A 2 Part, Randomized, Open-Label, Single Dose, Crossover Study to Assess the Relative Bioavailability of Phase II Tablet Formulation Compared to the Current Phase I Capsule Formulation and the Effect of Food and Taste Assessment on the Phase II Tablet Formulation in Healthy Participants
Phase: PHASE1
Conditions: Healthy Volunteers
Sponsor: Hoffmann-La Roche

 
Official Title: 
 
A 2 Part, Randomized, Open-Label, Single Dose, Crossover Study to 
Assess the Relative Bioavailabilty of Phase II Tablet Formulation 
Compared to the Current Phase I Capsule Formulation and the Effect 
of Food and Taste Assessment on the Phase II Tablet Formulation in 
Healthy Participants 
NCT Number: 
NCT03847987 
Document Date(s): 
Protocol Version 2: 28-February-2019 
 
 
 

FINAL PROTOCOL APPROVAL
CONFIDENTIAL
The information contained in this document, especially any unpublished data, is the property of 
F. Hoffmann-La Roche Ltd (or under its control) and therefore, is provided to you in confidence as 
an investigator, potential investigator, or consultant, for review by you, your staff, and an 
applicable Ethics Committee or Institutional Review Board. It is understood that this information 
will not be disclosed to others without written authorization from Roche except to the extent 
necessary to obtain informed consent from persons to whom the drug may be administered.
RO7017773 —F. Hoffmann-La Roche Ltd
Protocol BP40950, Version 2
PROTOCOL
TITLE:
A 2 PART, RANDOMIZED, OPEN-LABEL, SINGLE
DOSE, CROSSOVER STUDY TO ASSESS THE 
RELATIVE BIOAVAILABILTY OF PHASE II TABLET 
FORMULATION COMPARED TO THE CURRENT 
PHASE I CAPSULE FORMULATION AND THE 
EFFECT OF FOOD AND TASTE ASSESSMENT ON
THE PHASE II TABLET FORMULATION IN 
HEALTHY PARTICIPANTS
PROTOCOL NUMBER:
BP40950
VERSION:
2
IND NUMBER:
141893
TEST PRODUCT:
RO7017773
SPONSOR:
F. Hoffmann-La Roche Ltd
DATE FINAL:
Version 1: 19 December 2018
DATE AMENDED:
Version 2: See electronic date stamp below
 
26-Feb-2019 17:53:07
Title
Approver's Name
Company Signatory
Date and Time (UTC)
Page 443 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
3/Protocol BP40950, Version 2
PROTOCOL AMENDMENT, BP40950 VERSION 2
RATIONALE
RATIONALE FOR THE AMENDMENT
, additional clarification regarding the participation of women of 
non-childbearing potential and the use of contraception has been added (Section 5.1, 
Inclusion Criteria).
Some inconsistencies in the protocol were also corrected:

Vital signs - it was specified that temperature could be oral or tympanic
(Section 8.2.2)

Meals and study restrictions – duration of fasting was updated to 10 h instead of 8 h 
to be consistent with other parts of the protocol (Section 5.3.1)
New text is shown in italics.
Page 445 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
4/Protocol BP40950, Version 2
PROTOCOL AMENDMENT, BP40950 VERSION 2
SUMMARY OF CHANGES
1.1 Synopsis
The synopsis has been updated to reflect the changes to the protocol
5.1 Inclusion Criteria
Sex
6.
Male and female participants
The contraception and abstinence requirements are intended to prevent exposure of an 
embryo to the study treatment. The reliability of sexual abstinence for male and/or 
female enrollment eligibility needs to be evaluated in relation to the duration of the 
clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are 
not acceptable methods of contraception.
a)
Female Participants
Only women of non-childbearing potential (WONCBP) are allowed to be enrolled in 
this study.
A female participant is eligible to participate if she is not pregnant (see Appendix 5), not 
lactating, and the following condition applies:

Women of non-childbearing potential, as defined in Appendix 5, who have a 
negative pregnancy test (blood) within the 28 days prior to the first study drug 
administration.
Additional contraceptive measures are only required if menopausal status or 
non-childbearing potential is not completely certain. In this instance, one of the 
non-hormonal highly effective contraception methods described in Appendix 5 
should be used during the treatment period and for at least 28 days after the last 
dose of study drug.
b)
Male Participants
During the treatment period and for at least 28 days after the last dose of study drug 
agreement to: 

Remain abstinent (refrain from heterosexual intercourse) or use contraceptive 
measures such as a condom, with partners who are women of childbearing potential 
(WOCBP, as defined in Section 1 of Appendix 5), or pregnant female partners, to 
avoid exposing the embryo.
Page 446 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
5/Protocol BP40950, Version 2

Refrain from donating sperm for at least 28 days after the last dose of study drug.
5.3.1
Meals and Dietary Restrictions
Participants will have to be fasted for at least 4 hours prior to laboratory safety tests at 
screening and the follow-up visit, and for at least 8 hours prior to laboratory safety tests 
performed on Day -1 and Day 3. 
 
 
 
 
Consumption of nutrients known to modulate CYP3A activity (e.g., grapefruit or 
grapefruit juice, Seville orange) will not be permitted within 2 weeks prior to first dosing 
until the safety follow up visit.
Please note that participants should refrain from consumption of any foods containing 
poppy seeds within 48 hours (2 days) prior to screening and each admission to the 
clinical unit to avoid false positive drug screen results.
8.2.2
Vital Signs
Vital signs will include temperature (oral or tympanic), systolic and diastolic blood
pressure and pulse rate. The vital signs will be measured in a supine position after at 
least 5 minutes rest at the time point specified in the SoA table (Section 1.3).
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
When possible, the same arm should be used for all blood pressure measurements.
Page 447 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
6/Protocol BP40950, Version 2
TABLE OF CONTENTS
PROTOCOL ACCEPTANCE FORM .................................................................... 2
1.
PROTOCOL SUMMARY............................................................................. 13
1.1
Synopsis................................................................................ 13
1.2
Schematic of Study Design.................................................... 21
1.3
Schedule of Activities ............................................................ 22
2.
INTRODUCTION ........................................................................................ 25
2.1
Study Rationale ..................................................................... 25
2.2
Background ........................................................................... 25
2.2.1
Background on RO7017773 .................................................. 25
2.2.1.1
Previous and Ongoing Clinical Studies.................................. 26
29
3.
OBJECTIVES AND ENDPOINTS ............................................................... 31
4.
STUDY DESIGN......................................................................................... 33
4.1
Overall Design ....................................................................... 33
4.1.1
Dosing Regimen.................................................................... 33
4.1.2
Length of the Study ............................................................... 34
4.1.3
Individual Stopping Criteria.................................................... 35
4.2
Scientific Rationale for Study Design..................................... 35
4.2.1
Rationale for Study Population .............................................. 35
4.2.2
Rationale for Pharmacokinetic Assessments......................... 35
36
36
4.4
End of Study Definition .......................................................... 37
5.
STUDY POPULATION................................................................................ 37
5.1
Inclusion Criteria.................................................................... 37
5.2
Exclusion Criteria................................................................... 39
5.3
Lifestyle Considerations......................................................... 41
5.3.1
Meals and Dietary Restrictions.............................................. 41
5.3.2
Caffeine, Alcohol, and Tobacco............................................. 41
5.3.3
Activity ................................................................................... 42
Page 448 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
7/Protocol BP40950, Version 2
5.4
Screen Failures ..................................................................... 42
5.5
Recruitment Procedures........................................................ 42
6.
TREATMENTS............................................................................................ 42
6.1
Treatments Administered....................................................... 42
6.2
Preparation/Handling/Storage/Accountability ........................ 44
6.3
Measures to Minimize Bias: Randomization and 
Blinding.................................................................................. 45
6.3.1
Method of Treatment Assignment.......................................... 45
6.3.2
Blinding.................................................................................. 45
6.4
Treatment Compliance .......................................................... 45
6.5
Concomitant Therapy ............................................................ 45
6.5.1
Permitted Therapy................................................................. 45
6.5.2
Prohibited Therapy ................................................................ 46
46
6.7
Treatment after the End of the Study..................................... 46
7.
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL................................. 46
7.1
Discontinuation of Study Treatment....................................... 47
7.2
Participant Discontinuation/Withdrawal from the 
Study ..................................................................................... 47
7.3
Lost to Follow-Up................................................................... 48
8.
STUDY ASSESSMENTS AND PROCEDURES ......................................... 48
8.1
Efficacy Assessments............................................................ 48
8.2
Safety Assessments .............................................................. 48
8.2.1
Physical Examinations........................................................... 48
8.2.2
Vital Signs.............................................................................. 49
8.2.3
Electrocardiograms................................................................ 49
8.2.4
Clinical Safety Laboratory Assessments................................ 50
8.2.5
Medical History and Demographic Data ................................ 51
8.3
Adverse Events and Serious Adverse Events ....................... 51
8.3.1
Time Period and Frequency for Collecting 
Adverse Event and Serious Adverse Event 
Information............................................................................. 51
Page 449 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
8/Protocol BP40950, Version 2
8.3.2
Method of Detecting Adverse Events and Serious 
Adverse Events ..................................................................... 52
8.3.3
Follow-Up of Adverse Events and Serious 
Adverse Events ..................................................................... 52
8.3.3.1
Investigator Follow-Up........................................................... 52
8.3.3.2
Sponsor Follow-Up ................................................................ 53
8.3.4
Regulatory Reporting Requirements for Serious 
Adverse Events ..................................................................... 53
8.3.4.1
Emergency Medical Contacts................................................ 53
8.3.5
Pregnancy ............................................................................. 53
8.3.6
Non-Serious Adverse Events of Special Interest................... 54
8.3.7
Management of Specific Adverse Events .............................. 54
8.4
Treatment of Overdose.......................................................... 54
8.5
Pharmacokinetics .................................................................. 55
8.5.1
Taste Assessment................................................................. 55
8.6
Pharmacodynamics ............................................................... 55
8.7
Genetics ................................................................................ 55
8.8
Biomarkers ............................................................................ 55
8.9
Medical Resource Utilization and Health 
Economics............................................................................. 55
8.10
Timing of Study Assessments ............................................... 56
8.10.1
Screening and Pre-Treatment Assessments ......................... 56
8.10.2
Assessments during Treatment............................................. 56
8.10.3
Follow-Up Assessments ........................................................ 56
9.
STATISTICAL CONSIDERATIONS ............................................................ 57
9.1
Statistical Hypotheses ........................................................... 57
9.2
Sample Size Determination ................................................... 57
9.3
Populations for Analyses ....................................................... 58
9.4
Statistical Analyses................................................................ 58
9.4.1
Demographics and Baseline Characteristics ......................... 58
9.4.2
Safety Analyses..................................................................... 58
9.4.3
Pharmacokinetic Analyses..................................................... 59
9.4.3.1
Pharmacokinetic Parameters................................................. 59
9.5
Statistical Analysis................................................................. 60
Page 450 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
9/Protocol BP40950, Version 2
9.6
Summaries of Conduct of Study............................................ 61
10. REFERENCES ........................................................................................... 61
11. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS.................................................................................... 62
LIST OF TABLES
Table 1
Part 1 – 4 Period Crossover........................................................ 21
Table 2
Part 1 – Randomization to Treatment Sequences ...................... 21
Table 3
Part 2 – 2 Period Crossover........................................................ 21
Table 4
Part 2 – Randomization to Treatment Sequences ...................... 22
Table 5
Schedule of Activities for Part 1 and Part 2................................. 23
Table 6
Objectives and Endpoints ........................................................... 32
Table 7
Summary of Treatments Administered........................................ 43
Table 8
Analysis Populations................................................................... 58
Table 9
Safety Statistical Analysis Methods ............................................ 59
LIST OF APPENDICES
Appendix 1
Regulatory, Ethical, and Study Oversight Considerations........... 63
Appendix 2
Adverse Events: Definitions and Procedures for Evaluating, 
Follow-Up and Reporting ............................................................ 69
Appendix 3
Procedures for Recording Adverse Events ................................. 76
Appendix 4
Clinical Laboratory Tests ............................................................ 81
Appendix 5
Contraceptive Guidance and Collection of Pregnancy 
Information.................................................................................. 83
87
Appendix 7
Correction Formulae for QTc Intervals........................................ 88
Appendix 8
Formula for Calculation of Body Mass Index............................... 89
Page 451 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
10/Protocol BP40950, Version 2
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
AE
Adverse event
ALT
Alanine aminotransferase
aPTT
Activated partial thromboplastin time
ASD
Autism spectrum disorder
AST
Aspartate aminotransferase
AUC
Area under the curve
AUC0-inf
Area under the concentration-time curve from time 0 to 
infinity
BA
Bioavailability
BE
Bioequivalence
BP
Blood pressure
Cavg
Average concentration
Cmax
Maximum serum concentration
CL
Clearance
CL/F
Apparent clearance
CMC
Chemistry manufacturing and control
CNS
Central nervous system
COA
Clinical outcome assessments
CRO
Contract research organization
CSR
Clinical study report
CTCAE
Common terminology criteria for adverse events
DDI
Drug-drug interaction
EC
Ethics Committee
ECG
Electrocardiogram
eCRF
Electronic case report form
EDC
Electronic data capture
EEA
European Economic Area
eCOA
Electronic clinical outcome assessment
ESF
Eligibility screening form
EU
European Commission
FDA
Food and Drug Administration
FSH
Follicle-stimulating hormone
GCP
Good clinical practice
HBsAg
Hepatitis B surface antigen
HBcAb
Total hepatitis B core antibody
HCV
Hepatitis C
Page 452 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
11/Protocol BP40950, Version 2
HDL
High-density lipoproteins
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human immunodeficiency virus
IB
Investigator’s Brochure
ICH
International Council on Harmonisation
IEC
Independent Ethics Committee
IMP
Investigational medicinal product
IND
Investigational New Drug (application)
INR
International normalized ratio
IRB
Institutional Review Board
IRC
Independent Review Committee
IUD
Intrauterine device
IV
Intravenous
LDH
Lactate dehydrogenase
LDL
Low-density lipoproteins
LPLV
Last participant, last visit
LPLO
Last participant, last observation
MAD
Multiple-ascending doses
NOAEL
No-observed-adverse-effect level
NSAESI
Non-serious adverse event of special interest
OTC
Over-the-counter
PD
Pharmacodynamic
PK
Pharmacokinetic
PT
Prothrombin time
QRS
QRS complex
QT
QT interval
QTc
QT corrected for heart rate
QTcF
QT corrected for heart rate using the Fridericia’s 
correction factor
RBC
Red blood cell
RR
RR interval
SAD
Single-ascending dose
SAE
Serious adverse event
SD
Single dose
SoA
Schedule of activities
SOP
Standard operating procedure
SPA
Statistical Programmer
SUSAR
Suspected unexpected serious adverse reactions
Page 453 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
12/Protocol BP40950, Version 2
TSH
Thyroid-stimulating hormone
ULN
Upper limit of normal
US
United States
V
Volume
V/F
Apparent volume of distribution
WOCBP
Woman of Childbearing Potential
WONCBP
Woman of Non-Childbearing Potential
WBC
White blood cell
Page 454 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
14/Protocol BP40950, Version 2
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
PART 1

To assess the relative 
bioavailability of Phase II tablet 
formulation compared to Phase I 
capsule formulation of 
RO7017773 swallowed whole 
under fasting conditions following 
single oral dose administration.

RO7017773 concentrations and 
RO7017773 pharmacokinetics 
(PK) parameters
PART 2

To assess the taste masking of 
RO7017773 Phase II tablet 
formulation containing sweetener 
and flavor dispersed in water and 
the RO7017773 Phase II tablet 
formulation without sweetener 
and flavor dispersed in apple 
juice.

Taste questionnaire
Secondary
PART 1

To assess the PK of RO7017773 
Phase II tablet formulation 
dispersed in water or swallowed 
whole.

RO7017773 concentrations and 
RO7017773 PK parameters

To assess the effect of a high-fat 
meal on the PK of a single oral 
dose of RO7017773 Phase II 
tablet formulation.

RO7017773 concentrations and 
RO7017773 PK parameters

To assess the taste of 
RO7017773 Phase II tablet 
formulation without sweetener 
and flavor dispersed in water.

Taste questionnaire
PART 2

To assess the PK of RO7017773 
Phase II tablet formulation 
containing sweetener and flavor 
dispersed in water and the 
RO7017773 Phase II tablet 
formulation without sweetener 
and flavor dispersed in apple 
juice.

RO7017773 concentrations and 
RO7017773 PK parameters
ALL PARTS

To evaluate the safety and 
tolerability of single oral doses of 
different RO7017773 
formulations in healthy 
participants.

Incidence and severity of AEs.

Changes in vital signs, physical 
findings, ECG parameters, and 
clinical laboratory results during 
and following RO7017773 
administration
OVERALL DESIGN
This is a single-center, randomized, single-dose, open-label, crossover study in healthy 
participants. The study consists of two parts. Part 1 will enroll 16 participants to assess the 
performance of the Phase II tablet formulation as compared to the Phase I capsule formulation 
and a further 8 participants will assess the taste of RO7017773 in Part 2. See below for the 
details of the dosing regimen in both parts.
Page 456 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
15/Protocol BP40950, Version 2
Study Design
The primary objective of Part 1 is to determine the relative bioavailability of the two RO7017773 
formulations; phase I capsule formulation (Treatment A) and phase II tablet formulation 
(Treatment B) administered under fasting conditions. The food effect of the RO7017773 Phase 
II tablet formulation will be explored in Part 1 of the study, in order to understand whether the 
pharmacokinetic properties of the Phase II tablet formulation of RO7017773 are impacted when 
administered under fasting or fed conditions (Treatment C). As per the Food and Drug 
Administration (FDA) Guidance for Industry: Food Effect Bioavailability and Fed Bioequivalence 
Studies, the test meal provided will be a high-fat and high-calorie meal. 
The PK of the Phase II tablet formulation dispersed in water (Treatment D), will be compared 
with the Phase II tablet formulation swallowed in fasted state. Furthermore, a taste assessment 
of the Phase II tablet formulation dispersed in water will be conducted (Treatment D).
All participants in Part 1 will receive all four treatments in a randomized, crossover design. Each 
treatment will be given as a single dose on Day 1 of each Treatment Period.
In Part 2, the taste of the Phase II tablet containing flavor and sweetener dispersed in water will 
be investigated to understand how the taste is perceived (Treatment A). Additionally, the taste 
of the Phase II tablet without sweetener/flavor dispersed in apple juice will be assessed
(Treatment B). A maximum of eight participants will be enrolled in Part 2 of the study. All 
participants in Part 2 will receive both treatments in a randomized, crossover design.
The washout period between each dose in both study parts will be at least 7 to 10 days. 
Participants will have to stay in the clinic from the day before each dosing (Day -1) to Day 3 
after dosing for each Treatment Period. Ambulatory visits on Day 4 and Day 5 after each dosing 
are planned for PK sampling and safety monitoring. Approximately 7 to 14 days after their last 
dose participants will return to the clinic for a final follow-up visit.
Dosing regimen
Following a screening period of up to 4 weeks participants will receive 4 (Part 1) or 2 (Part 2) 
single oral doses of RO7017773. 
The following treatments will be administered in Part 1 (4 period crossover):

Treatment A: Phase I capsule swallowed whole under fasted conditions

Treatment B: Phase II tablet swallowed whole under fasted conditions

Treatment C: Phase II tablet swallowed whole under fed conditions

Treatment D: Phase II tablet dispersed in water under fasted conditions (taste assessment)
The following treatments will be administered in Part 2 (2 period crossover) in different 
participants to Part 1:

Treatment A: Phase II tablet containing flavor and/or sweetener dispersed in water under 
fasted conditions (taste assessment)

Treatment B: Phase II tablet without flavor and/or sweetener dispersed in apple juice under 
fasted conditions (taste assessment)
The Investigational Medicinal Products (IMPs) are RO7017773 Phase I capsules and Phase II 
film coated tablets with a dose strength of 
 mg.
Page 457 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
16/Protocol BP40950, Version 2
Length of Study
Part 1- 4 Period Crossover
The total duration of the study for each participant will be approximately 9 weeks divided as 
follows:

Screening: Up to 4 weeks.

In clinic periods: Day -1 to Day 3 for each of the 4 treatments.

Treatment Periods: Day 1 to Day 5 for each of the 4 treatments (with single dosing on Day 
1 of each period).

Washout period 7 to 10 days (washout period is counted from Day 1 dose, i.e., overlapping 
with treatment period).

Safety follow-up: 7 to 14 days after last dose.
Part 2 – 2 Period Crossover
The total duration of the study for each participant will be approximately 7 weeks divided as 
follows:

Screening: Up to 4 weeks.

In clinic Periods: Day -1 to Day 3 for each of the 2 treatments.

Treatment Periods: Day 1 to Day 5 for each of the 2 treatments (with single dosing on 
Day 1 of each period).

Washout period 7 to 10 days (washout period is counted from Day 1 dose, i.e., overlapping 
with treatment period).

Safety follow-up: 7 to 14 days after last dose.
End of Study
A participant is considered to have completed the study if he/she has completed all treatment 
periods within Part 1 or Part 2 and the safety follow-up visit.
The end of the study is defined as the date when the last participant last observation (LPLO) 
occurs. LPLO is expected to occur approximately 2 weeks after the last participant’s last dose.
PARTICIPANT POPULATION
The participants of this study are healthy participants between 18 and 55 years of age.
Inclusion/Exclusion Criteria
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria are met at 
screening and Day -1.
Informed Consent
1.
Able and willing to provide written informed consent and to comply with the study protocol 
according to International Council on Harmonisation Good Clinical Practice (ICH-GCP) 
guidelines and local regulations.
Age
2.
Participants 18 to 55 years of age inclusive, at the time of signing the informed consent.
Page 458 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
17/Protocol BP40950, Version 2
Type of Participants and Disease Characteristics
3.
Non-smoker for at least six months.
4.
Healthy, as judged by the Investigator.
Healthy status will be defined as the absence of evidence of any active or chronic disease 
following a detailed medical and surgical history, a complete physical examination, vital 
signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis.
Weight
5.
Body mass index (BMI) within the range 18 to 32 kg/m2 (inclusive).
Sex
6.
Male and female participants
The contraception and abstinence requirements are intended to prevent exposure of an embryo 
to the study treatment. The reliability of sexual abstinence for male and/or female enrollment 
eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred 
and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of 
contraception.
a)
Female Participants
Only women of non-childbearing potential (WONCBP) are allowed to be enrolled in this 
study.
A female participant is eligible to participate if she is not pregnant, not lactating, and the following 
condition applies:

Women of non-childbearing potential who have a negative pregnancy test (blood) within the 
28 days prior to the first study drug administration.
b)
Male Participants
During the treatment period and for at least 28 days after the last dose of study drug agreement 
to: 

Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures 
such as a condom, with partners who are women of childbearing potential, or pregnant 
female partners, to avoid exposing the embryo.

Refrain from donating sperm for at least 28 days after the last dose of study drug.
Additional contraceptive measures are only required if menopausal status or non-childbearing 
potential is not completely certain. In this instance, one of the non-hormonal highly effective 
contraception methods described in Appendix 5 should be used during the treatment period and 
for at least 28 days after the last dose of study drug.
Page 459 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
18/Protocol BP40950, Version 2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria are met at screening and 
Day -1.
Medical Conditions
1.
Any condition or disease detected during the medical interview/physical examination that 
would render the participant unsuitable for the study, place the participant at undue risk or 
interfere with the ability of the participant to complete the study, as determined by the 
Investigator.
2.
History or evidence of any medical condition potentially altering the absorption, metabolism or 
elimination of drugs. This includes a surgical history of the gastrointestinal tract affecting 
gastric motility or altering the gastrointestinal tract.
3.
History or evidence of any medical condition that potentially may alter the taste sensory 
perception including ageusia and dysgeusia.
4.
History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, 
neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, 
metabolic disorder, hypofertility, cancer or cirrhosis 
5.
Use of any psychoactive medication, or medications known to have effects on CNS or blood 
flow taken within 30 days prior to first dosing (or within 5 times the elimination half-life of the 
medication prior to first dosing, whichever is longer).
6.
History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, 
or personal history of significant cerebral trauma or CNS infections (e.g. meningitis).
7.
A history of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions.
8.
Any major illness within one month before the screening examination or any febrile illness 
within one week prior to screening and up to first study drug administration.
9.
Abnormal blood pressure, defined as confirmed (based on the average of 3 consecutive 
measurements at screening and Day -1) systolic blood pressure (SBP) greater than 140 or 
less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm 
Hg.
10. Abnormal pulse rate, defined as confirmed (based on the average of 3 consecutive 
measurements at screening and Day -1) resting pulse rate greater than 100 or less than 40 
bpm.
11. History or presence of clinically significant ECG abnormalities before study drug 
administration (e.g. PQ/PR interval ˃ 210 ms, QTcF > 450 ms) or cardiovascular disease (e.g. 
cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, 
family history of congenital long QT syndrome, family history of sudden death).
12. Clinically significant abnormalities in laboratory test results (including hepatic and renal 
panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or 
questionable results, tests performed during screening may be repeated before 
randomization to confirm eligibility.
Page 460 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
19/Protocol BP40950, Version 2
13. ALT and/or bilirubin ˃ 1.5 x ULN (isolated bilirubin ˃ 1.5 x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin ˂ 35%).
14. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones).
15. Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk, or any 
participant with a history of suicidal or homicidal attempts.
Prior/Concomitant Therapy
16. Have used or intend to use over-the-counter or prescription medication including herbal 
medications within 30 days prior to dosing. Specific medications listed under permitted 
medications will be allowed.
17. Participants likely to need concomitant medication during the study period (including for 
dental conditions).
Prior/Concurrent Clinical Study Experience
18. Participation in an investigational drug or device study within 90 days prior to screening, as 
calculated from the day of follow-up from the previous study, or more than 4 participations in 
an investigational drug or device study within a year prior dosing.
Diagnostic Assessments
19. Positive test for drugs of abuse or alcohol.
20. Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV 
antibodies.
21. Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at 
screening or within 3 months prior to starting study treatment.
Other Exclusions
22. Dietary restrictions that would prohibit the consumption of standardized meals.
23. Inability or unwillingness to fully consume standardized breakfast at Day 1 (for Part 1, 
Treatment C only).
24. Consumption of any prohibited food and beverages before study start and during the study.
25. Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of drug of 
abuse or previous history of or treatment for a dependence disorder.
26. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, 
in the opinion of the Investigator, contraindicates the participation in the study.
27. Participants who have donated over 500 mL of blood or blood products or had significant 
blood loss within 3 months prior to screening.
Page 461 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
20/Protocol BP40950, Version 2
NUMBER OF PARTICIPANTS
Part 1:
Sixteen participants will be enrolled in order to obtain at least 12 evaluable participants.
Part 2:
A maximum of 8 participants will be enrolled to assess the taste masking of RO7017773.
CONCOMITANT MEDICATIONS
Permitted Therapy
Use of the following therapies is permitted, as specified below:

Continuation of hormone-replacement therapy is permitted throughout the study for 
participants who already use them.

Acetaminophen/paracetamol is allowed up to a maximum dose of 2 g/day up to 48 hours 
prior to dosing and after the in-house period, but should not exceed 4 g total during the 
week prior to dosing.
Prohibited Therapy
As a general rule, no concomitant medication will be permitted, with the exception of 
medications to treat AEs and medications listed permitted medication, unless the rationale for 
exception is discussed and clearly documented between the Investigator and the Sponsor.
Use of the following therapies is prohibited during the study and for at least 30 days or at least 
5 half-lives prior to initiation of study treatment, unless otherwise specified below:

Any prescribed or over-the-counter medication (including herbal products, vitamin, mineral,
energy drinks and dietary supplements), unless specified in Section 6.5.1.

Any known inhibitor of CYP3A4 or P-glycoprotein taken within 4 weeks prior to start of 
administration of study drug (Day 1) or within 5 times the elimination half-life of the 
medication prior to start of study drug intake (whichever is longer) including but not limited 
to the following drugs: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin 
nefazodone, diltiazem and verapamil.

Any known inducer of CYP3A4 or P-glycoprotein taken within 2 weeks prior to start of 
administration of study drug (Day 1), including but not limited to the following drugs: 
rifampicin, rifabutin, glucocorticoids, carbamazepine, oxcarbazepine, phenytoin, 
phenobarbital, and St. John’s Wort. 
Page 462 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
21/Protocol BP40950, Version 2
1.2
SCHEMATIC OF STUDY DESIGN
The study is designed in two parts. Part 1 is described in Table 1 and Table 2. Part 2 is 
described in Table 3 and Table 4.
Table 1
Part 1 – 4 Period Crossover
Screening
Periods Treatment A – D*
Follow-up
Day -28 to Day -2

Randomization to treatment sequence prior to 
first period 

Dosing on Day 1 with PK sampling up to Day 5

Total of 7-10 days between each period including 
washout 
7 to 14 days after 
last dose
*Treatment A: Phase I capsule swallowed whole under fasted conditions
Treatment B: Phase II tablet swallowed whole under fasted conditions
Treatment C: Phase II tablet swallowed whole under fed conditions
Treatment D: Phase II tablet dispersed in water under fasted conditions including taste 
assessment
Prior to the first dosing, participants of Part 1 will be randomized to one of the four 
treatment sequences from a 4-period Williams Latin Square as defined in Table 2.
Table 2
Part 1 – Randomization to treatment sequences
Treatment 
Sequence
Period 1
Period 2
Period 3
Period 4
1
A
B
C
D
2
B
D
A
C
3
C
A
D
B
4
D
C
B
A
Table 3
Part 2 – 2 Period Crossover
Screening
Periods Treatment A – B*
Follow-up
Day -28 to Day -2

Randomization to treatment sequence prior to 
first Period 

Dosing on Day 1 with PK sampling up to Day 5

Total of 7-10 days between each period including 
washout 
7 to 14 days after 
last dose
*Treatment A: Phase II tablet containing flavor and/or sweetener dispersed in water under fasted 
conditions including taste assessment
Treatment B: Phase II tablet without flavor and/or sweetener dispersed in apple juice under 
fasted conditions including taste assessment
Page 463 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
22/Protocol BP40950, Version 2
Prior to the first dosing, participants of Part 2 will be randomized to one of the two 
treatment sequences as defined in Table 4.
Table 4
Part 2 – Randomization to treatment sequences
Treatment 
Sequence
Period 1
Period 2
1
A
B
2
B
A
For details of the dosing regimen in Part 1 and Part 2, see Section 4.1.1
1.3
SCHEDULE OF ACTIVITIES
The schedule of the activities is provided in Table 5.
Page 464 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
23/Protocol BP40950, Version 2
Table 5
Schedule of Activities for Part 1 and Part 2
Day
Day -1
Day 3
Day 4
Day 5
Scheduled Time 
Up to
-28 days
Informed Consent
x
Demography
x
Medical History 
x
Inclusion/exclusion 
criteria review
x
x
Physical Examination a
x
x
x
x
In-house Period
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Ambulatory visit
x
x
x
Discharge from unit
x
Vital Signs b
x
x
x
x
x
x
ECG-12 lead c
x
x
x
x
x
x
x
x
x
x
x
x
x
Serology
x
Pregnancy Test d
x
x
x
Hormone Panel e
x
Alcohol Breath Test
x
x
Urine Cotinine Test
x
x
Urine Drugs of abuse
x
x
Urinalysis
x
x
x
x
Blood Chemistry
x
x
x
x
Hematology
x
x
x
x
Coagulation
x
Randomizationf
x
Administration of Study 
Medication g
x
Standard Meal h
xi
x
x
x
x
Previous and 
Concomitant 
Treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Adverse Events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Day 1
Day 2
Follow Up 
Visitk
Screening
Study Days in Each Period 
Page 465 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
24/Protocol BP40950, Version 2
Table 5
Schedule of Activities for Part 1 and Part 2 (cont.)
a)
Physical examination will include body weight at screening and follow-up, and height at screening when BMI will be derived.
b)
Vital signs will include blood pressure, pulse rate and body temperature.  Temperature will be recorded at screening, Day 1 predose 
and follow-up. All measurements will be taken after the subject has rested in a supine position for at least 5 min. 
c)
Triplicate 12-lead ECGs will be collected after the subject has rested in a supine position for at least 10 min.
d)
Pregnancy test for females.  Serum test at screening, urine test at Day -1.
e)
Hormonal panel for postmenopausal women only.
f)
Randomization only in Period 1 of each Part
g)
 
 
h)
 
 
i)
 
 
k)
The follow up visit is 7 to 14 days after the last dosing.
Page 466 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
27/Protocol BP40950, Version 2
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Page 469 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
28/Protocol BP40950, Version 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 470 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
29/Protocol BP40950, Version 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Further information regarding pre-clinical drug metabolism, pharmacokinetics, safety and 
toxicology, and results from clinical studies with RO7017773 can be found in the 
Investigator’s Brochure (IB). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 471 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
30/Protocol BP40950, Version 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 472 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
31/Protocol BP40950, Version 2
 
 
 
3.
OBJECTIVES AND ENDPOINTS
The objectives and corresponding endpoints are provided in Table 6.
Page 473 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
32/Protocol BP40950, Version 2
Table 6
Objectives and Endpoints
Objectives
Endpoints
Primary
PART 1

To assess the relative 
bioavailability of Phase II tablet 
formulation compared to Phase I 
capsule formulation of 
RO7017773 swallowed whole 
under fasting conditions following 
single oral dose administration.

RO7017773 concentrations and 
RO7017773 pharmacokinetics 
(PK) parameters
PART 2

To assess the taste masking of 
RO7017773 Phase II tablet 
formulation containing sweetener 
and flavor dispersed in water and 
the RO7017773 Phase II tablet 
formulation without sweetener 
and flavor dispersed in apple 
juice.

Taste questionnaire
Secondary
PART 1

To assess the PK of RO7017773 
Phase II tablet formulation 
dispersed in water or swallowed 
whole.

RO7017773 concentrations and 
RO7017773 PK parameters

To assess the effect of a high-fat 
meal on the PK (PK) of a single 
oral dose of RO7017773 Phase II 
tablet formulation.

RO7017773 concentrations and 
RO7017773 PK parameters

To assess the taste of 
RO7017773 Phase II tablet 
formulation without sweetener 
and flavor dispersed in water.

Taste questionnaire
PART 2

To assess the PK of RO7017773 
Phase II tablet formulation 
containing sweetener and flavor 
dispersed in water and the 
RO7017773 Phase II tablet 
formulation without sweetener 
and flavor dispersed in apple 
juice.

RO7017773 concentrations and 
RO7017773 PK parameters
ALL PARTS

To evaluate the safety and 
tolerability of single oral doses of 
different RO7017773 
formulations in healthy 
participants.

Incidence and severity of AEs.

Changes in vital signs, physical 
findings, ECG parameters, and 
clinical laboratory results during 
and following RO7017773 
administration
Tertiary/Exploratory
ALL PARTS

To screen for the presence of 
RO7017773-derived metabolites.

PK concentrations of 
RO7017773-derived metabolites, 
if appropriate.

To assess the relative 
abundance and PK parameters 
of any metabolite as appropriate 

PK concentrations of 
RO7017773-derived metabolites, 
if appropriate.
Page 474 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
33/Protocol BP40950, Version 2
4.
STUDY DESIGN
4.1
OVERALL DESIGN
An overview of the study design is provided in Section 1.2.
This is a single-center, randomized, single-dose, open-label, crossover study in healthy 
participants. The study consists of two parts. Part 1 will enroll 16 participants to assess 
the performance of the Phase II tablet formulation as compared to the Phase I capsule 
formulation and a further eight participants will assess the taste of RO7017773 in Part 2. 
See Section 4.1.1 for the details of the dosing regimen in both parts.
The primary objective of Part 1 is to determine the relative bioavailability of the two 
RO7017773 formulations administered under fasting conditions; Phase I capsule 
formulation (Treatment A) and Phase II tablet formulation (Treatment B). The food effect 
of the RO7017773 Phase II tablet formulation will be explored in Part 1 of the study, in 
order to understand whether the pharmacokinetic properties of the Phase II tablet 
formulation of RO7017773 are impacted when administered under fasting or fed 
conditions (Treatment C). As per the Food and Drug Administration (FDA) Guidance for 
Industry: Food Effect Bioavailability and Fed Bioequivalence Studies, the test meal 
provided will be a high-fat and high-calorie meal (FDA 2002). The PK of the Phase II 
tablet formulation dispersed in water (Treatment D), will be compared with the Phase II 
tablet formulation swallowed in fasted state. Furthermore, a taste assessment of the 
Phase II tablet formulation dispersed in water will be conducted (Treatment D).
All participants in Part 1 will receive all four treatments in a randomized, crossover 
design. Each treatment will be given as a single dose on Day 1 of each Treatment 
Period.
In Part 2, the taste of the Phase II tablet containing flavor and sweetener dispersed in 
water (Treatment A) will be investigated to understand how the taste is perceived. 
Additionally, the taste of the Phase II tablet without sweetener/flavor dispersed in apple 
juice will be assessed (Treatment B). A maximum of eight participants will be enrolled in 
Part 2 of the study. All participants in Part 2 will receive both treatments in a randomized, 
crossover design.
The washout period between each dose in both study parts will be at least 7 to 10 days. 
Participants will have to stay in the clinic from the day before each dosing (Day -1) to 
Day 3 after dosing for each Treatment Period. Ambulatory visits on Day 4 and Day 5
after each dosing are planned for PK sampling and safety monitoring. Approximately 7 to 
14 days after their last dose participants will return to the clinic for a final follow-up visit.
4.1.1
Dosing regimen
Following a screening period of up to 4 weeks participants will receive 4 (Part 1) or 2 
(Part 2) single oral doses of RO7017773. 
Page 475 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
34/Protocol BP40950, Version 2
The following treatments will be administered in Part 1 (4 period crossover):

Treatment A: Phase I capsule swallowed whole under fasted conditions

Treatment B: Phase II tablet swallowed whole under fasted conditions

Treatment C: Phase II tablet swallowed whole under fed conditions

Treatment D: Phase II tablet dispersed in water under fasted conditions (taste 
assessment)
The following treatments will be administered in Part 2 (2 period crossover) in different 
participants to Part 1:

Treatment A: Phase II tablet containing flavor and/or sweetener dispersed in water 
under fasted conditions (taste assessment)

Treatment B: Phase II tablet without flavor and/or sweetener dispersed in apple 
juice under fasted conditions (taste assessment)
4.1.2
Length of the Study
Part 1- 4 Period Crossover
The total duration of the study for each participant will be approximately 9 weeks divided 
as follows:

Screening: Up to 4 weeks.

In clinic periods: Day -1 to Day 3 for each of the 4 treatments.

Treatment Periods: Day 1 to Day 5 for each of the 4 treatments (with single dosing 
on Day 1 of each period).

Washout period 7 to 10 days (washout period is counted from Day 1 dose, 
i.e., overlapping with treatment period).

Safety follow-up: 7 to 14 days after last dose.
Part 2 – 2 Period Crossover
The total duration of the study for each participant will be approximately 7 weeks divided 
as follows:

Screening: Up to 4 weeks.

In clinic Periods: Day -1 to Day 3 for each of the 2 treatments.

Treatment Periods: Day 1 to Day 5 for each of the 2 treatments (with single dosing 
on Day 1 of each period).

Washout period 7 to 10 days (washout period is counted from Day 1 dose, 
i.e., overlapping with treatment period).

Safety follow-up: 7 to 14 days after last dose.
Page 476 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
35/Protocol BP40950, Version 2
4.1.3
Individual Stopping Criteria
Dosing will be stopped at any time during the study in a given individual participant if one 
of the following circumstances occurs, unless it is determined by the Investigator that the 
occurrence is not related to the administration of the study drug:

a serious adverse event 

one (or more) severe adverse events

clinically significant changes in vital signs or ECG, such as a QTcF > 480 ms (if 
confirmed by repeated measurement within 30 minutes) or QTcF change-from-
baseline > 60 ms (if confirmed by repeated measurement within 30 minutes)

an elevation of ALT > 3 x ULN, with an associated increase in bilirubin > 2 x ULN 
and with ALP ˃ 2 ULN, in the absence of an alternative explanation

other findings, that at the joint discretion of the sponsor clinical pharmacologist, 
the sponsor safety science leader and the investigator, indicate that dosing in this 
individual should be stopped  
4.2
SCIENTIFIC RATIONALE FOR STUDY DESIGN
The study rationale is provided in Section 2.1.
A crossover design is used in each study part to reduce the residual variability as every 
subject acts as their own control. Subjects will be randomized to treatment sequences in 
each study part to minimize assignment bias. A washout of at least 7 days between 
RO7017773 doses is considered sufficient to prevent carryover effects of the treatments.
4.2.1
Rationale for Study Population
The participants of this study are healthy males and women of non-childbearing potential
(WONCBP) aged 18 to 55 years (inclusive), chosen because of the absence of 
confounding diseases, which will enable a clearer and more consistent assessment of 
drug disposition and safety profile. 
 
4.2.2
Rationale for Pharmacokinetic Assessments
The investigation of relative bioavailability of the Phase II tablet formulation compared to 
the Phase I capsule formulation is the primary objective of the study. Pharmacokinetic 
assessments of RO7017773 will be performed in plasma. The timings of PK samples 
collection are based on PK modelling and on observed PK data collected in study 
BP40091 and are considered adequate to allow for the characterization of the absorption, 
distribution and elimination phases RO7017773 following a single oral dose of the Phase 
I capsule and Phase II tablet formulation. Sample collection up to Day 5 is considered to 
be sufficient to allow for a reasonable estimation of the half-life of RO7017773.
Plasma PK samples may also be screened for exploratory RO7017773 metabolite 
identification with the use of non-validated methods to allow for an early identification of 
Page 477 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
37/Protocol BP40950, Version 2
4.4
END OF STUDY DEFINITION
A participant is considered to have completed the study if he/she has completed all 
treatment periods within Part 1 or Part 2 and the safety follow-up visit.
The end of the study is defined as the date when the last participant last observation 
(LPLO) occurs. LPLO is expected to occur approximately 2 weeks after the last 
participant’s last dose.
5.
STUDY POPULATION
The study population rationale is provided in Section 4.2.1.
The participants of this study are healthy participants between 18 and 55 years of age, 
inclusive, who fulfill all the inclusion criteria listed in Section 5.1 and none of the 
exclusion criteria listed in Section 5.2.
Prospective approval of protocol deviations from recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1
INCLUSION CRITERIA
Participants are eligible to be included in the study only if all of the following are met at 
screening and Day -1:
Informed Consent
1.
Able and willing to provide written informed consent and to comply with the study 
protocol according to International Conference on Harmonisation Good Clinical 
Practice (ICH-GCP) guidelines and local regulations.
Age
2.
Participants 18 to 55 years of age inclusive, at the time of signing the informed 
consent.
Type of Participants and Disease Characteristics
3.
Non-smoker for at least six months.
4.
Healthy, as judged by the Investigator.
Healthy status will be defined as the absence of evidence of any active or chronic
disease following a detailed medical and surgical history, a complete physical
examination, vital signs, 12-lead ECG, hematology, blood chemistry, serology and
urinalysis.
Weight
5.
Body mass index (BMI) within the range 18 to 32 kg/m2 (inclusive).
Page 479 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
38/Protocol BP40950, Version 2
Sex
6.
Male and female participants
The contraception and abstinence requirements are intended to prevent exposure of an 
embryo to the study treatment. The reliability of sexual abstinence for male and/or 
female enrollment eligibility needs to be evaluated in relation to the duration of the 
clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence 
(e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are 
not acceptable methods of contraception.
a)
Female Participants
Only women of non-childbearing potential (WONCBP) are allowed to be enrolled in 
this study.
A female participant is eligible to participate if she is not pregnant (see Appendix 5), not 
lactating, and the following condition applies:

Women of non-childbearing potential, as defined in Appendix 5, who have a 
negative pregnancy test (blood) within the 28 days prior to the first study drug 
administration.
Additional contraceptive measures are only required if menopausal status or 
non-childbearing potential is not completely certain. In this instance, one of the 
non-hormonal highly effective contraception methods described in Appendix 5 
should be used during the treatment period and for at least 28 days after the last 
dose of study drug.
b)
Male Participants
During the treatment period and for at least 28 days after the last dose of study drug 
agreement to:

Remain abstinent (refrain from heterosexual intercourse) or use contraceptive 
measures such as a condom, with partners who are women of childbearing potential 
(WOCBP, as defined in Section 1 of Appendix 5), or pregnant female partners, to 
avoid exposing the embryo.

Refrain from donating sperm for at least 28 days after the last dose of study drug.
Page 480 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
39/Protocol BP40950, Version 2
5.2
EXCLUSION CRITERIA
Participants are excluded from the study if any of the following are met at screening and 
Day -1:
Medical Conditions
1. Any condition or disease detected during the medical interview/physical examination 
that would render the participant unsuitable for the study, place the participant at 
undue risk or interfere with the ability of the participant to complete the study, as 
determined by the Investigator.
2. History or evidence of any medical condition potentially altering the absorption, 
metabolism or elimination of drugs. This includes a surgical history of the 
gastrointestinal tract affecting gastric motility or altering the gastrointestinal tract.
3. History or evidence of any medical condition that potentially may alter the taste 
sensory perception including ageusia and dysgeusia.
4. History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, 
neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic 
disease, metabolic disorder, hypofertility, cancer or cirrhosis 
5. Use of any psychoactive medication, or medications known to have effects on CNS 
or blood flow taken within 30 days prior to first dosing (or within 5 times the 
elimination half-life of the medication prior to first dosing, whichever is longer).
6. History of convulsions (other than benign febrile convulsions of childhood) including 
epilepsy, or personal history of significant cerebral trauma or CNS infections (e.g. 
meningitis).
7. A history of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic 
reactions.
8. Any major illness within one month before the screening examination or any febrile 
illness within one week prior to screening and up to first study drug administration.
9. Abnormal blood pressure, defined as confirmed (based on the average of 
3 consecutive measurements at screening and Day -1) systolic blood pressure 
(SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) 
greater than 90 or less than 50 mm Hg.
10. Abnormal pulse rate, defined as confirmed (based on the average of 3 consecutive 
measurements at screening and Day -1) resting pulse rate greater than 100 or less 
than 40 bpm.
11. History or presence of clinically significant ECG abnormalities before study drug 
administration (e.g. PQ/PR interval ˃ 210 ms, QTcF > 450 ms) or cardiovascular 
disease (e.g. cardiac insufficiency, coronary artery disease, cardiomyopathy, 
congestive heart failure, family history of congenital long QT syndrome, family history 
of sudden death).
12. Clinically significant abnormalities in laboratory test results (including hepatic and 
renal panels, complete blood count, chemistry panel and urinalysis). In the case of 
Page 481 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
40/Protocol BP40950, Version 2
uncertain or questionable results, tests performed during screening may be repeated 
before randomization to confirm eligibility.
13. ALT and/or bilirubin ˃ 1.5 x ULN (isolated bilirubin ˃ 1.5 x ULN is acceptable if 
bilirubin is fractionated and direct bilirubin ˂ 35%).
14. Current or chronic history of liver disease, or known hepatic or biliary abnormalities 
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
15. Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk, or 
any participant with a history of suicidal or homicidal attempts.
Prior/Concomitant Therapy
16. Have used or intend to use over-the-counter or prescription medication including 
herbal medications within 30 days prior to dosing. Specific medications listed in 
Section 6.5.1 will be allowed.
17. Participants likely to need concomitant medication during the study period (including 
for dental conditions).
Prior/Concurrent Clinical Study Experience
18. Participation in an investigational drug or device study within 90 days prior to 
screening, as calculated from the day of follow-up from the previous study, or more 
than 4 participations in an investigational drug or device study within a year prior 
dosing.
Diagnostic Assessments
19. Positive test for drugs of abuse or alcohol.
20. Show evidence of human immunodeficiency virus (HIV) infection and/or positive 
human HIV antibodies.
21. Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test 
result at screening or within 3 months prior to starting study treatment.
Other Exclusions
22. Dietary restrictions that would prohibit the consumption of standardized meals.
23. Consumption of any prohibited food and beverages before study start and during the 
study (see Section 5.3).
24. Inability or unwillingness to fully consume standardized breakfast at Day 1 (for Part 1, 
Treatment C only).
25. Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of 
drug of abuse or previous history of or treatment for a dependence disorder.
26. Sensitivity to any of the study treatments, or components thereof, or drug or other 
allergy that, in the opinion of the Investigator, contraindicates the participation in the 
study.
Page 482 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
41/Protocol BP40950, Version 2
27. Participants who have donated over 500 mL of blood or blood products or had 
significant blood loss within 3 months prior to screening.
5.3
LIFESTYLE CONSIDERATIONS
5.3.1
Meals and Dietary Restrictions
Participants will have to be fasted for at least 4 hours prior to laboratory safety tests at 
screening and the follow-up visit, and for at least 8 hours prior to laboratory safety tests 
performed on Day -1 and Day 3. 
 
 
 
 
Consumption of nutrients known to modulate CYP3A activity (e.g., grapefruit or 
grapefruit juice, Seville orange) will not be permitted within 2 weeks prior to first dosing 
until the safety follow up visit.
Please note that participants should refrain from consumption of any foods containing 
poppy seeds within 48 hours (2 days) prior to screening and each admission to the 
clinical unit to avoid false positive drug screen results.
5.3.2
Caffeine, Alcohol, and Tobacco
The consumption of food and beverages containing caffeine or other methylxanthine-
containing products (e.g., tea, coffee, caffeinated soft drinks, cola, chocolate) will not be 
permitted from 48 hours before each dosing until the end of each residential period. 
During the period from screening to the follow-up visit when participants are not resident 
in the unit, participants will be asked to limit coffee or tea consumption to no more than 
3 cups per day, and methylxanthine-containing products (e.g. cola and chocolate) must 
be limited to a maximum of 1 L per day.
Consumption of alcohol will not be allowed from 48 hours before each dosing until the 
end of each residential period and participants will be asked to limit alcohol to a 
maximum of 2 units/day (1 unit equates to approximately 330 mL beer, 125 mL of wine 
or 25 mL of spirits) during the out-clinic period until follow-up.
Page 483 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
42/Protocol BP40950, Version 2
Smoking is not permitted. For inclusion into this study, participants must be non-smokers. 
5.3.3
Activity
Participants should refrain from strenuous exercise from at least 96 hours prior to each 
admission to the clinical research unit until discharge from the unit and from 96 hours 
prior to the follow-up visit. The level of activities should be kept as similar as possible on 
all study days until the follow-up visit.
In addition, any participants who experience severe drowsiness or somnolence during 
their in-clinic stay will be advised to limit driving or operating dangerous machinery in the 
3 days after discharge.
5.4
SCREEN FAILURES
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized to study treatment/entered in the study.
The Investigator will maintain a screening log to record details of all participants 
screened and to confirm eligibility or record reasons for screening failure.
Individuals who do not meet the criteria for participation in this study (screen failure) will 
not be re-screened, unless agreed with the Sponsor. A repeat of a screening laboratory 
test because of uncertain or questionable results during screening is not considered a 
re-screening.
5.5
RECRUITMENT PROCEDURES
Participants will be identified for potential recruitment using pre-screening enrollment 
logs, clinical database and IEC/IRB approved newspaper/radio/social-media
advertisements prior to consenting to take place on this study.
6.
TREATMENTS
Study treatment is defined as any investigational treatment(s) intended to be 
administered to a study participant according to the study protocol.
All investigational medicinal products (IMPs) required for completion of this study 
(RO7017773 Phase I capsules and Phase II tablets) will be provided by the Sponsor. All 
study drug administration will be done at the study center under supervision of site staff.
6.1
TREATMENTS ADMINISTERED
Table 7 summarizes the treatments administered. Please see the Investigator’s 
Brochure and Pharmacy Manual for more details.
Page 484 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
44/Protocol BP40950, Version 2
6.2
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY
Study drug packaging will be overseen by the Roche clinical trial supplies department 
and bear a label with the identification required by local law, the protocol number, drug 
identification and dosage.
The packaging and labeling of the study medication will be in accordance with Roche 
standard and local regulations.
The investigational site will acknowledge receipt of IMPs and confirm the shipment
condition and content. Any damaged shipments will be replaced.
Upon arrival of the IMPs at the site, site personnel will complete the following:

Check the IMPs for damage.

Verify proper identity, quantity, integrity of seals and temperature conditions.

Report any deviations or product complaints to the Monitor upon discovery.
The qualified individual responsible for dispensing the study treatment will prepare the 
correct dose according to the treatment assignment schedule.
The Investigator or delegate must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are 
reported and resolved before use of the study treatment.
Only participants enrolled in the study may receive study treatment and only authorized 
site staff may supply or administer study treatment. All study treatments must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the Investigator 
and authorized site staff.
The Investigator, Institution, or the Head of the Medical Institution (where applicable) is
responsible for study treatment accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation and final disposition records).
IMPs will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure (SOP) or returned to the Sponsor with the appropriate 
documentation. The site's method of IMP destruction must be agreed upon by the 
Sponsor. Local or institutional regulations may require immediate destruction of used 
IMP for safety reasons. The site must obtain written authorization from the Sponsor 
before any IMP is destroyed, and IMP destruction must be documented on the 
appropriate form.
Further guidance and information for the final disposition of unused study treatment are 
provided in the Pharmacy Manual. 
Page 486 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
45/Protocol BP40950, Version 2
6.3
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND 
BLINDING
6.3.1
Method of Treatment Assignment
Study is open-label. The randomization numbers will be generated by the Sponsor or its 
designee.
To minimize the carryover effects, a Williams Latin Square design is used to assign 
participants to four different sequences in Part 1 (Table 1 and Table 2 and two different 
sequences in Part 2 (Table 3 and Table 4).
The randomization list will be made available to the Pharmacist preparing the study 
treatment (if necessary), to the individual responsible for PK sample bioanalysis (and PD 
bioanalysis, if appropriate) and to statisticians or programmers at Roche.
6.3.2
Blinding
This is an open-label study, blinding procedures are not applicable.
6.4
TREATMENT COMPLIANCE
The qualified individual responsible for dispensing the study treatment will prepare the 
correct dose according to the randomization schedule. This individual will write the date 
dispensed and participant number on the study treatment vial label and on the Drug 
Accountability Record. This individual will also record the study treatment received by 
each participant during the study.
6.5
CONCOMITANT THERAPY
Any medication or vaccine (including over the counter [OTC] or prescription medicines, 
approved dietary and herbal supplements, nutritional supplements) used by a participant 
from 4 weeks prior to screening until the follow-up visit must be recorded along with 
reason for use, dates of administration (including start and end dates) and dosage 
information (including dose and frequency).
All concomitant medications should be reported to the Investigator and recorded on the 
Concomitant Medications electronic Case Report Form (eCRF).
6.5.1
Permitted Therapy
Use of the following therapies is permitted, as specified below:
•
Continuation of hormone-replacement therapy is permitted throughout the study for 
participants who already use them.
•
Acetaminophen/paracetamol is allowed up to a maximum dose of 2 g/day up to 48 
hours prior to dosing and after the in-house period, but should not exceed 4 g total 
during the week prior to dosing.
Page 487 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
46/Protocol BP40950, Version 2
All therapy and/or medication administered to manage adverse events should be 
recorded on the Adverse Event eCRF.
6.5.2
Prohibited Therapy
All medications (prescription and OTC) taken within 30 days of study screening must be
recorded on the appropriate eCRF.
As a general rule, no concomitant medication will be permitted, with the exception of 
medications to treat AEs and medications listed in Section 6.5.1, unless the rationale for 
exception is discussed and clearly documented between the Investigator and the 
Sponsor.
Use of the following therapies is prohibited during the study and for at least 30 days or at 
least 5 half-lives prior to initiation of study treatment, unless otherwise specified below:

Any prescribed or over-the-counter medication (including herbal products, vitamin, 
mineral, energy drinks and dietary supplements), unless specified in Section 6.5.1.

Any known inhibitor of CYP3A4 or P-glycoprotein taken within 4 weeks prior to start 
of administration of study drug (Day 1) or within 5 times the elimination half-life of 
the medication prior to start of study drug intake (whichever is longer) including but 
not limited to the following drugs: ketoconazole, itraconazole, fluconazole, 
erythromycin, clarithromycin, mifebradil, nefazodone, diltiazem, verapamil and 
cimetidine.

Any known inducer of CYP3A4 or P-glycoprotein taken within 2 weeks prior to start 
of administration of study drug (Day 1), including but not limited to the following 
drugs: rifampicin, rifabutin, glucocorticoids, carbamazepine, oxcarbazepine, 
phenytoin, phenobarbital, and St. John’s Wort. 
6.6
DOSAGE MODIFICATION
RO7017773 will be administered as a single dose of 
 mg on Day 1 of each treatment 
period therefore dose modification is not applicable to this study. 
 
6.7
TREATMENT AFTER THE END OF THE STUDY
The Sponsor does not intend to provide RO7017773 or other study interventions to 
participants after conclusion of the study.
7.
DISCONTINUATION OF STUDY TREATMENT AND
PARTICIPANT DISCONTINUATION/WITHDRAWAL
An excessive rate of withdrawals (either participants discontinuing study treatment or 
withdrawing from the study) can render the study non-interpretable. Therefore, 
unnecessary withdrawal of participants should be avoided and efforts should be taken to 
Page 488 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
47/Protocol BP40950, Version 2
motivate participants to comply with all the study specific procedures as outlined in this 
protocol.
Details on study and site closures are provided in Appendix 1 Study Governance 
Considerations Study.
7.1
DISCONTINUATION OF STUDY TREATMENT
See the SoA (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that need to be completed.
Discontinuation of study intervention for abnormal liver function should be considered by 
the Investigator when a participant meets one of the conditions outlined (Section 6,
Appendix 3) or if the Investigator believes that it is in best interest of the participant.
Participants who discontinue study treatment prematurely will be asked to return to the 
clinic for a study completion visit and may undergo follow‑up assessments (see 
Section 8.10.3). The primary reason for premature study treatment discontinuation 
should be documented on the appropriate eCRF. Participants who discontinue study 
treatment prematurely may be replaced Participants who discontinue study treatment
due to safety reasons will not be replaced.
7.2
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE 
STUDY
Participants have the right to voluntarily withdraw from the study at any time for any 
reason.
In addition, the Investigator has the right to withdraw a participant from the study for 
medical conditions, circumstances that augment a subject’s risk, subject noncompliance, 
or any other unforeseen issues that the Investigator or Sponsor determines , may 
adversely influence the participant’s safety or data integrity if he/she continues in the 
study.
If possible, information on reason for withdrawal from the study should be obtained. The 
primary reason for withdrawal from the study should be documented on the appropriate 
eCRF. Participants will not be followed for any reason after consent has been withdrawn.
When a participant voluntarily withdraws from the study, or is withdrawn by the 
Investigator, samples collected until the date of withdrawal will be analyzed, unless the 
participant specifically requests for these to be discarded or local laws require their 
immediate destruction. However, if samples have been tested prior to withdrawal, results 
from those tests will remain as part of the overall research data. 
Participants who withdraw from the study for safety reasons will not be replaced. 
Participants who withdraw from the study for other reasons may be replaced.
Page 489 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
48/Protocol BP40950, Version 2
Replacement of participants for other reasons will be discussed between the Investigator 
and the Sponsor, based on existing data.
7.3
LOST TO FOLLOW-UP
A participant will be considered lost to follow-up if the participant repeatedly fails to
return for scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study.

Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant. These contact attempts 
should be documented in the participant’s medical record.

Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study.
Discontinuation of sites or of study as a whole are handled as part of Appendix 1.
8.
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and their time-points are summarized in the Schedules of Activities 
(SoA; Section 1.3). Protocol waivers or exemptions are not allowed.
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study treatment.
Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of the Informed Consent Form (ICF) may 
be utilized for screening or baseline purposes provided the procedure met the 
protocol-specified criteria and were performed within the time-frame defined in the SoA.
8.1
EFFICACY ASSESSMENTS
Efficacy parameters will not be evaluated in this study.
8.2
SAFETY ASSESSMENTS
Planned time-points for all safety assessments are provided in the SoA (Section 1.3).
8.2.1
Physical Examinations
A complete physical examination will be performed at the times indicated in the SoA 
(Section 1.3) and include, at a minimum, assessments of the cardiovascular, respiratory, 
Page 490 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
49/Protocol BP40950, Version 2
gastrointestinal, dermatological and neurological, musculoskeletal in addition to head, 
eyes, ears, nose, throat, neck and lymph nodes systems. Further examination of other 
body systems may be performed in case of evocative symptoms at the Investigator’s 
discretion. Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
Height will be recorded at screening and body weight will be recorded at screening and 
at follow-up. The BMI will be calculated from the screening measurements using the 
formula in Appendix 8. 
Any abnormality identified at baseline should be recorded on the General Medical
History and Baseline Conditions eCRF. 
At all other visits (or as clinically indicated), limited, symptom-based physical 
examinations should be performed. Changes from baseline abnormalities should be 
recorded in participant’s notes. New or worsened clinically significant abnormalities 
should be recorded as adverse events on the Adverse Event eCRF.
8.2.2
Vital Signs
Vital signs will include temperature (oral or tympanic), systolic and diastolic blood
pressure and pulse rate. The vital signs will be measured in a supine position after at 
least 5 minutes rest at the time point specified in the SoA table (Section 1.3).
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
When possible, the same arm should be used for all blood pressure measurements.
8.2.3
Electrocardiograms
Triplicate 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures QRS complex, 
PR, QT, and QTc intervals. 
At each time-point at which triplicate ECGs are required, three individual ECG tracings 
should be obtained as closely as possible in succession, but no more than 2 minutes 
apart. The full set of triplicates should be completed in less than 5 minutes.
To minimize variability, it is important that participants be in a resting position for at least 
10 minutes prior to each ECG evaluation. Body position should be consistently 
maintained for each ECG evaluation to prevent changes in heart rate. Environmental 
distractions (e.g., television, radio, conversation) should be avoided during the pre-ECG 
resting period and during ECG recording.
ECGs should be performed prior to meals and blood draws as appropriate.
Page 491 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
50/Protocol BP40950, Version 2
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. 
For safety monitoring purposes, the Investigator or designee must review, sign, and date 
all ECG tracings. Paper or electronic copies will be kept as part of the participant’s 
permanent study file at the site. If considered appropriate by Roche, ECGs may be 
analyzed retrospectively at a central laboratory.
ECG characteristics, including heart rate, QRS duration, and PR, and QT intervals, will 
be recorded on the eCRF or loaded electronically. QTcF (Appendix 7) and RR interval 
will be calculated automatically and recorded on the eCRF or loaded automatically. 
Changes in T‑wave and U‑wave morphology and overall ECG interpretation will be 
documented on the eCRF or loaded electronically. T-wave information will be captured 
as normal or abnormal, U- wave information will be captured in two categories: 
absent/normal or abnormal.
8.2.4
Clinical Safety Laboratory Assessments
Normal ranges for the study laboratory parameters must be supplied to the Sponsor 
before the study starts. A list of clinical laboratory tests to be performed is provided in 
Appendix 4 and these assessments must be conducted in accordance with the separate 
laboratory manual and the SoA (Section 1.3).
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the Investigator to be more severe than expected for the 
participant's condition.

In the event of unexplained abnormal clinically significant laboratory test values, the 
tests should be repeated immediately and followed up until they have returned to 
the normal range and/or an adequate explanation of the abnormality is found.

If such values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified and the Sponsor 
notified.

If laboratory values from non-protocol specified laboratory assessments performed 
at the local laboratory require a change in participant management or are 
considered clinically significant by the Investigator (e.g., SAE or AE) then, the 
results must be recorded in the CRF.
Results of clinical laboratory testing will be recorded on the eCRF or be received as 
electronically produced laboratory reports submitted directly from the local or central 
laboratory as appropriate.
Page 492 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
51/Protocol BP40950, Version 2
Additional blood or urine samples may be taken at the discretion of the Investigator if the 
results of any test fall outside the reference ranges, or clinical symptoms necessitate 
additional testing to monitor participant safety.
Where the clinical significance of abnormal lab results is considered uncertain, screening 
lab tests may be repeated before randomization to confirm eligibility.
If there is an alternative explanation for a positive urine or blood test for drugs of abuse, 
e.g., previous occasional intake of a medication or food containing for example, codeine, 
benzodiazepines or opiates, the test could be repeated to confirm washout.
8.2.5
Medical History and Demographic Data
Medical history includes clinically significant diseases and all medications (e.g., 
prescription drugs, OTC drugs, herbal or homeopathic remedies, nutritional supplements) 
used by the participant within 30 days prior to the screening visit.
Demographic data will include age, sex, and self‑reported race/ethnicity, if acceptable 
by local regulations
8.3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
The definitions of an AE or serious adverse event (SAE) can be found in Appendix 2.
The non-serious adverse events of special interest (NSAESI) and disease-related events 
and/or disease-related outcomes not qualifying as AEs or SAEs are discussed in 
Sections 8.3.6 and Section 8.3.7.
The Investigator and any qualified designees are responsible for ensuring that all 
adverse events (including assessment of seriousness, severity and causality; see
Appendix 2) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Appendix 2.
Procedures used for recording adverse events are provided in Appendix 3.
8.3.1
Time Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2.
Investigators will seek information on adverse events at each participant’s contact. All 
adverse events, whether reported by the participant or noted by study personnel, will be 
recorded in the participant’s medical record and on the Adverse Event eCRF as follows:
After informed consent has been obtained but prior to initiation of study treatment, 
only serious adverse events caused by a protocol-mandated intervention should be 
Page 493 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
52/Protocol BP40950, Version 2
reported (e.g., serious adverse events related to invasive procedures such as biopsies).
Any other adverse event should not be reported.
After initiation of study treatment, all adverse events, regardless of relationship to 
study treatment, will be reported until the follow-up visit (approximately 7 to 14 days after 
the last dosing).
Post-study adverse events and serious adverse events: The Investigator is not 
required to actively monitor participants for adverse events after the end of the adverse 
event reporting period (after the follow-up visit approximately 7 to 14 days after the last 
dosing).
However, if the Investigator learns of any SAE (including a death) or other adverse 
events of concern that are believed to be related to prior treatment with study treatment, 
at any time after a participant has been discharged from the study, and the Investigator
considers the event to be reasonably related to the study treatment or study participation, 
the Investigator must promptly notify the Sponsor. For the procedure of reporting, see
Appendix 2.
8.3.2
Method of Detecting Adverse Events and Serious Adverse 
Events
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all participant evaluation time-points.
8.3.3
Follow-Up of Adverse Events and Serious Adverse Events
8.3.3.1
Investigator Follow-Up
The Investigator should follow each adverse event until the event has resolved to 
baseline grade or better, the event is assessed as stable by the Investigator, the event is 
otherwise explained, the participant is lost to follow-up (Section 7.3), or the participant 
withdraws consent. Every effort should be made to follow all serious adverse events 
considered to be related to study treatment or trial-related procedures until a final 
outcome can be reported.
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the participant’s medical record to facilitate source 
data verification. If, after follow-up, return to baseline status or stabilization cannot be 
established, an explanation should be recorded on the Adverse Event eCRF.
All pregnancies reported during the study should be followed until pregnancy outcome 
and reported according to the instructions provided in Section 8.3.5.
Page 494 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
53/Protocol BP40950, Version 2
8.3.3.2
Sponsor Follow-Up
For SAEs, NSAESIs, and pregnancies, the Sponsor or a designee may follow up by 
telephone, fax, electronic mail, and/or a monitoring visit to obtain additional case details
and outcome information (e.g., from hospital discharge summaries, consultant reports, 
autopsy reports) in order to perform an independent medical assessment of the reported 
case.
8.3.4
Regulatory Reporting Requirements for Serious Adverse 
Events
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety 
of a study treatment under clinical investigation are met.
The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then, file it along with the Investigator’s Brochure and will notify the IRB/IEC, 
if appropriate according to local requirements.
For immediate and expedited reporting requirements from Investigator to Sponsor and 
from Sponsor to Health Authority, investigators, IRB and EC, see Appendix 2.
8.3.4.1
Emergency Medical Contacts
To ensure the safety of study participants, access to the Medical monitors is available 
24 hours a day 7 days a week. Medical monitors contact details will be available on a 
separate list generated by the study management team.
8.3.5
Pregnancy
Male participants will be instructed through the Informed Consent Form to immediately 
inform the Investigator if their partner becomes pregnant during the study or within 
28 days after the last dose of study drug.
Although not anticipated, as only women of non-childbearing potential will be included in 
the study, female participants will also be instructed to immediately inform the 
Page 495 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
54/Protocol BP40950, Version 2
Investigator if they become pregnant during the study or within 28 days after the last 
dose of study drug.
If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the pregnancy reporting process as detailed 
in Appendix 5.
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs (Appendix 5).
8.3.6
Non-Serious Adverse Events of Special Interest 
Non-serious adverse events of special interest are required to be reported by the 
Investigator to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Appendix 2 for reporting instructions).
Non-serious adverse events of special interest for this study include the following:

Cases of an elevated ALT or AST in combination with either an elevated bilirubin or 
clinical jaundice, as defined in Appendix 3.

Suspected transmission of an infectious agent by the study treatment, as defined 
below:
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent. A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an infection in 
a patient exposed to a medicinal product. This term applies only when a 
contamination of the study treatment is suspected.
8.3.7
Management of Specific Adverse Events
Treatment of specific AEs will be considered on a case-by-case basis according to local 
standard of care.
8.4
TREATMENT OF OVERDOSE
Study treatment overdose is the accidental or intentional use of the drug in an amount 
higher than the dose being studied. An overdose or incorrect administration of study 
treatment is not an adverse event unless it results in untoward medical effects (see 
Sections 5 and 5.2 of Appendix 2 for further details).
In the event of an overdose, the Investigator should:
1.
Contact the Sponsor’s Medical Monitor immediately.
2.
Closely monitor the participant for AE/SAE and laboratory abnormalities until 
resolved.
Page 496 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
55/Protocol BP40950, Version 2
3.
Document the quantity of the excess dose, as well as the duration of the overdose, 
in the CRF.
PK samples collected per protocol may be used to further evaluate an overdose or 
incorrect administration of study treatment.
8.5
PHARMACOKINETICS
Blood samples for the determination of plasma concentrations of RO7017773 will be 
collected as outlined in the SoA (see Section 1.3). Plasma RO7017773 concentrations 
will be measured by a specific and validated LC-MS/MS method. Plasma concentrations 
of RO7017773 metabolites may also be measured as appropriate using a specific assay.
PK parameters for RO7017773 (and its metabolite, as appropriate) will be read directly 
from the plasma concentration-time profiles or estimated using standard non-
compartmental methods where appropriate.
Any volume of blood samples remaining after the specified analyses may also be used 
for additional validation experiments specify for, e.g., metabolites and exploratory 
biomarkers.
The plasma samples will be destroyed up to 2 years after the date of final clinical study 
report (CSR). Details on sampling procedures, sample storage and shipment are given 
in the Sample Handling Manual.
8.5.1
Taste assessment
Taste assessments will be done as outlined in the SoA (see Section 1.3). One to two 
minutes after swallowing RO7017773 Phase II tablet formulation dispersed in an 
appropriate liquid, 
8.6
PHARMACODYNAMICS
Pharmacodynamic parameters are not evaluated in this study.
8.7
GENETICS
Genetics are not evaluated in this study.
8.8
BIOMARKERS
Biomarkers are not evaluated in this study.
8.9
MEDICAL RESOURCE UTILIZATION AND HEALTH 
ECONOMICS
Health Economics/Medical Resource Utilization and Health Economics parameters are 
not evaluated in this study.
Page 497 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
56/Protocol BP40950, Version 2
8.10
TIMING OF STUDY ASSESSMENTS
8.10.1
Screening and Pre-treatment Assessments
Written informed consent for participation in the study must be obtained before 
performing any study‑specific screening tests or evaluations. Nevertheless, if necessary 
and after agreement of the Sponsor, any measures identical to those planned in the 
protocol for the participants’ screening that have already been performed within the 
timelines given by the protocol for the screening exams could be used for the protocol in 
order to minimize the constraints on the participants. Informed Consent Forms (ICFs) for 
enrolled participant and for participants who are not subsequently enrolled will be 
maintained at the study site.
All screening and pre-treatment assessments must be completed and reviewed to 
confirm that participants meet all eligibility criteria. The Investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or 
record reasons for screening failure.
An Eligibility Screening Form (ESF) documenting the Investigator’s assessment of each 
screened participant with regard to the protocol’s inclusion and exclusion criteria is to be 
completed by the Investigator and kept at the investigational site.
Screening and pre-treatment assessments will be performed at the time-points indicated 
in the SoA (see Section 1.3), unless otherwise specified.
8.10.2
Assessments during Treatment
Under no circumstances will participants who enroll in this study and have completed 
treatment as specified, be permitted to re-enroll in the study. Participants may take part 
in only one part of the study.
All assessments must be performed as per SoA (see Section 1.3). Assessments 
scheduled on the day of study treatment administration should be performed prior to 
administration of study treatment, unless otherwise noted in the schedule of 
assessments.
8.10.3
Follow-Up Assessments
Participants who complete the study or discontinue from the study early will be asked to 
return to the clinic 7 to 14 days after the last dose of study treatment for a follow‑up visit.
Assessments at the follow-up will be performed as indicated in the SoA (see Section 1.3).
After the study completion/early termination visit, adverse events should be followed as 
outlined in Sections 8.3.1 and 8.3.3.
Page 498 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
58/Protocol BP40950, Version 2
9.3
POPULATIONS FOR ANALYSES
For purposes of analysis, the following populations are defined in Table 8.
Table 8
Analysis Populations
Population
Description
Safety
All participants randomized to study treatment and who 
received at least one dose of the study treatment, whether 
prematurely withdrawn from the study or not, will be included 
in the safety analysis. 
Pharmacokinetic
All participants who have received at least one dose of study 
treatment and who have data from at least one post-dose 
sample will be included in the PK analysis population.
Participants will be excluded from the PK analysis population if 
they significantly violate the inclusion or exclusion criteria, 
deviate significantly from the protocol, or if data are 
unavailable or incomplete which may influence the PK 
analysis. Excluded cases will be documented together with the 
reason for exclusion. All decisions on exclusions from the 
analysis will be made prior to database closure.
9.4
STATISTICAL ANALYSES
9.4.1
Demographics and Baseline Characteristics
Demographic and other baseline characteristics of the safety analysis population will be 
listed and summarized using descriptive statistics.
9.4.2
Safety Analyses
All safety analyses will be based on the safety analysis population.
Page 500 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
59/Protocol BP40950, Version 2
Table 9
Safety Statistical Analysis Methods
Endpoint
Statistical Analysis Methods
Adverse events
The original terms recorded on the eCRF by the Investigator for adverse 
events will be coded by the Sponsor.
Adverse events will be summarized by mapped term and appropriate 
thesaurus level.
Clinical laboratory 
tests
All clinical laboratory data will be stored on the database in the units in 
which they were reported. Laboratory test values will be presented in 
International System of Units (SI units; Système International d’Unités) by 
individual listings with flagging of abnormal results.
Vital signs
Vital signs data will be presented by individual listings with flagging of 
values outside the normal ranges and flagging of abnormalities. In addition, 
tabular summaries will be used, as appropriate.
ECG data analysis ECG data will be presented by individual listings. In addition, tabular 
summaries will be used, as appropriate.
Concomitant 
medications
The original terms recorded on the participants’ eCRF by the Investigator 
for concomitant medications will be standardized by the Sponsor by 
assigning preferred terms.
Concomitant medications will be presented in summary tables and listings.
Taste 
Questionnaire
Taste Questionnaire data will be presented by individual listings. In addition, 
tabular summaries will be used, as appropriate.
9.4.3
Pharmacokinetic Analyses
Analyses will be carried out on the PK analysis population.
9.4.3.1
Pharmacokinetic Parameters
The primary RO7017773 PK study variable will be the AUC (AUC0-inf if it can be derived, 
otherwise truncated as appropriate) and Cmax. For Treatment C of Part 1, Tmax is 
additionally considered as primary PK variable. All other PK parameters will be regarded 
as secondary.
The following PK parameters of RO7017773 will be read from the concentration versus 
time profiles or estimated using non-compartmental methods where appropriate:

Tmax : Time to maximum plasma concentration

Cmax : maximum observed plasma concentration

AUC0-t : area under the plasma concentration-time curve up to time t

AUC0-last : area under the plasma concentration-time curve up to the last 
measurable concentration
Page 501 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
60/Protocol BP40950, Version 2

AUC0-inf: area under the plasma concentration-time curve extrapolated to infinity

T1/2 : apparent terminal half-life, computed as ln(2)/λz

CL/F: apparent oral clearance, calculated as Dose/AUC0-inf
Additional PK parameters may be reported as appropriate.
All pharmacokinetic concentration and calculated PK parameters for RO7017773 will be 
presented in individual listings and summary tables (including descriptive summary 
statistics: mean, standard deviation, coefficient of variation, median, minimum, and 
maximum), and graphs (including concentration vs. time plots on linear and semi-
logarithmic scales) as appropriate.
9.5
STATISTICAL ANALYSIS
Part 1:
The following linear statistical model will be applied to the log-transformed, dose 
normalized PK variables AUC (AUC0-inf if it can be derived, otherwise truncated as 
appropriate) and Cmax from Part 1:
Yijkm = μ + τi + k + j + sm + εijkm.
In this model μ denotes the general mean of the log transformed variables, sm is the 
random effect for participant m, τi are fixed effects for treatment i (i = 1, , 4), k are 
fixed effects for period k (k = 1, , 4), and j are fixed effects for sequence j (j = 1, , 
4).  The random participant effects and the random errors εijkm are assumed to be 
independent and normally distributed with zero means and standard deviations s and 
, respectively.
From the model, 90% two-sided confidence intervals for the geometric mean ratios will 
be derived comparing treatments A vs B (assessing the primary objective of Part 1), as 
well as treatments B vs D and B vs C (assessing the first two secondary objectives). 
Part 2:
The following linear statistical model will be applied to the log-transformed, dose 
normalized PK variables AUC (AUC0-inf if it can be derived, otherwise truncated as 
appropriate) and Cmax from Part 2:
Yikm = μ + τi + k + sm + εikm.
In this model μ denotes the general mean of the log transformed variables, sm is the 
random effect for participant m, τi are fixed effects for treatment i (i = 1, 2) and k are 
fixed effects for period k (k = 1, 2).  The random participant effects and the random 
Page 502 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
61/Protocol BP40950, Version 2
errors εikm are assumed to be independent and normally distributed with zero means and 
standard deviations s and , respectively.
From the model, 90% two-sided confidence intervals for the geometric mean ratios will 
be derived comparing treatments A and B assessing the secondary objective of Part 2. 
9.6
SUMMARIES OF CONDUCT OF STUDY
All protocol deviations will be listed. Data for study drug administration and concomitant 
medications will be listed. The number of participants who were enrolled, discontinued, 
and completed the study will be summarized and listed.
10.
REFERENCES
Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal 
Investigators, Centers for Disease Control and Prevention (CDC). Prevalence of 
autism spectrum disorder among children aged 8 years - autism and 
developmental disabilities monitoring network, 11 sites, United States, 2010. 
MMWR Surveill Summ 2014;63:1-21.
Investigator’s Brochure RO7017773.
US FDA Guidance for Industry. Food-Effect Bioavailability and Fed Bioequivalence 
Studies. December 2002 (www.fda.gov/cder/guidance).
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental 
disorders (5th ed.). Washington, DC.
Page 503 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
62/Protocol BP40950, Version 2
11.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
The following section includes standard appendices such as Appendix 1 (for regulatory, 
ethical and study oversight considerations), Appendix 2 (for AE definitions, reporting) 
and Appendix 3 (procedures of recording), Appendix 5 (contraceptive guidance and 
collection of pregnancy information). Additional study-related appendices are in order of 
appearance in the protocol.
Page 504 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
63/Protocol BP40950, Version 2
Appendix 1
Regulatory, Ethical, and Study Oversight Considerations
1.
REGULATORY AND ETHICAL CONSIDERATIONS
1.1.
COMPLIANCE WITH LAWS AND REGULATIONS
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the laws and 
regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual. The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management: Definitions and Standards for 
Expedited Reporting). Studies conducted in the United States or under a U.S. 
Investigational New Drug (IND) application will comply with U.S. FDA regulations and 
applicable local, state, and federal laws. Studies conducted in the EU/EEA will comply 
with the EU Clinical Trial Directive (2001/20/EC).
1.2.
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE
This protocol, the ICFs, any information to be given to the participant (e.g. 
advertisements, diaries etc), and relevant supporting information must be submitted to 
the IRB/EC by the Principal Investigator and reviewed and approved by the IRB/EC 
before the study is initiated. In addition, any participant recruitment materials must be 
approved by the IRB/EC.
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the requirements, 
policies, and procedures established by the IRB/EC. Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (Section 2.3.1 of this 
Appendix).
The Investigator should follow the requirements for reporting all adverse events to the 
Sponsor. Investigators may receive written IND safety reports or other safety‑related 
communications from the Sponsor. Investigators are responsible for ensuring that such 
reports are reviewed and processed in accordance with Health Authority requirements 
and the policies and procedures established by their IRB/EC, and archived in the site’s 
study file.
1.3.
INFORMED CONSENT
The Sponsor’s Master Informed Consent Form (and ancillary sample ICFs such as a 
Child’s Assent or Caregiver's Informed Consent Form, if applicable) will be provided to 
each site. If applicable, it will be provided in a certified translation of the local language. 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Page 505 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
64/Protocol BP40950, Version 2
Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study center. The Sponsor or its designee must review and approve 
any proposed deviations from the Sponsor's sample ICFs or any alternate consent forms 
proposed by the site (collectively, the “Consent Forms”) before IRB/EC submission. The 
final IRB/EC‑approved Consent Forms must be provided to the Sponsor for Health 
Authority submission purposes according to local requirements. Participants must be re-
consented to the most current version of the ICF(s) during their participation in the study. 
A copy of the ICF(s) signed by all parties must be provided to the participant or the 
participant’s legally authorized representative.
The Consent Forms must be signed and dated by the participant or the participant’s 
legally authorized representative before his or her participation in the study. The case 
history or clinical records for each participant shall document the informed consent 
process and that written informed consent was obtained prior to participation in the study.
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the 
participant to take part. The final revised IRB/EC-approved Consent Forms must be 
provided to the Sponsor for Health Authority submission purposes if required as per local 
regulations.
Participants must be re-consented to the most current version of the Consent Forms (or 
to a significant new information/findings addendum in accordance with applicable laws 
and IRB/EC policy) during their participation in the study. For any updated or revised 
Consent Forms, the case history or clinical records for each participant shall document 
the informed consent process and that written informed consent was obtained using the 
updated/revised Consent Forms for continued participation in the study.
A copy of each signed Consent Form must be provided to the participant or the 
participant’s legally authorized representative. All signed and dated Consent Forms must 
remain in each participant’s study file or in the site file and must be available for 
verification by study monitors at any time.
1.4.
CONFIDENTIALITY
Participants will be assigned a unique identifier by the Sponsor. Any participant records 
or datasets that are transferred to the Sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
The participant must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the participant. 
Page 506 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
65/Protocol BP40950, Version 2
Medical information may be given to a participant’s personal physician or other 
appropriate medical personnel responsible for the participant’s welfare, for treatment 
purposes.
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities.
1.5.
FINANCIAL DISCLOSURE
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate Health Authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for one year after completion of the study (i.e., LPLV).
2.
DATA HANDLING AND RECORD
2.1.
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES
2.1.1.
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements.
2.1.3.
Source Data Records
Source documents (paper or electronic) are those in which participant data are recorded 
and documented for the first time. They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, COAs (paper or eCOA), 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
Page 507 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
66/Protocol BP40950, Version 2
instruments, copies of transcriptions that are certified after verification as being accurate 
and complete, microfiche, photographic negatives, microfilm or magnetic media, X-rays, 
patient files, and records kept at pharmacies, laboratories, and medico‑technical 
departments involved in a clinical trial.
Before study initiation, data to be entered directly into the eCRFs (i.e., no prior written or 
electronic record of the data) and considered source data must be defined in the Trial 
Monitoring Plan.
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described below.
To facilitate source data verification, the Investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial‑related 
monitoring, Sponsor audits, and IRB/EC review. The investigational site must also allow 
inspection by applicable Health Authorities.
2.1.4.
Use of Computerized Systems
When clinical observations are entered directly into an investigational site’s 
computerized medical record system (i.e., in lieu of original hardcopy records), the 
electronic record can serve as the source document if the system has been validated in 
accordance with Health Authority requirements pertaining to computerized systems used 
in clinical research. An acceptable computerized data collection system allows 
preservation of the original entry of data. If original data are modified, the system should 
maintain a viewable audit trail that shows the original data as well as the reason for the 
change, name of the person making the change, and date of the change.
2.2.
RETENTION OF RECORDS
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the Investigator for at least 15 years after study completion unless 
local regulations or institutional policies require a longer retention period. No records 
may be destroyed during the retention period without the written approval of the Sponsor. 
No records may be transferred to another location or party without written notification to 
the Sponsor.
2.3.
STUDY RECORDS
The Investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully reconstructed, including but not limited to the protocol, protocol 
amendments, ICFs, and documentation of IRB/EC and governmental approval. 
Page 508 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
67/Protocol BP40950, Version 2
2.3.1.
Protocol Amendments
Any substantial protocol amendments will be prepared by the Sponsor. Substantial 
protocol amendments will be submitted to the IRB/EC and to regulatory authorities in 
accordance with local regulatory requirements.
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to participants or any non-substantial changes, as 
defined by regulatory requirements.
2.3.2.
Publication Policy
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
for approval prior to submission. This allows the Sponsor to protect proprietary 
information and to provide comments based on information from other studies that may 
not yet be available to the Investigator.
The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data. In this case, a coordinating Investigator will be designated by mutual agreement.
Any formal publication of the study in which contribution of Sponsor personnel exceeded 
that of conventional monitoring will be considered as a joint publication by the 
Investigator and the appropriate Sponsor personnel.
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise.
2.3.4.
Site Inspections
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, participants’ medical records, and eCRFs. The Investigator will 
permit national and local Health Authorities, Sponsor monitors, representatives, and 
collaborators, and the IRBs/ECs to inspect facilities and records relevant to this study.
Page 509 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
68/Protocol BP40950, Version 2
3.
STUDY AND SITE CLOSURE
The Sponsor (or designee) has the right to close the study site or terminate this study at 
any time. Reasons for terminating the study may include, but are not limited to, the 
following:

The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to participants.

Participant enrollment is unsatisfactory.
The Sponsor will notify the Investigator and Health Authorities if the study is placed on 
hold, or if the Sponsor decides to discontinue the study or development program.
Study sites will be closed upon study completion. A study site is considered closed when 
all required documents and study supplies have been collected and a study-site closure 
visit has been performed.
The Investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or Investigator may include 
but are not limited to:

Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local Health Authorities, the Sponsor's procedures, or GCP guidelines.

Inadequate recruitment of participants by the Investigator.

Discontinuation of further study treatment development.
Page 510 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
69/Protocol BP40950, Version 2
Appendix 2
Adverse Events: Definitions and Procedures for Evaluating, 
Follow-up and Reporting
1.
DEFINITION OF ADVERSE EVENTS
According to the E2A ICH guideline for Good Clinical Practice, an adverse event is any 
untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have to 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 of a medicinal product, 
whether or not considered related to the medicinal product.
Events Meeting the AE Definition:

Any deterioration in a laboratory value (hematology, clinical chemistry, or urinalysis) 
or other clinical test (e.g., ECG, X-ray) that is associated with symptoms or leads to 
a change in study treatment or concomitant treatment or discontinuation from study 
treatment.

Exacerbation of a chronic or intermittent pre-existing condition, including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study.

Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., screening invasive 
procedures such as biopsies).
Events NOT Meeting the AE Definition:

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the Investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE.

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
Page 511 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
70/Protocol BP40950, Version 2
2.
DEFINITION OF SERIOUS ADVERSE EVENTS
If an event is not an AE per definition above, then it cannot be a serious adverse event 
(SAE) even if serious conditions are met (e.g., hospitalization for signs/symptoms of the 
disease under study, death due to progression of disease).
A serious adverse event is defined as any untoward medical occurrence that at any dose:

Results in death.

Is life-threatening.
The term "life-threatening" in the definition of "serious" refers to an event in which 
the participant was at risk of death at the time of the event; it does not refer to an 
event which hypothetically might have caused death if it was more severe.

Requires inpatient hospitalization or prolongation of existing hospitalization
(see Appendix 3).
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.

Results in persistent or significant disability/incapacity
Disability means substantial disruption of the participant’s ability to conduct normal 
life functions.
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.

Is a congenital anomaly/birth defect.

Other significant events:
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should 
usually be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
Page 512 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
71/Protocol BP40950, Version 2
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.
3.
RECORDING OF ADVERSE EVENT AND/OR SERIOUS 
ADVERSE EVENT
When an AE/SAE occurs, it is the responsibility of the Investigator to review all
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.
The Investigator will then record all relevant AE/SAE information in the CRF.
It is not acceptable for the Investigator to send photocopies of the participant’s medical 
records to Medical Monitor in lieu of completion of the eCRF.
There may be instances when copies of medical records for certain cases are requested 
by the sponsor. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to the sponsor.
The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
3.1.
ASSESSMENT OF SEVERITY
The Investigator will make an assessment of severity for each AE and SAE reported 
during the study and assign it to one of the categories provided in Table 1 (as a 
guidance for assessing adverse event severity).
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of 
an adverse event (rated as mild, moderate, or severe, or according to a pre-defined 
grading criteria [e.g., National Cancer Institute Common Terminology Criteria for 
Adverse Events [NCI CTCAE] criteria); the event itself may be of relatively minor medical 
significance (such as severe headache without any further findings).
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF.
Serious adverse events are required to be reported by the Investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event.
Page 513 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
72/Protocol BP40950, Version 2
Table 1
Adverse Event Severity Grading Scale
Severity
Description
Mild
Discomfort noticed, but no disruption of normal daily activity
Moderate
Discomfort sufficient to reduce or affect normal daily activity
Severe
Incapacitating with inability to work or to perform normal daily activity
Note: Regardless of severity, some events may also meet seriousness criteria. Refer to 
definition of a serious adverse event (see above).
3.2.
ASSESSMENT OF CAUSALITY
Investigators should use their knowledge of the participant, the circumstances 
surrounding the event, and an evaluation of any potential alternative causes to 
determine whether or not an adverse event is considered to be related to the study 
treatment, indicating "yes" or "no" accordingly. The following guidance should be taken 
into consideration:

Temporal relationship of event onset to the initiation of study treatment.

Course of the event, considering especially the effects of dose-reduction, 
discontinuation of study treatment, or reintroduction of study treatment (where 
applicable).

Known association of the event with the study treatment or with similar treatments.

Known association of the event with the disease under study.

Presence of risk factors in the participant or use of concomitant medications known 
to increase the occurrence of the event.

Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event.
For participant receiving combination therapy, causality will be assessed individually for 
each protocol-mandated therapy.
4.
FOLLOW-UP OF AES AND SAES
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals.
If a participant dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor with a copy of any post-mortem findings 
including histopathology
New or updated information will be recorded in the originally completed eCRF.
Page 514 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
73/Protocol BP40950, Version 2
The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information.
5.
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial. The Investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the Investigator learns of the event. The following is a list 
of events that the Investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study treatment:

Serious adverse events

Non-serious adverse events of special interest (NSAESI)

Pregnancies (see Section 8.3.5)

Accidental overdoses or medication errors
The Investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the 
information). New significant information includes the following:

New signs or symptoms or a change in the diagnosis.

Significant new diagnostic test results.

Change in causality based on new information.

Change in the event’s outcome, including recovery.

Additional narrative information on the clinical course of the event.
Investigators must also comply with local requirements for reporting serious adverse 
events to the local Health Authority and IRB/EC.
5.1
REPORTING REQUIREMENTS OF SERIOUS ADVERSE 
EVENTS AND NON-SERIOUS ADVERSE EVENTS OF SPECIAL 
INTEREST
Events that Occur prior to Study Treatment Initiation
After informed consent has been obtained but prior to initiation of study treatment, only 
serious adverse events caused by a protocol-mandated intervention should be reported. 
The Serious Adverse Event/Adverse Event of Special Interest Reporting Form provided 
to Investigators should be completed and submitted to the Serious Adverse Event 
Responsible immediately (i.e., no more than 24 hours after learning of the event).
Page 515 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
74/Protocol BP40950, Version 2
Events that Occur after Study Treatment Initiation
For reports of serious adverse events and non-serious adverse events of special interest 
(Section 8.3.6) that occur after initiation of study treatment (Section 8.3.1), investigators 
should record all case details that can be gathered on the appropriate Serious Adverse 
Event/Adverse Event of Special Interest Reporting Form provided to investigators and 
submit the report to the Serious Adverse Event Responsible immediately (ie no more 
than 24 hours after learning of the event), either by faxing or by scanning and emailing 
the form using the fax number or email address provided to investigators.Reporting of 
Post-Study Adverse Events and Serious Adverse Events
If the Investigator becomes aware of any other serious adverse event occurring after the 
end of the AE reporting period, if the event is believed to be related to prior study
treatment the event should be reported directly to the Sponsor or its designee, either by 
faxing or by scanning and emailing the SAE Reporting Form using the fax number or 
email address provided to investigators.
5.2
Reporting Requirements for Cases of Accidental Overdose or 
Medication Error 
Accidental overdose and medication error (hereafter collectively referred to as "special 
situations"), are defined as follows:

Accidental overdose:  accidental administration of a drug in a quantity that is higher 
than the assigned dose

Medication error: accidental deviation in the administration of a drug
In some cases, a medication error may be intercepted prior to administration of 
the drug.
Special situations are not in themselves adverse events, but may result in adverse 
events. All special situations associated with RO7017773, regardless of whether they 
result in an adverse event, should be recorded on the Adverse Event eCRF and reported 
to the Sponsor immediately (i.e., no more than 24 hours after learning of the event).
Special situations should be recorded as described below:

Accidental overdose: Enter the drug name and "accidental overdose" as the event 
term.  Check the "Accidental overdose" and "Medication error" boxes.

Medication error that does not qualify as an overdose: Enter the name of the drug 
administered and a description of the error (e.g., wrong dose administered, wrong 
dosing schedule, incorrect route of administration, wrong drug, expired drug 
administered) as the event term. Check the "Medication error" box.

Medication error that qualifies as an overdose:  Enter the drug name and "accidental 
overdose" as the event term.  Check the "Accidental overdose" and "Medication 
error" boxes.  Enter a description of the error in the additional case details.
Page 516 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
75/Protocol BP40950, Version 2

Intercepted medication error:  Enter the drug name and "intercepted medication 
error" as the event term.  Check the "Medication error" box.  Enter a description of 
the error in the additional case details.
For RO7017773, each adverse event associated with a special situation should be 
recorded separately on the Adverse Event eCRF. If the associated adverse event fulfills 
seriousness criteria, the event should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning of the event; see Appendix 2,Section 5.1). For 
RO7017773, adverse events associated with special situations should be recorded as 
described below for each situation:

Accidental overdose:  Enter the adverse event term.  Check the "Accidental 
overdose" and "Medication error" boxes.

Medication error that does not qualify as an overdose: Enter the adverse event term.  
Check the "Medication error" box.

Medication error that qualifies as an overdose: Enter the adverse event term.  
Check the "Accidental overdose" and "Medication error" boxes.
As an example, an accidental overdose that resulted in a headache would require the 
completion of two Adverse Event eCRF pages, one to report the accidental overdose 
and one to report the headache. The "Accidental overdose" and "Medication error" 
boxes would need to be checked on both eCRF pages.
6.
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES
The Sponsor will promptly evaluate all serious adverse events and NSAESI against 
cumulative product experience to identify and expeditiously communicate possible new 
safety findings to investigators, IRBs, ECs, and applicable Health Authorities based on 
applicable legislation.
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events using the following reference document{s}:

RO7017773 Investigator's Brochure
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document.
Reporting requirements will also be based on the Investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed.
Page 517 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
76/Protocol BP40950, Version 2
Appendix 3
Procedures for Recording Adverse Events
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF. Avoid colloquialisms and abbreviations.
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF.
1.
DIAGNOSIS VERSUS SIGNS AND SYMPTOMS
For adverse events, a diagnosis (if known) should be recorded on the Adverse Event 
eCRF rather than individual signs and symptoms (e.g., record only liver failure or 
hepatitis rather than jaundice, asterixis, and elevated transaminases). However, if a 
constellation of signs and/or symptoms cannot be medically characterized as a single 
diagnosis or syndrome at the time of reporting, each individual event should be recorded 
on the Adverse Event eCRF. If a diagnosis is subsequently established, all previously 
reported adverse events based on signs and symptoms should be nullified and replaced 
by one adverse event report based on the single diagnosis, with a starting date that 
corresponds to the starting date of the first symptom of the eventual diagnosis.
2.
ADVERSE EVENTS OCCURRING SECONDARY TO OTHER 
EVENTS
In general, adverse events occurring secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events. However, medically significant adverse events 
occurring secondary to an initiating event that are separated in time should be recorded 
as independent events on the Adverse Event eCRF. For example:

If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF.

If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF.

If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF.

If dizziness leads to a fall and subsequent fracture, all three events should be 
reported separately on the eCRF.
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated.
Page 518 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
77/Protocol BP40950, Version 2
3.
PERSISTENT OR RECURRENT ADVERSE EVENTS
A persistent adverse event is one that extends continuously, without resolution, between 
participant evaluation time-points. Such events should only be recorded once on the 
Adverse Event eCRF. The initial severity of the event should be recorded, and the 
severity should be updated to reflect the most extreme severity any time the event 
worsens. If the event becomes serious, the Adverse Event eCRF should be updated to 
reflect this.
A recurrent adverse event is one that resolves between participant evaluation 
time-points and subsequently recurs. Each recurrence of an adverse event should be 
recorded separately on the Adverse Event eCRF.
4.
ABNORMAL LABORATORY VALUES
Not every laboratory abnormality qualifies as an adverse event. A laboratory test result 
should be reported as an adverse event if it meets any of the following criteria:

Accompanied by clinical symptoms.

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation).

Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy.

Clinically significant in the Investigator’s judgment.
It is the Investigator’s responsibility to review all laboratory findings. Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event.
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5 times the upper limit of normal [ULN]
associated with cholecystitis), only the diagnosis (i.e., cholecystitis) should be recorded 
on the Adverse Event eCRF.
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating if the test result is above or below the normal range (e.g., "elevated 
potassium", as opposed to "abnormal potassium"). If the laboratory abnormality can be 
characterized by a precise clinical term per standard definitions, the clinical term should 
be recorded as the adverse event. For example, an elevated serum potassium level of 
7.0 mEq/L should be recorded as “hyperkalemia”.
Observations of the same clinically significant laboratory abnormality from visit to visit
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
Page 519 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
78/Protocol BP40950, Version 2
changes. The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens.
5.
ABNORMAL VITAL SIGN VALUES
Not every vital sign abnormality qualifies as an adverse event. A vital sign result should 
be reported as an adverse event if it meets any of the following criteria:

Accompanied by clinical symptoms.

Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation).

Results in a medical intervention or a change in concomitant therapy.

Clinically significant in the Investigator’s judgment.
It is the Investigator’s responsibility to review all vital sign findings. Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event.
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF.
Observations of the same clinically significant vital sign abnormality from visit to visit 
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes. The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens.
6.
ABNORMAL LIVER FUNCTION TESTS
The finding of an elevated ALT or AST (3ULN) in combination with either an elevated 
total bilirubin (2ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury. 
Therefore, investigators must report as an adverse event the occurrence of either of the 
following:

Treatment-emergent ALT or AST3ULN in combination with total 
bilirubin2ULN.

Treatment-emergent ALT or AST3ULN in combination with clinical jaundice.
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Appendix 2) and 
reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event), either as a serious adverse event or a non-serious adverse event of special 
interest (see Section 8.3.6).
Page 520 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
79/Protocol BP40950, Version 2
7.
DEATHS
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5 of Appendix 2), regardless of relationship to study treatment, must be recorded 
on the Adverse Event eCRF and immediately reported to the Sponsor. 
Death should be considered an outcome and not a distinct event. The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF. Generally, only one such event should be reported. 
If the cause of death is unknown and cannot be ascertained at the time of reporting, 
“unexplained death” should be recorded on the Adverse Event eCRF. If the cause of 
death later becomes available (e.g., after autopsy), “unexplained death” should be 
replaced by the established cause of death. The term "sudden death" should not be 
used unless combined with the presumed cause of death (e.g., "sudden cardiac death").
8.
PREEXISTING MEDICAL CONDITIONS
A preexisting medical condition is one that is present at the screening visit for this study. 
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF.
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study. When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., “more frequent headaches”).
9.
HOSPITALIZATION OR PROLONGED HOSPITALIZATION
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event (per the definition of serious 
adverse event in Appendix 2), except as outlined below.
An event that leads to hospitalization under the following circumstances should not be 
reported as an adverse event or a serious adverse event:

Hospitalization for respite care

Planned hospitalization required by the protocol (e.g., for study treatment 
administration or insertion of access device for study treatment administration).
Page 521 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
80/Protocol BP40950, Version 2

Hospitalization for a preexisting condition, provided that all of the following criteria 
are met:
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected 
normal progression of the disease.
The participant has not suffered an adverse event.
An event that leads to hospitalization under the following circumstances is not 
considered to be a serious adverse event, but should be reported as an adverse event 
instead:

Hospitalization for an adverse event that would ordinarily have been treated in an 
outpatient setting had an outpatient clinic been available.
Page 522 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
81/Protocol BP40950, Version 2
Appendix 4
Clinical Laboratory Tests
The tests detailed in Table 1 will be performed by the local or central laboratory
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Sections 5.1 and 5.2, respectively, of the protocol.
Additional tests may be performed at any time during the study as determined necessary 
by the Investigator or required by local regulations.
Table 1
Protocol-Required Safety Laboratory Assessments
Laboratory Assessments
Parameters
Hematology

Leucocytes, erythrocytes, hemoglobin, hematocrit, 
platelets, differential count (neutrophils, eosinophils, 
basophils, monocytes, lymphocytes).
Clinical Chemistry

Sodium, potassium, chloride, bicarbonate, glucose
(fasting) urea, creatinine, protein, albumin, phosphate, 
calcium, total and direct bilirubin, alkaline 
phosphatase, ALT, AST, gamma-glutamyl-transferase 
(g-GT), creatine phosphokinase (CPK), urate, LDH.
Coagulation

Prothrombin time (INR) and activated thromboplastin 
time (aPTT).
Viral Serology

HIV (specific tests HIV-1 antibody, HIV-1/2 antibody, 
HIV-2 antibody), hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV) antibody.
Hormone

For post-menopausal women only to confirm 
postmenopausal status: Estradiol, follicle-stimulating 
hormone (FSH).
Pregnancy Test

Serum or urine human chorionic gonadotropin (hCG)
pregnancy test.
Urinalysis

Dipstick: pH, glucose, protein, blood, ketones, 
If there is a clinically significant positive result 
(confirmed by a positive repeated sample), urine will 
be sent to the laboratory for microscopy and culture. If 
there is an explanation for the positive dipstick results 
(e.g., menses), it should be recorded and there is no 
need to perform microscopy and culture.

Microscopic examination (sediment, RBCs, WBCs, 
casts, crystals, epithelial cells, bacteria), if blood or 
protein is abnormal.
Other Screening Tests

Urine drug screen (to include at minimum: 
amphetamines, barbiturates, cocaine, opiates, 
cannabinoids and benzodiazepines).

Alcohol breath test.

Urine cotinine
Page 523 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
82/Protocol BP40950, Version 2
The results of each test must be entered into the CRF.
Investigators must document their review of each laboratory safety report.
Additional Statistical Considerations for Clinical Laboratory Data

Standard Reference Ranges and Transformation of Data
Roche standard reference ranges, rather than the reference ranges of the Investigator, 
will be used for all parameters. For most parameters, the measured laboratory test result 
will be assessed directly using the Roche standard reference range. Certain laboratory 
parameters will be transformed to Roche’s standard reference ranges.

A transformation will be performed on certain laboratory tests that lack sufficiently 
common procedures and have a wide range of Investigator ranges, e.g., enzyme 
tests that include AST, ALT, and alkaline phosphatase and total bilirubin. Since the 
standard reference ranges for these parameters have a lower limit of zero, only the 
upper limits of the ranges will be used in transforming the data. Definition of 
Laboratory Abnormalities
For all laboratory parameters included, there exists a Roche predefined standard 
reference range. Laboratory values falling outside this standard reference range will be 
labeled “H” for high or “L” for low in participant listings of laboratory data.
In addition to the standard reference range, a marked reference range has been 
predefined by Roche for each laboratory parameter. The marked reference range is 
broader than the standard reference range. Values falling outside the marked reference 
range that also represent a defined change from baseline will be considered marked 
laboratory abnormalities (i.e., potentially clinically relevant). If a baseline value is not 
available for a participant, the midpoint of the standard reference range will be used as 
the participant’s baseline value for the purposes of determining marked laboratory 
abnormalities. Marked laboratory abnormalities will be labeled in the participant listings 
as “HH” for very high or “LL” for very low.
Page 524 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
83/Protocol BP40950, Version 2
Appendix 5
Contraceptive Guidance and Collection of Pregnancy 
Information
1.
DEFINITIONS

Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile.

Women in the following categories are considered to be Woman of Non-
Childbearing Potential (WONCBP)
a)
Pre-menarchal
b)
Pre-menopausal female with one of the following:
–
Documented hysterectomy.
–
Documented bilateral salpingectomy.
–
Documented bilateral oophorectomy.
Note: Documentation can come from the site personnel’s: review of 
participant’s medical records, medical examination, or medical history interview.
c)
Post-menopausal female
–
A post-menopausal state is defined as no menses for 12 months without an 
alternative medical cause other than menopause. A high follicle-stimulating 
hormone (FSH) level in the post-menopausal range may be used to confirm a 
post-menopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, a single FSH measurement is insufficient.
–
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-hormonal highly effective contraception methods if they wish 
to continue their HRT during the study. Otherwise, they must discontinue HRT 
to allow confirmation of post-menopausal status before study enrollment.
Page 525 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
84/Protocol BP40950, Version 2
2.
CONTRACEPTION GUIDANCE

Female Participants
Table 1
Highly Effective Contraceptive Methods
Highly Effective Non-hormonal Methods That Are User-Independenta
(Failure rate of 1% per year when used consistently and correctly)

Non-hormonal Intrauterine device (IUD)

Bilateral tubal occlusion
Vasectomized partner
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.
Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.
a) Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies.
3.
PREGNANCY TESTING
For WONCBP enrolled in the study, blood sample and urine pregnancy tests will be 
performed according to Schedule of Activity tables (see Section 1.3). If a urine 
pregnancy test is positive, it must be confirmed by a blood pregnancy test.
4.
COLLECTION OF PREGNANCY INFORMATION

Male participants with partners who become pregnant
The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study (see 
Section 8.3.5 Pregnancy). This applies only to male participants who receive study 
treatment.
Attempts should be made to collect and report details of the course and outcome of any 
pregnancy in the partner of a male participant exposed to study treatment. The
Investigator will record pregnancy information on the Clinical Trial Pregnancy Reporting 
Form and submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. 
When permitted by the site, the pregnant partner would need to sign an Authorization for 
Use and Disclosure of Pregnancy Health Information to allow for follow-up on her 
pregnancy. If the authorization has been signed, the Investigator should update the 
Clinical Trial Pregnancy Reporting Form with additional information on the course and 
outcome of the pregnancy when available. An Investigator who is contacted by the male 
participant or his pregnant partner may provide information on the risks of the pregnancy 
and the possible effects on the fetus, to support an informed decision in cooperation with 
Page 526 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
85/Protocol BP40950, Version 2
the treating physician and/or obstetrician. The female partner will be followed to 
determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to the Sponsor. Monitoring of the participant’s partner should 
continue until conclusion of the pregnancy. Any termination of the pregnancy will be 
reported regardless of fetal status (presence or absence of anomalies) or indication for 
procedure.

Female participants who become pregnant
The Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study (see Section 8.3.5 Pregnancy). 
Information will be recorded on the appropriate form and submitted to the Sponsor within
24 hours of learning of a participant's pregnancy. The participant will be followed to 
determine the outcome of the pregnancy. The Investigator will collect follow-up 
information on the participant and the neonate, which will be forwarded to the Sponsor. 
Monitoring of the participant should continue until conclusion of the pregnancy. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.
While pregnancy itself is not considered to be an AE or SAE, and should not be 
recorded on the AE eCRF, any pregnancy complication will be reported as an AE or 
SAE. A spontaneous abortion is always considered to be an SAE and will be reported as 
such. Any post-study pregnancy related SAE considered reasonably related to the study 
treatment by the Investigator, will be reported to the Sponsor as described in Appendix 2.
While the Investigator is not obligated to actively seek this information in former study 
participants, he/she may learn of an SAE through spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will be 
withdrawn from the study.
5
ABORTIONS
Any spontaneous abortion should be classified as a serious adverse event (as the 
Sponsor considers spontaneous abortions to be medically significant events), recorded 
on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no more 
than 24 hours after learning of the event; see Section 5 of Appendix 2).
Any induced abortion due to maternal toxicity and/or embryo-fetal toxicity should also be 
classified as serious adverse event, recorded on the Adverse Event eCRF, and reported 
to the Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5 of Appendix 2).
Elective abortion not associated with toxicity (e.g., induced abortion for personal reasons) 
does not require expedited reporting but should be reported as outcome of pregnancy on 
the Clinical Trial Pregnancy Reporting Form.
Page 527 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
86/Protocol BP40950, Version 2
6
CONGENITAL ANOMALIES/BIRTH DEFECTS
Any congenital anomaly/birth defect in a child born to a female participant or female 
partner of a male participant exposed to study treatment should be classified as a 
serious adverse event, recorded on the Adverse Event eCRF, and reported to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5 of Appendix 2).
Page 528 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
87/Protocol BP40950, Version 2
Page 529 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
88/Protocol BP40950, Version 2
Appendix 7
Correction Formulae for QTc Intervals
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 530 of 5056

RO7017773—F. Hoffmann-La Roche Ltd
89/Protocol BP40950, Version 2
Appendix 8
Formula for Calculation of Body Mass Index
BMI
Weight (kg)
Height (m)2
Unit Conversion:
1 kg2.2 lbs
1 inch2.54 cm
Example:
BMI of a participant being 1.70 m tall and weighing 80 kg:
80
27.7 kg/m2
(1.70)2
The participant’s standing height will be measured in bare feet standing with his/her 
heels and back in contact with the vertical bar of a wall-mounted measuring device. The 
head is held, so the participant looks straight forward. A level will be placed on the 
participant’s head to ensure that they are looking straight forward. The point at which the 
lower surface of the level intersects with the vertical measuring device will be the 
standing height.
Page 531 of 5056