Relative Bioavailability and Effect of Food on DSM265-TPGS 34% SDD Powder in Healthy Adult Subjects
Phase: PHASE1
Conditions: Healthy Volunteers
Sponsor: Medicines for Malaria Venture

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Protocol for Study B19-227 (MMV_DSM265_18_01)
Malaria:  Relative Bioavailability and Food Effect of DSM265
VERSION:
1.0
DATE:
13 August 2018
SPONSOR:
Medicines for Malaria 
Venture (MMV)
NUMBER OF SITES:
1
INVESTIGATIONAL 
PRODUCT:
DSM265, A-1400550
FULL TITLE:  Relative Bioavailability and Effect of Food on DSM265-TPGS 34% SDD Powder in Healthy 
Adult Subjects
PRINCIPAL INVESTIGATOR:
David Carter, MD
Medical Director
AbbVie Clinical Pharmacology Research Unit (ACPRU)
Dept. R42P, Bldg. J50
480 S. US Highway 45
Grayslake, IL  60030
Office: +1 (847) 937-8515
Fax:
+1 (847) 935-4402
Email: david.carter@abbvie.com
SPONSOR/EMERGENCY MEDICAL 
CONTACT:*
Stephan Chalon, MD
Medical Director
MMV
Route de Pre-Bois 20 Box 1826
1215 Geneva 15
Switzerland
Mobile:+ 41-79-962-6244
Fax:
+ 41-22-555-0369
Email: chalons@mmv.org
EMERGENCY 24 hour Number:  +1 973-784-6402
*Additional study contact information can be found in the Operations Manual (Appendix E).
p. 1 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
SYNOPSIS
4
2
INTRODUCTION
5
2.1
BACKGROUND AND RATIONALE
5
2.2
BENEFITS AND RISKS TO SUBJECTS
5
3
STUDY OBJECTIVES AND ENDPOINTS
5
3.1
OBJECTIVES
5
3.2
SAFETY ENDPOINTS
6
3.3
PHARMACOKINETIC ENDPOINTS
6
4
INVESTIGATIONAL PLAN
6
4.1
OVERALL STUDY DESIGN AND PLAN
6
4.2
DISCUSSION OF STUDY DESIGN
7
5
STUDY ACTIVITIES
8
5.1
ELIGIBILITY CRITERIA
8
5.2
PRIOR AND CONCOMITANT THERAPY
10
5.3
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
11
5.4
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY
11
5.5
STUDY DRUG
11
5.6
RANDOMIZATION/DRUG ASSIGNMENT
12
5.7
PROTOCOL DEVIATIONS
12
6
SAFETY CONSIDERATIONS
12
6.1
COMPLAINTS AND ADVERSE EVENTS
12
6.2
PRODUCT COMPLAINT
16
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
16
7.1
STATISTICAL AND ANALYTICAL PLANS
16
7.2
STATISTICAL ANALYSES FOR PHARMACOKINETICS
16
7.3
STATISTICAL ANALYSES FOR SAFETY
16
p. 2 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
8
ETHICS
16
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
16
8.2
ETHICAL CONDUCT OF THE STUDY
17
8.3
SUBJECT CONFIDENTIALITY
17
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
17
10 DATA QUALITY ASSURANCE
17
11 COMPLETION OF THE STUDY
17
12 REFERENCES
17
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCTS
12
LIST OF FIGURES
FIGURE 1.
SINGLE-DOSE, OPEN-LABEL, RANDOMIZED PARALLEL GROUP DESIGN IN HEALTHY VOLUNTEERS
7
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
18
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
20
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
21
APPENDIX D.
ACTIVITY SCHEDULE
22
APPENDIX E.
OPERATIONS MANUAL
24
p. 3 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 SYNOPSIS
Title:  Relative Bioavailability and Effect of Food on DSM265-TPGS 34% SDD Powder in Healthy Adult Subjects
Background and Rationale:
The current clinical formulation requires reconstitution/administration 
with a 240 mL sucralose-based vehicle (for a 400 mg adult dose).  The 
new formulation was selected to dissolve in a smaller volume with 
water (approximately 60 mL for 400 mg adult dose).
Objectives and Endpoints:
The primary objective of this study is to compare the relative 
bioavailability of the oral DSM265-TPGS 34% SDD powder with the 
reference DSM265 25% SDD powder for suspension formulation.  
Another objective of the study is to evaluate the effect of food on the 
bioavailability of DSM265-TPGS 34% SDD powder.
Investigator(s):
David Carter, MD
Study Site(s):
AbbVie Clinical Pharmacology Research Unit (ACPRU)
Study Population and Number of 
Subjects to be Enrolled:
Approximately 42 healthy adult subjects
Investigational Plan:
This Phase 1, single-dose, open-label study will be conducted according 
to a randomized parallel group design in adult male and female 
subjects (3 groups of 14 subjects each).  Subjects will be confined for 
3 days with outpatient assessments through 21 days.  Blood samples 
will be collected for 480 hours after dosing.
Key Eligibility Criteria:
Volunteers in general good health.  Women must be of non-child 
bearing potential (WONCBP).
Study Drug and Duration of 
Treatment:
Single dose of 400 mg DSM265 25% SDD (Reference)
Single dose of 400 mg DSM265 TPGS 34% SDD (Test)
Date of Protocol Synopsis:
13 August 2018
p. 4 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted
DSM265 is a new antimalarial drug candidate targeted for acute uncomplicated malaria (single dose 
cure) and possibly chemoprevention (repeated administration) being developed by Medicines for 
Malaria Venture (MMV).  This new chemical entity is being evaluated in various Phase 1 studies and has 
been also tested in a Phase 2A trial in patients with acute uncomplicated malaria.  The highest dose 
tested in the first-in-human study was 1200 mg and it has been shown to be well tolerated.  Clinical data 
from a human malaria challenge model in healthy subjects as well as efficacy results from the Phase 2A 
trial suggests that efficacy in acute uncomplicated malaria with Plasmodium falciparum can be achieved 
with a single 400 mg dose of DSM265.
The median time to the maximum observed plasma concentration (Cmax), time to Cmax (Tmax), was
approximately 4 hours at a dose of 400 mg and the mean terminal phase elimination half-life (t1/2) 
remained constant across doses, ranging from 85 to 112 hours.  A major metabolite, DSM450, was 
identified with Tmax of 96 to 144 hours after dosing, a mean t1/2 ranging from 131 to 168 hours, and an 
area under the plasma concentration-time curve (AUC) of approximately 0.19 to 0.28 relative to that of 
DSM265.
This Phase 1 study is designed to evaluate the relative bioavailability of a single dose of a test 
formulation, DSM265-TPGS 34% SDD powder, with the reference DSM265 25% SDD powder for 
suspension formulation used in previous clinical trials.  This Phase 1 study is also designed to evaluate 
the effect of food on the bioavailability of DSM265-TPGS 34% SDD powder.
2.2 Benefits and Risks to Subjects
There are no expected direct benefits for subjects who enroll in this healthy volunteer study.  Study 
drugs may be associated with adverse effects as detailed in the subject informed consent form(s).  Not 
all of the potential side effects of the study drugs may be known.  In addition, subjects may experience 
discomfort or inconvenience related to study procedures.
For further details, reference findings from completed studies, including safety data in the DSM265 
Investigator's Brochure.1
3 STUDY OBJECTIVES AND ENDPOINTS
3.1 Objectives
The primary objective of this study is to compare the relative bioavailability of the oral DSM265-TPGS 
34% SDD powder to the reference DSM265 25% SDD powder for suspension formulation.  Another 
p. 5 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
objective of the study is to evaluate the effect of food on the bioavailability of DSM265-TPGS 34% SDD 
powder.
3.2 Safety Endpoints
Safety evaluations will include adverse event (AE) monitoring, physical examinations, vital signs 
measurements, electrocardiogram (ECG) variables and clinical laboratory testing.
3.3 Pharmacokinetic Endpoints
The values for the pharmacokinetic parameters of DSM265 and possible metabolite(s) including Cmax, 
Tmax, apparent terminal phase elimination rate constant (β), t1/2, AUC from time 0 until the last 
measurable concentration (AUCt), AUC from time 0 to 168 hours (AUC168) and AUC from time 0 to 
infinity (AUCinf) will be determined using non-compartmental methods.  Plasma concentration at 
168 hours (C168) will also be measured.  Additional parameters may be estimated if useful in the 
interpretation of the data.  In addition, the blood samples may be used for other exploratory analysis.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in the Operations Manual (Appendix E).
See Section 5.1 for information regarding eligibility criteria.
p. 6 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Figure 1.
Single-Dose, Open-Label, Randomized Parallel Group Design in Healthy 
Volunteers
4.2 Discussion of Study Design
Discussion of Study Design and Choice of Control Groups
Each subject will be randomly assigned to one of the regimens to avoid bias.  Parallel groups will be 
utilized as the half-life of DSM265 ranges from 85 to 112 hours.
Appropriateness of Measurements
Standard pharmacokinetic, statistical, clinical, and laboratory procedures will be utilized in this study.
Suitability of Subject Population
The selection of subjects in general good health is standard for pharmacokinetic studies.
Selection of Doses in the Study
The dose of 400 mg was tested in the Phase 2A proof-of-concept clinical study and demonstrated the 
potential to be an efficacious dose for the treatment of uncomplicated malaria with Plasmodium 
falciparum with an acceptable safety profile.
Blinding
This is an open-label study.
p. 7 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Meals and Dietary Requirements
At least a ten-hour fast is required prior to dosing for Regimen A and Regimen B, a high-fat breakfast is 
required for Regimen C; otherwise, standard moderate-fat meals will be provided during confinement.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the questions below will result in exclusion from study participation.  A subject 
who has failed screening may be re-screened at investigator's discretion.
Consent
1. Subjects or their legally authorized representative must voluntarily sign and date each 
informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB), prior to the initiation of any screening or study-specific procedures.
Demographic
2. Male or female between 18 and 55 years of age inclusive at the time of screening.
3. Body Mass Index (BMI) is ≥ 18.0 to ≤ 29.9 kg/m2 after rounding to the tenths decimal.  BMI is 
calculated as weight in kg divided by the square of height measured in meters.
Contraception Eligibility and Guidance
4. Females must be of Non-Childbearing Potential as defined below:
Females do not need to use birth control during or following study drug treatment if considered 
of non-childbearing potential due to meeting any of the following criteria:

Postmenopausal, age ≤ 55 years with no menses for 12 or more months without an 
alternative medical cause AND an follicle stimulating hormone (FSH) level > 40 IU/L.

Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or 
hysterectomy).
5. Female who is not pregnant, breastfeeding, or considering becoming pregnant during the 
study or for approximately 120 days after the last dose of study drug.
6. Male subjects who are sexually active with a female partner of childbearing potential, must 
agree to use condoms, even if the male subject has undergone a successful vasectomy, from 
Study Day 1 through 120 days after the last dose of study drug.  His female partner(s) must also 
use at least one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, intravaginal, 
injectable, transdermal) associated with inhibition of ovulation initiated at least 30 days 
prior to study Baseline Day 1.
p. 8 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to study Baseline Day 1.

bilateral tubal occlusion/ligation

intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)
7. Male who is not considering fathering a child or donating sperm during the study or for 
approximately 120 days after the last dose of study drug.
Laboratory Assessments and ECG Criteria
8. Laboratory values meet the following criteria:

serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ the upper limit of 
normal (ULN) at the Screening Visit and upon initial confinement.

negative test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface 
antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab) and human immunodeficiency virus 
(HIV) at screening visit.

negative screen for drugs of abuse, alcohol or cotinine at screening and upon initial 
confinement.

for non-postmenopausal female subjects, a negative urine pregnancy test at the screening 
visit and a negative serum pregnancy test upon initial confinement and prior to the 
first dose of study drug.

no other laboratory results that the investigator determines are clinically significant.

platelets greater than or equal to the lower limit of normal.
9. No clinically significant ECG abnormalities including

no evidence of 2nd or 3rd degree AV block at screening visit and upon initial confinement.

QT interval corrected for heart rate (QTc) using Fridericia's correction formula (QTcF) is 
≤430 msec (males) or ≤ 450 msec (females) at screening visit and upon initial confinement.
Subject History/Physical Exam and Vital Signs
10. A condition of general good health, based upon the results of a medical history, physical 
examination, vital signs, laboratory profile and a 12-lead ECG.
11. No history of: epilepsy, any clinically significant cardiac, respiratory (except mild asthma as a 
child), renal, hepatic, gastrointestinal, hematologic or psychiatric disease or disorder, or any 
uncontrolled medical illness.
12. No history of any clinically significant sensitivity or allergy to any medication or food.
13. No history of or active medical condition(s) or surgical procedure(s) that might affect 
gastrointestinal motility, pH, or absorption [e.g., Crohn's disease, celiac disease, gastroparesis, 
short bowel syndrome, gastric surgery (except pyloromyotomy for pyloric stenosis during 
infancy), cholecystectomy, vagotomy, bowel resection].
p. 9 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
14. No evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other 
than successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma or 
localized carcinoma in situ of the cervix.
15. No history of any clinically significant illness/infection/major febrile illness, hospitalization, 
or any surgical procedure within 30 days prior to the first dose of study drug.
16. Has not donated blood (including plasmapheresis), lost ≥ 550 mL blood volume, or received 
a transfusion of any blood product within 8 weeks prior to study drug administration.
17. No consumption of alcohol, grapefruit products, Seville oranges, starfruit products or 
quinine/tonic water within the 72-hour period prior to study drug administration.
18. No use of tobacco or nicotine-containing products within 180 days prior to the first dose of 
study drug.
19. No history of clinically significant (per Investigator's judgment) drug or alcohol abuse within 
the last 6 months.
20. Is not currently enrolled in another interventional clinical study.
21. Has not been previously enrolled in this study.
22. In the opinion of the investigator, this subject is a suitable candidate for enrollment in the 
study.
Concomitant Medications
23. Subjects must not have been treated with any investigational drug within 30 days or 
5 half-lives of the drug (whichever is longer) prior to the first dose of study drug.
24. Subject must not have received any live vaccine within 4 weeks prior to the first dose of 
study drug, or expected need of live vaccination during study participation including at least 
4 weeks after the last dose of study drug.
25. Subject must not require any over-the-counter and/or prescription medication, vitamins 
and/or herbal supplements, with the exception of contraceptives or hormonal replacement 
therapies for females, on a regular basis.
26. Subject must not use any medications within the 2-week period prior to study drug 
administration.
27. Receipt of any drug by injection within 30 days or within a period defined by 5 half-lives, 
whichever is longer, prior to study drug administration.
28. No use of known inhibitors (e.g., ketoconazole) or inducers (e.g., carbamazepine) of 
cytochrome P450 3A (CYP3A) within 1 month prior to study drug administration.
29. No exposure to DSM265 within the past 90 days prior to first dose of study drug.
5.2 Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medications) that the subject 
receives after enrollment into the study must be recorded through the last study visit.
p. 10 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5.3 Withdrawal of Subjects and Discontinuation of Study
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following:

The Investigator believes it is in the best interest of the subject.

The subject requests withdrawal from the study.

The subject becomes pregnant while on study drug.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the trial.
AbbVie or MMV may terminate this study prematurely, either in its entirety or at any site.  The 
Investigator may also stop the study at his/her site if he/she has safety concerns.  If AbbVie or MMV 
terminates the study for safety reasons, AbbVie will promptly notify the Investigator.
5.4 Follow-Up for Subject Withdrawal from Study
In the event that a subject withdraws or is discontinued from the study, the primary reason for 
discontinuation and any other reason(s) for the discontinuation from the study will be recorded and a 
physical examination, body weight, vital signs measurement, ECG, laboratory analyses, and an 
assessment of adverse events will be performed as soon as possible after discontinuation from the 
study.  Additional blood samples for drug measurement may be collected at the time of discontinuation 
from subjects who are discontinued due to adverse events; the clock time, time in relation to dose, and 
date the sample was taken will be recorded.
If a subject is discontinued from the study with an ongoing adverse event or an unresolved laboratory 
result that is significantly outside of the reference range, the investigator will attempt to provide 
follow-up until a satisfactory clinical resolution of the laboratory result or adverse event is achieved.
5.5 Study Drug
Information about the DSM265 formulations to be used in this study is presented in Table 1.
p. 11 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 1.
Identity of Investigational Products
DSM265 Regimens
Reference
Test
Dosage Form
Powder for suspension
Powder for suspension
Formulation
25% SDD
TPGS 34% SDD
Strength (mg)
400
400
Drug Preparation
Reconstitute in 100 mL supplied vehicle; rinse 
twice with 70 mL supplied vehicle
Reconstitute in 40 mL water + 
20 mL rinse water
Additional Information
Store at 2 to 8°C/35 to 46°F
Store at 2 to 8°C/35 to 46°F
5.6 Randomization/Drug Assignment
All subjects will be assigned a unique identification number prior to dosing.  This number will encode the 
subject's assignment according to the randomization schedule generated by the statistics department at 
AbbVie.
5.7 Protocol Deviations
The Investigator is responsible for complying with all protocol requirements, written instructions, and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when 
necessary to eliminate an immediate hazard to study subjects.  If a protocol deviation occurs (or is 
identified), the Investigator is responsible for notifying IEC/IRB, regulatory authorities (as applicable), 
and AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
Complaints
A complaint is any written, electronic, or oral communication that alleges deficiencies related to the 
physical characteristics, identity, quality, purity, potency, durability, reliability, safety, effectiveness, or 
performance of a product/device.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Medical Complaints/Adverse Events and Serious Adverse Events
An adverse event is defined as any untoward medical occurrence in a subject or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and unintended
sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use 
p. 12 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
of a medicinal (investigational) product, whether or not the event is considered causally related to the 
use of the product.
The investigators will monitor each subject for clinical and laboratory evidence of adverse events on a 
routine basis throughout the study.  All adverse events will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an adverse 
event if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre planned prior to study entry.  However, if the pre-existing condition 
deteriorates unexpectedly during the study (e.g., surgery performed earlier than planned), then the 
deterioration of the condition for which the elective surgery/procedure is being done will be considered 
an adverse event.
If an adverse event meets any of the following criteria, it is to be reported to MMV/PrimeVigilance as a 
serious adverse event within 24 hours of the site being made aware of the serious adverse event:
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have resulted 
in immediate fatality if medical intervention had not been taken.  This 
does not include an event that would have been fatal if it had occurred 
in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any length of 
time or prolongs the subject's hospital stay.  This does not include an 
emergency room visit or admission to an outpatient facility.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with 
the activities of daily living of a study subject.  Disability is not intended 
to include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require medical 
or surgical intervention to prevent any of the outcomes listed above 
(i.e., death of subject, life threatening, hospitalization, prolongation of 
hospitalization, congenital anomaly, or persistent or significant 
disability/incapacity).  Additionally, any elective or spontaneous 
abortion or stillbirth is considered an important medical event.  
Examples of such events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse.
p. 13 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
All adverse events reported from the time of study drug administration until 30 days or 5 half-lives after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, serious adverse events and protocol-related non-serious adverse 
events will be collected from the time the subject signs the study-specific informed consent.
MMV/PrimeVigilance will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) 
reporting for the Investigational Medicinal Product (IMP) in accordance with global and local 
requirements.
Adverse Events of Special Interest (AESI)
Adverse events will be monitored throughout the study to identify any of special interest that may 
indicate a trend or risk.
All the abnormalities listed below should be reported as an AESI:

Related to hematotoxicity:

A fall in hemoglobin of > 20 g/L or 25% from the baseline value,

A fall in absolute neutrophils count to < 1000/mm3,

A fall in platelet level to < 100,000/mm3.

Related to hepatotoxicity:

ALT or AST > 3 × ULN with the appearance of worsening of fatigue, nausea, vomiting, fever, 
rash, or eosinophilia,

AST or ALT increase > 8 × ULN,

ALT or AST rises rapidly to > 5 × ULN in less than 4 weeks or persists for more than 2 weeks,

ALT or AST > 3 × ULN and TBL > 2 × ULN or INR > 1.5 × ULN (Hy's Law if ALP < 2 × ULN), to 
also be reported as an SAE in case of Hy's Law.

Related to cardiotoxicity:

QTcF prolongation from baseline of > 60 ms,

QTcF at any time > 450 ms,

T wave liability, or T wave morphologic changes during therapy,

Bundle branch block, complete or partial,

Any arrhythmia.

Related to dermatotoxicity, clinical signs of possible cutaneous adverse reactions such as:

Dermatitis,

Rash,

Erythematous rash,

Macular rash,
p. 14 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Papular rash,

Maculo-papular rash,

Pruritic rash,

Pustular rash,

Vesicular rash.

Related to pregnancy:

Pregnancy in subject or in partner of a male subject.
Adverse Event Severity and Relationship to Study Drug
The investigator will rate the severity of each adverse event according to Common Terminology Criteria 
for Adverse Events (CTCAE, version 5.0).
The investigators will rate the severity of each adverse event as mild, moderate, or severe.  The 
investigator will use the following definitions to assess the relationship of the adverse event to the use 
of study drug:
Reasonable Possibility – After consideration of factors including timing of the event, biologic plausibility, 
clinical judgment, and potential alternative causes, there is sufficient evidence (information) to suggest 
a causal relationship.
No Reasonable Possibility – After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is insufficient evidence 
(information) to suggest a causal relationship.
Pregnancy
While not an adverse event, pregnancy in a study subject must be reported to MMV/PrimeVigilance 
within 1 working day after the site becomes aware of the pregnancy.  Subjects who become pregnant 
during the study must be discontinued from study procedures (Section 5.3).  If a pregnancy occurs in a 
study subject or in the partner of a study subject, information regarding the pregnancy and the outcome 
will be collected.
In the event of pregnancy occurring in a subject's partner during the study, written informed consent 
from the partner must be obtained prior to collection of any such information.  Pregnancy in a subject's 
partner will be collected from the date of the first dose through 120 days following the last dose of 
study drug.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a serious adverse event (SAE) and must be reported to MMV/PrimeVigilance within 24 hours 
after the site becomes aware of the event.
p. 15 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.2 Product Complaint
A product complaint is any complaint related to the biologic or drug component of the product or to the 
medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (e.g., printing illegible), missing components/product, device not working properly, 
or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 1 business day of the study site's knowledge of the event.  Product complaints occurring during 
the study will be followed up to a satisfactory conclusion.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
Completed and specific details of the statistical analysis will be described and fully documented in the 
Statistical Analysis Plan (SAP).  The statistical analyses will be performed using SAS (SAS Institute Inc., 
Cary, NC, USA).
7.2 Statistical Analyses for Pharmacokinetics
Primary Analysis
For DSM265, an analysis of variance (ANOVA) will be performed for Tmax, β, the natural logarithms of 
Cmax, AUC, and C168.  Significant pharmacokinetic sample time deviations will be identified and listed.
Sample Size Estimation
Refer to the SAP for details on sample size determinations.
7.3 Statistical Analyses for Safety
Refer to the SAP for details on the safety analysis.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
p. 16 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study 
conduct and the ethical principles that have their origin in the Declaration of Helsinki.  Responsibilities of 
the Investigator are specified in 0.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The Investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).
10 DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
are generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
11 COMPLETION OF THE STUDY
The end-of-study is defined as the date of the last subject's last visit.
12 REFERENCES
1.
MMV.  DSM265 Investigator's Brochure Version 7.0.  31 July 2018.
p. 17 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
Ab
Antibody
AE
Adverse event
AESI
Adverse event of special interest
ALT
Alanine transaminase
AST
Aspartate transaminase
AUC
Area under the plasma concentration-time curve
AUCt
Area under the plasma concentration-time curve from time 0 until the last measurable 
concentration
AUCinf
Area under the plasma concentration-time curve from time 0 to infinity
β
Apparent terminal phase elimination rate constant
BMI
Body mass index
C168
Plasma concentration at 168 hours
Cmax
Time to the maximum observed plasma concentration
CTCAE
Common Terminology Criteria for Adverse Event
ECG
Electrocardiogram
FSH
Follicle stimulating hormone
GCP
Good Clinical Practice
HAV-IgM
Hepatitis A virus immunoglobulin M
HBsAg
Hepatitis B surface antigen
HCV
Hepatitis C virus
HIV
Human immunodeficiency virus
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IMP
Investigational Medicinal Product
IRB
Institutional Review Board
IUD
Intrauterine device
MMV
Medicines for Malaria Venture
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using Fridericia's correction formula
SAE
Serious adverse event
p. 18 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
SAP
Statistical analysis plan
SUSAR
Suspected unexpected serious adverse reactions
t1/2
Terminal phase elimination half-life
Tmax
Time to maximum observed plasma concentration (Cmax)
ULN
Upper limit of normal
WONCBP
Women of Non-Child Bearing Potential
p. 19 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol B19-227:  Relative Bioavailability and Food Effect of DSM265
Protocol Date:  13 August 2018
Clinical research studies performed at AbbVie are subject to the International Council for Harmonisation 
(ICH) Good Clinical Practices (GCP) and local regulations and guidelines governing the study at the site 
location.  In signing the Investigator Agreement, the investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, 
current protocol and operations manual, and making changes to a protocol only after notifying 
AbbVie and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC), except when necessary to protect the subject from immediate harm.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed consent and 
ethics committees (e.g., IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
5.
Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
9.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
p. 20 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Joerg Moehrle
DSM265 Project Director
Clinical Program Development (MMV)
Stephan Chalon
Medical Director
Group MD or MA TA (MMV)
Stephan Duparc
Chief Medical Officer
Clinical Program Development (MMV)
p. 21 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities and time-points.  The individual activities are described 
in detail in the Operations Manual (Appendix E).
Study Activities Table
Activity
Screening
Day -1
Initial Confinement
Day 1
Day 2
Day 4
Day 6
Day 8
Day 10
Day 14 +/– 1 day
Day 21  +/– 1 day or 
Premature
Discontinuation
INTERVIEWS & 
QUESTIONNAIRES
Informed consent

Eligibility criteria


Medical/surgical history (update only 
upon initial confinement)


Drug alcohol and nicotine use


Adverse event assessment










Prior/concomitant therapy








LOCAL LABS & EXAMS
HAV-IgM, HBsAg, HCV Ab, HIV Ab

Height (Screening and Initial 
confinement only) and weight



Physical examination




Drug, Alcohol and Cotinine Screen


12-lead ECG single





Vital signs










FSH test (postmenopausal women)

Pregnancy test (non-postmenopausal 
women) (u = urine; s = serum)
(u)
(s)
(s)
Blood Chemistry Hematology (CBC), and 
Urinalysis






Blood samples for DSM265 assay








Administration
DSM265 Administration

Confinement



p. 22 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Day 1
Day 1 Activity
Pre-Dose
0 Hour
0.5 Hour
1 Hour
2 Hour
4 Hour
6 Hour
8 Hour
12 Hour
24 Hour
Blood samples for DSM265 PK assay









Study drug administration

12-lead ECG single

Vital signs






p. 23 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E. OPERATIONS MANUAL
p. 24 of 41

p. 1 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Operations Manual for Clinical Study Protocol B19-227 
(MMV_DSM265_18_01)
Malaria:  Relative Bioavailability and Food Effect of DSM265
SPONSOR:
Medicines for Malaria 
Venture (MMV)
INVESTIGATIONAL 
PRODUCT:
DSM265, A-1400550
INVESTIGATOR:
David Carter, MD
Medical Director
AbbVie Clinical 
Pharmacology Research Unit
480 S. US Highway 45
Grayslake, IL  60030
Phone: (847) 937-8515
Fax:
(847) 935-4402
p. 25 of 41

p. 2 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
1 CONTACTS
Sponsor/
Emergency Contact 
and Safety Concerns:
Stephan Chalon, MD
Medical Director
MMV
Route de Pre-Bois 20 Box 1826
1215 Geneva 15
Switzerland
Email:  chalons@mmv.org
EMERGENCY 24 hour Number:  
+1 (973) 784-6402
Mobile: + 41-79-962-6244
Fax:
+ 41-22-555-0369
If not available:
Phone: (973) 784-6402
Serious Adverse 
Event (SAE) 
Reporting
Email: MMV@primevigilance.com
FAX:
+44 800 471 5694
Protocol Deviations 
and Product 
Complaints
Meredith McDonald
Study Management Associate III
One North Waukegan Road
North Chicago, IL 60064
OR
Alyssa O'Neill
Assistant Director
One North Waukegan Road
North Chicago, IL 60064
Mobile: +1 847-393-5792
Fax:
+1 847-654-6836
Email:
meredith.mcdonald@abbvie.com
OR
Office:
+1 847-938-0387
Mobile: +1 847-513-2129
Email: 
alyssa.b.oneill@abbvie.abbvie.com
Bioanalytical Lab
Swiss BioQuant A.G/Anita Kress, Ph.D.
Kägenstrasse 18
4153 Reinach, Switzerland
Phone: +41 61 716 98 12
Fax:
+41 61 716 98 15
E-mail:
anita.kress@swissbioquant.com
p. 26 of 41

p. 3 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
CONTACTS
2
2
INVESTIGATION PLAN
5
2.1
STUDY ACTIVITIES
5
3
STUDY PROCEDURES
5
3.1
STUDY INFORMATION AND INFORMED CONSENT
5
3.2
MEDICAL/SURGICAL HISTORY
5
3.3
HEPATITIS SCREEN
5
3.4
HIV SCREEN
6
3.5
DRUG, ALCOHOL AND COTININE SCREEN
6
3.6
12-LEAD ECG
6
3.7
HEIGHT AND WEIGHT
7
3.8
VITAL SIGNS
7
3.9
PHYSICAL EXAMINATION
8
3.10 CLINICAL LABORATORY TESTS
8
3.11 PREGNANCY TEST
9
3.12 PHARMACOKINETIC SAMPLING
9
3.13 MEALS
9
3.14 CONFINEMENT
10
3.15 OUTPATIENT VISITS
10
4
SAFETY MANUAL
10
4.1
METHODS AND TIMING OF SAFETY ASSESSMENT
10
4.2
RECORDING DATA AND ANALYSES OF SAFETY FINDINGS
11
4.3
REPORTING ADVERSE EVENTS
11
6
STUDY DRUG
12
6.1
TREATMENTS ADMINISTERED
12
6.2
PACKAGING AND LABELING
13
6.3
METHOD OF ASSIGNING SUBJECTS TO TREATMENT GROUPS
13
p. 27 of 41

p. 4 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.4
SELECTION AND TIMING OF DOSE FOR EACH SUBJECT
13
6.5
PREPARATION/RECONSTITUTION OF DOSAGE FORM
13
LIST OF APPENDICES
APPENDIX A.
STUDY SPECIFIC ABBREVIATIONS AND TERMS
14
APPENDIX B.
PHARMACOKINETIC HANDLING, PROCESSING AND SHIPMENT
15
p. 28 of 41

p. 5 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 INVESTIGATION PLAN
2.1 Study Activities
Information regarding specific procedures is provided in Section 3.  The timing of the activities for this 
study is presented in tabular form in the Study Activities Tables attached to the protocol.
3 STUDY PROCEDURES
3.1 Study Information and Informed Consent
Prior to the initiation of any screening or study-specific procedures, the investigator or his/her 
representative will explain the nature of the study.  After the nature of the testing has been explained 
and the subject has had an opportunity to ask questions and questions have been answered to the 
subject's satisfaction, the subject will be presented the opportunity to sign the informed consent 
form(s).  Each consent form must be voluntarily signed and dated before any related study activities are 
performed.  Each informed consent form will be reviewed, signed and dated by the subject, the person 
who administered the informed consent, and any other signatories according to local requirements.  A 
signed copy of each informed consent will be given to the subject and each original will be placed in the 
subject's study record.  An entry must also be made in the subject's dated source documents to confirm 
that informed consent was obtained prior to any study-related procedures and that the subject received 
a signed copy.
Information regarding incentives for subjects and information regarding provisions for treating and/or 
compensating subjects who are harmed as a consequence of participation in the study can be found in 
the informed consent form.
3.2 Medical/Surgical History
A complete medical/surgical history, including history of tobacco, alcohol and drug use, will be taken.  
The subject's medical history updated on initial confinement will serve as the baseline for clinical 
assessment.
Medication (prescription or over-the-counter, including vitamins and herbal supplements) use from 
2 weeks prior to study drug administration through the end of the study will also be recorded.
3.3 Hepatitis Screen
HAV-IgM, hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibody (HCV Ab) tests will be 
performed.  The hepatitis test panel will be performed by a certified laboratory.
p. 29 of 41

p. 6 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
3.4 HIV Screen
Subjects will have blood tested by a certified laboratory for the presence of human immunodeficiency 
virus antibody (HIV Ab).  Only those subjects negative for the presence of antibodies will be allowed to 
enroll in the study.
3.5 Drug, Alcohol and Cotinine Screen
Urine specimens will be tested for the presence of drugs of abuse.  The panel for drugs of abuse will 
minimally include the drugs listed below.  Any positive result must be assessed for clinical significance. 
These analyses will be performed by the certified laboratory chosen for the study.  The cotinine test may 
be performed by the clinical site.  Results of the cotinine test will be retained by the study site.

Cannabinoids

Opiates

Barbiturates

Amphetamines

Cocaine

Benzodiazepines

Alcohol

Phencyclidine

Propoxyphene

Methadone
3.6 12-Lead ECG
Resting single 12-lead ECGs will be obtained.
The ECG acquired prior to dosing will serve as the baseline measurements for clinical assessment.
When an ECG is scheduled at the same time as a blood collection, the ECG will be obtained prior to the 
blood collection.  ECGs occurring near meals will take place prior to meals.
ECGs will be acquired after the subject has been in the supine position for at least 5 minutes.  Subjects 
will be instructed to remain completely stationary (no talking, laughing, deep breathing, sleeping, or 
swallowing) for approximately 10 seconds during the ECG recording.  While ECGs are being acquired, 
subjects and staff are prohibited from having devices (e.g., cellular telephones, fans, heaters, etc.) that 
emit electrical interference in the room.
p. 30 of 41

p. 7 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
ECG Safety Review
Each ECG will be evaluated by an appropriately qualified physician (preferably a cardiologist) at the 
study site (the "local reader").  The local reading of the ECG will be used by the investigator for subject 
safety assessments, including adverse event (AE) determination and management, and decision on 
whether a subject will be discontinued from the study.
The local reader will sign and date all the ECGS collected in this study and provide a global interpretation 
for each ECG using the following categories:

Normal ECG

Abnormal ECG – Not clinically significant (NCS)

Abnormal ECG – Clinically significant (CS)

Unable to evaluate
All local reader evaluations of ECGs will be entered into the source documents.  If the global 
interpretation is Abnormal (NCS or CS), the local reader will provide further information (e.g., sinus 
bradycardia, arrhythmia).  The QT interval corrected for heart rate using Fridericia's formula (QTcF) will 
be calculated and documented for all ECGs.
All ECG source documentation will be retained at the study site.  The automatic cardiograph reading 
(i.e., cardiograph-generated measurements and interpretations) will not be collected for analysis.
3.7 Height and Weight
Height and weight will be measured in order to calculate body mass index (BMI).  Body weight may be 
measured at additional timepoints throughout the study.  The subject will wear lightweight clothing and 
no shoes during height measurement and weighing.
3.8 Vital Signs
Body temperature (oral), blood pressure and pulse will be measured.  The vital signs measurements just 
prior to dosing on Study Day 1 will serve as the baseline measurements for clinical assessment.
Blood pressure and pulse rate will be measured after the subject has been sitting for at least 3 minutes.
When measurements of vital signs are scheduled at the same time as a blood collection, the 
measurements of vital signs will be obtained prior to the blood collection.
Measurements of vital signs occurring near meals or dosing will take place prior to meals or dosing.
p. 31 of 41

p. 8 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
3.9 Physical Examination
Physical examinations will be performed.  A symptom-directed physical examination will be performed 
when necessary.  The last physical examination performed prior to the first dose will serve as the
baseline physical examination for clinical assessment.  Any significant physical examination findings after 
dosing will be recorded as adverse events.
3.10 Clinical Laboratory Tests
The blood samples for serum chemistry tests should be collected following a minimum 8-hour fast.
The site's local laboratory will be utilized to process and provide results for the clinical laboratory test.  
The laboratory must be certified and must provide laboratory reference ranges prior to the initiation of 
the study.  The baseline laboratory test results for clinical assessment for a particular test will be defined 
as the last measurement prior to the initial dose of study drug.  Follow-up safety labs may be performed 
by a certified lab other than the site's local laboratory.  An out of range laboratory test at screening or 
check in may be repeated at the discretion of the investigator.
For any laboratory test value outside the reference range that the investigator considers to be clinically 
significant:

The investigator will repeat the test to verify the out-of-range value.

The investigator will follow the out-of-range value to a satisfactory clinical resolution.

A laboratory test value that requires a subject to be discontinued from the study or requires a 
subject to receive treatment will be recorded as an adverse event.
p. 32 of 41

p. 9 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Hematology
Clinical Chemistry
Urinalysis
Hematocrit
Hemoglobin
Red blood cell (RBC) count
White blood cell (WBC) count
Neutrophils
Bands (if detected)
Lymphocytes
Monocytes
Basophils (if detected)
Eosinophils (if detected)
Platelet count (estimate not
acceptable)
Mean corpuscular hemoglobin 
(MCH)
Mean corpuscular volume
(MCV)
Mean corpuscular hemoglobin 
concentration (MCHC)
Reticulocyte count
Blood urea nitrogen (BUN)
Creatinine
Total bilirubin
Albumin
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphate
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Chloride
Carbon Dioxide
Lactate dehydrogenase (LDH)
Specific gravity
Ketones
pH
Protein
Glucose
Blood
Bilirubin
Microscopic examination if the 
results are positive
3.11 Pregnancy Test
A urine pregnancy test and quantitative serum pregnancy tests will be performed for all 
non-postmenopausal women.
3.12 Pharmacokinetic Sampling
Blood Samples for DSM265 Assay
Blood samples for DSM265 will be collected at time points specified in Study Activities Table in the 
protocol.
Additional information on the disposition, handling and measurement methods can be found in 
Appendix B.
3.13 Meals
At least a 10-hour fast is required prior to dosing for Regimen A and Regimen B, a high-fat breakfast is 
required for Regimen C; otherwise, standard moderate-fat meals will be provided during confinement.
Fasting:  Subjects will receive a standardized diet.  Subjects will fast for at least 10 hours prior to dosing 
in the fasting regimens (A and B).  For Regimen C (non-fasting), subjects will start the high-fat breakfast
approximately 30 minutes prior to dosing.
p. 33 of 41

p. 10 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Non-fasting:  With the exception of the high-fat breakfast for Regimen C, meals will be identical on the 
intensive pharmacokinetic sampling days (Study Day 1) except for the breakfast in Regimen C.  The 
composition (protein, fat, carbohydrate, and total calories) of these meals will be determined by a 
dietician and a record will be kept with the source documents.  For moderate fat meals, approximately 
30% of the total caloric content of the meals must be from fat. For the high-fat breakfast, approximately 
50% of the total caloric content of the meal must be from fat.
3.14 Confinement
Subjects will be confined to the study site and supervised for approximately 3 days.  Confinement in 
each period will begin on Study Day –1 and end after the collection of the 24-hour blood samples and 
scheduled study procedures are completed on Study Day 2.  Strenuous activity during confinement will 
not be permitted.
3.15 Outpatient Visits
Subjects will return to the study site in the morning of designated days for study procedures as indicated 
in the Study Activities Table.
4 SAFETY MANUAL
4.1 Methods and Timing of Safety Assessment
All serious adverse events as well as protocol-related nonserious adverse events (e.g., occurrence during 
screening) will be collected from the time the subject signed the study-specific informed consent until 
study drug administration and reported to the sponsor.  From the time of study drug administration 
until 30 days or 5 half-lives whichever is longer following discontinuation of study treatment has 
elapsed, all adverse events and serious adverse events will be collected, whether solicited or 
spontaneously reported by the subject.
p. 34 of 41

p. 11 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
4.2 Recording Data and Analyses of Safety Findings
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).  The 
number and percentage of subjects with treatment-emergent adverse events (i.e., any event that begins 
or worsens in severity after initiation of study drug through 30 days post-study drug dosing) will be 
tabulated by primary MedDRA System Organ Class (SOC) and preferred term (PT) with a breakdown by 
regimen.  The tabulation of the number of subjects with treatment-emergent adverse events by severity 
grade and relationship to study drug also will be provided.  Subjects reporting more than 1 adverse 
event for a given MedDRA preferred term will be counted only once for that term using the most severe 
grade according to the severity grade table and the most related according to the relationship to study 
drug tables.  Subjects reporting more than 1 type of event within an SOC will be counted only once for 
that SOC.
4.3 Reporting Adverse Events
In the event of an SAE, whether associated with study drug or not, the Investigator will notify MMV 
Pharmacovigilance within 24 hours of the site being made aware of the SAE by email.  The study specific 
SAE and AESI forms will be used by the Investigator.
Email: MMV@primevigilance.com
FAX to: +44 800 471 5694
For any subject safety concerns, please contact the physician listed below:
Stephan Chalon, MD
Medical Director
MMV
Route de Pre-Bois 20 Box 1826
1215 Geneva 15
Switzerland
Email: chalons@mmv.org
Mobile:+ 41-79-962-6244
Fax:
+ 41-22-555-0369
HOTLINE:  +1 (973) 784-6402
Serious adverse events that meet the reporting criteria, as dictated by local regulations, will be reported 
to both responsible Ethics Committees and Regulatory Agencies as required by local regulations.  During 
the conduct of the study, the investigator should promptly provide written reports (e.g., International 
p. 35 of 41

p. 12 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Conference on Harmonization (ICH) Expedited Reports or any additional reports required by local 
regulations) to the independent ethics committee (IEC)/Institutional Review Board (IRB) of any changes 
that affect the conduct of the study and/or increase the risk to subjects.  Written documentation of the 
submission to the IEC/IRB should also be provided to MMV/PrimeVigilance.
For protocol-related non-serious adverse events in volunteers that sign the study specific informed 
consent, and are not randomized or dosed, provide to the monitor and the [TA] Safety Team 
(SafetyManagement_[TA]@abbvie.com) at minimum, the following information:

a brief description of the adverse event, including onset and resolution dates

a volunteer identifier

the protocol-defined study procedure(s) and/or other factor(s) that caused the AE

a brief description of the treatment or intervention
5 ADDITIONAL REQUIREMENTS
There are no additional requirements.
6 STUDY DRUG
6.1 Treatments Administered
Study drug will be administered in the morning on Study Day 1 as follows:
Regimen A
400 mg DSM265 25% SDD powder for suspension administered under 
fasting conditions (reference).
Regimen B
400 mg DSM265-TPGS 34% SDD powder administered under fasting 
conditions (test).
Regimen C
400 mg DSM265-TPGS 34% SDD powder administered under nonfasting 
conditions (test).
Regimen A will be taken orally with approximately 240 mL of vehicle (100 mL followed by 2 rinses of 
70 mL each) after at least a 10-hour fast and approximately 4 hours before lunch.  Regimen B will be 
taken orally with approximately 60 mL of water (40 mL followed by a rinse of 20 mL) after at least a
10-hour fast and approximately 4 hours before lunch.  Regimen C will be taken orally with approximately 
60 mL of water (40 mL followed by a rinse of 20 mL) approximately 30 minutes after starting breakfast.  
The time of each drug administration will be recorded to the minute.  The subjects will be instructed to 
remain in a sitting or standing position for at least 2 hours after dosing.
p. 36 of 41

p. 13 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.2 Packaging and Labeling
All study drugs will be supplied in bags.
Each bag will be labeled as required per country requirements.
Storage and Disposition of Study Drug
DSM265 SDD powder must be stored at 5°C (2 to 8°C/35 to 46°F).  The investigational products are for 
investigational use only and are to be used only within the context of this study.  The study drug 
supplied for this study must be maintained under adequate security and stored under the conditions 
specified on the label until dispensed for subject use or destroyed on site as appropriate.
6.3 Method of Assigning Subjects to Treatment Groups
As they are enrolled in the study, subjects will be assigned unique consecutive numbers beginning with 
101.  The subjects will be randomly assigned in equal numbers to receive one of the three regimens.  
The randomization schedule will be computer-generated before the start of the study by the Statistics 
Department, AbbVie.
6.4 Selection and Timing of Dose for Each Subject
The same dose will be administered to all subjects.  Dosing will be accomplished in the morning of Study 
Day 1.
6.5 Preparation/Reconstitution of Dosage Form
The DSM265 drug product will be provided as a powder in bags.  Each dose of DSM265 will be 
reconstituted following the specific dose preparation that will be provided to the site pharmacist in a 
pharmacy manual.
p. 37 of 41

p. 14 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AE
Adverse event
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
BMI
Body Mass Index
BUN
Blood urea nitrogen
ECG
Electrocardiogram
HBsAg
Hepatitis B surface antigen
HCV Ab
Hepatitis C virus antibody
HIV Ab
Human immunodeficiency virus antibody
ICH
International Conference on Harmonization
IEC
Independent ethics committee
IRB
Institutional Review Board
MedDRA
Medical Dictionary for Regulatory Activities
PT
Preferred term
QTcF
QTc using Fridericia's correction formula
RBC
Red blood cell
SAE
Serious adverse event
SOC
System Organ Class
p. 38 of 41

p. 15 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. PHARMACOKINETIC HANDLING, PROCESSING 
AND SHIPMENT
Collection of Samples for Analysis
Blood samples for DSM265 analysis will be collected by venipuncture at the protocol specified times 
after dosing.  The timing of blood collections will take priority over all other scheduled study activities 
except for dosing.  The order of blood collections will be maintained to the minute such that the time 
intervals relative to the preceding dose will be the same for all subjects. The time that each blood 
sample is collected will be recorded to the minute.
The blood samples will be collected in 1 mL evacuated Lithium heparin-containing collection tubes.  
Sufficient blood will be collected to yield approximately 0.4 mL plasma from each sample.  Immediately 
after collection, the blood samples will be inverted to ensure good mixing of the blood and 
anticoagulant, and will be placed in an ice bath.
Handling/Processing of Samples
The blood samples for DSM265 will be centrifuged at approximately 1400 x g for approximately 10 
minutes using a refrigerated centrifuge to separate the plasma within 1 hour of collection.  The plasma 
samples will be transferred using plastic pipettes into screw-capped polypropylene tubes labeled with 
the drug number name, type of sample (plasma), the protocol number, the subject number, the study 
day, and the planned time of sampling relative to dosing.  The plasma samples will be placed in a freezer 
within 2 hours after collection and maintained at –20°C or colder until shipped to Swiss BioQuant.
Disposition of Samples
The frozen plasma samples for DSM265 will be packed in dry ice sufficient to last during transport.  
Pick-up and shipment of samples to Swiss BioQuant will be organized by MMV. An inventory of the 
samples included will accompany the package.  Temperature excursions during transit will be 
tracked/recorded by the use of loggers included in the package.
Arrangements will be made with AbbVie for the shipment of samples to:
Swiss BioQuant/Anita Kress, Ph.D.
Kägenstrasse 18
4153 Reinach, Switzerland
Phone: +41 61 716 98 12
Fax:
+41 61 716 98 15
E-mail: anita.kress@swissbioquant.com
p. 39 of 41

p. 16 of 16
OPERATIONS MANUAL FOR CLINICAL STUDY PROTOCOL B19-227 Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Measurement Methods
Plasma concentrations of DSM265 will be determined using a validated method at:
Swiss BioQuant
Kägenstrasse 18
4153 Reinach, Switzerland
p. 40 of 41

STUDY B19-227  |  Version 1.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
SIGNATURE PAGE
Relative Bioavailability and Effect of Food on DSM265-TPGS 34% SDD 
Powder in Healthy Adult Subjects
Medicines for Malaria Venture (MMV)
Protocol B19-227 (MMV_DSM265_18_01)
Approved by:
Sponsor
Signature and Date
Stephan Chalon, MD, PhD
VP-Head of Experiment Medicine
DSM265 Medical Director
Joerg Moehrle, PhD
VP-Head of Translational Medicine
DSM265 Project Director
Stephan Duparc, MD
Chief Medical Officer
Affiliated to:
Medicines for Malaria Venture
20 route de Pré-Bois
PO Box 1826
1215 Geneva 15 - Switzerland
p. 41 of 41