
• 
Decreases the hospitalization rate due to COVID-19 disease by Day 12 
• 
Decreases the number of medical follow-up visits by Day 12 
4.3 
Exploratory 
The exploratory objectives are to determine the time to maximum severity of COVID-19 symptoms 
and time to resolution of COVID-19 symptoms, with COVID-19 symptoms of interest being increased 
respiratory rate, fever, cough, and shortness of breath. 
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5 
STUDY ENDPOINTS 
5.1 
 Efficacy Endpoints 
5.1.1 Primary 
• 
Proportion of patients with clinical recovery of COVID-19 symptoms at Day 12 [± 1 day]  
5.1.2 Secondary 
• 
Proportion of patients with negative SARS-CoV-2 RT-PCR on Day 12  
• 
Hospitalization rates due to COVID-19 symptoms (excluding admittance only for 
administrative or observations purposes)  
• 
Number of COVID-19-related medical follow up visits (Doctor’s office or ER visit) 
• 
Proportion of patients with COVID-19 symptoms at Day 12 by individual symptom   
5.1.3 Exploratory  
• 
Time to maximum severity of COVID-19 symptoms after start of treatment  
• 
Time to resolution of COVID-19 symptoms including cough, fever, shortness of breath and 
elevated respiratory rate 
• 
Proportion of individuals clinically recovered at Day 28 [± 1 day]  
5.2 
Safety Endpoints 
• Adverse events (AEs) and serious adverse events (SAEs) events 
• Vital signs (respiratory rate, temperature, heart rate, blood pressure, O2 saturation) 
• New clinical symptoms of COVID-19 disease not present at screening 
• Clinical chemistry and hematology 
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6 
STUDY DESIGN 
6.1 
Study Description 
This study is a phase 2, multiple-dose, double-blind, placebo-controlled, study to assess the safety and 
efficacy of TQ in patients with mild to moderate COVID-19. Approximately 275 patients with 
COVID-19 will be enrolled with the goal of reaching 250 patients meeting the criteria for the mITT 
population at the end of the study (~125 TQ, ~125 placebo).  
After signing the informed consent form, patients will have medical history taken and undergo 
laboratory testing including G6PD, FDA-authorized RT-PCR from nasopharyngeal [NP] swab 
specimens) to confirm presence or absence of SARS-CoV-2, pregnancy testing, hematology, blood 
chemistry, vital signs, O2 saturation, physical exams, and will be assessed for COVID 19 symptoms 
including presence/severity of cough, presence/severity of shortness of breath, oral or skin 
temperature, and respiration rate. Patients who are eligible to participate in the study will be 
randomized in a 1:1 ratio to TQ or placebo within 2 days of the screening visit and will receive 
treatment on Day 1. Patients not meeting eligibility criteria will be considered a screen failure. 
Rescreening is permitted if first SARS-CoV-2 RT-PCR is negative, provided the patient has not been 
symptomatic for five days when the first dose of study medication is administered. 
On Day 1, eligible patients will either return to the clinic or may have a telemedicine visit. Continued 
eligibility will be reviewed, and if still eligible, patients will be randomized and will receive and self-
administer 200 mg TQ or matching placebo on Days 1, 2, 3, and 10 (each administration of drug will 
be within ± 1 day with the exception of the first dose). If the Day 1 visit is a telemedicine visit, the 
randomized blinded study drug will be couriered to the patient. Patients will be provided an oral 
thermometer to check and record their daily temperature and a home pulse oximeter to record their 
daily oxygen saturation. Patients will also be provided with an electronic study diary (eDiary) (loaded 
onto a device of their choosing) and be required to complete the eDiary entries from Day 1 through 
Day 12 [± 1 day]. Patients will record respiration rate, temperature, COVID-19 clinical signs including 
presence and severity of cough, respiration rate and shortness of breath, AEs, and concomitant 
medications in the electronic diary daily. They will also record study drug administrations in the diary 
to monitor compliance. Daily diary data will be automatically uploaded to the electronic data 
management system and will be reviewed daily by clinical staff. 
Patients will be contacted by telephone or videoconferencing by designated study personnel on a daily 
basis to review AEs for severity by asking an open ended question, check for use of concomitant 
medications, and if there are new or worsening signs and symptoms of COVID-19 disease from Day 1 
through Day 11 [± 1 day]. Telemedicine interviews will follow a script and information will be 
recorded in source documents. If a suspected SAE or worsening of signs and symptoms of COVID-19 
are reported, a study physician will be contacted to determine if the patient needs additional support 
(clinic visit, medication, or emergency room visit). If the patient cannot be reached an individual from 
their emergency contact list will be contacted to determine if the patient has been hospitalized. Patients 
will return to clinic on Day 12 [± 1 day] for the assessments listed in Table 1. From Day 13 [± 1 day] 
through Day 28 [± 1 day], patients will be instructed to complete the eDiary and will have a final 
telemedicine call on Day 28 [± 1 day]. 
The schedule of study procedures is illustrated in Table 1. 
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6.1.1 Study Duration Per Patient 
The total duration of the study will be up to 33 days for each patient, including 4 days for screening on 
Days -4 to -1, self-administration of study drug on Days 1, 2, 3, and 10, daily recording and remote 
collection of signs and symptoms from Day 1 through Day 11, an in-clinic visit on Day 12, and a 
telemedicine call on Day 28 ± day to assess AEs and clinical recovery.  
6.1.2 Planned Number of Sites and Patients 
The study will be conducted at multiple locations in the USA, Australia, or elsewhere as appropriate. 
Each site must have the capacity to conduct point of care COVID-19 RT-PCR test from NP swabs with 
a turn-around time no more than 48 hours. Sites must have access to point of care G6PD testing or be 
able to receive G6PD test result from an in-house or commercial laboratory within 48 hours. Sites must 
have pharmacy with capability to dispense study medication in secondary child-proof containers with 
appropriate labelling. 
Approximately 275 patients with COVID-19 will be enrolled with the goal of reaching 250 patients 
meeting the mITT criteria at the end of the study. 
6.1.3 Randomization 
Eligible patients will be randomized at 1:1 ratio to receive TQ or placebo and stratified by site. 
Randomization will be performed through a centralized, web-based, validated system that automates 
the assignment of patients to treatment assignment. The randomization scheme will be reviewed and 
approved by the sponsor or designee. For study medication dispensation, the Investigator or designee 
will access the randomization system to determine which blinded study medication bottle the patients 
will be assigned. 
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6.2 
Schedule of Study Assessments 
Table 1 
Schedule of Procedures 
Procedure 
Screening 
Day -4 to -1 
Day 
1 
Day 
1 
Days 2 and 3 
± 1 day 
Days 
4 to 9 
Day 10 
± 1 day 
Day 
11  
Day 12 
± 1 day 
Day 28 
± 1 day 
Clinic Visit # 
1 
If in clinic 
If at home 
 
 
 
 
2 or 3 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
X 
X 
 
 
 
 
 
 
Pregnancy testing1 
X 
 
 
 
 
 
 
X 
 
Demography 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
updated 
updated 
 
 
 
 
 
 
G6PD test 
X 
 
 
 
 
 
 
 
 
Physical exam 
X 
 
 
 
 
 
 
X 
 
Vital signs2 
X 
 
 
 
 
 
 
X 
 
Clinical symptoms of 
COVID-193 
 
 
 
 
 
 
 
 
 
Temperature4 
X 
X 
Self-measured by patient daily and recorded in eDiary 
X 
 
Respiration rate5 
X 
X 
Self-measured by patient daily and recorded in eDiary 
 
 
Shortness of breath 
(severity scale) 6 
X 
X 
Self-reported by patient daily and recorded in eDiary 
X 
 
Cough (severity scale) 7 
X 
X 
Self-reported by patient daily and recorded in eDiary 
X 
 
Pulse oximetry for oxygen 
saturation 
X 
X 
Self-measured by patient daily and recorded in eDiary 
X 
 
Prior and concomitant 
medications8 
X 
updated 
Recorded by clinician at telemedicine visit 
X 
Recorded by 
clinician at 
telemedicine 
visit 
Adverse events  
 
 
Self-reported by patient and recorded in eDiary, and recorded 
during telemedicine visit including severity and relationship to 
study drug, plus actions taken to treat AE or if drug discontinued 
X 
Recorded by 
clinician at 
telemedicine 
visit 
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Procedure 
Screening 
Day -4 to -1 
Day 
1 
Day 
1 
Days 2 and 3 
± 1 day 
Days 
4 to 9 
Day 10 
± 1 day 
Day 
11  
Day 12 
± 1 day 
Day 28 
± 1 day 
Clinic Visit # 
1 
If in clinic 
If at home 
 
 
 
 
2 or 3 
 
RT-PCR 
X 
 
 
 
 
 
 
X 
 
Hematology9 
X 
 
 
 
 
 
 
X 
 
Blood chemistry10 
X 
 
 
 
 
 
 
X 
 
Randomization 
 
X 
X 
 
 
 
 
 
 
Load eDiary to Patient 
Device, provide pulse ox 
device,thermometer, and 
instructions for use 
 
X 
X 
 
 
 
 
 
 
Dispense study drug11 
 
X 
X 
 
 
 
 
 
 
Study drug administration 
 
 
X 
Each day 
 
X 
 
 
 
Medication compliance  
 
 
eDiary 
eDiary 
 
eDiary 
 
 
 
Final drug accountability 
 
 
 
 
 
 
 
X 
 
1 A serum pregnancy test will be performed at screening and a urine or serum pregnancy test will be performed at Day 12. 
2Vital signs include blood pressure and heart rate 
3  COVID-19 symptoms will be assessed by designated clinical staff at in-clinic visits and will be checked at home by the patients and reported by the patient in 
the electronic diary (eDiary). Once the data is recorded in the diary it will be uploaded to the study database for clinician review. 
4 Temperatures will be taken orally or on the skin surface and recorded in degrees Centigrade. 
5 After resting for 3 minutes the number of breaths will be taken over one minute. 
6 The severity of shortness of breath will be reported by the patient using the Modified Borg Scale for Grading the Severity of Dyspnea shown in Section 15.2.1. 
7 The severity of coughing will be reported by the patient using the Cough Severity Scale shown in Section 15.2.2. 
8 Prior medications used in the 14 days prior to the start of screening will be recorded. 
9 Hematology tests include: WBC count, absolute neutrophil count, RBC count hematocrit, hemoglobin, platelet count; C-reactive protein, INR, PT/PTT. 
10 Clinical chemistry tests include: BUN, creatinine, ALT and AST. 
11 Study drug will either be dispensed in the clinic, if the patient has a clinic visit on Day 1, or will be delivered by same day courier service to the patient at home 
on Day 1, after final eligibility has been determined the patient is randomized.
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6.3 
Rationale for Study Design and Selection of Dose 
COVID-19 is a serious infectious disease that affected more than 11,190,000 people worldwide in 
2020 (Worldometer 2020). There are currently no approved treatments for mild to moderate COVID-
19 disease. 
The dose of TQ selected for this study is consistent with the current label. Pharmacokinetic modeling 
suggests unbound lung concentrations at this dose exceed the EC90 of tafenoquine against SARS-CoV-
2 in cell culture studies [see Section 3.4]. Double-blind procedures are included to reduce bias. A 
placebo control is included to demonstrate the effect of treatment with TQ. 
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7 
SELECTION AND WITHDRAWAL OF PATIENTS 
7.1 
Inclusion Criteria 
To be eligible to participate in this study, all of the following criteria must be met: 
(1) 
Male or female, aged ≥18 years of age 
(2) 
Laboratory confirmed infection with SARS-CoV-2 virus by an FDA-authorized RT-PCR 
test 
(3) 
Able and willing to give written informed consent; 
(4) 
Willing to keep a study diary from Study Day 1 to Day 12 [± 1 day] and have daily phone 
or videoconferences with study team personnel 
(5) 
At least one of the following clinical symptoms of COVID-19 infection within the 4 days 
prior to and inclusive of the day of screening: 
(i) 
Respiratory rate ≥ 24/min; 
(ii) 
New cough or shortness of breath that has presented within the last 4 days; and/or 
(iii) 
Fever ≥ 37.7ºC (oral or skin surface by infrared) 
(6) 
Must agree not to enroll in another study of an investigational agent prior to completion of 
Day 28 of the study; 
(7) 
Able to take ARAKODA or KODATEF according to Prescribing Information 
(8) 
Have been symptomatic no longer than 5 days when the first dose of study medication is 
administered 
(9) 
If female, agree to use an acceptable method of birth control from the time of consent 
through 56 days after the last dose of study drug 
7.2 
Exclusion Criteria 
Patients are not permitted to enroll in the study if any of the following criteria is met: 
(1) 
Have any of the contraindications for ARAKODA or KODATEF  in the prescribing 
information (Section 15.1) including: 
a. G6PD deficiency 
b. Breastfeeding 
c. Psychotic disorder or current psychotic symptoms 
d. Known hypersensitivity reaction to TQ 
(2) 
Evidence of severe or critical illness, defined by at least one of the following:  
a. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory 
rate ≥30 breaths per minute, heart rate ≥ 125 beats per minute, SpO2 ≤93% on room air  
b. Respiratory failure defined based on resource utilization requiring at least one of the 
following:  
i. Endotracheal intubation and mechanical ventilation, oxygen delivered by high 
flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal 
cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), 
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noninvasive positive pressure ventilation, extracorporeal membrane oxygenation 
(ECMO), or clinical diagnosis of respiratory failure (i.e., clinical need for one of 
the preceding therapies, but preceding therapies not able to be administered in 
setting of resource limitation)  
ii. Shock (defined by systolic blood pressure < 90 mmHg, or diastolic blood 
pressure <60 mmHg or requiring vasopressors)  
iii. Multi-organ dysfunction/failure  
(3) 
Any other clinically significant acute illness unrelated to COVID-19 within seven days 
prior to first study drug administration 
(4) 
Receipt of any experimental treatment for COVID-19 (off-label, compassionate use, or 
study-related) within the 30 days prior to the time of the screening evaluation 
(5) 
Any excluded concomitant medication as described in the ARAKODA package insert 
(Section 15.1)  
(6) 
Any COVID-19 symptoms which, in the opinion of the investigator, is suggestive of 
possible requirement to hospitalize within 48 hours of enrollment 
(7) 
Positive pregnancy test 
(8) 
Have been symptomatic for more than five days when the first dose would be administered 
7.3 
Withdrawal Criteria 
Patients are free to withdraw from the study at any time, without prejudice to their continued care.  
Patients should have their Investigational Product withheld and continue to be followed for Safety per 
the protocol should any of the following events occur: 
1. Patient develops an illness that would interfere with his/her continued participation. 
2. Patient is noncompliant with the study procedures or medications in the opinion of the 
investigator. Patients who receive at least 1 dose of study drug should be followed for 
safety, if possible, until Day 28. 
3. Patient takes prohibited concomitant medications as defined in this protocol. 
4. There is confirmation of a pregnancy during the study, as evidenced by a positive 
pregnancy test. 
5. The sponsor or a regulatory agency requests withdrawal of the patient. 
Investigators should attempt to obtain information on patients in the case of withdrawal. For patients 
considered as lost to follow up, the investigator should make an effort (at least 1 phone call and 1 
written message to the patient), and document his/her effort (date and summary of the phone call and 
copy of the written message in the source documents), to complete the final evaluation. All results of 
these evaluations and observations, together with a narrative description of the reason(s) for removing 
the patient, must be recorded in the source documents. The case report form (CRF) must document 
the primary reason for withdrawal. 
If patients are hospitalized during the study period for anything other than being administratively 
registered in the hospital for observation, efforts should be made to continue the patient in the study 
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through Day 28. The Medical Monitor should assess the patient’s ability to continue receiving study 
drug. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal of a 
patient in advance. 
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8 
STUDY TREATMENTS 
8.1 
Identity of Investigational Products and Additional Products 
Tafenoquine tablets for oral administration are pink, film-coated, capsule shaped tablets containing 125 
mg of TQ succinate, which is equivalent to 100 mg of free base. 
Tafenoquine tablets also contain: microcrystalline cellulose; mannitol; magnesium stearate; 
hypromellose; titanium dioxide; iron oxide; and macrogol (also known as polyethylene glycol). 
Placebo tablets are identical in appearance and contain the excipients without the active substance 
(TQ). 
8.2 
Treatment(s) to be Administered 
8.3 
Packaging 
The study drugs will be manufactured, packaged, and labeled according to Good Manufacturing 
Practice (GMP) guidelines and applicable laws or regulations.  
Tafenoquine or matching placebo tablets will be conveyed to study sites by the sponsor in 
aluminum/aluminum blister cards with 8 tablets per blister card. The investigational pharmacist will 
remove tafenoquine or placebo tablets from the blisters and dispense 8 of each tablet into child-
resistant HDPE bottles with labeling provided by the CRO. 
8.4 
Labeling 
Clinical drug supplies will be labeled in accordance with the current International Council for 
Harmonization (ICH) guidelines and Good Clinical Practice (GCP) and GMP and will include any 
locally required statements.  
8.5 
Storage and Handling Procedures 
The investigator (or designee) is responsible for the safe and proper storage of study drug at the site. 
Investigational medicinal product stored by the investigator is to be kept in a secured area with limited 
access according to the storage conditions mentioned on the label. 
The study drug should be stored at room temperature between 20 to 25ºC (or 68 to 77ºF). Appropriate 
storage conditions must be ensured and confirmed by completion of a temperature log (e.g. every 
working day). 
In case an out of range storage temperature is noted, it must be immediately reported as per 
instructions contained in the Study Drug Handling Manual. 
The investigator (or designee) will instruct the patient to store the study drug following the instructions 
on the label. 
8.6 
Drug Accountability 
A Drug Accountability form will be used to record study drug dispensing and return information on a 
by patient basis and will serve as source documentation during the course of the study. Details of any 
study drug lost, damaged (due to breakage or wastage), not used, partially used, disposed of at the 
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study site, or returned to the sponsor or designee must also be recorded on the appropriate forms. All 
supplies and pharmacy documentation must be made available throughout the study for the sponsor (or 
designee) to review. 
The investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study drug until returned or destroyed. 
The investigator may assign some of the investigator’s duties for drug accountability at the study site 
to an appropriate pharmacist/designee. 
The investigator must ensure that the study drug is used only in accordance with the protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired study drug must be reconciled and either 
destroyed at the site according to local laws, regulations, and the sponsor’s SOPs or returned to the 
sponsor (or designee). Investigational medicinal product intended for the study cannot be used for any 
other purpose than that described in this protocol. 
8.7 
Procedures for Monitoring Patient Compliance 
Patients will self-administer study drug and record the administration in the patient diary. The study 
personnel will record this information after each phone call/videoconference. 
At the Day 12 [± 1 day] visit, the patient must return all unused study drug to the site for destruction. 
8.8 
Study Restrictions 
TQ is contraindicated in:  
• Patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia. 
Patients must be tested for G6PD deficiency prior to treatment with TQ 
• Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the 
G6PD status of the infant is unknown  
• Patients with a history of psychotic disorders or current psychotic symptoms (i.e., 
hallucinations, delusions, and/or grossly disorganized behavior)  
• Patients with known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any 
component of ARAKODA. 
8.9 
Important Administration Instructions 
Patients will be instructed to: 
• Administer study drug with food.  
• Swallow the tablet(s) whole. Do not break, crush or chew the tablets. 
• Complete the full course of study drug according to the schedule in Table 1. 
8.10 Concomitant Medication(s)/treatment(s) 
Any medications taken prior to administration of study drug will be recorded as prior medications. Any 
medications taken during the dosing period will be recorded as concomitant medications All 
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medications reported by the patient will be recorded on a source document and in the electronic case 
report form (eCRF). 
8.10.1 Permitted Concomitant Treatments (Medications and Therapies) 
The following concomitant medications are permitted during the study: over-the-counter cough, cold, 
and flu medication, and any medications routinely taken by the Patient other than prohibited 
medications as described in Section 8.10.2. If taking medications for a chronic condition (i.e., 
depression, diabetes, hypertension) patients must be on a stable dose and have been taking medication 
for at least one week. 
8.10.2 Prohibited Concomitant Treatments (Medications and Therapies) 
Prohibited concomitant medications include: 
• Targeted COVID-19 therapeutics or therapies including remdesivir, dexamethasone, and 
convalescent plasma 
• OCT2 and MATE substrates (e.g., dofetilide, metformin). If coadministration cannot be 
avoided, monitor for drug-related toxicities and consider dosage reduction if needed based on 
approved product labeling of the coadministered drug 
8.11 Blinding 
All patients will be assigned a unique identifier and randomized to treatment using a randomization 
code provided by an IWRS system. Neither the patient nor the site staff will know to which treatment 
group the patient has been assigned. 
8.11.1 Procedures for Maintaining and Breaking the Treatment Blind 
8.11.1.1 Maintenance of Study Treatment Blind 
The tablets are identical but will have been repackaged by the investigational pharmacist in child-proof 
HDPE bottles and labelled so that the blind is maintained.  
8.11.1.2 Breaking the Treatment Blind in an Emergency Situation 
All procedures taken during the unblinding process should be documented properly and reported to the 
Sponsor. The emergency unblinding process usually occurs in the following situations, but not limited 
to: 
• 
In the case of an AE, where it is necessary for the Principal Investigator (PI) to know which 
treatment the patient is receiving so that the participant can be treated appropriately. 
• 
The Data and Safety Monitoring Committee (DSMB) or other regulatory bodies (i.e., FDA, 
IRB) should have access to the unblinded data, when requested, or concerns during the 
conduct of the clinical research study. 
• 
If someone not participating in the study ingests the study drug. For example, if a child in 
the patient’s household takes the study drug, the blind may be broken to determine the 
appropriate treatment for the child. 
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• In the case of accidental overdose, the blind should be broken. Hemoglobin decline and 
methemoglobinemia may be encountered in an overdose with TQ. Treatment of overdosage 
consists of institution of appropriate symptomatic and/or supportive therapy. 
The PI should follow the defined procedure to ensure the randomization code is broken only in 
accordance with the study protocol and per the Sponsor policy. 
The PI may not break the blind except in an emergency situation as described above. In a 
nonemergency situation, the PI should contact the study sponsor’s chief medical officer to obtain 
permission to break the blind.  
Each site must create procedures to break the blind and maintain documentation regarding the any 
unblinding whether the blinding was due to an emergency situation or not.  
 
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9 
STUDY PROCEDURES 
9.1 
Recruitment of Patients 
Study recruitment will be accomplished through selection of qualified investigator(s)/institution(s) that 
are qualified by training and experience, and that are deemed to have adequate staff and resources to 
properly conduct the trial, and with access to the appropriate patient population. Prospective study 
subjects may be identified through an investigator’s existing database, referral from an external 
clinician,  or through new patients treated as part of an investigator’s daily practice.  
9.2 
Screening Period 
9.2.1 Informed Consent 
At the first screening visit, candidates will meet with either the principal investigator or his/her 
designee and receive an explanation of the study purpose and requirements. If still interested after 
receiving an explanation of the study, the candidate will be given an opportunity to review, inquire 
about, and sign the study informed consent form approved by the IRB. Patients will be given a copy of 
the signed informed consent form. 
9.2.2 Week 1/Day -4 to Day -1 – In-Clinic 
After signing informed consent, patients will have medical history taken and undergo laboratory 
testing including G6PD, FDA-authorized RT-PCR) from nasopharyngeal [NP] swab specimens), 
pregnancy testing, hematology, blood chemistry, vital signs, O2 saturation, physical exams, and will be 
assessed for COVID 19 symptoms as described in Section 10.6. Patients who are eligible to participate 
in the study will be randomized in a 1:1 ratio to TQ or placebo within 2 days of the screening visit and 
will receive treatment on Day 1. Patients not meeting eligibility criteria will be considered a screen 
failure. Rescreening is permitted if first SARS-CoV-2 RT-PCR is negative, provided the patient has 
not been symptomatic for five days when the first dose of study medication is administered. Screening 
may be completed up to 48 hours prior to the Treatment Period. 
9.3 
Treatment Period 
9.3.1 Week 1/Day 1 through Week 1/Day 3 (± 1 day for self-administration of study 
drug) – In-home 
On Day 1, eligible patients will either return to the clinic or may have a telemedicine visit. Continued 
eligibility will be reviewed, and if eligible, patients will be randomized and will receive and self-
administer 200 mg TQ or matching placebo on Days 1, 2, 3 ± 1 day. If the patient has an in clinic visit, 
s/he will be given sufficient study drug for the entire study. If the Day 1 visit is a telemedicine visit, the 
randomized blinded study drug will be sent via courier to the patient. Patients will be provided with an 
eDiary application (loaded onto a device of their choosing). The patient will self-administer study drug 
with food (per the label instructions [Section 15.1]) and record compliance in the eDiary. Patients will 
be provided an oral thermometer to check and record their daily temperature and a home pulse 
oximeter to record their daily oxygen saturation. Patients will record respiration rate, temperature, 
COVID-19 clinical signs including presence and severity of cough, respiration rate and shortness of 
breath, doctor’s office and emergency room visits, AEs, and concomitant medications in the eDiary. 
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They will also record study drug administrations in the diary to monitor compliance. Daily diary data 
will be automatically uploaded to the electronic data management system and will be reviewed daily 
by clinical staff. Patients will be contacted by telephone or videoconferencing by designated study 
personnel on a daily basis to review AEs for severity by asking an open ended question, check for use 
of concomitant medications and more details such as dose, frequency, indication, and route of 
administration, and if there are new or worsening signs and symptoms of COVID-19 disease. 
Telephone interviews will follow a script and information will be recorded in source documents. If a 
suspected SAE or worsening of signs and symptoms of COVID-19 are reported, a study physician will 
be contacted to determine if the patient needs additional support (clinic visit, medication, or emergency 
room visit). If the patient cannot be reached an individual from their emergency contact list will be 
contacted to determine if the patient has been hospitalized.   
9.3.2 Week 1/Day 4 through Week 2/Day 9 – In-home 
Patients will record presence/severity of cough, presence/severity of shortness of breath, respiration 
rate, temperature, O2 saturation, AEs, and concomitant medications in the eDiary. Daily telemedicine 
phone calls or videoconferences from study site personnel will be conducted as described directly 
above. 
9.3.3 Week 2/Day 10 (± 1 day) – In-home 
Study drug will be self-administered with food (per the label instructions [Section 15.1]) and 
compliance recorded. Patients will record presence/severity of cough, presence/severity of shortness of 
breath, respiration rate, temperature, O2 saturation, AEs, and concomitant medications in the eDiary. 
The daily telemedicine phone call or videoconference with a study site staff member will be conducted 
as described directly above. 
9.3.4 Week 2/Day 11 – In-home 
Day 11 procedures will be the same as Days 4 through 9. 
9.4 
Follow-up Period  
9.4.1 Week 2/Day 12 (± 1 day) – In-clinic 
Assessments will be carried out according to the Schedule of Procedures (Table 1). Laboratory 
assessments will be conducted, including an FDA-authorized RT-PCR test for presence or absence of 
SARS-CoV-2. Physical exam, vital signs, pregnancy test, and clinical assessment of COVID-19 
symptoms, including respiration rate, presence/severity of cough, presence/severity of shortness of 
breath, and oxygen saturation, will be recorded on a source document and entered into the eCRF. 
Patient eDiary data will be reviewed, and AEs will be assessed for severity and relationship to study 
drug and concomitant drug use will be recorded. All data will be recorded in a source document or 
eCRF. 
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9.4.2 Week 2/Day 13 to Week 4/Day 27 (± 1 day) – In-home 
Patients will continue to enter data into the eDiary as done previously. The eDiary data will be 
reviewed by a clinical staff member, and if needed a telephone call will be made in the event that they 
patient reports worsening signs or symptoms of COVID-19 or a severe AE. 
 
9.4.3 Week 4/Day 28 (± 1 day) – In-home 
Patients will be contacted by telephone or videoconferencing by designated study personnel at Day 28 
to review the status of any ongoing AEs at Visit 2, check for use of concomitant medications, and if 
there are new or worsening signs and symptoms of COVID-19 disease. 
9.5 
Withdrawal Early Termination Visit/ Unscheduled Visit 
In the event a patient is withdrawn from treatment, they will be encouraged to continue in the study 
and undergo the follow-up assessments. Adverse event and concomitant medication reporting should 
be continued until the end of the study period. 
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10 ASSESSMENT OF SAFETY 
10.1 Adverse Events 
10.1.1 Definitions 
10.1.1.1 Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medical (investigational product, 
whether or not related to the medical (investigational) product. 
10.1.1.2 Serious Adverse Event 
As provided by the ICH criteria, an SAE is any adverse drug experience occurring at any dose that 
results in any of the following outcomes: 
• Death 
Death represents an outcome and a SAE criterion, not an event term. The medical condition 
with the fatal outcome should be reported unless the cause of death is unknown, in which case 
the term “Death” is acceptable. 
• A life-threatening adverse drug experience 
Any adverse drug experience that places the patient or patient, in the view of the Investigator, 
at immediate risk of death from the reaction as it occurred, i.e., it does not include a reaction 
that had it occurred in a more severe form, might have caused death. 
• Inpatient hospitalization or prolongation of existing hospitalization 
(A patient admitted to a hospital, even if he/she is released on the same day, meets the criteria 
for the initial inpatient hospitalization. An emergency room visit that results in admission to the 
hospital would also qualify for the initial inpatient hospitalization criteria. However, emergency 
room visits that do not result in admission to the hospital would not qualify for this criteria and, 
instead, should be evaluated for 1 of the other criteria in the definition of serious [e.g., life 
threatening adverse experience, important medical event]. 
Initial and prolonged hospitalizations that do not meet this SAE criterion include those due to 
social and /or convenience reasons (e.g., lack of personal care at home, unable to transfer to 
non-acute facility), and those for preplanned surgery or elective surgery for a pre-existing 
condition that has not worsened or manifested in an unusual or uncharacteristic manner. For 
example, if a patient has a condition recorded on his/her medical history and later has a 
preplanned surgery for this condition, it is not appropriate to record the surgery or 
hospitalization as an SAE, since there is no AE upon which to assess the serious criteria. Please 
note that, if the preexisting condition has worsened or manifested in an unusual or 
uncharacteristic manner, this would then qualify as an AE and, if necessary, the seriousness of 
the event would need to be determined) 
• A persistent or significant disability/incapacity (a substantial disruption of a person’s ability to 
conduct normal life functions) 
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• A congenital anomaly/birth defect 
• Other important medical event 
NOTE:  Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or patient or may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
hospitalization, or the development of drug dependency or drug abuse. 
In addition, any laboratory result abnormality fulfilling the criteria for an SAE should be 
reported as such, in addition to being recorded as an AE in the CRF. Any abnormal laboratory 
result which is clinically significant (i.e., meets one or more of the following conditions) should 
be recorded as a single diagnosis on the AE page in the CRF:  
• Accompanied by clinical symptoms 
• Leads to permanent discontinuation of study medication 
• Requires a change in concomitant therapy [e.g. addition of, interruption of, discontinuation of, 
or any other change in a concomitant mediation, therapy or treatment]. 
This does not apply to abnormal laboratory results that do not meet the clinical significance criteria or 
those which are a result of an AE which has already been reported. 
10.1.2 Assessing Adverse Events 
When completing appropriate forms for reporting an AE, the Investigator will be asked to assess the 
AE as follows: 
Seriousness of Adverse Event: 
• 
Serious:  The AE meets a criterion of the SAE definition. 
• 
Not Serious:  The AE does not meet a criterion of the SAE definition. 
Severity of Adverse Event: 
• 
Mild:  No interference with functioning. 
• 
Moderate:  No significant interference with functioning. 
• 
Severe:  Significant interference with functioning. 
Relationship of Adverse Event: 
• 
Definitely:  The adverse event follows a reasonable temporal sequence from the 
administration of the study medication; follows a known or expected response pattern to 
the study medication; is confirmed by improvement on stopping or reducing the dosage 
of the study medication (de-challenge) and reappearance of the event on repeat 
exposure (re-challenge); and cannot be reasonably explained by the patient’s clinical 
state. 
• 
Probably:  The adverse event follows a reasonable temporal sequence from the 
administration of the study medication; follows a known or expected response pattern to 
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the study medication that is confirmed by improvement on de-challenge; and cannot be 
reasonably explained by the patient’s clinical state. 
• 
Possibly:  The adverse event follows a reasonable temporal sequence from the 
administration of the study medication and follows a known or plausible response 
pattern to the study mediation but could readily have been produced by a number of 
other factors. 
• 
Unlikely:  A causal role of the study medication cannot be excluded, but the temporal 
relationship is atypical, and another plausible causal factor is present. 
• 
Unrelated:  The adverse event precedes the first administration of the study medication, 
or sufficient information exists to indicate that the etiology is clearly related to a cause 
other than the study medication. 
Action Taken with Regard to Study Medication:   
• 
Dose Not Changed 
• 
Drug Interruption 
• 
Drug Withdrawn 
• 
Not Applicable 
• 
Unknown 
Other Action Taken: 
• 
None 
• 
Concomitant Therapy or Additional Treatment Given 
• 
Therapeutic/Diagnostic Procedure 
• 
Other 
Outcome to Date: 
• 
Recovered/Resolved:  The patient recovered from the AE with no sequelae. 
• 
Recovering/Resolving:  The patient has not yet recovered from the AE, however the 
event is improving (follow-up of all serious AEs will be continued until the overall 
clinical outcome has been ascertained). 
• 
Not Recovered/Not Resolved:  The patient has not yet recovered from the AE; the event 
has not improved (follow-up of all serious AEs will be continued until the overall 
clinical outcome has been ascertained). 
• 
Recovered/Resolved with Sequelae:  The patient recovered from the AE with sequelae. 
• 
Fatal:  The patient’s death was a result of the AE. 
• 
Unknown:  The outcome of the adverse event is unknown. 
10.1.3 Reporting Adverse Events 
The patient will be given instructions to record AEs on their eDiary and will be asked about AEs at the 
clinic visit on Day 12 and on the telephone visit at Day 28. In addition, the investigator should review 
AEs reported in the eDiary employed in the study. 
When recording an AE, the investigator should use the overall diagnosis or syndrome using standard 
medical terminology, rather than recording individual symptoms or signs. The eCRF and source 
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documents should be consistent. Any discrepancies between the patient’s own words on his/her own 
records (e.g., eDiary entry) and the corresponding medical terminology should be clarified in the 
source documentation. 
Details for completion of the Adverse Event CRF (including judgment of relationship to 
investigational device or study procedure) are described in the eCRF Completion Guidelines. 
10.1.3.1 Data Safety Monitoring Board (DSMB) 
An independent DSMB of external advisors will meet prior to the start of the study, and periodically 
during enrollment and follow-up and at trial end to review safety data. The Board will be blinded to 
patients’ actual randomized group assignments but may request at any time that the blind be broken by 
the data center, if concerns arise from the blinded data. Ad hoc meetings will be convened if SAEs 
occur that are considered at least possibly related to the investigational product. 
The subject will be given the opportunity to report AEs spontaneously. A general, nonleading, prompt 
will also be given at each study visit and during each study phone call to solicit AEs.  
When recording an AE, the investigator should use the overall diagnosis or syndrome, using standard 
medical terminology, whenever possible, rather than recording individual symptoms or signs. The 
eCRF and source documents should be consistent. Any discrepancies between the subject’s own words 
on his/her own records (e.g., diary card) and the corresponding medical terminology should be 
clarified in the source documentation. 
Details for completion of the Adverse Event eCRF (including the judgment of relationship to 
investigational product or study procedure) are described in the eCRF Completion Guidelines (CCGs). 
10.1.3.2 Adverse Event and Serious Adverse Event Reporting Procedures 
• 
Safety Contact Information: 
Drug Safety Navigator (DSN) 
Email: PVG@DrugSafetyNavigator.com 
• 
AE Reporting: 
AEs occurring (initial occurrence or a worsening of a pre-existing condition) after the subject signs the 
informed consent form and up to the final follow-up visit at Day 28 will be reported and included in 
the study database. 
AEs will be reported on the AE CRF Form, and any related questions should be directed to DSN. 
• 
SAE Reporting: 
Any SAE experienced from the time the subject signs the informed consent up to the final follow-up 
visit at Day 28 will be reported to DSN as described below. Additionally, SAEs that occur after 
completion of the Follow-up period will also be reported to DSN if the Investigator considers the SAE 
related to study drug. 
SAEs must be reported to DSN within 24 hours of the Investigator’s (site’s) awareness or notification 
of the event. To report the SAE, the site must complete the SAE Form for the study. This form is not 
part of the eCRF and will be provided separately to the Investigator by DSN. Initial and follow-up 
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SAE reports will be sent to DSN via email to PVG@DrugSafetyNavigator.com, and to the sponsor’s 
Chief Medical Officer and to the Medical Monitor. 
The SAE reporting should not be delayed, and the sites may call and provide the available SAE 
information within 24 hours of Investigator’s awareness. A written SAE Form should be sent via email 
to PVG@DrugSafetyNavigator.com, as soon as possible. 
The Investigators should make every effort to provide complete information on the SAE Form. At the 
minimum, the initial SAE report must contain the subject’s identifiers, event term as known, SAE 
criterion and the Investigator’s causality assessment. Additional information (or updates to the 
previously reported information) may be provided, as it becomes available through a follow-up SAE 
report. 
The Investigator must continue to follow the subject until the SAE resolves, the condition becomes 
chronic in nature, stabilizes (in the case of persistent impairment), or the subject dies. Within 24 hours 
of receipt of follow-up information, the Investigator must complete the SAE Form and submit any 
supporting documentation, as necessary (e.g., laboratory test reports, subject discharge summary, or 
autopsy reports) to DSN via email to PVG@DrugSafetyNavigator.com. 
The Investigator is also required to submit SAE reports to the IRB in accordance with applicable 
requirements. 
10.2 Pregnancy and Birth Control 
All females should use an acceptable method of birth control (to be recorded on a source document and 
eCRF). Since a fetus would have an unknown G6PD status, TQ should not be used in pregnant women 
or in lactating mothers with infants of deficient or unknown G6PD status. If a patient becomes 
pregnant during the study or within 56 days of discontinuing study medication, the Investigator should 
report the pregnancy to Medical Monitor within 24 hours of being notified. CRO personnel will then 
forward the Exposure In Utero form to the Investigator for completion. 
The patient should be followed by the Investigator until completion of the pregnancy. If the pregnancy 
ends for any reason before the anticipated date, the Investigator should notify the Medical Monitor. At 
the completion of the pregnancy, the Investigator will document the outcome of the pregnancy. If the 
outcome of the pregnancy meets the criteria for immediate classification as an SAE (i.e., spontaneous 
abortion, stillbirth, neonatal death, or congenital anomaly), the Investigator should follow the 
procedures for reporting an SAE. 
10.3 Overdose of Investigational Medicinal Product 
Excessive dosing (beyond that prescribed in the protocol and including overdose) should be recorded 
in the CRF. Any SAE or nonserious AE associated with excessive dosing must be followed as any 
other SAE or nonserious AE. These events are only considered AEs or SAEs if there are associated 
clinical signs and symptoms or if the act of taking the excess medicine itself is an AE or SAE 
(e.g., suicide attempt). 
There is no experience of acute overdose with TQ, and management should be as clinically indicated. 
Hemolytic anemia and methemoglobinemia have been observed in clinical studies and are likely to be 
encountered in overdose. 
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10.4 Safety Signal Detection 
Selected data from this study will be reviewed periodically to detect as early as possible any safety 
concern(s) related to TQ so that investigators, patients, regulatory authorities, and IRBs/IECs will be 
informed appropriately and as early as possible. 
The Medical Monitor or medically qualified designee/equivalent will conduct an ongoing review of 
SAEs and perform ongoing SAE reconciliations in collaboration with the safety group representative. 
TQ should be discontinued immediately, if signs of hemolysis (anemia, dark colored urine) or 
methemoglobinemia (cyanosis) develop during administration. Due to the risk of hemolytic anemia in 
patients with G6PD deficiency, G6PD testing must be performed before administering TQ. Due to the 
limitations of G6PD tests, physicians need to be aware of residual risk of hemolysis, and adequate 
medical support and follow-up to manage hemolytic risk should be available. In clinical studies, 
declines in hemoglobin levels were reported in some G6PD-normal patients. Monitor patients for 
clinical signs or symptoms of hemolysis. 
10.5 Laboratory Measurements 
The following laboratory parameters will be measured: 
• 
RT-PCR in NP swab 
• 
Hematology: red blood cells (RBC), white blood cells (WBC) absolute neutrophil count, 
hematocrit, hemoglobin, platelets; C-reactive protein, international normalized ratio (INR), 
prothrombin time (PT)/ partial thromboplastin time (PTT) 
• 
Blood chemistry: blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT) and 
aspartate aminotransferase (AST) 
• 
G6PD  
• 
Pregnancy test (serum at screening and urine or serum at Day 12) 
10.6 Other Measurements 
10.6.1 Demographics 
Patient demographics (gender, race, ethnicity, and age) will be recorded. Height and weight will be 
recorded. 
10.6.2 Medical History 
Medical history will be recorded including comorbid conditions and COVID-19 disease history. 
10.6.3 Physical Examination 
A physical examination of the oral cavity, head, eyes, ears, nose, and throat, cardiovascular system, 
lungs, abdomen, extremities, skin, neuropsychiatric mental status and sensory/motor status, 
musculoskeletal system and general appearance. Abnormal findings will be recorded. 
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10.6.4 Vital Signs  
Vital signs including blood pressure, heart rate, oral or skin temperature and breathing rate (respiratory 
rate), will be recorded at the screening and Day 12 clinic visit after sitting for a least 3 minutes. 
Temperature, respiratory rate taken over a one minute period and oxygen saturation will be recorded 
daily at by the patient at home in the eDiary. Patients will be provided an oral thermometer to check 
and record in the eDiary their daily temperature and a home pulse oximeter to record their daily 
oxygen saturation. 
10.6.5 Hospitalizations 
Hospitalization information will be recorded on a hospitalization form and included in the case book 
that captures the PIs assessment of the hospitalization including the reason for hospitalization, length 
of stay, and details of the hospital visit. Patients will be asked to provide hospital records. Patients will 
be followed up as described in Section 10.4. 
10.6.6 Prior and Concomitant Medications 
Medications including indication, start/stop date, dose, frequency, and route taken by the patient 14 
days before the start of screening and for the duration of the follow-up period will be recorded on a 
source document and transcribed into an eCRF. 
 
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11 STUDY MANAGEMENT AND ADMINISTRATION 
11.1 Adherence to Protocol 
The investigator should not deviate from the protocol. However, the investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect patients from 
any immediate hazard to their health and safety. In this case, this action should be taken immediately, 
without prior notification of the regulatory authority, IRB/IEC, or sponsor. 
After implementation of such measure, the investigator must notify the sponsor within 24 hours and 
follow any local regulatory requirements. 
11.2 Monitoring 
Monitoring visits will be conducted by 60º Pharmaceuticals or designee according to applicable 
regulations and guidelines for GCP. The Investigator will permit the 60º Pharmaceuticals and/or 
designated representative(s) to make regular site visits during the study. The frequency of monitoring 
visits will be agreed upon by 60º Pharmaceuticals and/or designee. At each visit, the Investigator and 
staff will be expected to cooperate with 60º Pharmaceuticals or designee for the review and verification 
of protocol compliance, AE reporting, eCRFs, source documents, clinical supplies and inventory 
records, and any additional records as may have been previously arranged between the Investigator and 
60º Pharmaceuticals or designated representative(s). 
The Investigator and/or other designated study personnel are expected to contact the monitor of 
60º Pharmaceuticals or designee as needed regarding study concerns and/or questions. 
A Medical Monitor has been appointed by the Sponsor for the study. The Medical Monitor will be 
available for making recommendations to the investigator and the sponsor on the severity of any SAEs, 
and the relatedness to the study interventions. The Medical Monitor will also be responsible for 
tracking and assessing trends in the AEs reported. 
11.2.1 Definition of Source Documents 
It is the responsibility of the Investigator to collect and record all study data on source documents. The 
Investigator must provide access to source data/documents for study-related monitoring, audits, 
IRB/IEC review and regulatory inspection. 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being audited. 
They should be made using some permanent form of recording (ink, typing, printing, optical disc). 
They should not be obscured by correction fluid or have temporary attachments (such as removable 
self-stick notes). Photocopies and/or printouts of eCRFs are not considered acceptable source 
documents.  
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x rays, laboratory results, printouts, 
pharmacy records, care records, or other printouts, completed scales, quality of life questionnaires, or 
video, for example. Source documents should be kept in a secure, limited access area. In cases where a 
device or instrument is the data originator (e.g., eDiary application) and data are automatically 
transmitted to the eCRF, then the eCRF is considered a source document.  
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Source documents that are computer generated and stored electronically must be printed for review by 
the monitor. Once printed, these copies should be signed and dated by the investigator and become a 
permanent part of the patient’s source documents. The investigator will facilitate the process for 
enabling the monitor to compare the content of the printout and the data stored in the computer to 
ensure all data are consistent. In some cases, electronic source documents will be monitored 
electronically by the sponsor or designee and will not be printed. The Investigator must ensure that the 
sponsor or designee has access to the electronic medical record for patients if such a system is used. 
Electronic data records must be saved and stored as instructed by 60º Pharmaceuticals (or designee). 
Patient-reported outcome (PRO) measures will be completed by each patient and will be collected 
electronically.  
The data collection and database management system will be supplied by a vendor and will be 
compliant with regulations. All data collected including data collected from the ePRO diary will be 
uploaded to a central server database and will be sent electronically to 60º Pharmaceuticals (or 
designee). 
11.2.2 Source Data Verification 
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from source 
documents (e.g., patient files, recordings from automated instruments, x ray films, laboratory notes). 
All data reported on the CRF should be supported by source documents. 
11.3 Data Handling 
It is the Investigator’s responsibility to ensure that data are collected and reported according to the 
study protocol. The Investigator will ensure the accuracy, completeness, and timeliness of the data 
reported on the eCRF and in all required reports. Efforts should be made to complete the eCRFs as 
soon after the scheduled visit as possible, and to have all eCRFs completed within 3 days after the 
Follow-up Visit. 
Additionally, laboratory data will be received by Clinical Data Management from the appropriate 
clinical laboratory in electronic format. These data files may be merged with the clinical database. 
11.3.1 Case Report Forms 
Electronic CRFs will be produced according to protocol requirements, and access/training will be 
provided to all active sites in order for the Research Staff to record the data obtained on each patient 
during the study. 
eCRFs must be completed for each patient enrolled (randomized) in the study. Data from patients that 
were screened but were ineligible for the study will not be included in the eCRFs, except that a Screen 
failure eCRF will be created to report the reason(s) that the patient was not eligible. 
The CRFs must be kept up-to-date so that they always reflect the latest observations of the patients 
enrolled in the study. All records should be kept in conformance to applicable national laws and 
regulations. 
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11.3.2 Database Entry and Reconciliation 
Case Report forms/external electronic data will be entered/loaded into a validated electronic database 
using a clinical data management system (CDMS). Computerized data cleaning checks will be used in 
addition to manual review to check for discrepancies and to ensure consistency of the data. Case 
Report form data are entered into the clinical database using independent, double data entry, with the 
exception of comment fields, which are verified by a second person. The data are entered into the 
electronic CRFs once and are subsequently verified if the study is performed using electronic data 
capture. 
An electronic audit trail system will be maintained within the CDMS to track all data changes in the 
database once the data have been saved initially into the system or electronically loaded. Regular 
backups of the electronic data will be performed. 
11.3.3 Patient Screening and Enrollment Log/Patient Identification Code List 
The patient’s screening and enrollment will be recorded in the Patient Screening and Enrollment Log. 
The investigator will keep a Patient Identification Code list. This list remains with the investigator and 
is used for unambiguous identification of each patient. 
 
The patient’s consent and enrollment in the study must be recorded in the patient’s medical record. 
These data should identify the study and document the dates of the patient’s participation. 
11.3.4 Quality Control and Quality Assurance 
The following steps will be taken to ensure the accuracy, consistency, completeness, and reliability of 
the data: 
• Routine site monitoring; 
• CRF review against source documents; 
• Data management quality control checks; 
• Statistical quality control checks; 
• Continuous data acquisition and cleaning; and 
• Quality control of final report. 
A representative from 60º Pharmaceuticals and /or authorized representatives may conduct periodic 
audits of the clinical sites and study processes, including, but not limited to, the clinical database and 
the final report. The study may also be patient to inspection by regulatory authorities. The Investigator 
herby agrees to allow access to required patient records and other documentation and facilities related 
to the review and conduct of the study. 
11.4 Study Termination 
The study may be terminated at any time at the request of 60º Pharmaceuticals or the Investigator with 
proper and timely notification of all parties concerned. The IRB/IEC will be informed promptly and 
reasons for the termination or suspension will be provided by the Investigator, as specified by the 
applicable regulatory requirements. The study can be considered complete and/or terminated after 60º 
Pharmaceuticals has received the following data and materials: 
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• Laboratory findings, clinical data, and all special test results from screening through the end 
of the follow-up period 
• CRFs properly completed (including all system or manually-generated edit checks properly 
answered and closed) by appropriate study personnel and signed by the Investigator 
• Completed Drug Accountability Records 
• Statement of outcome for each serious adverse event reported 
• Approval/notification of protocols and protocol amendments from IRB/IEC as well as 
relevant health authorities (if applicable). 
11.5 Archiving and Data Retention 
An Investigator is required to maintain adequate records of the disposition of the drug, including dates, 
quantity, and use by patients. If the investigation is terminated, suspended, discontinued, or completed, 
the Investigator shall return the unused supplies of the drug to the sponsor, or otherwise provide for 
disposition of the unused supplies of the drug under the U.S. Code of Federal Regulations 21 part 
312.59. 
An Investigator shall retain records required to be maintained under this part for a period of two years 
following the date a marketing application is approved for the drug for the indication for which it is 
being investigated; or, if no application is to be filed or if the application is not approved for such 
indication, until two years after the investigation is discontinued and FDA is notified. 
60º Pharmaceuticals should inform the Investigator(s)/institutions(s) in writing of the need for record 
retention and should notify the Investigator(s)/institutions(s) in writing when the study related records 
are no longer needed. 
Custody of the records may be transferred to another responsible part, acceptable to 60º 
Pharmaceuticals, who agrees to abide by the retention policies. Written notice of transfer must be 
submitted to 60º Pharmaceuticals. The Investigator must contact, and obtain the prior written 
permission of, 60º Pharmaceuticals prior to disposing of or so transferring any study records. 
11.6 Audit and Inspection 
The investigator will permit study related audits mandated by 60º Pharmaceuticals, after reasonable 
notice, and inspections by domestic or foreign regulatory authorities. The main purposes of an audit or 
inspection are to confirm that the rights and well-being of the patients enrolled have been protected, 
that enrolled patients (i.e., signing consent and undergoing study procedures) are appropriate for the 
study, and that all data relevant for the evaluation of the study drug have been processed and reported 
in compliance with the planned arrangements, the protocol, investigational site, and IRB/IEC SOPs, 
ICH GCP, and applicable regulatory requirements. 
The investigator will provide direct access to all study documents, source records, and source data. If 
an inspection by a regulatory authority is announced, the investigator will immediately inform 60º 
Pharmaceuticals (or designee). 
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11.7 Good Clinical Practice 
This study will be conducted in compliance with the protocol, GCP as defined by the U.S. Code of 
Federal Regulations 21 parts 50, 56 and 312, Sponsor policies and procedures and all applicable state 
regulations. 
Noncompliance with the protocol, ICH GCP, or local regulatory requirements by the investigator, 
institution, institution staff, or designees of the sponsor will lead to prompt action by 60º 
Pharmaceuticals to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study. 
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12 STATISTICAL METHODS 
This section describes the planned statistical analyses in general terms. A complete description of the 
methodology will be specified in a statistical analysis plan (SAP), which will be finalized prior to 
database lock and unblinding. Any changes in the statistical methods described in this protocol that 
occur prior to database lock and unblinding will be documented in the statistical analysis plan and will 
not require a protocol amendment. 
12.1 General Statistical Considerations 
Statistical hypothesis testing will be performed at two sided alpha level of 0.05. For continuous 
variables, population size (N for sample size and n for available data), the mean, the standard deviation 
(SD), the median, the minimum and maximum values will be tabulated. For categorical variables, 
number and percentage in each category will be tabulated. 
12.2 Analysis Populations for Analyses 
Three patient populations will be defined: 
• The modified Intention-to-Treat (mITT) population will include all patients who took at least 
one dose of study medication and had at least one post start of treatment assessment. The mITT 
population is analyzed as randomized, regardless of which treatment a patient received.  
• Safety population: Any patient randomized and received any dose of study drug. Safety 
population is analyzed based on the actual treatment received. 
• The PP population includes all mITT patients completing the Day 12 [± 1 day] in clinic visit 
without any major protocol deviations. Protocol deviation category (minor or major) will be 
determined prior to the database lock and unblinding.   
Efficacy endpoints will be analyzed for the mITT population. Analyses of efficacy endpoints in the PP 
population will provide supportive evidence. Safety summaries will be based on the Safety population. 
12.2.1 Patient Disposition 
Study completion, number of patients in mITT, PP, Safety populations, and reasons for discontinuation 
for all randomized patients in the double-blind phase will be summarized for each treatment group by 
simple tabulation. Discontinuations by reason will be tabulated for each treatment group. The reasons 
that patients did not meet eligibility criteria (screen failures) will be provided in a listing. 
12.2.2 Demography and Other Baseline Data 
Demographic data will be tabulated by treatment group in the mITT population. Past and current 
medical history will be summarized by treatment group using the system organ class (SOC) as coded 
using the Medical Dictionary for Regulatory Activities (MedDRA) coding dictionary. 
12.2.3 Study Medication 
Exposure and compliance will be presented as summary statistics by treatment group. 
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12.2.4 Prior/Concomitant Therapy 
Prior/concomitant therapy will be summarized. 
Any medications or therapy present before the first dose of study medication will be considered as 
prior medications. Concomitant medications (medications present while on study medication) will be 
recorded throughout the study and at early discontinuation. These medications will be coded using the 
WHO-drug dictionary. The number and percentage of patients from the safety population using prior 
or concomitant medications will be categorized by the WHO-drug class 4 name and presented for each 
treatment group. In any given category (e.g., drug category) a participant will be counted only once. 
12.3 Planned Efficacy Analyses 
12.3.1 Analysis of the Primary Efficacy Variable 
The proportion of patients with clinical recovery at Day 12 will be analyzed using two methods: a 2x2 
contingency table and logistic regression. The contingency table will provide unadjusted estimates of 
the proportions of patients with clinical recovery at Day 12. Copper-Pearson exact 95% confidence 
intervals around the recovery proportion within each treatment group will be provided. If 95% or more 
patients on the TQ arm have clinically recovered, then no logistic regression will be performed due to 
too few events then a Fisher’s exact test will be used to compare treatment groups. However, if the rate 
is less than that then a logistic regression will be utilized. Treatment group will be the primary 
independent factor in the logistic regression. Additional covariates will be included in the model for 
every 10 events observed (eg, if at least 20 events then clinical site will be included, at least 30 events 
dichotomized number of symptoms (1-2 vs 3-4). Selection of additional covariates will be based on 
their relationship to the primary endpoint and correlation with other covariates. Patients who do not 
have a Day 12 visit due to hospitalization for COVID-19 symptoms will be considered treatment 
failures.  
12.3.2 Other Efficacy Analyses 
Dichotomous secondary endpoints will be analyzed in the same manner as the primary endpoint. The 
number of medical follow-up visits tabulated to determine if the endpoint can be considered 
continuous or ordinal. If the data are continuous the treatment groups will be compared by t-test. If the 
frequency distribution indicates few numbers of visits (eg 0, 1, 2, and 3 visits) then the analysis will 
use a chi-squared test to compare treatment groups. The methods for the conduct of the exploratory 
efficacy analyses will be provided in the SAP. Other ad hoc analyses not specified in the SAP may 
also be performed to further explore the data to aid in the design of future studies. 
12.4 Planned Safety Analyses 
12.4.1 Adverse Events 
AEs will be coded using the most recent version of the Medical Dictionary of Regulatory Activities 
(MedDRA) preferred terms and will be grouped by system, organ, and class (SOC) designation. The 
incidence of new COVID-19 symptoms not present at screening will be reported separately from other 
AEs including the maximum severity and time of maximum severity relative to the start of 
investigational product. The severity, frequency, and relationship of AEs to investigational product 
will be presented by preferred term by SOC grouping. Listings of each individual AE including start 
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date, stop date, severity, relationship, outcome, and duration will be provided. Each AE (based on 
preferred terminology) will be counted once only for a given patient. If the same AE occurred on 
multiple occasions, the highest severity and relationship to investigational product will be assumed. 
Thus, study participants are not counted multiple times in a given numerator in the calculation of 
frequencies for a specific AE.  
12.4.2 Laboratory Data 
Clinical chemistry and hematology parameters will be summarized for absolute values and change 
from baseline (as appropriate) with descriptive statistics (means, medians, standard deviations, ranges).  
12.4.3 Physical Examination 
Physical examination findings will be coded using MedDRA preferred terms and SOC. The number 
and percentage of patients with abnormal finding physical examination will be provided by preferred 
term and SOC, and the individual data listing of abnormal findings will also be provided. 
12.4.4 Vital Signs and Body Measurements 
Data from vital signs will be summarized and listed, abnormal values will be flagged, and any other 
information collected will be listed. Data will be summarized by group using mean change from 
baseline and proportions of patients with values outside the normal range, and values that were 
clinically notable. 
Summary tables and data listings of vital signs, including body temperature, blood pressure, pulse 
(heart rate), and breathing rate (respiratory rate), oxygen saturation will be provided for raw values and 
change from baseline (as appropriate). 
12.5 Planned Interim Analysis and Data Monitoring 
No interim analyses are planned. 
12.6 Determination of Sample Size 
The sample size calculation is based on the primary endpoint of recovery rate. 
In a study of nonhospitalized patients with COVID-19 disease reported by Skipper (2020), placebo 
treated patients had resolution of clinical symptoms of COVID-19 by Day 14 in 70% of patients. 
Assuming an 85% clinical recovery rate in the TQ group and a 70% clinical recovery rate in the 
placebo group, sample sizes of 125 per treatment group will achieve 80% power with a two-sided 
alpha of 0.05 by logistic regression analysis. 
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13 ETHICS AND REGULATORY REQUIREMENTS 
13.1 Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
An Investigator shall assure that an IRB/IEC that complies with the requirements set forth in the U.S. 
Code of Federal Regulations 21 part 56 or requirements of the local regulatory authority (ex-USA) and 
will be responsible for the initial and continuing review and approval of the proposed clinical study. 
The Investigator shall also assure that he or she will promptly report to the IRB/IEC all changes in the 
research activity and all unanticipated problems involving risk to human patients or others, and that he 
or she will not make any changes in the research without IRB/IEC approval, except where necessary to 
eliminate apparent immediate hazards to human patients.  
All advertisements used in conjunction with this study must be reviewed and approved by 60º 
Pharmaceuticals prior to use and the IRB/IEC, if applicable. The IRB/IEC’s approval will be 
documented in writing and sent to the Investigator. The Investigator will forward a copy of the 
ITB/IEC approval document to 60º Pharmaceuticals. 
The Investigator will not begin the study until 60º Pharmaceuticals has authorized release of 
investigational drug product.  
Any amendments to the protocol must be approved in writing by the IRB/IEC prior to implementation 
by the Investigator. However, any change to the protocol to eliminate an apparent immediate hazard to 
the patients may be implemented immediately, provided that the IRB/IEC is subsequently notified in 
accordance with code of federal regulations (CFR) Part 56.104C. 
The Investigator will also provide the IRB/IEC with a current copy of the Investigator’s Brochure at 
the start of the study, as well as an updated version of the Investigator’s Brochure if revised during the 
study. 
A progress report will be submitted by the Investigator to the IRB/IEC at intervals established by the 
IRB/IEC, and not less than annually. The Investigator will retain a copy of this report in the 
Investigator’s Documentation File. After completion or termination of the study, the Investigator will 
submit a final report to the IRB/IEC. A copy of both reports will be sent to 60º Pharmaceuticals. 
13.2 Informed Consent 
In obtaining and documenting informed consent, the Investigator should comply with the applicable 
regulatory requirement(s) [21 CFR Par 50] and should adhere to GCP regulations. Prior to the 
beginning of the study, the Investigator should have the IRB/IEC written approval of the written 
informed consent form and any other written information to be provided to patients. 
The written informed consent form and any other written information to be provided to patients must 
be revised whenever important new information becomes available that may be relevant to the 
patient’s consent. Any revised written informed consent form, and written information must receive 
the IRB/IEC approval in advance of use. The patient must be informed in a timely manner if new 
information becomes available that may be relevant to the patient’s willingness to continue 
participation in the study. The communication of this information should be documented. 
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The Investigator, or a person designated by the Investigator, should fully inform the patient of all 
pertinent aspects of the study including the written information and the approval by the IRB/IEC. A 
copy shall be given to the patient. 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form. 
The patient may withdraw his/her consent to participate in the study at any time. A patient is 
considered as enrolled in the study when he/she has signed the Informed Consent form. A CRF must 
not be started, nor may any study specific procedure be performed for a given patient, without having 
obtained his/her written consent to participate in the study. 
13.3 Patient Confidentiality 
The Investigator, 60º Pharmaceuticals, and its representatives, agree to protect the privacy and 
confidentiality of the protected health information in accordance with applicable laws and regulations. 
Patient medical information obtained by the study is confidential and disclosure to third parties other 
than those noted below is prohibited unless required by law. The Investigator shall retain all such 
information, and any other information designated by 60º Pharmaceuticals as confidential, or is 
otherwise of reasonably confidential nature, in confidence and shall not use such information for any 
purpose other than the performance of your obligations pursuant to your agreement with us, our 
affiliate or our contractor, as the case may be, without prior written authorization from 60º 
Pharmaceuticals. 
At the patient’s request, medical information may be given to his or her personal physician or other 
appropriate medical personnel responsible for his or her welfare. 
Data generated by this study must be available for inspection on request by representatives of 
regulatory authorities, 60º Pharmaceuticals, and the IRB(s)/IEC(s) if appropriate. 
13.4 Protocol Amendments  
With the exception of emergency situations, implementation of any change in the protocol that affects 
the safety of the patients, the scope of the investigation, or the scientific quality of the study will not be 
permitted until 60º Pharmaceuticals and the Investigator have approved the protocol amendment and 
the IRB/IEC responsible for review and approval of the study has reviewed and approved the protocol 
change. 
Implementation of changes that do not affect the safety of the patients, the scope of the investigation, 
or the scientific quality of the study cannot be made until the protocol changes are reviewed and 
approved by 60º Pharmaceuticals and the Investigator. The IRB/IEC must be notified of these protocol 
changes. 
13.5 Publications 
The Investigator agrees that all data, calculations, interpretations, opinions and recommendations 
regarding the study shall be the sole and exclusive property of 60º Pharmaceuticals, and that 60º 
Pharmaceuticals may make any use thereof at its discretion without obligation to Investigator. The 
Investigator agrees to consider the results as information patient to confidential and use restrictions. 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
In the event that the study results are published in the scientific literature by 60º Pharmaceuticals, 
acknowledgment will be made to the Investigator(s) in the accepted style, as appropriate. The names of 
the Investigators or their representatives shall not be used by 60º Pharmaceuticals in publications, for 
advertising, for other commercial purposes, or otherwise, without appropriate written permission, 
unless required by law or government regulation. 
Individual study center manuscript(s) for publication, text for talks, abstracts of papers, poster 
presentations, and similar material will be submitted to 60º Pharmaceuticals for review and comment 
prior to publication or disclosure. In order to ensure that 60º Pharmaceuticals will be able to make 
comments and suggestions where pertinent, material for public dissemination will be submitted to 60º 
Pharmaceuticals for review at least sixty (60º) days prior to submission for publication, public 
dissemination, or review by a third-party committee. 60º Pharmaceuticals will have sixty (60) days 
from receipt of such information to review and comment on and discuss the contents thereof with the 
Investigator. If 60º Pharmaceuticals requests, that the Investigator will remove any and all Confidential 
Information (other than Study results) prior to submitting or presenting the material. Upon the request 
of 60º Pharmaceuticals, Investigator will delay so submitting or presenting the materials for a further 
sixty (60) days to permit 60º Pharmaceuticals to take necessary actions to protect its Confidential 
Information, including the filing of patent applications. 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
14 REFERENCES 
Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group Members. Remdesivir for the 
treatment of Covid-19 — preliminary report. N Engl J Med. 2020. doi:10.1056/NEJMoa2007764 
Brueckner RP, Lasseter KC, Lin ET, Schuster BG. First-time-in-humans safety and pharmacokinetics 
of WR 238605, a new antimalarial. Am J Trop Med Hyg. 1998;58(5):645-649. 
doi:10.4269/ajtmh.1998.58.645 
Center for Disease Control. CDC Covid-19 data tracker. https://www.cdc.gov/covid-data-
tracker/index.html#cases. Accessed March 7, 2020. 
Crisafulli E, Clini EM. Measures of dyspnea in pulmonary rehabilitation. Multidiscip Respir Med. 
2010;5(3):202-210. Published 2010 Jun 30. doi:10.1186/2049-6958-5-3-202 
Dow GS, Luttick A, Fenner J, Wesche D, Yeo KR, Rayner C. Tafenoquine inhibits replication of 
SARS-Cov-2 at pharmacologically relevant concentrations in vitro. bioRxiv. January 
2020:2020.07.12.199059. doi:10.1101/2020.07.12.199059 
Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with 
Covid-19. N Engl J Med. 2020;382:2411-2418. 
Jia HP, Look DC, Shi L, et al. ACE2 Receptor Expression and Severe Acute Respiratory Syndrome 
Coronavirus Infection Depend on Differentiation of Human Airway Epithelia. J Virol. 
2005;79(23):14614 LP - 14621. doi:10.1128/JVI.79.23.14614-14621.2005 
Skipper CP, Pastick KA, Engen NW et al. Hydroxychloroquine in Nonhospitalized Adults With Early 
COVID-19: A Randomized Trial. Ann Intern Med. 2020:M20-4207. 
Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health. 2020;25(3):278-280. 
doi:10.1111/tmi.13383 
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-
blind, placebo-controlled, multicenter trial. Lancet. 2020;395:1569-1578.  
Worldometer. Coronavirus Update (Live). https://www.worldometers.info/coronavirus/. Accessed 
March 7, 2020. 
Xiao F, Tang M, Zheng X, Liu Y, Li X, and Shan H. Evidence for Gastrointestinal Infection of SARS-
CoV-2. Gastroenterology. 2020;158:1831-1833.  
Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of 
probable bat origin. Nature. 2020;579(7798):270-273. doi:10.1038/s41586-020-2012-7 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
TQ 2020_06 
CONFIDENTIAL 
1.0/11 Aug 2020 
15 APPENDICES 
15.1 Appendix A Prescribing Information ARAKODA 
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CENTER FOR DRUG EVALUATION AND 
RESEARCH
APPLICATION NUMBER:
210607Orig1s000
LABELING
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use 
ARAKODA™safely and effectively.  See full prescribing information for 
ARAKODA™.
ARAKODA™ (tafenoquine) tablets, for oral use
Initial U.S. Approval: 2018
----------------------------INDICATIONS AND USAGE---------------------------
ARAKODA is an antimalarial indicated for the prophylaxis of malaria in 
patients aged 18 years and older. (1)
----------------------DOSAGE AND ADMINISTRATION-----------------------
x All patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) 
deficiency prior to prescribing ARAKODA. (2.1)
x Pregnancy testing is recommended for females of reproductive potential 
prior to initiating treatment with ARAKODA. (2.1)
Regimen Name
Timing
Dosage
Loading regimen
For each of the 3 
days before travel 
to a malarious area
200 mg (2 of the 100 mg 
tablets) once daily for 3 days
Maintenance 
regimen
While in the 
malarious area
200 mg (2 of the 100 mg 
tablets) once weekly – start 7 
days after the last loading 
regimen dose
Terminal 
prophylaxis 
regimen
In the week 
following exit from 
the malarious area
200 mg (2 of the 100 mg 
tablets) one-time 7 days after 
the last maintenance dose
x
Administer ARAKODA with food. (2.2)
x
See full prescribing information for instructions on how to replace 
missed doses. (2.2)
---------------------DOSAGE FORMS AND STRENGTHS----------------------
Tablets: 100 mg of tafenoquine (3)
-------------------------------CONTRAINDICATIONS------------------------------
x
G6PD deficiency or unknown G6PD status (4)
x
Breastfeeding by a lactating woman when the infant is found to be 
G6PD deficient or if G6PD status is unknown (4, 8.2)
x
Patients with a history of psychotic disorders or current psychotic 
symptoms (4. 5.4)
x
Known hypersensitivity reactions to tafenoquine, other 8-
aminoquinolines, or any component of ARAKODA. (4)
-----------------------WARNINGS AND PRECAUTIONS------------------------
x
Hemolytic Anemia: G6PD testing must be performed before prescribing 
ARAKODA due to the risk of hemolytic anemia. Monitor patients for 
signs or symptoms of hemolysis. (5.1)
x
G6PD Deficiency in Pregnancy or Lactation: ARAKODA may cause 
fetal harm when administered to a pregnant woman with a G6PD-
deficient fetus. ARAKODA is not recommended during pregnancy. A 
G6PD-deficient infant may be at risk for hemolytic anemia from 
exposure to ARAKODA through breast milk. Check infant’s G6PD 
status before breastfeeding begins. (5.2, 8.1, 8.2)
x
Methemoglobinemia: Asymptomatic elevations in blood methemoglobin 
have been observed. Initiate appropriate therapy if signs or symptoms of 
methemoglobinemia occur. (5. 3)
x
Psychiatric Effects: Serious psychotic adverse reactions have been 
observed in patients with a history of psychosis or schizophrenia, at
doses different from the approved dose. If psychotic symptoms 
(hallucinations, delusions, or grossly disorganized thinking or behavior) 
occur, consider discontinuation of ARAKODA therapy and, evaluation
by a mental health professional as soon as possible. (5.4)
x
Hypersensitivity Reactions: Serious hypersensitivity reactions have been 
observed with administration of ARAKODA. If hypersensitivity 
reactions occur, institute appropriate therapy. (5.5)
x
Delayed Adverse Reactions: Due to the long half-life of ARAKODA
(approximately 17 days), psychiatric effects, hemolytic anemia, 
methemoglobinemia, and hypersensitivity reactions may be delayed in 
onset and/or duration. (5.6, 12.3)
------------------------------ADVERSE REACTIONS-------------------------------
The most common adverse reactions (incidence ≥1%) were: headache,
dizziness, back pain, diarrhea, nausea, vomiting, , increased alanine 
aminotransferase (ALT), motion sickness, insomnia, depression, abnormal 
dreams, anxiety. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact 60 Degrees 
Pharmaceuticals at 1-888-834-0225 or FDA at 1-800-FDA-1088 or 
www.fda.gov/medwatch
------------------------------DRUG INTERACTIONS-------------------------------
Avoid co-administration with drugs that are substrates of organic cation 
transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) transporters
(7.1)
-----------------------USE IN SPECIFIC POPULATIONS------------------------
Lactation: Advise women not to breastfeed a G6PD-deficient infant or infant 
with unknown G6PD status during treatment and for 3 months after the last 
dose of ARAKODA. (5.2, 8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication 
Guide.
Revised: 8/2018
FULL PRESCRIBING INFORMATION: CONTENTS*
1
INDICATIONS AND USAGE
2
DOSAGE AND ADMINISTRATION
2.1
Tests to be Performed Prior to ARAKODA Dose Initiation
2.2
Recommended Dosage and Administration
3
DOSAGE FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5
WARNINGS AND PRECAUTIONS
5.1
Hemolytic Anemia
5.2
G6PD Deficiency in Pregnancy or lactation
5.3
Methemoglobinemia
5.4
Psychiatric Effects
5.5
Hypersensitivity Reactions
5.6   Delayed Adverse Reactions, Including Hemolytic Anemia, 
Methemoglobinemia, Psychiatric Effects, and Hypersensitivity 
Reactions
6
ADVERSE REACTIONS
6.1
Clinical Trial Experience
7
DRUG INTERACTIONS
7.1 Effect of ARAKODA on OCT2 and MATE Substrates
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
8.2
Lactation
8.3
Females and Males of Reproductive Potential
8.4
Pediatric Use
8.5
Geriatric Use
8.6
Renal Impairment
8.7
Hepatic Impairment
10
OVERDOSAGE
11
DESCRIPTION
12
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.4 Microbiology
13
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14
CLINICAL STUDIES
16
HOW SUPPLIED/STORAGE AND HANDLING
17
PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not 
listed
Reference ID: 4303405
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Page 2 of 19
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
ARAKODA is indicated for the prophylaxis of malaria in patients aged 18 years and older.
2
DOSAGE AND ADMINISTRATION
2.1 Tests to be Performed Prior to ARAKODA Dose Initiation
All patients must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to 
prescribing ARAKODA [see Contraindications (4), Warnings and Precautions (5.1)].
Pregnancy testing is recommended for females of reproductive potential prior to initiating 
treatment with ARAKODA [see Use in Specific Populations (8.1 and 8.3)].
2.2 Recommended Dosage and Administration Instructions
The recommended dosage of ARAKODA is described in Table 1 below. ARAKODA can be 
administered for up to 6 months of continuous dosing.
Table 1: Recommended Dosage of ARAKODA in Patients (18 Years of Age and Older)
Regimen Name
Timing
Dosage
Loading regimen
For each of the 3 days before 
travel to a malarious area
200 mg (2 of the 100 mg tablets) 
once daily for 3 days
Maintenance regimen
While in the malarious area
200 mg (2 of the 100 mg tablets) 
once weekly – start 7 days after the 
last loading regimen dose
Terminal prophylaxis 
regimen
In the week following exit from 
the malarious area
200 mg (2 of the 100 mg tablets) 
taken one time, 7 days after the last 
maintenance dose
x
Administer ARAKODA with food. [see Clinical Pharmacology (12.3)].
x
Swallow the tablet whole. Do not break, crush or chew the tablets.
x
Complete the full course of ARAKODA including the loading dose and the terminal dose.
Reference ID: 4303405
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Page 3 of 19
Table 2: How to Replace Missed Doses of ARAKODA
Dose(s) Missed
How to Replace Missed Dose(s):
1 Loading dose 
1 dose of 200 mg (2 of the 100 mg tablets) so that a
total of 3 daily loading doses have been taken. Begin 
maintenance dose 1 week after the last loading dose. 
2 Loading doses 
2 doses of 200 mg (2 of the 100 mg tablets) on 2 
consecutive days so that a total of 3 daily loading doses 
have been taken. Begin maintenance dose 1 week after 
the last loading dose. 
1 Maintenance (weekly)
dose 
1 dose of 200 mg (2 of the 100 mg tablets) on any day 
up to the time of the next scheduled weekly dose.
2 Maintenance (weekly)
doses
1 dose of 200 mg (2 of the 100 mg tablets) on any day 
up to the time of the next scheduled weekly dose. 
3 or more Maintenance 
(weekly) doses
2 doses of 200 mg (2 of the 100 mg tablets), taken as 
200 mg (2 of the 100 mg tablets) once daily for 2 days 
up to the time of the next weekly dose. 
Terminal prophylaxis dose 
1 dose of 200 mg (2 of the 100 mg tablets) as soon as 
remembered. 
3
DOSAGE FORMS AND STRENGTHS
ARAKODA tablets are dark pink, film-coated, capsule-shaped tablets debossed with ‘TQ100’ on 
one side containing 100 mg of tafenoquine.
4
CONTRAINDICATIONS
ARAKODA is contraindicated in:
x
patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia
[see Warnings and Precautions (5.2)].
x
breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the 
G6PD status of the infant is unknown [see Warnings and Precautions (5.3), Use in Specific 
Populations (8.2)].
x
patients with a history of psychotic disorders or current psychotic symptoms (i.e., 
hallucinations, delusions, and/or grossly disorganized behavior) [see Warnings and 
Precautions (5.4)]
x
patients with known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or 
any component of ARAKODA [see Warnings and Precautions (5.5)].
Reference ID: 4303405
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Page 4 of 19
5
WARNINGS AND PRECAUTIONS
5.1.
Hemolytic Anemia 
Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing must be 
performed before prescribing ARAKODA [see Contraindications (4)]. Due to the limitations 
with G6PD tests, physicians need to be aware of residual risk of hemolysis and adequate medical 
support and follow-up to manage hemolytic risk should be available. Treatment with 
ARAKODA is contraindicated in patients with G6PD deficiency or unknown G6PD status [see 
Contraindications (4)]. In clinical trials, declines in hemoglobin levels were reported in some 
G6PD-normal patients [see Adverse Reactions (6.1)]. Monitor patients for clinical signs or 
symptoms of hemolysis [see Warnings and Precautions (5.6)]. Advise patients to discontinue 
ARAKODA and seek medical attention if signs of hemolysis occur.
5.2
G6PD Deficiency in Pregnancy and Lactation
Potential Harm to the Fetus
The use of ARAKODA during pregnancy may cause hemolytic anemia in a G6PD-deficient
fetus. Even if a pregnant woman has normal levels of G6PD, the fetus could be G6PD deficient.
Advise females of reproductive potential that treatment with ARAKODA during pregnancy is 
not recommended and to avoid pregnancy or use effective contraception during treatment and for 
3 months after the last dose of ARAKODA. If a pregnancy is detected during ARAKODA use, 
discontinue ARAKODA as soon as possible and switch to an alternative prophylactic drug for 
malaria during pregnancy [see Use in Specific Populations (8.1 and 8.3)].
Potential Harm to the Breastfeeding Infant
A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to ARAKODA
through breast milk. Infant G6PD status should be checked before breastfeeding begins.
ARAKODA is contraindicated in breastfeeding women when the infant is found to be G6PD
deficient or the G6PD status of the infant is unknown [see Contraindications (4)]. Advise the 
woman with a G6PD-deficient infant or if the G6PD status of the infant is unknown not to 
breastfeed during treatment with ARAKODA and for 3 months after the final dose [see Use in
Specific Populations (8.2)].
5.3
Methemoglobinemia
Asymptomatic elevations in methemoglobin have been observed in the clinical trials of 
ARAKODA [see Adverse Reactions (6.1)]. Institute appropriate therapy if signs or symptoms of 
methemoglobinemia occur [see Warnings and Precautions (5.6)]. Carefully monitor individuals 
with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase
deficiency. Advise patients to discontinue ARAKODA and seek medical attention if signs of 
methemoglobinemia occur.
5.4
Psychiatric Effects
In patients receiving ARAKODA in clinical trials, psychiatric adverse reactions included sleep 
disturbances (2.5%), depression/depressed mood (0.3%), and anxiety (0.2%) [see Adverse 
Reference ID: 4303405
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Page 5 of 19
Reactions (6.1)]. ARAKODA was discontinued in a subject with an adverse reaction of suicide 
attempt (0.1%). Subjects with a history of psychiatric disorders were excluded from three of five 
ARAKODA trials in which mefloquine was included as a comparator. 
Psychosis was reported in three patients with a history of psychosis or schizophrenia who 
received tafenoquine doses (350 mg to 500 mg single dose, or 400 mg daily for 3 days) different 
from the approved ARAKODA regimen. Safety and effectiveness of ARAKODA have not been 
established at doses or regimens other than the approved regimen; use of ARAKODA at doses or 
regimens other than a 200-mg weekly dose is not approved by FDA.
ARAKODA is contraindicated in patients with a history of psychotic disorders or current 
psychotic symptoms [see Contraindication (4)]. If psychotic symptoms (hallucinations, 
delusions, or grossly disorganized thinking or behavior) occur, consider discontinuation of 
ARAKODA and prompt evaluation by a mental health professional as soon as possible. Other 
psychiatric symptoms, such as changes in mood, anxiety, insomnia, and nightmares, should be 
promptly evaluated by a medical professional if they are moderate and last more than three days 
or are severe [see Warnings and Precautions (5.6)].
5.5
Hypersensitivity Reactions
Serious hypersensitivity reactions (e.g., angioedema and urticaria) have been observed with 
administration of tafenoquine. Hypersensitivity reactions have been reported in clinical trials of 
ARAKODA [see Adverse Reactions (6.1)]. Discontinue prophylaxis with ARAKODA and 
institute appropriate therapy if hypersensitivity reactions occur [see Warnings and Precautions
(5.6)]. ARAKODA is contraindicated in patients who develop hypersensitivity to tafenoquine or 
any component of ARAKODA or other 8-aminoquinolines [see Contraindications (4)].
5.6
Delayed Adverse Reactions, Including Hemolytic Anemia, Methemoglobinemia, 
Psychiatric Effects, and Hypersensitivity Reactions
Adverse reactions including hemolytic anemia, methemoglobinemia, psychiatric effects, and 
hypersensitivity reactions were reported with the use of ARAKODA or tafenoquine in clinical 
trials [see Warnings and Precautions (5.1, 5.3, 5.4, 5.5)]. Due to the long half-life of 
ARAKODA (approximately 17 days), psychiatric effects, hemolytic anemia, 
methemoglobinemia, and signs or symptoms of hypersensitivity reactions that may occur could 
be delayed in onset and/or duration. Advise patients to seek medical attention if signs of 
hypersensitivity occur [see Clinical Pharmacology (12.3)].
6
ADVERSE REACTIONS
The following clinically significant adverse reactions observed with ARAKODA are discussed 
in detail in the Warnings and Precautions section:
x
Hemolytic Anemia [see Warnings and Precautions (5.2)]
x
Methemoglobinemia [see Warnings and Precautions (5.3)]
x
Psychiatric Effects [see Warnings and Precautions (5.4)]
Reference ID: 4303405
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Page 6 of 19
x
Hypersensitivity Reactions [see Warnings and Precautions (5.5)]
6.1
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates 
observed in the clinical trials of a drug cannot be directly compared with rates in the clinical 
trials of another drug and may not reflect the rates observed in practice.
The safety of tafenoquine was studied in clinical trials at various doses and regimens in 3,184
subjects. The recommended ARAKODA regimen was evaluated in 825 subjects in 5 controlled 
clinical trials (Trials 1, Trial 2, Trial 3, Trial 4 and Trial 5). The mean duration of exposure to 
ARAKODA in these five clinical trials was 21 weeks (range 10-29 weeks). Trial 1, 2 and 4 were 
conducted in healthy semi-immune volunteers in Ghana or Kenya and were placebo-controlled; a
mefloquine arm was included in Trials 2 and 4 as a benchmark. Trial 3, an active comparator
(mefloquine) controlled trial was conducted in healthy soldiers deployed in East Timor (Timor 
Leste). A placebo-controlled Trial 5 was conducted in healthy volunteers in the United States
and United Kingdom. The mean age of the subjects included in the five trials was 29 years 
(range 17 to 69 years); 84% were male.
Adverse Reactions Reported with ARAKODA in Trial 3 and Pooled Trials 1, 2, 4, and 5
Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the placebo-
controlled pooled Trials 1, 2, 3, and 4 are presented in Table 3.
Reference ID: 4303405
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Laboratory Abnormalities 
Methemoglobinemia: Asymptomatic methemoglobin elevations were observed in 13% of 
subjects receiving ARAKODA.  
Hemoglobin decrease: Hemoglobin decreases of ≥3 g/dL were observed in 2.3% of subjects 
receiving ARAKODA.
Adverse Reactions Reported in < 1% of Subjects Receiving ARAKODA in Trials 1 to 5
The following selected adverse reactions were reported in subjects receiving ARAKODA in 
Trials 1 to 5 at a rate of less than 1%.
Blood and lymphatic system disorders: hemolytic anemia, anemia, thrombocytopenia
Ear and labyrinth disorders: hyperacusis, Meniere’s disease
Eye disorders: night blindness, photophobia, blurred vision, visual acuity reduced, visual 
impairment, vitreous floaters
Hepatobiliary disorders: hyperbilirubinemia, jaundice cholestatic
Immune system disorders: hypersensitivity
Investigations: blood bilirubin increased, blood creatinine increased, glomerular filtration rate 
decreased
Nervous system disorders: amnesia, coordination abnormal, hyperesthesia, hypoesthesia, 
somnolence, syncope, tremor, visual field defect
Psychiatric disorders: agitation, neurosis
Skin and subcutaneous tissue disorders: urticaria.
7
DRUG INTERACTIONS
7.1
Effect of ARAKODA on Organic Cation Transporter-2 (OCT2) and Multidrug and 
Toxin Extrusion (MATE) Substrates
The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE 
substrates in humans is unknown. However, in vitro observations suggest the potential for 
increased concentrations of these substrates [see Clinical Pharmacology (12.3)] which may 
increase the risk of toxicity of these drugs. 
Avoid coadministration of ARAKODA with OCT2 and MATE substrates (e.g., dofetilide, 
metformin). If coadministration cannot be avoided, monitor for drug-related toxicities and 
consider dosage reduction if needed based on approved product labeling of the coadministered 
drug.
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8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
Risk Summary
The use of ARAKODA during pregnancy may cause hemolytic anemia in a fetus who is G6PD-
deficient. Treatment with ARAKODA during pregnancy is not recommended. If a pregnancy is 
detected during ARAKODA use, discontinue ARAKODA as soon as possible and switch to an
alternative prophylactic drug for malaria during pregnancy [see Warnings and Precautions 
(5.2)]. Available data with use of ARAKODA in pregnant women are insufficient to establish a
drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In 
animal studies, there were increased abortions, with and without maternal toxicity when 
tafenoquine was given orally to pregnant rabbits at and above doses equivalent to about 0.4 times 
the clinical exposure based on body surface area comparisons. No fetotoxicity was observed at 
doses about 1.5 times the clinical exposure (based on body surface area comparisons) in a similar 
study in rats.
The estimated background risk of major birth defects and miscarriage for the indicated 
population is unknown. All pregnancies have a background risk of birth defect, loss, or other 
adverse outcomes. In the U.S. general population, the estimated background risk of major birth 
defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, 
respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk: 
Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal 
anemia, prematurity, spontaneous abortion and stillbirth.
Data
Animal Data: 
Tafenoquine resulted in dose-related abortions when given orally to pregnant rabbits during 
organogenesis (Gestation Days 6 to 18), at doses of 7 mg/kg (about 0.4 times the clinical 
exposure based on body surface area comparisons) and above. Doses higher than 7 mg/kg were 
also associated with maternal toxicity (mortality and reduced body weight gain). In a similar 
study in rats, doses of 3, 10, or 30 mg/kg/day resulted in maternal toxicity (enlarged spleen, 
reduced body weight and reduced food intake) but no fetotoxicity at the high dose (about 1.5 
times the clinical exposure based on body surface area comparisons). There was no evidence of 
malformations in either species. In a pre- and postnatal development study in rats, tafenoquine 
administered throughout pregnancy and lactation produced maternal toxicity and a reversible 
decrease in offspring body weight gain and decrease in motor activity at 18 mg/kg/day, which is 
equivalent to about 0.6 times the clinical dose based on body surface area comparisons.
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8.2
Lactation
Risk Summary
A breastfed infant with G6PD deficiency is at risk for hemolytic anemia from exposure to 
ARAKODA. Infant G6PD status should be checked before breastfeeding begins. ARAKODA is 
contraindicated in breastfeeding women when the infant is found to be G6PD deficient or the 
G6PD status of the infant is unknown [see Contraindications (4) and Clinical Considerations].
There is no information regarding the presence of ARAKODA in human milk, the effects of the 
drug on the breastfed infant, or the effects of the drug on milk production. In a breastfed infant 
with normal G6PD, the developmental and health benefits of breastfeeding should be considered 
along with the mother’s clinical need for ARAKODA and any potential effects on the breastfed 
infant from ARAKODA or from the underlying maternal condition.
Clinical Considerations
Check the infant’s G6PD status before maternal breastfeeding commences.  If an infant is G6PD-
deficient, exposure to ARAKODA during breastfeeding may result in hemolytic anemia in the 
infant; therefore, advise the woman with an infant who has G6PD deficiency or whose G6PD 
status is unknown, not to breastfeed during treatment with ARAKODA and for 3 months after 
the final dose of ARAKODA.
8.3
Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status in females of reproductive potential prior to initiating treatment with
ARAKODA. [see Dosage and Administration (2.2), Warnings and Precautions, (5.2), and Use
in Specific Populations (8.1)].
Contraception
ARAKODA may cause hemolytic anemia in a G6PD-deficient fetus [see Warnings and 
Precautions (5.2), Use in Specific Populations (8.1)]. Advise females of reproductive potential 
that treatment with ARAKODA during pregnancy is not recommended and to avoid pregnancy 
or use effective contraception for 3 months after the final dose of ARAKODA.
8.4
Pediatric Use
Safety and effectiveness of ARAKODA in pediatric patients have not been established.
8.5
Geriatric Use
Clinical trials of ARAKODA did not include sufficient numbers of patients aged 65 years and 
older to determine whether they respond differently from younger patients. Other reported 
clinical experience has not identified differences in responses between the elderly and younger 
patients [see Clinical Pharmacology (12.3)].
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8.6
Renal Impairment
The pharmacokinetics of ARAKODA have not been studied in patients with renal impairment.  
If ARAKODA is administered to such patients, monitoring for adverse reactions associated with 
ARAKODA is needed [see Warnings and Precautions (5), Adverse Reactions (6)]. 
8.7
Hepatic Impairment
The pharmacokinetics of ARAKODA have not been studied in patients with hepatic impairment.  
If ARAKODA is administered to such patients, monitoring for adverse reactions associated with 
ARAKODA is needed [see Warnings and Precautions (5), Adverse Reactions (6)].
10
OVERDOSAGE
There were no reported cases of ARAKODA overdose. Hemoglobin decline and 
methemoglobinemia may be encountered in an overdose with ARAKODA. Treatment of 
overdosage consists of institution of appropriate symptomatic and/or supportive therapy.
11
DESCRIPTION
ARAKODA contains tafenoquine succinate, an antimalarial agent for oral administration. The 
structural formula of tafenoquine succinate is:
Figure 1:
Tafenoquine Succinate Structure
The chemical name of tafenoquine succinate is (±)-8-[(4-amino-1-methylbutyl) amino]-2,6-
dimethoxy-4-methyl-5-[3-(trifluoromethyl) phenoxy]quinoline succinate. The molecular formula 
of tafenoquine succinate is C24H28F3N3O3∙C4H6O4 and its molecular weight is 581.6 as the 
succinate salt (463.49 as free base).
Each ARAKODA tablet contains 100 mg of tafenoquine (equivalent to 125.5 mg of tafenoquine 
succinate). Inactive ingredients include magnesium stearate, mannitol, and microcrystalline 
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cellulose. The tablet film coating inactive ingredients include: hypromellose, iron oxide red, 
macrogol/polyethylene glycol and titanium dioxide.
12
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Tafenoquine is an 8-aminoquinoline antimalarial drug [see Microbiology (12.4)].
12.2 Pharmacodynamics
Cardiac Electrophysiology
The effect of tafenoquine on the QT interval was evaluated in a study of healthy adult subjects. 
In this study, subjects received once daily 400 mg (2 times the approved recommended dosage) 
doses of tafenoquine for 3 days. The results suggest that the mean increase in the QTcF interval 
for tafenoquine is less than 20 msec.
12.3 Pharmacokinetics
Absorption
A food effect study was not conducted with the 100 mg ARAKODA tablet. In majority of the 
clinical trials, tafenoquine was administered under fed conditions. Table 4 provides the 
pharmacokinetics of tafenoquine following single dose administration of 200 mg ARAKODA
(two 100-mg ARAKODA tablets) in 65 healthy adult subjects under fed conditions. In this study, 
ARAKODA was administered with a high-calorie, high-fat meal (approximately 1000 calories 
with 19% protein, 31% carbohydrate, and 50% fat). 
Table 4. Mean (%CV) Pharmacokinetic Parameters of Tafenoquine Following Single Oral 
Administration of Two 100-mg ARAKODA Tablets Under Fed Conditions in Healthy 
Adult Subjects (N=65)
Parameter
Value
Cmax
147 ng/mL (20.7%)a
Tmax
14 hr (6 – 72 hr)b
AUCinf
70 hr*mcg/mL (24.6%)a, c
a Coefficient of Variance (CV) 
b Median and (Range)
c Plasma tafenoquine AUCinf increased by 41% when tafenoquine was administered as an investigational capsule 
formulation with a high-calorie, high-fat meal compared with the fasted state.
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Following administration of a single dose of tafenoquine orally under fasted conditions in 
healthy adult subjects, AUC and Cmax increased dose proportionally over the dose range from
100 mg to 400 mg. When healthy adult subjects received once-weekly administrations of 200 mg 
tafenoquine orally for ten weeks without a loading dose under fasting conditions, the mean
plasma accumulation ratio of tafenoquine was approximately 4.4.
Distribution
Tafenoquine is greater than 99.5% bound to protein in humans. The apparent volume of 
distribution of tafenoquine in healthy adult subjects is 2470 L [Inter-Individual Variability (IIV): 
24.1 %].
Elimination
The apparent oral clearance of tafenoquine is approximately 4.2 L/hr (IIV: 23.6 %) in healthy 
adult subjects. The mean terminal half-life following administration of ARAKODA is 
approximately 16.5 days (range: 10.8 days to 27.3 days) in healthy adult subjects.
Metabolism
Negligible metabolism of tafenoquine was observed in vitro in human liver microsomes and 
hepatocytes. Following administration of tafenoquine orally, once daily for three days to healthy 
adult subjects, unchanged tafenoquine represented the only notable drug-related component in 
plasma at approximately 3 days following the first dose of tafenoquine.
Excretion
The full excretion profile of tafenoquine in humans is unknown.
Specific Populations
The pharmacokinetics of tafenoquine were not significantly impacted by age, sex, ethnicity, and 
body weight. The effect of renal or hepatic impairment on tafenoquine pharmacokinetics is 
unknown. 
Drug Interaction Studies
Clinical Studies
No clinically significant effects on the pharmacokinetics of substrates of cytochrome P450 
isoenzymes (CYP)1A2 (caffeine), CYP2D6 (desipramine), CYP2C9 (flurbiprofen), or CYP3A4 
(midazolam) were observed following coadministration with tafenoquine in healthy adult 
subjects.
In Vitro Studies Where Drug Interaction Potential Was Not Further Evaluated Clinically
Tafenoquine inhibited metformin transport via human OCT2, MATE1 and MATE2-K
transporters [see Drug Interactions (7)].
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Tafenoquine is not an inhibitor of human breast cancer resistance protein (BCRP), P-
glycoprotein (P-gp), Organic anion transporter 1/3 (OAT1 or OAT3), Organic anion transporting 
polypeptide 1B1/1B3 (OATP1B1 or OATP1B3) mediated transport at clinically relevant 
concentrations. Tafenoquine is also not a substrate of human OATP1B1 or OATP1B3 at 
clinically relevant concentrations. It is inconclusive as to whether tafenoquine is a substrate of P-
gp and/or BCRP mediated transport. 
12.4 Microbiology
Mechanism of Action
Tafenoquine, an 8-aminoquinoline antimalarial, is active against all the stages of Plasmodium
species that include the hypnozoite (dormant stage) in the liver. Studies in vitro with the 
erythrocytic forms of Plasmodium falciparum suggest that tafenoquine may exert its effect by 
inhibiting hematin polymerization and inducing apoptotic like death of the parasite. In addition
to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. The molecular 
target of tafenoquine is not known.
Antimicrobial activity
Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as 
gametocytes of Plasmodium species that include P. falciparum and P. vivax. The activity of 
tafenoquine against the pre-erythrocytic liver stages of the parasite, prevents the development of 
the erythrocytic forms of the parasite [see Clinical Studies (14)].
Resistance 
A potential for development of resistance of Plasmodium species to tafenoquine was not 
evaluated. 
Studies with the erythrocytic forms of P. falciparum strains/isolates suggest a potential for cross-
resistance with primaquine, an 8-aminoquinoline.  Clinical relevance of such findings is not 
known.
13
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Two-year oral carcinogenicity studies were conducted in rats and mice. Renal cell adenomas and 
carcinomas were increased in male rats at doses 1 mg/kg/day and above (0.5 times the clinical 
exposure based on AUC comparisons). Tafenoquine was not carcinogenic in mice. The relevance 
of these findings to a carcinogenic risk in humans is unclear. 
Mutagenesis 
Tafenoquine did not cause mutations or chromosomal damage in 2 definitive in vitro tests 
(bacterial mutation assay and mouse lymphoma L5178Y cell assay) or in an in vivo oral rat 
micronucleus test.
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Impairment of Fertility 
In a rat fertility study, tafenoquine was given orally at 1.5, 5, and 15 mg/kg/day (up to about 0.5 
times the human dose based on body surface area comparisons) to males for at least 67 days, 
including 29 days prior to mating, and to females from 15 days prior to mating through early 
pregnancy. Tafenoquine resulted in reduced number of viable fetuses, implantation sites, and 
corpora lutea at 15 mg/kg in the presence of maternal toxicity (mortality, piloerection, rough 
coat, and reduced body weight).
14
CLINICAL STUDIES
Clinical Trials 1, 2, and 3 
Three double-blind, randomized, controlled studies have been performed to evaluate the efficacy 
of ARAKODA.
Trial 1 (NCT #02491606) was a Phase IIb, placebo-controlled study conducted in Kenya, an area 
of holoendemic P. falciparum malaria.  After taking a three-day presumptive course of 
halofantrine to eliminate any existing parasitemia, subjects were randomized into one of four 
groups (placebo and three different ARAKODA dosing groups; one group received 200 mg once 
daily for 3 days, then a maintenance regimen of weekly dose of 200 mg for 10-15 weeks). Sixty-
one percent of subjects were male. The mean age was 32.4 years (range 17-55). Subjects were 
evaluated for parasitemia by weekly blood smears. Protective efficacy at 15 weeks was defined 
based on the reduced incidence of parasitemia during the prophylaxis phase relative to placebo.  
The results in the intention-to-treat population, which included all subjects who received three 
doses of halofantrine and were randomized, are shown in Table 5 below.
Table 5: Incidence of Parasitemia and Protective Efficacy of ARAKODA at 15 weeks for 
Trial 1
Placebo
ARAKODA1
Number of subjects
62
61
Subjects free of parasitemia
5 (8.1%)
46 (75.4)
Subjects with parasitemia
54 (87.1%)
7 (11.5%)
Subjects with missing data
3 (4.8%)
8 (13.1%)
Protective efficacy 
[98.3% CI] 2
–
73.3%
[54.0%, 84.5%]
1 200 mg once daily for 3 days, then 200 mg weekly for 10-15 weeks
2 Protective efficacy is reduced incidence of parasitemia relative to placebo (0: no protection; 1: full protection); CI: 
confidence interval. Bonferroni adjustment was used for multiple comparisons. Missing outcome was considered a 
failure due to parasitemia for this analysis.
Trial 2 (NCT #02488902) was a comparison of tafenoquine to placebo for prophylaxis in healthy 
semi-immune residents of a malarious region in Ghana. After treating existing parasitemia with 
quinine/doxycycline/primaquine, subjects were randomized into prophylactic groups including 
ARAKODA and placebo. Patients were administered a loading regimen of daily drug or placebo
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for 3 days followed by a maintenance regimen of weekly drug or placebo for 12 weeks.  For the 
ARAKODA and placebo groups, males were 65% of the total population. The mean age was 
38.4 years and 53.5 years for males and females, respectively, as women in reproductive ages 
were excluded from the study. The mean weight was 55.4 kg and 47.5 kg for males and females, 
respectively. Subjects were evaluated for parasitemia by weekly blood smears. Parasitemia 
required a blood smear positive for asexual stage of P. falciparum. The incidence of parasitemia 
at week 12 for all randomized subjects who received at least one dose of ARAKODA or placebo
is presented in Table 6 below.
Table 6: Incidence of Parasitemia and Protective Efficacy of ARAKODA at Week 12 for 
Trial 2
Placebo
ARAKODA
Number of subjects
94
93
Subjects free of parasitemia
6 (6.4%)
68 (73.1%)
Subjects with parasitemia 
86 (91.5%)
12 (12.9%)
Subjects with missing data
2 (2.1%)
13 (14.0%)
Protective efficacy 
[98.75% CI]2
–
71.3%
[55.8%, 81.4%]
1 200 mg once daily for 3 days, then 200 mg weekly for 12 weeks
2 Protective efficacy is reduced incidence of parasitemia relative to placebo; CI: confidence interval. Bonferroni 
adjustment was used for multiple comparisons. Missing outcome was considered a failure due to parasitemia for this 
analysis.
Trial 3 compared ARAKODA with mefloquine for the prophylaxis of both P. falciparum and P. 
vivax malaria in healthy non-immune soldiers deployed to East Timor (now Timor-Leste). No 
subject developed malaria during the 26-week prophylactic phase. Subjects were exposed to P. 
vivax and there is a high likelihood that the study subjects were also exposed to P. falciparum.
Since the precise degree of exposure to malaria in study subjects is unknown, this study provides 
only supportive evidence of efficacy.
Clinical Trial 7
In a randomized, double-blind, placebo-controlled trial (Trial 7) in healthy, non-immune 
volunteers, ARAKODA was shown to have prophylactic activity directed against blood-stage P.
falciparum parasites. Twelve subjects received ARAKODA (200 mg once daily for 3 days, then 
200 mg on 10 day) and 4 subjects received placebo. On Day 13, subjects were inoculated with 
erythrocytes containing viable P. falciparum parasites. Fifteen subjects (93.8%) were of white
race. The mean age was 27.5 years (range 20-42). The mean body weight was 72.3 kg (range 56-
97.7). The efficacy endpoint was parasitemia by Day 34; parasitemia was based on detection of 
P. falciparum 18S ribosomal DNA by real time polymerase chain reaction assay (PCR). There 
was a statistically significant difference in malaria incidence between the two groups; 4/4 
(100%) subjects in the placebo group had detectable parasites from Day 17 compared to 0/12 
(0%) subjects on ARAKODA were PCR negative at all visits (p<0.0005).
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16
HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
ARAKODA tablets contain 100 mg of tafenoquine (equivalent to 125.5 mg of tafenoquine 
succinate) and are dark pink, film-coated, capsule-shaped, and debossed with ‘TQ100’ on one
side.
ARAKODA tablets are packed in polyamide aluminum and PVC formable laminate backed 
blisters with a peelable polyethylene terephthalate aluminum foil cover.  Each blister card 
contains 8 tablets. Each carton contains 16 tablets (2 blister cards) (NDC 71475-257-01). 
Storage
Store at 20°C to 25°C (68°F to 77°F). Temperature excursions are permitted to 15°C to 30°C 
(59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense only 
in the original carton.
17
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
G6PD Testing and Hemolytic Anemia
Inform patients of the need for testing for G6PD deficiency before starting ARAKODA. Advise 
patients on the symptoms of hemolytic anemia and instruct them to seek medical advice 
promptly if such symptoms occur. Patients should contact their health care provider if they have 
darker lips or urine as these may be signs of hemolysis or methemoglobinemia [see Warnings 
and Precautions (5.1)].
Important Administration Instructions
x
Advise patients to take ARAKODA with food.
x
Advise patients to swallow the tablet whole and not to break, crush or chew it.
x
Advise patients to complete the full course of ARAKODA including the loading dose,
maintenance dose and terminal dose.
Potential Harm to the Fetus
Advise females of reproductive potential of the potential risk of ARAKODA to a fetus and to 
inform their healthcare provider of a known or suspected pregnancy [see Warnings and
Precautions (5.2) and Use in Specific Populations 8.1)]. 
Advise females of reproductive potential to avoid pregnancy or use effective contraception 
during treatment with ARAKODA and for 3 months after the final dose [see Use in Specific 
Populations (8.3)].
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Lactation 
Advise women with a G6PD-deficient infant, or if they do not know the G6PD status of their 
infant, not to breastfeed during treatment with ARAKODA and for 3 months after the final dose 
[see Contraindication (4), Warnings and Precautions (5.2), Use in Specific Populations (8.2)].
Methemoglobinemia
Inform patients that methemoglobinemia has occurred with ARAKODA. Advise patients on the 
symptoms of methemoglobinemia and instruct them to seek medical advice promptly if such 
symptoms occur [see Warnings and Precautions (5.3)].
Psychiatric Symptoms
Advise patients who experience hallucinations, delusions, or confused thinking while taking 
ARAKODA to seek medical attention as soon as possible. Other psychiatric symptoms, such as 
changes in mood, anxiety, insomnia, and nightmares, should be promptly evaluated by a medical 
professional if they last more than three days or severe [see Warnings and Precautions (5.4)].
Hypersensitivity Reactions
Inform patients that hypersensitivity reactions have occurred with ARAKODA. Advise patients 
on the symptoms of hypersensitivity reactions and instruct them to seek medical advice promptly 
if such symptoms occur [see Warnings and Precautions (5.5)].
Manufactured For: 
60 Degrees Pharmaceuticals LLC, 
1025 Connecticut Avenue NW, Suite 1000,
Washington DC 20036
1217a
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MEDICATION GUIDE
ARAKODA (AIR-uh-KOH-duh) 
(tafenoquine)
tablets, for oral use
What is the most important information I should know about ARAKODA?
ARAKODA can cause serious side effects including:
x
Breakdown of red blood cells (hemolytic anemia). See “Do not take ARAKODA if you:”
ARAKODA can cause a breakdown of red blood cells (hemolysis) in people with glucose-6-phosphate 
dehydrogenase (G6PD) deficiency. Your healthcare provider will test you for G6PD deficiency before you start 
taking ARAKODA. Signs of hemolytic anemia may not happen right away (delayed reaction).Tell your healthcare 
provider or get emergency medical help right away if you develop signs of hemolytic anemia which include 
darkening of the urine, dizziness, confusion, feeling tired, light-headedness, or shortness of breath, pale skin or 
yellowing of the skin and whites of the eyes.
x
Decrease of oxygen in your blood caused by a certain type of abnormal red blood cell 
(methemoglobinemia). Signs and symptoms of methemoglobinemia may not happen right away (delayed 
reaction). Get medical help right away if you have bluish coloring of the lips or skin, headache, fatigue, shortness of 
breath, or lack of energy.
x
Mental health (psychiatric) symptoms. See “Do not take ARAKODA if you:”
Sleep problems, depression, anxiety and psychosis have happened while taking ARAKODA. Psychiatric symptoms 
may not happen right away (delayed reaction). Get emergency medical help right away if you develop
hallucinations (seeing or hearing things that are really not there), delusions (false or strange thoughts or beliefs), or 
if you get confused or have problems thinking while taking ARAKODA. Call your healthcare provider if you develop 
changes in your mood, anxiety, trouble sleeping (insomnia), or nightmares for 3 days or longer while taking 
ARAKODA.
x
ARAKODA can have other serious side effects. See “What are the possible side effects of ARAKODA?”
What is ARAKODA?
x
ARAKODA is a prescription medicine used to help prevent malaria in people 18 years of age and older.
x
Malaria is a serious disease of the blood that is spread by infected mosquitos.
x
It is not known if ARAKODA is safe and effective in children.
Do not take ARAKODA if you:
x
have G6PD deficiency.
x
are breastfeeding a child known to have G6PD deficiency or breastfeeding a child that has not been tested for 
G6PD deficiency.
x
have a history of psychotic disorders, or you currently have psychotic symptoms including  hallucinations (seeing or 
hearing things that are not really there), delusions (false or strange thoughts or beliefs), or disorganized thinking or 
behavior.
x
are allergic to tafenoquine, other 8-aminoquinolines, or any of the ingredients in ARAKODA. See the end of this 
Medication Guide for a complete list of ingredients in ARAKODA.
Before taking ARAKODA, tell your health care provider about all your medical conditions, including if you:
x
have nicotinamide adenine dinucleotide (NADH) reductase deficiency. People with NADH reductase deficiency 
have a higher risk for methemoglobinemia if they take ARAKODA. 
x
have or have had mental health problems.
x
are pregnant or plan to become pregnant. ARAKODA can harm an unborn baby who has G6PD deficiency.
o
You should not become pregnant during treatment with ARAKODA.
o
Females who are able to become pregnant should use effective birth control (contraception) during treatment 
with ARAKODA. Talk with your healthcare provider about birth control methods that may be right for you.
o
Your healthcare provider may suggest you take a pregnancy test before you start taking ARAKODA. Tell your 
healthcare provider right away if you become pregnant or think you might be pregnant during treatment with 
ARAKODA.
x
are breastfeeding or plan to breastfeed. It is not known if ARAKODA passes into breast milk. See “Do not take
ARAKODA if you:”
o
Your healthcare provider should check your child for G6PD deficiency before you start breastfeeding.
o
If you know your child has G6PD deficiency, do not breastfeed during treatment with ARAKODA and for 3 
months after your last dose of ARAKODA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, 
vitamins, and herbal supplements. ARAKODA and other medicines may affect each other causing side effects.
How should I take ARAKODA?
x
Take ARAKODA exactly as your healthcare provider tells you to take it. 
x
ARAKODA is given as 2 tablets that you will take together as a single dose. Each ARAKODA tablet has 100 mg of 
tafenoquine.
x
You will start taking ARAKODA 3 days before you travel to a malaria area.
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o
Take 2 tablets, 1 time each day for 3 days.
x
You will continue to take ARAKODA while you are in the malaria area.
o
Take 2 tablets, 1 time each week.
o
Start taking this dose of ARAKODA 7 days after the last dose of ARAKODA that you took before your travel 
to the malaria area.
x
You will take your last dose of ARAKODA after you leave the malaria area.
o
Take 2 tablets.
o
Take this dose of ARAKODA 7 days after the last dose of ARAKODA that you took while you were in the 
malaria area.
x
Take ARAKODA tablets whole. Do not break, crush, or chew the tablets before swallowing.
x
Take ARAKODA with food.
x
It is important that you take the full course of treatment with ARAKODA. Do not stop taking ARAKODA 
without first talking to your healthcare provider because the medicine may not work as well to prevent malaria.
x
If you miss 1 or 2 daily doses of ARAKODA before your travel to the malaria area:
o
1 daily dose: take 2 tablets (missed dose), and then continue to take your daily dose of ARAKODA until you 
have taken a total of 3 daily doses before your travel to the malaria area. Start taking your weekly doses or 
ARAKODA 1 week after your last daily dose.
o
2 daily doses: take 2 tablets (missed dose), 1 time each day for 2 days in a row (consecutive days) so that 
you have taken a total of 3 daily doses before your travel to the malaria area. Start taking your weekly doses of 
ARAKODA 1 week after your last daily dose.
x
If you miss any weekly doses of ARAKODA while you are in the malaria area:
o
1 weekly dose: take 2 tablets, 1 time on any day up to the time of your next scheduled weekly dose.
o
2 weekly doses: take 2 tablets, 1 time on any day before your next scheduled weekly dose. 
o
3 or more weekly doses: take 2 tablets, 1 time each day for 2 days up to the time of your next scheduled 
weekly dose.
x
If you miss taking your last dose of ARAKODA 7 days after the last dose of ARAKODA you took while you were in 
the malaria area, take this last dose of ARAKODA as soon as you remember.
What are the possible side effects of ARAKODA?
ARAKODA may cause serious side effects, including:
x
See “What is the most important information I should know about ARAKODA?”
x
Allergic (hypersensitivity) reactions. See “Do not take ARAKODA if you:”
Allergic reactions can happen after you take ARAKODA. Signs and symptoms of an allergic reaction may not 
happen right away (delayed reaction). Get medical help right away if you have any signs or symptoms of an allergic 
reaction including:
o
swelling of the face, lips, tongue or throat
o
itching
o
trouble breathing or wheezing
o
vomiting
o
fainting and feeling lightheaded
o
rash
o
hives
The most common side effects of ARAKODA include: diarrhea, headache, back pain, nausea, vomiting, dizziness,
increased liver enzyme levels in your blood, motion sickness, insomnia, depression, abnormal dreams and anxiety.
Other side effects of ARAKODA include eye problems. Some people who take ARAKODA can have a problem with 
the cornea of the eye called vortex keratopathy. This problem can be seen during an eye exam. Vortex keratopathy 
does not cause vision problems and will usually go away after you stop taking ARAKODA.
These are not all the possible side effects of ARAKODA.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. 
You may also report side effects to Sixty Degrees Pharmaceuticals, LLC at 1-888-834-0225.
How should I store ARAKODA?
x
Store ARAKODA at room temperature between 68°F to 77°F (20°C to 25°C).
x
Protect tablets from moisture. 
Keep ARAKODA and all medicines out of the reach of children.
General information about the safe and effective use of ARAKODA.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ARAKODA 
for a condition for which it was not prescribed. Do not give ARAKODA to other people, even if they have the same 
symptoms that you have. It may harm them. 
You can ask your pharmacist or healthcare provider for information about ARAKODA that is written for health 
professionals.
What are the ingredients in ARAKODA?
Active ingredient: tafenoquine succinate 
Inactive ingredients: microcrystalline cellulose, mannitol, and magnesium stearate. The tablet film-coating contains 
the following inactive ingredients: hypromellose, iron oxide red, titanium dioxide, and macrogol/polyethylene glycol. 
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Manufactured for:
Sixty Degrees Pharmaceuticals, LLC
Washington, DC 20036
For more information, go to https://60degreespharma.com or call 1-888-834-0225.
This Medication Guide has been approved by the U.S. Food and Drug Administration
Issued: August 2018
            
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--------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed
electronically. Following this are manifestations of any and all
electronic signatures for this electronic record.
--------------------------------------------------------------------------------------------
/s/
------------------------------------------------------------
EDWARD M COX
08/08/2018
Signature Page 1 of 1
Reference ID: 4303405
(
 
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60º Pharmaceuticals LLC  
Clinical Study Protocol:  TQ 2020_06 
Investigational Compound: tafenoquine 
 
 
TQ 2020_06 
CONFIDENTIAL 
 
1.0/11 Aug 2020 
15.2 Appendix B: Dyspnea and Cough Severity Scales 
15.2.1 Rating of Perceived Dyspnea (RPD) Scale 
Modified Borg Scale (MBS) during exercise or tasks. This scale allows you to rate the amount of 
shortness of breath you feel. The MBS goes from 0 to 10. A score of 0 means you have no shortness of 
breath at all (Crisafulli 2010).   
 
Modified Borg Scale for Grading the Severity of Dyspnea 
0 
(Dyspnea) NONE 
0.5 
(Dyspnea) EXTREMELY MILD 
1 
(Dyspnea) VERY MILD 
2 
(Dyspnea) MILD 
3 
(Dyspnea) MODERATE 
4 
(Dyspnea) INTENSE 
5 
(Dyspnea) RATHER INTENSE 
6 
 
7 
(Dyspnea) VERY INTENSE 
8 
 
9 
(Dyspnea) ALMOST UNBEARABLE 
10 
(Dyspnea) UNBEARABLE 
15.2.2 Cough Severity Scale 
Rate your cough as one of the following: 
1 – absent  
2 – mild (may need a nonprescription medication) 
3 – moderate (definitely needed a medication to control) 
4 – severe (interfered with activities of daily living) 
 
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