Clinical trial NCT05136404
Conditions: Healthy
Sponsor: Loxo Oncology, Inc.
Start date: 2021-12-03; Completion date: 2022-03-14
Enrollment: 42 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The main purpose of this study is to compare the amount of selpercatinib that gets into the blood stream and how long it takes the body to get rid of it, when given as three different formulations in adult healthy participants. The information about any adverse effects experienced will be collected and the tolerability of selpercatinib will also be evaluated. The study may last up to 59 days including the 28 days of screening period.

Detailed description:

Arms: arm 1: Period 1: 20 milligram (mg) Selpercatinib capsule single oral dose administered orally on Day 1.

Period 2: 20 mg per milliliter (mL) Selpercatinib Powder for Oral suspension (PFOS) single oral suspension dose on Day 8.

Period 3: 20 mg/mL Selpercatinib Ready to Use (RTU) single oral suspension on Day 15. arm 2: Period 1: 20 mg/mL Selpercatinib RTU single oral suspension on Day 1.

Period 2: 20 mg Selpercatinib capsule single oral dose administered orally on Day 8.

Period 3: 20 mg/mL PFOS single oral suspension dose on Day 15. arm 3: Period 1: 20 mg/mL PFOS single oral suspension dose on Day 1.

Period 2: 20 mg/mL Selpercatinib RTU single oral suspension on Day 8.

Period 3: 20 mg Selpercatinib capsule single oral dose administered orally on Day 15.
Interventions: intervention 1: Selpercatinib
Intervention descriptions: intervention 1: Administered orally

Protocol documents:
Prot_000.pdf: 
Protocol 05 Protocol (b) J2G-MC-JZJU
An Open-Label, Randomized Study to Evaluate the Relative Bioavailbility of Selpercatinib in 3 Formulations 
for Pediatric Use
NCT05136404
Approval Date: 22-Nov-2021


CONFIDENTIAL 
Protocol number J2G-MC-JZW(b) 
Title Page 
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of selpercatinib (L Y3527723) unless such persons are bound by a confidentiality agreement with Eli Lilly and 
Company or its subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act Exemption 4 and may not be reproduced or otherwise 
disseminated without the written approval of Eli Lilly and Company or its subsidiaries. 
Protocol Title: An Open-Label, Randomized Study to Evaluate the Relative Bioavailability of 
Selpercatinib in 3 Formulations for Pediatric Use 
Protocol Number: J2G-MC-JZm 
Amendment Number: (b) 
Compound: L Y3527723 
Brief Title: A Relative Bioavailability Study ofSelpercatinib Fornmlations for Pediatric Use 
Study Phase: 1 
Sponsor Name: Eli Lilly and Company on behalf ofLoxo Oncology, Inc., a wholly owned 
subsidiary of Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana 46285 USA 
Regulatory Agency Identifier Number(s) 
IND: 133193 
Approval Date: Protocol Electronically Signed and Approved by Lilly on date provided below. 
Approval Date: 22-Nov-2021 GMT 
1 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
2
Medical Monitor Name and Contact Information will be provided separately.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
3
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Original Protocol
19-July-2021
Amendment (a)
07-Sep-2021
Amendment [b] 
This amendment is considered to be nonsubstantial.
Overall Rationale for the Amendment:
The protocol is amended to correct the timepoints for clinical laboratory assessments in the 
Schedule of Activities. The following table describes the change made in amendment (b).
Section # and Name
Description of Change
Brief Rationale
1.3 Schedule of 
Activities
Physical examination added to 
Day 21.
Missing assessments added.
1.3 Schedule of 
Activities
Pregnancy test removed from 
early discontinuation.
Not required.
1.3 Schedule of 
Activities
Added ECG assessments to 
Day 21.
Missing assessments added.
1.3 Schedule of 
Activities
Added vital signs assessments to 
Day 21.
Missing assessments added.
1.3 Schedule of 
Activities
Moved time points for collection 
of clinical laboratory tests from 
Day 8 to Day 9 (24 hours 
postdose).
Moved time points for collection 
of clinical laboratory tests from 
Day 15 to Day 16 (24 hours 
postdose).
Added collection of clinical 
laboratory tests on Day 21.
To correct the schedule of 
activities for incorrect and 
missing clinical laboratory 
assessment time points.
5.1 Inclusion Criteria
Amended the age range for 
participant inclusion.
Per site request.
10.2 Appendix 2: 
Clinical Laboratory
Tests
Added total Cholesterol, HDL-C, 
and LDL-C as clinical chemistry 
parameters.
New parameters now 
required as part of clinical 
chemistry assessment.
10.2 Appendix 2: 
Clinical Laboratory 
Tests
Added footnote ‘e’ to outline 
timing of pregnancy tests.
For accuracy.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
4
Table of Contents
1.
Protocol Summary......................................................................................................7
1.1.
Synopsis.......................................................................................................................7
1.2.
Schema.........................................................................................................................9
1.3.
Schedule of Activities (SoA) ......................................................................................10
2.
Introduction..............................................................................................................14
2.1.
Study Rationale ..........................................................................................................14
2.2.
Background ................................................................................................................14
2.3.
Benefit/Risk Assessment ............................................................................................14
3.
Objectives and Endpoints.........................................................................................16
4.
Study Design .............................................................................................................17
4.1.
Overall Design............................................................................................................17
4.1.1.
Screening....................................................................................................................17
4.1.2.
Treatment and Assessment Period...............................................................................17
4.2.
Scientific Rationale for Study Design .........................................................................18
4.3.
Justification for Dose..................................................................................................18
4.4.
End of Study Definition..............................................................................................18
5.
Study Population ......................................................................................................19
5.1.
Inclusion Criteria........................................................................................................19
5.2.
Exclusion Criteria.......................................................................................................20
5.3.
Lifestyle Considerations .............................................................................................22
5.3.1.
Meals and Dietary Restrictions ...................................................................................23
5.3.2.
Caffeine, Alcohol, and Tobacco..................................................................................23
5.3.3.
Activity ......................................................................................................................23
5.4.
Screen Failures...........................................................................................................23
6.
Study Intervention(s) and Concomitant Therapy ...................................................24
6.1.
Study Intervention(s) Administered ............................................................................24
6.1.1.
Administration Details................................................................................................24
6.2.
Preparation, Handling, Storage, and Accountability....................................................24
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................25
6.4.
Study Intervention Compliance...................................................................................25
6.5.
Dose Modification......................................................................................................25
6.6.
Continued Access to Study Intervention After the End of the 
Study..........................................................................................................................25
6.7.
Treatment of Overdose ...............................................................................................25
6.8.
Concomitant Therapy .................................................................................................26
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................27
7.1.
Discontinuation of Study Intervention ........................................................................27
7.1.1.
Liver Chemistry Stopping Criteria ..............................................................................27
7.1.2.
QTc Stopping Criteria.................................................................................................28
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................28
7.3.
Lost to Follow-up .......................................................................................................28


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
5
8.
Study Assessments and Procedures .........................................................................30
8.1.
Efficacy Assessments .................................................................................................30
8.2.
Safety Assessments ....................................................................................................30
8.2.1.
Physical Examinations................................................................................................30
8.2.2.
Vital Signs..................................................................................................................30
8.2.3.
Electrocardiograms.....................................................................................................31
8.2.4.
Clinical Safety Laboratory Tests.................................................................................31
8.2.5.
Pregnancy Testing ......................................................................................................31
8.2.6.
Safety Monitoring.......................................................................................................32
8.3.
Adverse Events, Serious Adverse Events, and Product 
Complaints .................................................................................................................34
8.3.1.
Timing and Mechanism for Collecting Events ............................................................34
8.3.2.
Pregnancy...................................................................................................................36
8.3.3.
Product Complaints ....................................................................................................37
8.4.
Pharmacokinetics........................................................................................................37
8.5.
Pharmacodynamics.....................................................................................................38
8.6.
Genetics .....................................................................................................................38
8.7.
Biomarkers.................................................................................................................38
8.8.
Immunogenicity Assessments.....................................................................................38
8.9.
Health Economics.......................................................................................................38
8.10.
Product Acceptability and Palatability Assessments....................................................38
9.
Statistical Considerations.........................................................................................39
9.1.
Statistical Hypotheses.................................................................................................39
9.2.
Analyses Sets .............................................................................................................39
9.2.1.
Study Participant Disposition......................................................................................39
9.2.2.
Study Participant Characteristics.................................................................................39
9.2.3.
Treatment Compliance................................................................................................39
9.3.
Statistical Analyses.....................................................................................................39
9.3.1.
Safety Analyses ..........................................................................................................39
9.3.2.
Pharmacokinetic Analyses ..........................................................................................40
9.3.3.
Pharmacodynamic Analyses .......................................................................................40
9.3.4.
Pharmacokinetic/Pharmacodynamic Analyses ............................................................40
9.4.
Interim Analysis .........................................................................................................41
9.5.
Sample Size Determination.........................................................................................41
10.
Supporting Documentation and Operational Considerations ................................42
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................42
10.1.1.
Regulatory and Ethical Considerations........................................................................42
10.1.2.
Informed Consent Process ..........................................................................................43
10.1.3.
Data Protection...........................................................................................................43
10.1.4.
Dissemination of Clinical Study Data .........................................................................43
10.1.5.
Data Quality Assurance ..............................................................................................44
10.1.6.
Source Documents......................................................................................................45
10.1.7.
Study and Site Start and Closure.................................................................................45
10.1.8.
Publication Policy.......................................................................................................46
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................47


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
6
10.2.1.
Blood Sampling Summary..........................................................................................48
10.3.
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting .......................................................................................................49
10.3.1.
Definition of AE.........................................................................................................49
10.3.2.
Definition of SAE.......................................................................................................50
10.3.3.
Definition of Product Complaints ...............................................................................51
10.3.4.
Recording and Follow-Up of AE and/or SAE and Product 
Complaints .................................................................................................................51
10.3.5.
Reporting of SAEs......................................................................................................53
10.3.6.
Regulatory Reporting Requirements ...........................................................................53
10.4.
Appendix 4: Contraceptive and Barrier Guidance .......................................................55
10.4.1.
Definitions..................................................................................................................55
10.4.2.
Contraception Guidance..............................................................................................55
10.5.
Appendix 5: Genetics .................................................................................................58
10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ...............................................................................................................59
10.7.
Appendix 7: Abbreviations and Definitions ................................................................64
10.8.
Appendix 8: Protocol Amendment History .................................................................66
11.
References.................................................................................................................68


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
7
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: An Open-Label, Randomized Study to Evaluate the Relative Bioavailability of 
Selpercatinib in 3 Formulations for Pediatric Use
Brief Title: A Relative Bioavailability Study of Selpercatinib Formulations for Pediatric Use
Rationale:
This is a bioavailability testing the different formulation that has been used in pediatric studies
Objectives, Endpoints, and Estimands:
Objectives
Endpoints
Primary

To evaluate the relative bioavailability 
of RTU and PFOS suspensions
compared to the capsule formulation

Cmax, AUC(0-∞), AUC0-tlast, and 
tmax of selpercatinib
Secondary

To evaluate the safety and tolerability 
of a single dose of 20-mg oral dose of 
selpercatinib RTU and PFOS
suspensions

To assess the palatability of 
selpercatinib RTU and PFOS 
suspensions

Summary of the number, severity, and 
type of treatment-emergent AEs and 
serious adverse events

Responses to palatability 
questionnaire (RTU suspension only)
Overall Design:
Study JZJU will be an open-label, Phase 1 randomized, 3-formulation, 3-period, crossover study 
in adult heathy male and female participants. The ready-to-use (RTU) 20 mg suspension and the 
powder for oral suspension (PFOS) 20 mg/mL suspension will be compared to the 20 mg capsule 
formulation
Safety assessments, including AEs, concomitant medications, medical assessments, clinical 
laboratory tests, vital signs, and ECGs, and blood sampling for PK, will be performed.
Screening
All participants will be screened within 28 days prior to enrollment.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
8
Treatment and Assessment Period
Participants will be admitted to the CRU on Day -1. On the morning of Day 1, participants will 
be randomized to 1 of 3 treatment sequences and will receive single doses of 20-mg selpercatinib 
on each of Days 1, 8, and 15 as either the RTU suspension, the PFOS, or the capsule, and will be 
dosed according to the randomization sequence following an overnight fast of at least 10 hours.
The treatment sequences to be used are as follows:
Abbreviations: PFOS = powder for oral suspension; RTU = ready to use.
There will be a washout of 7 days between doses of selpercatinib.
Participants will remain resident at the CRU for the full duration of the treatment period (i.e., up 
to Day 21).
Number of Participants:
Up to approximately 42 participants will be enrolled to ensure that at least approximately 
36 participants complete the study.
Intervention Groups and Duration:
Participants will participate in 1 treatment.
The study duration for all participants is expected to be up to 59 days.
Data Monitoring Committee: No
Treatment Sequence A 
•LI ~~'===~f--=..,.•I •==-, .. 1 
Treatment Sequence B 
.1 
Treatment Sequence C 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
9
1.2.
Schema
Abbreviations: CRU = clinical research unit; PFOS = powder for oral suspension; RTU = ready to use.
T* 
* 
* 
-28 
-1 
1 
8 
15 
21 
screening 
* 
20 mg selpercatinib as either the RTU suspension, the PFOS, or the capsule, according to the randomization schedule 
T admission to the CRU 
T discharge from the CRU / study discharge 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
10
1.3.
Schedule of Activities (SoA)
Screening
Days
ED
Comments
Procedure 
-28 to -2 
days prior 
to Day 1
-
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Informed 
consent
X
Inclusion and 
exclusion 
criteria
X
Demography
X
Participant 
Admission to 
CRU
X
Participant 
Discharge 
from CRU
X
Outpatient visit
X
Medical 
history 
(includes 
substance 
usage [and 
family history 
of premature 
cardiovascular 
disease])
X
Past and 
current 
medical 
conditions
X
Physical 
examination
X
X
X
X
Full physical 
examination 
(including 
height and 
weight) to be 
performed at 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
11
Screening
Days
ED
Comments
Procedure 
-28 to -2 
days prior 
to Day 1
-
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
screening. 
Symptom-
driven 
physical 
examination
s to be 
performed at 
all other 
timepoints.
Serum or urine 
pregnancy test 
(all females)
X
X
Serum 
pregnancy 
test will be 
performed at 
screening. 
Urine 
pregnancy 
test will be 
performed at 
admission to 
the CRU.
HIV, and 
hepatitis B and 
C screen
X
Urine or breath 
ethanol test 
X
X
Urine drug 
screen
X
X
12-lead ECG
X
P, 
2h
P, 
2h
P, 
2h
X
X
Single ECGs 
are required.
Vital signs 
(supine)
X
X
P, 
1, 
2h
24
h
X
P, 
1, 
2h
24
h
X
P, 
1, 
2h
24
h
X
X
X
Time points 
may be 
added, if 
warranted 
and agreed 
upon 
between 


CONFIDENTIAL 
Protocol number J2G-MC-JZW(b) 
Screening 
Days 
ED 
Comments 
-28 to -2 
Procedure 
days prior 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
to Da 1 
Lilly and the 
investigator. 
Assessments 
on Days 5 
12, and 19 
should be 
pe1formed in 
themoming 
at a time 
relative to 
predose on 
Days I, 8 
and 15, 
res ectivel 
See 
Appendix 2 
Clinical 
(Section 
laboratory tests 
X 
X 
24 
X 
24 
X 
24 
X 
X 
10.2), 
(include liver 
h 
h 
h 
Clinical 
chemistrie,s) 
Laborato1y 
Tests, for 
details. 
Genetic sample 
X 
12 


CONFIDENTIAL 
Procedure 
Randomization 
Selpercatinib 
administration 
Taste 
Assessment 
Questiollllaire 
Adverse event 
/Serious 
adverse event 
review 
Concomitant 
medication 
review 
Screening 
-28 to -2 
X 
X 
2 
3 
4 
X 
X 
X 
X 
X 
5 
6 
7 
8 
X 
X 
Protocol number J2G-MC-JZW(b) 
Days 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
X 
X 
ED 
Comments 
X 
X 
Tobe 
performed 
for theRTU 
suspension 
andPFOS 
fonnulations 
only 
immediately 
after dosin . 
Abbreviations: CRU = clinical research unit; ECG = electrocardiogram; ED = early discontinuation; HIV = human immunodeficiency vims; P = predose; 
PFOS = powder for oral suspension; PK= phaimacokinetic; RTU = ready to use. 
13 


CONFIDENTIAL 
Protocol number J2G-MC-JZW(b) 
2. 
Introduction 
Selpercatinib (L Y3527723) has been developed by Loxo Oncology, Inc and acquired by Eli Lilly 
and Company (Lilly), and has been approved by the Food and Drng Administration for the 
t1eatment of advanced or metastatic RET-mutant MTC; advanced or metastatic RET fusion-
positive thyroid cancer, in adults and children 2'.12 years; and for the treatment of metastatic RET 
fusion-positive non-small cell lung carcinoma (NSCLC) in adults. Full details of the preclinical 
and clinical safety and tolerability data are contained in the investigator's brochure (IB). 
2.1. 
Study Rationale 
This is a relative bioavailability study testing the different fo1mulations that has been used in 
pediatric studies. 
2.2. 
Background 
Selpercatinib (L Y3527723) is a highly potent and specific small-molecule inhibitor of the RET 
kinase, with minimal inhibition of other kinase and nonkinase targets. 
Selpercatinib doses have been evaluated in healthy paiticipants and patients with advanced or 
metastatic RET-mutant MTC, advanced or metastatic RET fusion-positive thyroid cancer, other 
RET fusion-positive solid tumors, and metastatic RET fusion-positive NSCLC across Phase 1, 2, 
and 3 clinical studies. Across these studies, single oral doses of selpercatinib were administered 
over a range of 20 to 720 mg. Multiple oral doses of 160 mg/day selpercatinib were administered 
orally twice daily for 10 days in healthy volunteers. Pediactric dose was selected to be 92 mg/m2, 
(maximum 160 mg BID). 
The phaimacokinetics of selpercatinib is characterized by good oral bioavailability, with a tmax 
of approxin1ately 2 hours (range Oto 8.1 hours). CYP3A4 mediated metabolism constitutes the 
major route of elimination, and the t½ is approximately 32 hours in healthy volunteers. The 
V ss/F and CL/F of selpercatinib increased with increasing body weight (2 7 kg to 177 kg). No 
clinically significant differences in the PK of selpercatinib were observed based on age (15 years 
to 90 years), or sex. As the PK of selpercatinib have been demonstrated to be linear in the dose 
range of 20 to 160 mg in adult cancer patients, results from study JZm can be expected to be 
applicable across the therapeutic dose range. 
More detailed info1mation about the pha1macokinetics (PK) and absorption, distribution, 
metabolism, and excretion properties of selpercatinib may be found in the IB. 
2.3. 
Benefit/Risk Assessment 
There is no anticipated therapeutic benefit for the healthy pa1ticipants in this study. However, 
participants may benefit from the screening procedures (through detection of unknown health 
issues) even if they receive no therapeutic benefit from the study. 
14 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
15
The dose of selpercatinib to be given in this study is 20 mg. The safety profile of selpercatinib is 
very well tolerated in healthy volunteers, with the low rates of study drug discontinuation due to 
adverse events (AEs). 
As outlined in the IB, the most common toxicities associated with selpercatinib in patients are 
monitorable and reversible and include dry mouth, diarrhea, hypertension, fatigue, constipation, 
AST/ALT elevation, headache, nausea, edema peripheral, abdominal pain, rash, 
electrocardiogram (ECG) QT prolonged, cough, vomiting, dyspnea and increased blood 
creatinine. Events of special interest include hypersensitivity, liver-function test abnormalities, 
thrombocytopenia, and hypertension. None of these events of special interest have been observed 
to date in healthy participants.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of selpercatinib may be found in the IB.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
16
3.
Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the relative bioavailability 
of RTU and PFOS suspensions
compared to the capsule formulation

Cmax, AUC(0-∞), AUC0-tlast, and 
tmax of selpercatinib
Secondary

To evaluate the safety and tolerability 
of a single 20-mg oral dose of 
selpercatinib RTU and PFOS
suspensions

To assess the palatability of 
selpercatinib RTU and PFOS
suspensions

Summary of the number, severity, and 
type of treatment-emergent AEs and 
serious adverse events

Responses to palatability 
questionnaire (RTU suspension only)
Abbreviations: AE = adverse event; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC0-tlast = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; PFOS = powder for 
oral suspension; RTU = ready to use; tmax = time to maximum observed drug concentration.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
17
4.
Study Design
4.1.
Overall Design
Study JZJU will be an open-label, Phase 1 randomized, 3-formulation, 3-period, crossover study 
in adult heathy male and female participants. The ready-to-use (RTU) 20-mg suspension and the 
powder for oral suspension (PFOS) 20 mg/mL formulation will be compared to the 20 mg 
capsule formulation.
The schematic in Section 1.2 illustrates the study design. 
Safety assessments, including AEs, concomitant medications, medical assessments, clinical 
laboratory tests, vital signs, and ECGs, and blood sampling for PK, will be performed according 
to the SoA (Section 1.3).
4.1.1.
Screening
All participants will be screened within 28 days prior to enrollment.
4.1.2.
Treatment and Assessment Period
Participants will be admitted to the clinical research unit (CRU) on Day -1. On the morning of 
Day 1, participants will be randomized to 1 of 3 treatment sequences and will receive single 
doses of 20 mg selpercatinib on each of Days 1, 8, and 15 as either the RTU suspension, the 
PFOS, or the capsule, and will be dosed according to the randomization sequence following an 
overnight fast of at least 10 hours.
The treatment sequences to be used are as follows:
Abbreviations: PFOS = powder for oral suspension; RTU = ready to use.
There will be a washout of 7 days between doses of selpercatinib.
Participants will remain resident at the CRU for the full duration of the treatment period (i.e., up 
to Day 21).
Treatment Sequence A 
Treatment Sequence B 
Treatment Sequence C 


CONFIDENTIAL 
Protocol number J2G-MC-JZW(b) 
4.2. 
Scientific Rationale for Study Design 
In order to allow each paiticipant to act as his/her own control for safety and PK compai·isons, a 
3-period crossover design has been selected. This study will also be open label as the study 
prima1y endpoint PK measures are objective rather than subjective. 
Conducting the study in healthy adult pa1ticipants mitigates the potential confounding effects of 
the disease state and concomitant medications in pa1ticipants with metastatic RET 
:fosion-positive NSCLC, advanced or metastatic RET-mutant MTC, or advanced or metastatic 
RET :fosion-positive thyroid cancer. A population of healthy pa1ticipants is frequently used in the 
assessment of the PK of both small and large molecules. 
The doses, paiticipant population, study duration, and sample collection timing are considered 
adequate to achieve the study objectives. 
4.3. 
Justification for Dose 
Dose being used is representative of the typical dose size to be used in pediatric studies. As the 
PK of selpercatinib have been demonstrated to be lineai· in the dose range of 
m 
adult cancer patients, results from study JZm can be expected to be applicable across the 
therapeutic dose range. 
4.4. 
End of Study Definition 
A pa1ticipant is considered to have completed the study if he/she has completed all required 
periods of the study including the last visit or the last scheduled procedure shown in the SoA. 
The end of the study is defined as the date of the last visit of the last pa1ticipant in the study. 
18 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
19
5.
Study Population
Eligibility of participants for enrollment in the study will be based on the results of screening 
medical history, physical examination, vital signs, clinical laboratory tests, and ECG.
The inclusion and exclusion criteria used to determine eligibility should be applied at screening 
only, and not continuously throughout the study. Clinical laboratory assessments and vital signs 
may be repeated from screening through Day -1 at the discretion of the investigator in order to 
confirm eligibility.
Screening may occur up to 28 days prior to enrollment. Participants who are not enrolled within 
28 days of screening may undergo an additional medical assessment and/or clinical 
measurements to confirm their eligibility. In such instances, the following screening tests and 
procedures should be repeated: clinical laboratory assessments and vital signs.
Prospective approval of protocol deviations to 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 criteria apply:
Age
1. Participant must be 18 to 65 years of age, inclusive, at the time of signing the informed 
consent form (ICF).
Type of Participant and Disease Characteristics
2. Participants who are overtly healthy as determined by medical evaluation including 
medical history, physical examination, and vital signs.
3. Participants who have clinical laboratory test results within the normal reference range 
for the population or investigative site, or results with acceptable deviations that are 
judged to be not clinically significant by the investigator.
4. Participants who have venous access sufficient to allow for blood sampling as per the 
protocol.
Weight
5. Have a body mass index within the range 18.0 to 35.0 kg/m2 (inclusive).
Sex and Contraceptive/Barrier Requirements
6. Male or female participants - contraceptive use by men or women should be consistent 
with local regulations regarding the methods of contraception for those participating in 
clinical studies.
a.
Male participants:

Are not required to adhere to contraceptive requirements.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
20
b. Female participants:

Female participants of childbearing potential (see Appendix 4 [Section 10.4]) who 
are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) 
or in a same-sex relationship (as part of their preferred and usual lifestyle) must 
agree to either remain abstinent or stay in a same-sex relationship without sexual 
relationships with males.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods), declaration of abstinence just for the duration of a study, and 
withdrawal, are not acceptable methods of contraception.

Female participants of childbearing potential, who are not abstinent as described 
above, must agree to use a highly effective method of contraception (that is, one 
with less than 1% failure rate) such as combination oral contraceptives, 
implanted/injected contraceptives, intrauterine devices, or sterile partner until 
30 days after the last dose of study medication.

Female participants not of childbearing potential are not required to use 
contraception. This includes females who are:
o
Infertile due to surgical sterilization (hysterectomy, bilateral 
oophorectomy, bilateral salpingectomy, bilateral tubal occlusion, or 
bilateral tubal ligation), or congenital anomaly (for example, Müllerian 
agenesis)
o
Postmenopausal as defined in Appendix 4 (Section 10.4).
Informed Consent
7. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1),
which includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Have a positive pregnancy test at screening or Day -1, where applicable.
2. Are planning to become pregnant during the study or within 1 month of study 
completion.
3. Are women who are lactating.
4. Have known allergies to selpercatinib-related compounds or any components of the 
formulation of selpercatinib, or history of significant atopy.
5. Have a history of allergic reactions to medications or food products.
6. Have a clinically significant abnormality of blood pressure and/or pulse rate as
determined by the investigator.
7. Clinically significant abnormalities on ECG as determined by the investigator or
prolongation of the corrected QT interval using or Fridericia’s formula (QTcF) >450 
msec at screening.


CONFIDENTIAL 
Protocol number J2G-MC-JZJU(b)  
 
21 
8. Have clinically significant active cardiovascular disease or history of myocardial 
infarction within 6 months prior to the planned start of selpercatinib. 
9. Have a history or presence of cardiovascular, respiratory, renal, gastrointestinal, 
endocrine, hematological, or neurological disorders capable of significantly altering the 
absorption, metabolism, or elimination of drugs; of constituting a risk when taking the 
investigational product; or of interfering with the interpretation of data. Appendectomy, 
uncomplicated hernia, splenectomy, and cholecystectomy are considered as acceptable. 
10. Have a creatinine clearance <60 mL/min, as calculated using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) equation (Levey et al, 2009). 
eGFR = 141 × min(Scr/K, 1)α × max(Scr/K, 1)-1.209 × 0.993age 
× 1.018 (if female) 
× 1.159 (if black) 
11. Show a history of central nervous system conditions such as strokes, transient ischemic 
attacks, significant head trauma, seizures, central nervous system infections, migraine, 
brain surgery, or any other neurological conditions that, in the opinion of the 
investigator, increase the risk of participating in the study. 
12. Have a history or presence of neuropsychiatric disease (e.g., bipolar disorder, 
schizophrenia, depression) considered as clinically significant by the investigator. 
13. Regularly use known drugs of abuse or show positive findings on drug screening. 
14. Show evidence of human immunodeficiency virus infection and/or positive human 
immunodeficiency virus antibodies. 
15. Presence of hepatitis B surface antigen at screening or within 3 months prior to first 
dose of study intervention. 
16. Positive hepatitis C antibody test result at screening or within 3 months prior to first 
dose of study intervention.  
NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can 
be enrolled if a confirmatory negative hepatitis C RNA test is obtained. 
17. Positive hepatitis C RNA test result at screening or within 3 months prior to first dose 
of study intervention.  
NOTE: Test is optional and participants with negative hepatitis C antibody test are not 
required to also undergo hepatitis C RNA testing. 
18. Have donated blood of more than 500 mL within the previous 3 months of study 
screening. 
19. Have any medical conditions, medical history, or are taking any medications that are 
contraindicated in the selpercatinib label. 
Prior/Concomitant Therapy
 
20. Have participated, within the last 30 days of admission, in a clinical study involving an 
investigational product. If the previous investigational product has a long half-life, 
5 half-lives or 30 days (whichever is longer) should have passed. 
21. Have previously completed or withdrawn from this study or any other study 
investigating selpercatinib, and have previously received the investigational product. 


C O N FI D E N TI A L  
Pr ot oc ol n u m ber J 2 G- M C -J ZJ U( b)  
 
2 2 
2 2.  Use of H 2  bl oc kers, pr ot o n- p u m p i n hi bit ors, a n d ot her a ntaci ds wit hi n 7 d a ys of 
scree ni n g. 
2 3.  Are i nte n di n g t o use o ver-t he-c o u nter or prescri pti o n me dicati o n, i ncl u di n g dietar y 
s u p ple me nts, wit hi n 1 4 da ys pri or t o d osi n g a n d u ntil st u d y disc h ar ge (a part fr o m 
occasi o nal aceta mi n o p he n ( ≤2 g/ 2 4 h o urs), h or m o nal c o ntrace pti o n, or 
h or m o ne- re pl ace m e nt t hera p y). 
Prior/Concurent Clinical Study Experience 
2 4.  Are c urre ntl y e nr olle d i n a n y ot h er cli nical st u d y i n v ol vi n g a n i n vesti gati o n al pr o d uct 
or a n y ot her t y pe of me di cal res earc h j u d ge d n ot t o be scie ntificall y or me dicall y 
c o m pati ble wit h t his st u d y  
Other Exclusions
 
2 5.  Ha ve a n a ver a ge w ee kl y alc o h ol i nta ke t hat e x cee ds 2 1 u nits per wee k ( m ales) a n d 1 4 
u nits per wee k (fe mal es ); 1 u nit = 1 2 oz or 3 6 0 m L of b eer; 5 oz or 1 5 0 m L of wi ne; 
1. 5 oz or 4 5 m L of distille d s pirit(s) 
2 6.  Are u n willi n g t o st o p alc o h ol c o ns u m pti o n 4 8 h o urs pri or t o eac h a d missi o n t o t he 
C R U, a n d w hile resi de nt at t he C R U. At all ot her ti mes, partici pa nts m ust a gree t o 
c o ns u me n o m ore t ha n 2 u nits per da y 
2 7.  Are s m o kers of m ore t ha n 1 0 ci garettes or e-ci garettes, or 3 ci gars or 3 pi pes, per da y 
a n d are u n a ble t o r efr ai n fr o m s m o ki n g w hile resi de nt at t he C R U 
2 8.  C o ns u me e x cessi ve a m o u nts of c offee, tea, c ola, or ot her caffei nate d be v era ges per 
da y, or ar e u n willi n g t o st o p caffei ne c o ns u m pti o n 4 8 h o urs pri or t o a d missi o n a n d 
w hil e resi de nt at t he C R U. E x cessi ve a m o u nt is defi ne d as greater t ha n 6 s er vi n gs 
( 1 ser vi n g is a p pr o xi matel y e q ui val e nt t o 1 2 0 m g of caffei ne). 
2 9.  Ar e u na ble t o c o ns u me a sta n dar d meal.  
3 0.  C urre ntl y us e or s h o w e vi de nce of s u bsta n ce a b us e (i ncl u di n g alc o h ol a b us e) or 
de pe n de n ce wit hi n t he past 6 m o nt hs base d o n me dical hist or y at scree ni n g visit 
3 1.  I n a bilit y t o c o m pl y wit h t he dietar y re gi me n of t he C R U 
3 2.  Are Lill y e m pl o yees or are a n e m pl o yee of a n y t hir d  part y i n v ol ve d i n t he st u d y w h o 
re q uire e x cl usi o n of t heir e m pl o yees 
3 3.  Are i n vesti gat or site pers o n nel directl y affiliate d wit h t his st u d y a n d/ or t heir i m me diate 
fa milies. I m me di ate fa mil y is defi ne d as a s p o use, pare nt, c hil d, or si bli n g, w het her 
bi ol o gical or le gall y a d o pte d 
3 4.  I n t he o pi ni o n of t h e i n vesti gat or or s p o ns or, are u ns uita ble f or i ncl usi o n i n t he st u d y 
5.3.
 
Lifestyle Considerations
 
T hr o u g h o ut t he st u d y, partici pa nts ma y u n d er g o me dical assess me nts a n d re vie w of c o m plia nce 
wit h re q uire me nts bef ore c o nti n ui n g i n t he st u d y. 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
23
5.3.1.
Meals and Dietary Restrictions
During the confinement period, participants will consume only food and beverages that are 
provided to them by the CRU staff. Standard meals (e.g., breakfast, lunch, dinner, and snack) 
will be provided to the participants while resident at the CRU.
Selpercatinib will be dosed in the fasted state on Days 1, 8, and 15. On these dosing occasions, 
the participants will be fasted overnight (at least 10 hours) prior to dosing and refrain from 
consuming water from 1 hour predose until 2 hours postdose, excluding the amount of water 
consumed at dosing. Food is allowed from 4 hours postdose. At all other times during the study, 
participants may consume water ad libitum. 
5.3.2.
Caffeine, Alcohol, and Tobacco
Participants will abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, 
tea, cola drinks, and chocolate) for 48 hours prior to admission until after discharge from the 
study.
Participants will abstain from alcohol for 48 prior to admission until after discharge from the 
study.
Participants who use tobacco products will be instructed that use of nicotine-containing products 
(including nicotine patches) will not be permitted while they are in the clinical unit.
5.3.3.
Activity
Participants will abstain from strenuous exercise for 48 hours before each blood collection for 
clinical laboratory tests. Participants may participate in light recreational activities during the 
study (e.g., watching television, reading).
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently assigned to study intervention. 
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened. Repeating of laboratory tests during the screening period or repeating screening tests 
to comply with the protocol-designated screening period does not constitute rescreening.


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Protocol number J2G-MC-JZJU(b) 
24
6.
Study Intervention(s) and Concomitant Therapy
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
6.1.
Study Intervention(s) Administered
Table JZJU.1.
Study Interventions Administered
Arm Name
Capsule
Ready to use
PFOS
Study Intervention 
Selpercatinib
Selpercatinib
Selpercatinib
Dosage Formulation
Capsule
Suspension
Suspension
Unit dose 
strengths/Dosage Levels
1 20-mg capsule
20 mg/mL
20 mg/mL
Route of Administration
Oral
Oral
Oral
Dosing Instructions
1 capsule taken 
on Day 1, 8, or 15, 
according to the 
randomization schedule
1 mL taken 
on Day 1, 8, or 15, 
according to the 
randomization schedule
1 mL taken 
on Day 1, 8, or 15, 
according to the 
randomization schedule
Abbreviations: PFOS = powder for oral suspension.
6.1.1.
Administration Details
A single oral dose of selpercatinib 20 mg will be administered in the morning of Days 1, 8, 
and 15. Capsules and suspension of selpercatinib will be administered with approximately 
240mL of room-temperature water. All doses will be administered while in a sitting position. 
Participants will not be allowed to lie supine for 2 hours after dosing, unless clinically indicated 
or for study procedures.
Selpercatinib capsules should be swallowed whole. Participants should not break, empty, or 
chew the capsules.
Further instructions will be provided.
On dosing days, participants will adhere to meal restrictions as outlined in Section 5.3.1.
6.2.
Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate storage conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention. Only authorized 
study personnel may supply, prepare, or administer study intervention. All study 
intervention must be stored in a secure, environmentally controlled, and monitored 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
25
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized study personnel.
3. The investigator or authorized study personnel are responsible for study intervention 
accountability, reconciliation, and record maintenance (i.e., receipt, reconciliation, and 
final disposition records).
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the study reference manual.
Note: in some cases, sites may destroy the material if the evaluator has verified and documented 
that the site has appropriate facilities and written procedures to dispose of clinical materials.
Samples of the specific batches of selpercatinib used in the study will be retained; details will be 
provided separately.
6.3.
Measures to Minimize Bias: Randomization and Blinding
This is an open-label study. There is no bias as the primary endpoint is PK and objective in 
measure.
Participants will be assigned a unique number (randomization number) on Day 1. The 
randomization number encodes the participant’s assignment to be dosed with either the capsule, 
RTU suspension, or PFOS on Days 1, 8, and 15, according to the randomization schedule 
generated prior to the study by the Statistics Department at Covance.
6.4.
Study Intervention Compliance
Participants are dosed at the site and will receive study intervention directly from the investigator 
or designee, under medical supervision. The date and time of each dose administered in the clinic 
will be recorded in the source documents and recorded in the electronic case report form (eCRF). 
The dose of study intervention and study participant identification will be confirmed at the time 
of dosing by a member of the study site staff other than the person administering the study 
intervention. Study site personnel will examine each participant’s mouth to ensure that the study 
intervention was ingested.
When the individual dose for a participant is prepared from a bulk supply, the preparation of the 
dose will be confirmed by a second member of the study site staff. 
6.5.
Dose Modification
Dose modification will not be permitted in this study.
6.6.
Continued Access to Study Intervention After the End of the Study
Selpercatinib will not be made available to participants after completion of the study.
6.7.
Treatment of Overdose
For the purposes of this study, an overdose of selpercatinib is considered as any dose higher than 
the dose assigned. There is no specific antidote for selpercatinib.
In the event of an overdose, the investigator/treating physician should:


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
26
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/serious adverse events (SAE) and laboratory 
abnormalities until study intervention can no longer be detected systemically (at least 5
days).
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF.
Decisions regarding dose interruptions will be made by the investigator in consultation with the 
medical monitor based on the clinical evaluation of the participant.
6.8.
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with:
a. Reason for use
b. Dates of administration including start and end dates
c.
Dosage information including dose and frequency for concomitant therapy of special 
interest
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.
Participants must abstain from taking prescription or nonprescription drugs (including vitamins 
and dietary or herbal supplements) within 14 days before the start of study intervention until 
discharge from the study.
Acetaminophen, at doses of ≤2 grams/24 hours, is permitted for use at the discretion of the 
investigator for the treatment of headache, etc. Contraceptive medication is permitted as per the 
contraception requirements (Appendix 4 [Section 10.4]), and hormone-replacement therapy is 
also allowed.
Other medication may be considered on a case-by-case basis by the investigator in consultation 
with the Lilly clinical pharmacologist (CP)/clinical research physician (CRP), or designee.


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Protocol number J2G-MC-JZJU(b) 
27
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
Participants discontinuing from the study or study intervention prematurely for any reason 
should complete AE and other early discontinuation procedures as per the SoA (Section 1.3). 
Discontinuation of the study as a whole is described in Appendix 1 (Section 10.1).
7.1.
Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will remain in the 
study to be evaluated for safety. See the SoA for data to be collected at the time of 
discontinuation of study intervention and discharge from the study, and for any further 
evaluations that need to be completed.
7.1.1.
Liver Chemistry Stopping Criteria
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are 
met.
Phase 1 Liver Chemistry Stopping Algorithm
Abbreviations: ALT = alanine transaminase; INR = international normalized ratio; SAE = serious adverse event; 
ULN = upper limit of normal.
Liver Safety: Suggested Actions and Follow-up Assessments can be found in Appendix 6 
(Section 10.6).
Continue Study Treatment 
Discontinue Study Treatment 
*INR value not applicable to subjects on anticoagulants 
ALT ≥3xULN 
No
Yes
Must refer to Liver Safety Required Actions and Follow up Assessments  section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*
i D 
! 


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Protocol number J2G-MC-JZJU(b) 
28
7.1.2.
QTc Stopping Criteria
A participant who meets either bulleted criterion following single ECG assessment should have 
ECG repeated. If the participant still meets either bulleted criterion they will be withdrawn from 
the study.

QTc, QTcB, or QTcF >500 msec

Change from baseline: QTc >60 msec
If a clinically significant finding is identified (including, but not limited to changes from baseline 
in QTcB or QTcF) after enrollment, the investigator or qualified designee will determine if the 
participant can continue in the study and if any change in participant management is needed. 
This review of the ECG printed at the time of collection must be documented. Any new 
clinically relevant finding should be reported as an AE.
See the SoA for data to be collected at the time of intervention discontinuation and discharge 
from the study, and for any further evaluations that need to be completed.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study: 

at any time at his/her own request 

at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons

if the participant becomes pregnant during the study

if enrolled in any other clinical study involving an investigational product or enrolled in 
any other type of medical research judged not to be scientifically or medically compatible 
with this study

if the participant, for any reason, requires treatment with another therapeutic agent that 
has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new agent.
Discontinuation is expected to be uncommon.
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA. See SoA for data to be collected at the time of study 
discontinuation and for any further evaluations that need to be completed. The participant will be 
permanently discontinued from both the study intervention and the study at that time.
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, he/she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records.
7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel or designee are 


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Protocol number J2G-MC-JZJU(b) 
29
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site.


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Protocol number J2G-MC-JZJU(b) 
30
8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA (Section 1.3). 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention.
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
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, as applicable.
8.1.
Efficacy Assessments
Not applicable to 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
Physical examinations should be conducted according to the SoA (Section 1.3). 
A full physical examination will include, at a minimum, assessments of the 
cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight 
will also be measured and recorded.
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.2.2.
Vital Signs
For each participant, vital signs measurements should be conducted according to the SoA
(Section 1.3).
Blood pressure and pulse rate should be measured singly after at least 5 minutes supine. For each 
individual participant, the same cuff size should be used throughout the study for the 
measurements of blood pressure. The cuff should be attached to the participant’s dominant arm.
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms. Where orthostatic measurements are required, participants should be 
supine for at least 5 minutes and then participants will stand, and standing blood pressure will be 
measured after 2 minutes, but no longer than 3 minutes. If the participant feels unable to stand, 
supine vital signs only will be collected. Additional vital signs may be measured if warranted.


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Protocol number J2G-MC-JZJU(b) 
31
8.2.3.
Electrocardiograms
For each participant, single 12-lead ECGs will be obtained as outlined in the SoA (see 
Section 1.3). Refer to Section 7 for QTc withdrawal criteria and any additional QTc
readings that may be necessary.
Electrocardiograms must be recorded before collecting any blood samples. Participants must be 
supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake 
during ECG collection. Electrocardiograms may be obtained at additional times, when deemed 
clinically necessary. All ECGs recorded should be stored at the investigational site.
Electrocardiograms will be interpreted by the investigator at the site as soon after the time of 
ECG collection as possible, and ideally while the participant is still present, to determine whether 
the participant meets entry criteria at the relevant visit(s) and for immediate participant 
management, should any clinically relevant findings be identified. 
If a clinically significant finding is identified (including, but not limited to, changes in QT/QTc 
interval from baseline) after enrollment, the investigator will determine if the participant can 
continue in the study. The investigator, or qualified designee, is responsible for determining if 
any change in participant management is needed and must document his/her review of the ECG 
printed at the time of collection. Any new clinically relevant finding should be reported as an 
AE.
8.2.4.
Clinical Safety Laboratory Tests
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and 
to the SoA for the timing and frequency.
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 eCRF. The 
laboratory reports must be filed with the source documents.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study after the last dose of study intervention should be repeated until 
the values return to normal or baseline or are no longer considered clinically significant 
by the investigator or medical monitor.

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.

All protocol-required laboratory assessments, as defined in Appendix 2 
(Section 10.2), must be conducted in accordance with the laboratory manual and 
the SoA.
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s 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 eCRF.
8.2.5.
Pregnancy Testing 
Where applicable, pregnancy tests will be performed as outlined in the SoA (see Section 1.3).


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Protocol number J2G-MC-JZJU(b) 
32
8.2.6.
Safety Monitoring
The Lilly CP or CRP/scientist will monitor safety data throughout the course of the study.
Lilly will review SAEs within time frames mandated by company procedures. The Lilly CP or 
CRP will periodically review the following data:

trends in safety data

laboratory analytes including hematology and chemistry
When appropriate, the Lilly CP or CRP will consult with the functionally independent Global 
Patient Safety therapeutic area physician or clinical research scientist.
8.2.6.1.
Hepatic Safety
Close hepatic monitoring
Laboratory tests (Appendix 6 [Section 10.6]), including ALT, AST, alkaline phosphatase (ALP), 
total bilirubin (TBL), direct bilirubin, gamma-glutamyl transferase, and creatine kinase, should 
be repeated within 48 to 72 hours to confirm the abnormality and to determine if it is increasing 
or decreasing, if one or more of these conditions occur:
If a participant with baseline 
results of ... 
develops the following elevations:
ALT or AST <1.5 × upper 
limit of normal (ULN)
ALT or AST ≥3 × ULN
ALP <1.5 × ULN
ALP ≥2 × ULN
TBL <1.5 × ULN
TBL ≥2 × ULN (except for patients with 
Gilbert’s syndrome)
ALT or AST ≥1.5 × ULN
ALT or AST ≥2 × baseline
ALP ≥1.5 × ULN
ALP ≥2 × baseline
TBL ≥1.5 × ULN
TBL ≥2 × baseline (except for patients with 
Gilbert’s syndrome)
If the abnormality persists or worsens, clinical and laboratory monitoring and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated medical monitor. At a minimum, this evaluation should include physical 
examination and a thorough medical history, including symptoms, recent illnesses (for example, 
heart failure, systemic infection, hypotension, or seizures), recent travel, history of concomitant 
medications (including over-the-counter), herbal and dietary supplements, and history of alcohol 
drinking and other substance abuse. 
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels.


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Protocol number J2G-MC-JZJU(b) 
33
Comprehensive hepatic evaluation 
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur:
If a participant with baseline 
results of... 
develops the following elevations:
ALT or AST <1.5 × ULN
ALT or AST ≥3 × ULN with hepatic signs/symptoms*, or
ALT or AST ≥5 × ULN
ALP <1.5 × ULN
ALP ≥3 × ULN
TBL <1.5 × ULN
TBL ≥2 × ULN (except for patients with Gilbert’s syndrome)
ALT or AST ≥1.5 × ULN
ALT or AST ≥2 × baseline with hepatic signs/symptoms*, or
ALT or AST ≥3 × baseline
ALP ≥1.5 × ULN
ALP ≥2 × baseline
TBL ≥1.5 × ULN
TBL ≥1.5 × baseline (except for patients with Gilbert’s 
syndrome) 
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time/international normalized ratio; 
tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal imaging 
study (for example, ultrasound or computed tomography scan). 
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus, 
cytomegalovirus, Epstein-Barr virus, acetaminophen levels, acetaminophen protein adducts, 
urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl glucuronide, and 
serum phosphatidylethanol. Based on the circumstances and the investigator’s assessment of the 
participant’s clinical condition, the investigator should consider referring the participant for a 
hepatologist or gastroenterologist consultation, magnetic resonance cholangiopancreatography, 
endoscopic retrograde cholangiopancreatography, cardiac echocardiogram, or a liver biopsy. 
Additional hepatic data collection (hepatic safety eCRF) in study participants who have 
abnormal liver tests during the study:
Additional hepatic safety data collection in hepatic safety eCRFs should be performed in study 
participants who meet 1 or more of the following 5 conditions:
1. Elevation of serum ALT to ≥5 × ULN on 2 or more consecutive blood tests (if baseline 
ALT <1.5 × ULN)
In participants with baseline ALT ≥1.5 × ULN, the threshold is ALT 
≥3 × baseline on 2 or more consecutive tests
2. Elevated TBL to ≥2 × ULN (if baseline TBL <1.5 × ULN) (except for cases of known 
Gilbert’s syndrome)
In participants with baseline TBL ≥1.5 × ULN, the threshold should be TBL 
≥2 × baseline
3. Elevation of serum ALP to ≥2 × ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5 × ULN)


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Protocol number J2G-MC-JZJU(b) 
34
In participants with baseline ALP ≥1.5 × ULN, the threshold is ALP ≥2 × baseline 
on 2 or more consecutive blood tests
4. Hepatic event considered to be an SAE
5. Discontinuation of study drug due to a hepatic event 
NOTE: the interval between the 2 consecutive blood tests should be at least 2 days.
8.3.
Adverse Events, Serious Adverse Events, and Product Complaints
Product Complaints are covered in Section 8.3.3.
The definitions of the following events can be found in Appendix 3 (Section 10.3):

AEs

SAEs

Product complaints (PCs)
These events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study intervention/study (see Section 7).
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences.
8.3.1.
Timing and Mechanism for Collecting Events
This table describes the timing, deadlines, and mechanism for collecting events.
Event
Collection 
Start
Collection 
Stop
Timing for Reporting 
to Sponsor or 
Designee
Mechanism for 
Reporting
Back-up 
Method of 
Reporting
Adverse Event
AE
Signing of 
the ICF
Participation 
in study has 
ended
As soon as possible 
upon site awareness
AE eCRF
N/A
Serious Adverse Event


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Protocol number J2G-MC-JZJU(b) 
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Event
Collection 
Start
Collection 
Stop
Timing for Reporting 
to Sponsor or 
Designee
Mechanism for 
Reporting
Back-up 
Method of 
Reporting
SAE and SAE 
updates – prior 
to start of study 
intervention and
deemed 
reasonably 
possibly related 
with study 
procedures
Signing of 
the ICF
Start of 
intervention
Within 24 hours of 
awareness
SAE paper form
SAE paper 
form
SAE and SAE 
updates – after 
start of study 
intervention
Start of 
intervention
Participation 
in study has 
ended
Within 24 hours of 
awareness
SAE paper form
SAE paper 
form
SAE – after 
participant’s 
study 
participation has 
ended and the 
investigator 
becomes aware
After 
participant’s 
study 
participation 
has ended
N/A
Promptly
SAE paper form
N/A
Pregnancy
Pregnancy in 
female 
participants and 
female partners 
of male 
participants
After the 
start of study 
intervention
At least 
5 terminal 
half-lives or 
30 days after 
the last dose, 
whichever is 
longer
Within 24 hours (see 
Section 8.3.2)
SAE paper form
SAE paper 
form
Product Complaints
PC associated 
with an SAE or
might have led 
to an SAE
Start of study 
intervention
End of study 
intervention
Within 24 hours of 
awareness
Product Complaint 
form
N/A
PC not 
associated with 
an SAE
Start of study 
intervention
End of study 
intervention
Within 1 business day 
of awareness
Product Complaint 
form
N/A


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Protocol number J2G-MC-JZJU(b) 
36
Event
Collection 
Start
Collection 
Stop
Timing for Reporting 
to Sponsor or 
Designee
Mechanism for 
Reporting
Back-up 
Method of 
Reporting
Updated PC 
information
—
—
As soon as possible 
upon site awareness
Originally 
completed Product 
Complaint form 
with all changes 
signed and dated by 
the investigator
N/A
PC (if 
investigator 
becomes aware)
Participation 
in study has 
ended
N/A
Promptly
Product Complaint 
form
8.3.2.
Pregnancy
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. This applies only to male participants who receive study 
intervention.
●
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
partner’s pregnancy. The female partner will also be followed to determine the 
outcome of the pregnancy. Information on the status of the mother and child will 
be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy 
will be reported regardless of gestational age, fetal status (presence or absence of 
anomalies), or indication for the procedure. 
Female participants who become pregnant
●
The investigator will collect pregnancy information on any female participant 
who becomes pregnant while participating in this study. The initial 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 
and the information will be forwarded to the sponsor. Generally, follow-up will 
not be required for longer than 6 to 8 weeks beyond the estimated delivery date. 
Any termination of pregnancy will be reported, regardless of gestational age, fetal 
status (presence or absence of anomalies), or indication for the procedure.


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Protocol number J2G-MC-JZJU(b)  
 
37 
● While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.  
● A spontaneous abortion (occurring at <20 weeks gestational age) or still birth 
(occurring at ≥20 weeks gestational age) is always considered to be an SAE and 
will be reported as such.  
● Any poststudy pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
protocol Section 8.3.1. While the investigator is not obligated to actively seek this 
information in former study participants, he or she may learn of an SAE through 
spontaneous reporting. 
● Any female participant who becomes pregnant while participating in the study 
will discontinue study intervention. If the participant is discontinued from the 
study, follow the standard discontinuation process and continue directly to the 
follow-up phase. The follow-up on the pregnancy outcome should continue 
independent of intervention or study discontinuation. 
Prior to continuation of study intervention following pregnancy, the following must occur: 
● The sponsor and the relevant institutional review board (IRB)/independent ethics 
committee (IEC) give written approval. 
● The participant gives signed informed consent. 
● The investigator agrees to monitor the outcome of the pregnancy and the status of the 
participant and her offspring. 
8.3.3. 
Product Complaints 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
study intervention.  
The sponsor collects PCs on investigational products and drug delivery systems used in clinical 
studies in order to ensure the safety of study participants, monitor quality, and to facilitate 
process and product improvements. 
Participants will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed. 
NOTE: AEs/SAEs that are associated with a product complaint will also follow the processes 
outlined in Section 8.3.1 and Appendix 3 (Section 10.3) of the protocol. 
8.4. 
Pharmacokinetics 
● Venous blood samples of approximately 2 mL will be collected for measurement 
of plasma concentrations of selpercatinib as specified in the SoA (Section 1.3).  


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Protocol number J2G-MC-JZJU(b) 
38
●
A maximum of 3 samples may be collected at additional time points during the 
study if warranted and agreed upon between the investigator and the sponsor. The 
timing of sampling may be altered during the course of the study based on newly 
available data (e.g., to obtain data closer to the time of peak plasma 
concentrations) to ensure appropriate monitoring. 
●
Instructions for the collection and handling of biological samples will be provided 
by the sponsor. The actual date and time (24-hour clock time) of each sample will 
be recorded.
8.5.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.6.
Genetics
A blood OR saliva sample for DNA isolation will be collected from participants. 
See Appendix 5 (Section 10.5) for information regarding genetic research and Appendix 1 
(Section 10.1) for details about sample retention and custody. 
8.7.
Biomarkers
Biomarkers are not evaluated in this study.
8.8.
Immunogenicity Assessments
Not applicable for this study.
8.9.
Health Economics
This section is not applicable for this study.
8.10.
Product Acceptability and Palatability Assessments
The participant will be asked to provide responses to questions designed to assess the
acceptability and palatability of the RTU suspension. The questionnaire will assess the 
participant’s experience relating to the taste, smell, and after taste in the oral cavity.
The questionnaire will be completed by the participant immediately after administration of the
RTU suspension and PFOS formulations.


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Protocol number J2G-MC-JZJU(b) 
39
9.
Statistical Considerations
9.1.
Statistical Hypotheses
The primary objective will be evaluated to assess the relative bioavailability of the RTU
suspension and drug-in-bottle formulations compared to the commercial formulation (capsule).
9.2.
Analyses Sets
The following populations are defined:
Population
Description
Entered
All participants who sign the ICF.
Safety
All enrolled participants who take at least 1 dose of selpercatinib, whether or 
not they completed all protocol requirements.
Pharmacokinetic Analysis
All participants who received at least 1 dose of selpercatinib and have 
evaluable PK data.
9.2.1. Study Participant Disposition
A detailed description of participant disposition will be provided at the end of the study.
9.2.2.
Study Participant Characteristics
The participant’s age, sex, and other demographic characteristics will be recorded and 
summarized.
9.2.3.
Treatment Compliance
The date and time of dosing will be recorded and listed.
9.3.
Statistical Analyses
Statistical analysis of this study will be the responsibility of the sponsor or its designee. 
Pharmacokinetic analyses will be conducted on data from all participants who received at least 
1 dose of selpercatinib and have evaluable PK data. 
Safety analyses will be conducted for all enrolled participants who received at least 1 dose of 
selpercatinib, whether or not they completed all protocol requirements. 
Additional exploratory analyses of the data will be conducted as deemed appropriate.
9.3.1.
Safety Analyses
All investigational product and protocol procedure AEs will be listed, and if the frequency of 
events allows, safety data will be summarized using descriptive methodology. 


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Protocol number J2G-MC-JZJU(b) 
40
The incidence of AEs for each treatment will be presented by severity and by association with 
investigational product as perceived by the investigator. Adverse events reported to occur prior 
to enrollment will be distinguished from those reported as new or increased in severity during the 
study. Each AE will be classified by the most suitable term from the medical regulatory 
dictionary. 
The number of investigational product related SAEs will be reported.
9.3.1.1.
Statistical Evaluation of Safety
Safety parameters that will be assessed include safety laboratory parameters, vital signs, and 
ECG parameters. Additional analysis will be performed if warranted upon review of the data.
9.3.2.
Pharmacokinetic Analyses
9.3.2.1.
Pharmacokinetic Parameter Estimation
Pharmacokinetic parameter estimates will be calculated by standard noncompartmental methods. 
The primary PK parameters for analysis of selpercatinib will be: maximum observed drug 
concentration (Cmax), area under the concentration versus time curve from time zero to infinity 
(AUC[0-∞]), area under the concentration versus time curve from time zero to time t, where t is 
the last time point with a measurable concentration (AUC0-tlast), and time to Cmax (tmax). 
Other noncompartmental parameters, such as terminal half-life (t1/2), apparent total body 
clearance of drug calculated after extravascular administration, and apparent volume of 
distribution during the terminal phase after extravascular administration, may be reported as 
appropriate.
9.3.2.2.
Pharmacokinetic Statistical Inference
Pharmacokinetic parameters will be evaluated to estimate relative bioavailability. For the 
primary analysis, log-transformed Cmax, AUC(0-∞), and AUC0-tlast will be evaluated in a linear 
mixed-effect model with fixed effects for formulation, period, and sequence, and a random effect 
for subject. The treatment differences will be back-transformed to present the ratios of geometric 
means and the corresponding confidence intervals (CIs).
For secondary analysis, the tmax will be analyzed using a Wilcoxon signed rank test. Estimates of 
the median difference based on the observed medians, 90% CIs, and p-values from the Wilcoxon 
test will be calculated. Pharmacokinetic parameters will be summarized using descriptive 
statistics.
9.3.3.
Pharmacodynamic Analyses
Not applicable for this study.
9.3.4.
Pharmacokinetic/Pharmacodynamic Analyses
Not applicable for this study.


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Protocol number J2G-MC-JZJU(b) 
41
9.4.
Interim Analysis 
No interim analyses are planned for this study. If an unplanned interim analysis is deemed 
necessary for reasons other than a safety concern, the protocol must be amended.
9.5.
Sample Size Determination
Up to approximately 42 participants will be enrolled to ensure that at least approximately 
36 participants complete the study. The sample size for this study is justified based on a 
precision for the ratio of geometric means and it is represented by the half-width of the 90% CI 
of the point estimate on the logarithmic scale. Based on an intra-subject variability of 70%
(LOXO-RET-19075), with a probability of 90%, a 90% CI for the ratio of the geometric means 
for Cmax and AUC will be obtained with a precision about 0.288 in the log scale, which 
corresponds to approximately 0.334 in the natural scale.


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Protocol number J2G-MC-JZJU(b) 
42
10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
●
This study will be conducted in accordance with the protocol and with the 
following:
○
Consensus ethical principles derived from international guidelines including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences International Ethical Guidelines
○
Applicable International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP) Guidelines
○
Applicable laws and regulations
●
The protocol, protocol amendments, ICF, IB, and other relevant documents (for 
example, advertisements) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated.
●
Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.
●
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants.
●
The investigator will be responsible for the following:
○
Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC
○
Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures
○
Providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations
●
Investigator sites are compensated for participation in the study as detailed in the 
Clinical Trial Agreement.


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Protocol number J2G-MC-JZJU(b) 
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10.1.2.
Informed Consent Process
●
The investigator or his/her representative will explain the nature of the study, 
including the risks and benefits, to the participant and answer all questions 
regarding the study.
●
Participants must be informed that their participation is voluntary. Participants 
will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data 
protection requirements, where applicable, and the IRB/IEC or study center.
●
The medical record must include a statement that written informed consent was 
obtained before the participant was entered in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF.
●
Participants must be reconsented to the most current version of the ICF(s) during 
their participation in the study.
●
A copy of the ICF(s) must be provided to the participant and is kept on file.
10.1.3.
Data Protection
●
Participants will be assigned a unique identifier by the sponsor. Any participant 
records, datasets or tissue samples that are transferred to the sponsor will contain 
the identifier only; participant names or any information that 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 who will be required to give 
consent for his/her data to be used as described in the informed consent.
●
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.
●
The sponsor has processes in place to ensure data protection, information security 
and data integrity. These processes include appropriate contingency plan(s) for 
appropriate and timely response in the event of a data security breach.
10.1.4.
Dissemination of Clinical Study Data
Communication of Suspended or Terminated Dosing
If a decision is taken to suspend or terminate dosing in the trial due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, by phone and/or email) 
as soon as possible. It will be a requirement that investigators respond upon receipt to confirm 
that they understand the communication and have taken the appropriate action prior to further 
dosing any participants with study intervention. Any investigator not responding will be 
followed up by Lilly personnel prior to any further planned dosing. If a dose is planned 


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Protocol number J2G-MC-JZJU(b) 
44
imminently, Lilly personnel will immediately, and continually, use all efforts to reach 
investigators until contact is made and instructions verified. 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
Data 
The sponsor does not proactively share data from Phase 1 clinical trials. Requests for access to 
Phase 1 clinical trial data are evaluated on a case-by-case basis taking into consideration the 
ability to anonymize the data and the nature of the data collected.
10.1.5.
Data Quality Assurance
●
All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (for example, 
laboratory data). The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the eCRF.
●
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF.
●
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.
●
Quality tolerance limits (QTLs) will be predefined to identify systematic issues 
that can impact participant safety and/or reliability of study results. These 
pre-defined parameters will be monitored during the study and important 
excursions from the QTLs and remedial actions taken will be summarized in the 
clinical study report.
●
Monitoring details describing strategy (for example, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and 
analytical risk-based monitoring), methods, responsibilities, and requirements, 
including handling of noncompliance issues and monitoring techniques, are 
provided in the Monitoring Plan.
●
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.
●
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations).
●
Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF 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.


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Protocol number J2G-MC-JZJU(b) 
45
●
Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the investigator for the time period outlined in the 
Clinical Trial Agreement 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.
●
In addition, the sponsor or its representatives will periodically check a sample of 
the participant data recorded against source documents at the study site. The study 
may be audited by the sponsor or its representatives, and/or regulatory agencies at 
any time. Investigators will be given notice before an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An electronic data capture system (EDC) will be used in this study for the collection of eCRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the eCRF.
Data collected via a sponsor-provided data capture system will be stored at a third party. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and electronic transfers will be provided to the investigator 
for review and retention. Data will subsequently be transferred from the central vendor to the 
sponsor data warehouse.
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system.
10.1.6.
Source Documents
●
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site.
●
Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies 
must be explained. The investigator may need to request previous medical records 
or transfer records, depending on the study. Also, current medical records must be 
available.
●
Definition of what constitutes source data can be found in Section 10.1.4.
10.1.7.
Study and Site Start and Closure
First Act of Recruitment


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Protocol number J2G-MC-JZJU(b) 
46
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
Study or Site Termination
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. 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:
For study termination:
●
Discontinuation of further study intervention development.
For site termination:
●
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 (evaluated after a reasonable amount of time) of 
participants by the investigator
●
Total number of participants included earlier than expected.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
10.1.8.
Publication Policy
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal if the results are deemed to be of significant medical 
importance.


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Protocol number J2G-MC-JZJU(b) 
47
10.2.
Appendix 2: Clinical Laboratory Tests
The tests detailed in the table below will be performed by the local laboratory.
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 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.
Investigators must document their review of the laboratory safety results.
Safety Laboratory Tests
Hematology
Clinical Chemistry
Hematocrit
Sodium
Hemoglobin
Potassium
Erythrocyte count (RBC)
Bicarbonate (total CO2)
Mean cell volume 
Chloride 
Mean cell hemoglobin 
Calcium 
Mean cell hemoglobin concentration 
Phosphorus 
Leukocytes (WBC) 
Platelets
Glucose (random)
Creatine kinase
Differential WBC (absolute counts) of
Blood urea nitrogen (BUN)
Neutrophils
Uric acid 
Lymphocytes
Total Cholesterol, HDL-C, LDL-C
Monocytes
Total protein
Eosinophils
Albumin
Basophils
Total bilirubin
Alkaline phosphatase (ALP)
Urinalysisa
Aspartate aminotransferase (AST)
Specific gravity
Alanine aminotransferase (ALT)
pH
Creatinine
Protein
Glucose
Ethanol testingb
Ketones
Urine drug screenb
Bilirubin
Hepatitis B surface antigenc
Urobilinogen
Hepatitis C antibodyc, d
Blood
HIVc
Nitrite
Pregnancy teste
Leukocyte esterase
FSH (if applicable)c
Abbreviations: FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; RBC = red blood cell; 
WBC = white blood cell.
a
Performed by dipstick. Reflex microscopy to be performed if microscopy is abnormal.
b
Urine drug screen and ethanol (urine or breath) level performed at screening, and may be repeated prior to 
admission to the Clinical Research Unit.
c
Performed at screening only.
d
Participants with a positive hepatitis C antibody test result can have a confirmatory hepatitis C RNA test.
e
Screening and Day -1 only.


CONFIDENTIAL 
Protocol number J2G-MC-JZW(b) 
10.2.1. 
Blood Sampling Summary 
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study. 
Protocol J2G-MC-JZJU Sam 
Blood Volume per 
Numbe1· of Blood 
Total Volume 
Pm ose 
Sam le mL 
Sam Jes 
mL 
Screening testsa 
45 
45 
Clinical laboratory testsa 
12 
7 
84 
"-------+----~~ -----If---- ----+---
---t 
Blood discard for cammla patency 
1 
Genetic sam le 
Total 
260 
Total for clinical m oses 
260 
a Additional samples may be drawn if needed for safety pmposes. 
48 


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Protocol number J2G-MC-JZJU(b) 
49
10.3.
Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a participant administered a 
pharmaceutical product and which does not necessarily have a causal relationship with 
the study intervention. An AE can therefore be any unfavourable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated)
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (that is, not related 
to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that 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 (for example, endoscopy, appendectomy): the condition 
that leads to the procedure is the AE.


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Protocol number J2G-MC-JZJU(b) 
50

Situations in which 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.
10.3.2.
Definition of SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed:
d.
Results in death
e.
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 were more severe.
f.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been admitted to hospital or 
emergency ward (usually involving at least an overnight stay) 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.
g.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’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 (for example, sprained ankle), which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
h.
Is a congenital anomaly/birth defect

Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs.
i.
Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical 


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Protocol number J2G-MC-JZJU(b) 
51
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 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.
10.3.3.
Definition of Product Complaints
Product Complaint

A product complaint is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness,
or performance of a study intervention. When the ability to use the study intervention 
safely is impacted, the following are also product complaints:
o
Deficiencies in labeling information, and
o
Use errors for device or drug-device combination products due to ergonomic 
design elements of the product.

Product complaints related to study interventions used in clinical trials are collected in 
order to ensure the safety of participants, monitor quality, and to facilitate process and 
product improvements.

Investigators will instruct participants to contact the site as soon as possible if he or she 
has a product complaint or problem with the study intervention so that the situation can 
be assessed.

An event may meet the definition of both a product complaint and an AE/SAE. In such 
cases, it should be reported as both a product complaint and as an AE/SAE.
10.3.4.
Recording and Follow-Up of AE and/or SAE and Product Complaints
AE, SAE, and Product Complaint Recording

When an AE/SAE/product complaint occurs, it is the responsibility of the investigator 
to review all documentation (for example, hospital progress notes, laboratory reports, 
and diagnostics reports) related to the event.

The investigator will then record all relevant AE/SAE/product complaint information 
in the participant’s medical records, in accordance with the investigator’s normal 
clinical practice. AE/SAE information is reported on the appropriate eCRF page and 
product complaint information is reported on the Product Complaint Form.
Note: An event may meet the definition of both a product complaint and an AE/SAE. 
In such cases, it should be reported as both a product complaint and as an AE/SAE.


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Protocol number J2G-MC-JZJU(b) 
52

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the sponsor or designee in lieu of completion of the eCRF page for AE/SAE 
and the Product Complaint Form for product complaints.

There may be instances when copies of medical records for certain cases are requested 
by the sponsor or designee. 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 or designee.

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.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories:

Mild: A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living.

Moderate: A type of adverse event that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, 
causing discomfort but poses no significant or permanent risk of harm to the research 
participant.

Severe: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic intervention. 
An AE that is assessed as severe should not be confused with an SAE. Severe is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
An event is defined as ‘serious’ when it meets at least one of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.


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Protocol number J2G-MC-JZJU(b) 
53

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor or designee. 
However, it is very important that the investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to the sponsor 
or designee.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
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 
or designee 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 or designee with a copy of any 
post-mortem findings including histopathology. 
10.3.5.
Reporting of SAEs
SAE Reporting via Paper Form

Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the medical monitor or the SAE coordinator.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE report within the designated reporting time frames.

Contacts for SAE reporting can be found in the SAE report.
10.3.6.
Regulatory Reporting Requirements
SAE Regulatory Reporting
Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and 
the safety of a study intervention under clinical investigation are met.


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Protocol number J2G-MC-JZJU(b) 
54
●
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
IRB/IEC, and investigators.
●
An investigator who receives an investigator safety report describing an 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 IB and will notify the 
IRB/IEC, if appropriate according to local requirements.


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Protocol number J2G-MC-JZJU(b) 
55
10.4.
Appendix 4: Contraceptive and Barrier Guidance
10.4.1.
Definitions
Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Women in the following categories are not considered women of childbearing potential
1. Premenarchal
2. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy

Documented bilateral tubal ligation

Bilateral tubal occlusion 
For individuals with permanent infertility due to an alternate medical cause other than the 
above (e.g., Müllerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
NOTE: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.
3. Postmenopausal female is defined as women with:

12 months of amenorrhea for women ≥55, with no need for follicle-stimulating hormone

12 months of amenorrhea for women >40 to ≤54 years old with follicle-stimulating 
hormone ≥40 mIU/mL and no other medical condition such as anorexia nervosa and not 
taking medications during the amenorrhea (e.g., oral contraceptives, hormones, 
gonadotropin-releasing hormone, anti-estrogens, selective estrogen-receptor modulators, 
or chemotherapy that induced amenorrhea)
10.4.2.
Contraception Guidance
Contraceptive use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
Male participants:

are not required to adhere to contraceptive requirements
Female participants:

Female participants of childbearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of 
their preferred and usual lifestyle) must agree to either remain abstinent or stay in a 
same-sex relationship without sexual relationships with males. Periodic abstinence (e.g., 


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Protocol number J2G-MC-JZJU(b) 
56
calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence 
just for the duration of a study, and withdrawal are not acceptable methods of 
contraception.

Female participants of childbearing potential, who are not abstinent as described above, 
must agree to use a highly effective method of contraception (that is, one with less than 
1% failure rate) such as combination or oral contraceptives, implanted/injected 
contraceptives, intrauterine devices, or sterile partner until 30 days after the last dose of 
study medication. 
o
Female participants not of childbearing potential are not required to use 
contraception. This includes females who are:

Infertile due to surgical sterilization (hysterectomy, bilateral 
oophorectomy, bilateral salpingectomy, bilateral tubal occlusion or tubal 
ligation) or congenital anomaly (for example, Müllerian agenesis)

Postmenopausal, as defined above.
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. This applies only to male participants who receive study 
intervention.
●
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
partner’s pregnancy. The female partner will also be followed to determine the 
outcome of the pregnancy. Information on the status of the mother and child will 
be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy 
will be reported including fetal status (presence or absence of anomalies) and
indication for the procedure. 
Female participants who become pregnant
●
The investigator will collect pregnancy information on any female participant 
who becomes pregnant while participating in this study. The initial 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, 
and the information will be forwarded to the sponsor. Generally, follow-up will 
not be required for longer than 6 to 8 weeks beyond the estimated delivery date. 
Any termination of pregnancy will be reported, including fetal status (presence or 
absence of anomalies) or indication for the procedure.


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Protocol number J2G-MC-JZJU(b) 
57
●
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
●
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth 
(occurring at >20 weeks gestational age) is always considered to be an SAE and 
will be reported as such. 
●
Any poststudy pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.2. While the investigator is not obligated to actively seek this 
information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention. If the participant is discontinued from the study intervention, follow the 
standard discontinuation process and continue directly to the follow-up phase.


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Protocol number J2G-MC-JZJU(b) 
58
10.5.
Appendix 5: Genetics
Use/Analysis of DNA
●
Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Variable response to 
study intervention may be due to genetic determinants that impact drug 
absorption, distribution, metabolism, and excretion; mechanism of action of the 
drug; disease etiology; and/or molecular subtype of the disease being treated. 
Therefore, where local regulations and IRB/IEC allow, a blood/saliva sample will 
be collected for DNA analysis from consenting participants.
●
DNA samples will be used for research related to selpercatinib or advanced or 
metastatic RET-mutant MTC/advanced or metastatic RET fusion-positive thyroid 
cancer/metastatic RET fusion-positive NSCLC. They may also be used to develop 
tests/assays including diagnostic tests related to selpercatinib advanced or 
metastatic RET-mutant MTC/advanced or metastatic RET fusion-positive thyroid 
cancer/metastatic RET fusion-positive NSCLC. Genetic research may consist of 
the analysis of one or more candidate genes or the analysis of genetic markers 
throughout the genome or analysis of the entire genome (as appropriate).
●
Additional analyses may be conducted if it is hypothesized that this may help 
further understand the clinical data.
●
The samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to selpercatinib or study interventions of this 
class to understand study disease or related conditions.
●
The results of genetic analyses may be reported in the clinical study report or in a 
separate study summary.
●
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.

The samples will be retained while research on selpercatinib or study 
interventions of this class or indication continues but no longer than 15 years or 
other period as per local requirements.


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Protocol number J2G-MC-JZJU(b) 
59
10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments 
Hepatic Evaluation Testing – Refer to protocol Hepatic Safety Section 8.2.6.1 for guidance on 
appropriate test selection.

For testing selected, analysis is required to be completed by the Lilly-designated central 
laboratory except for Microbiology.

Local testing may be performed in addition to central testing when required for immediate 
participant management.

Results will be reported if a validated test or calculation is available.
Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs - Red Blood Cells)
Alkaline phosphatase (ALP)
Leukocytes (WBCs - White Blood Cells) 
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
  Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
  Lymphocytes
Creatine kinase (CK)
  Monocytes
Other Chemistry
  Basophils
Acetaminophen
  Eosinophils
Acetaminophen Protein Adducts
Platelets
Alkaline Phosphatase Isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl Alcohol (EtOH)
Prothrombin Time, International Normalized 
Ratio (PT-INR)
Haptoglobin
Serology
Immunoglobulin IgA (Quantitative)
Hepatitis A Virus (HAV) Testing:
Immunoglobulin IgG (Quantitative)
  HAV Total Antibody
Immunoglobulin IgM (Quantitative)
  HAV IgM Antibody
Phosphatidylethanol (PEth)
Hepatis B Virus (HBV) Testing:
Urine Chemistry
  Hepatitis B surface antigen (HBsAg)
Drug Screen
  Hepatitis B surface antibody (Anti-HBs) 
Ethyl glucuronide (EtG)
  Hepatitis B core total antibody (Anti-HBc)
Other Serology
  Hepatitis B core IgM antibody 
Anti-nuclear antibody (ANA)
  Hepatitis B core IgG antibody 
Anti-smooth muscle antibody (ASMA) a


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Protocol number J2G-MC-JZJU(b) 
60
  HBV DNA d
Anti-actin antibody b
Hepatis C Virus (HCV) Testing:
Epstein-Barr Virus (EBV) Testing:
  HCV antibody
  EBV antibody
  HCV RNA d
  EBV DNA d
Hepatitis D Virus (HDV) Testing:
Cytomegalovirus (CMV) Testing:
  HDV antibody
  CMV antibody
Hepatitis E Virus (HEV) Testing:
  CMV DNA d
  HEV IgG antibody
Herpes Simplex Virus (HSV) Testing:
  HEV IgM antibody
  HSV (Type 1 and 2) antibody
  HEV RNA d
  HSV (Type 1 and 2) DNA d
Microbiology c
Liver Kidney Microsomal Type 1 (LKM-1) 
Antibody
Culture:
  Blood
  Urine
a This is not required if anti-actin antibody is tested.
b This is not required if ASMA is tested.
c Assayed by investigator-designated local laboratory ONLY; no Central Testing available.
d Reflex/confirmation dependent on regulatory requirements and/or testing availability.
Evaluation of participants with treatment-emergent abnormal hepatic biochemical tests 
during a clinical trial *
Test/Procedure: 
Rationale 
Action
Close Hepatic Monitoring
Clinical Chemistry:
  Total bilirubin
  Direct bilirubin
  Alkaline phosphatase (ALP)
  Alanine aminotransferase (ALT)
  Aspartate aminotransferase (AST) b
  Gamma-glutamyl transferase (GGT)
  Creatine kinase (CK)
All: Routine follow-up
CK: Muscle injury/rhabdomyolysis
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
Clinical Chemistry 
Hematology
  Hemoglobin
  Hematocrit
  Erythrocytes (RBCs – Red Blood 
Cells)
  Leukocytes (WBCs – White Blood 
Cells)
  Differential:
  Neutrophils, segmented
Infection
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
Hematology


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Protocol number J2G-MC-JZJU(b) 
61
  Lymphocytes
  Monocytes
  Basophils
  Eosinophils
  Platelets
  Cell Morphology (RBCs and WBCs)
Medical history: a, h
  Symptoms
  Co-existing medical conditions
  Concomitant medications
  Dietary and nutritional supplements
  Exercise (excessive)
  Muscle Injury
  Alcohol consumption
  Illicit substances
Used to evaluate/rule out:
  Systemic infection or sepsis
  Ischemic or congestive hepatic injury
  Gallstone disease
  Alcoholic liver disease
  Muscle injury/rhabdomyolysis
  Acetaminophen toxicity
  Drug-Induced Liver Injury (DILI) due 
to another drug, herbal or dietary 
substances
If findings are clinically 
significant, report as an 
adverse event.
Hepatitis A Virus (HAV) Testing:
  HAV Total Antibody
  HAV IgM Antibody
Used to evaluate/rule out: Acute HAV 
infection
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
Hepatitis A
Hepatis B Virus (HBV) Testing:
  Hepatitis B surface antigen (HBsAg)
  Hepatitis B surface antibody 
(Anti-HBs) 
  Hepatitis B core total antibody 
(Anti-HBc)
  Hepatitis B core IgM antibody
  Hepatitis B core IgG antibody 
  HBV DNA
Used to evaluate/rule out: Acute or 
exacerbation of chronic HBV infection. 
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
Hepatitis B
Hepatis C Virus (HCV) testing: c, d
  HCV antibody
  HCV RNA
Used to evaluate/rule out: Acute or 
exacerbation of chronic HCV infection. 
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
Hepatitis C
Hepatitis E Virus (HEV) Testing: e
  HEV IgG antibody
  HEV IgM antibody
  HEV RNA
Used to evaluate/rule out: Acute HEV 
infection.
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
Hepatitis E
Anti-nuclear antibody (ANA)
Anti-smooth muscle antibody (ASMA)
Anti-actin antibody
Immunoglobulin IgA
Immunoglobulin IgG
Immunoglobulin IgM
Used to evaluate/rule out: Autoimmune 
hepatitis
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
only the specific test/s 
required. 
Hepatobiliary imaging: a, h
  Ultrasonography
  Computed tomography scan
  Magnetic resonance imaging
  Magnetic resonance 
cholangiopancreatography (MRCP) g
Endoscopic retrograde 
cholangiopancreatography (ERCP) g
Used to evaluate/rule out: 
  Biliary obstruction
  Pancreatitis
  Gallstones
  Portal-vein/ hepatic vein thrombosis 
  Hepatic metastasis
Performed locally.
If findings are clinically 
significant, report as an 
adverse event.
Comprehensive Hepatic Monitoring
Coagulation:
Prothrombin Time, INR (PT-INR)
Used to evaluate/rule out:
Suspected liver failure, for patients with 
elevated Total Bilirubin
Utilize a Hepatic 
Monitoring central lab 
collection kit


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Protocol number J2G-MC-JZJU(b) 
62
Epstein-Barr Virus (EBV) Testing:
  EBV antibody
  EBV DNA
Cytomegalovirus (CMV) Testing:
  CMV antibody
  CMV DNA
Herpes Simplex Virus (HSV) 
Testing:
  HSV (Type 1 and 2) antibody
  HSV (Type 1 and 2) DNA
Used to evaluate/rule out:
EBV or 
Hepatic injury due to CMV, or
HSV infection.
Utilize a Hepatic 
Monitoring central lab 
collection kit and select 
only the specific test/s 
needed.
Liver biopsy f
Used to evaluate/rule out:
Autoimmune hepatitis (AIH)
If findings are clinically 
significant, report as an 
adverse event.
Additional Hepatic Monitoring Tests
Alkaline Phosphatase Isoenzymes
Used to evaluate/differentiate: Elevated 
Alkaline Phosphatase origination from
bone or liver
Utilize a Hepatic 
Monitoring central lab 
collection kit
Liver Kidney Microsomal Type 1 
(LMK-1) Antibody
Used to evaluate: Autoimmune hepatitis 
Utilize a Hepatic 
Monitoring central lab 
collection kit
Urine Chemistry:
  Ethyl glucuronide (EtG) i
Other Chemistry:
  Phosphatidylethanol (PEth) j
Used to evaluate: Alcoholic liver 
disease 
Utilize a Hepatic 
Monitoring central lab 
collection kit
Other Chemistry:
  Acetaminophen
  Acetaminophen Protein Adducts
Used to evaluate: Acetaminophen 
toxicity 
Utilize a Hepatic 
Monitoring central lab 
collection kit
Ethyl Alcohol (EtOH)
Used to evaluate recent alcohol 
consumption
Utilize a Hepatic 
Monitoring central lab 
collection kit
Haptoglobin
Used to evaluate a diagnosis of 
hemolysis
Utilize a Hepatic 
Monitoring central lab 
collection kit
Cardiology consult a
Electrocardiogram
Echocardiogram
Vital Signs:
  Blood pressure
  Pulse
Used to evaluate: Ischemic or 
congestive hepatic injury
Performed locally.
If findings are clinically 
significant, report as an 
adverse event.
Urine Chemistry:
  Drug screen
Used to evaluate: Hepatotoxicity due to 
cocaine, opiates and other illicit 
substances 
Utilize a Hepatic 
Monitoring central lab 
collection kit
Hepatitis D Virus (HDV) Testing:
  HDV antibody
Used to evaluate/rule out: Acute HDV 
infection.
Utilize a Hepatic 
Monitoring central lab 
collection kit and only 
select required test needed.
Microbiology: 
Cultures:
  Blood
  Urine
Used to evaluate/rule out: 
Sepsis or systemic infection
Perform locally.
If findings are clinically 
significant, report as an 
adverse event.
Slit-lamp eye examination 
(Kayser-Fleisher rings)
Genetic evaluation
Used to evaluate/rule out: 
Wilson’s disease 
Perform locally. 
If findings are clinically 
significant, report as an 
adverse event.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
63
Other Chemistry:
  Ceruloplasmin
  Copper
Used to evaluate/rule out: 
Wilson’s disease 
Utilize a Hepatic 
Monitoring central lab 
collection kit
*This tool is to be used by the investigative site for reference during the evaluation of a participant who met hepatic 
monitoring criteria based on laboratory results and clinical judgment for a suspected liver injury during protocol 
participation. 
a Extent and type of work-up may vary by participant’s history, severity of liver injury, underlying disease, and 
geography.
b Serum AST typically (although not always) is higher than ALT.
c If anti-HCV is positive, HCV RNA is required to confirm HCV infection.
d Acute hepatitis C may be anti-HCV negative but HCV RNA positive.
e If anti-HEV IgM is positive, consider confirmation with HEV RNA by nested polymerase chain reaction.
f A liver biopsy is needed to confirm a diagnosis of AIH.
gIf cholestatic injury, MRCP or ERCP may be recommended.
h Based on medical history and clinical judgment.
i Alcohol consumption in past 3 to 5 days.
j Alcohol consumption in past 3 weeks.


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
64
10.7.
Appendix 7: Abbreviations and Definitions
Term
Definition
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CFR
Code of Federal Regulations
CI
confidence interval
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CP
clinical pharmacologist
CRP
clinical research physician: Individual responsible for the medical conduct of the study. 
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
enroll
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment.
enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
GCP
good clinical practice
IB
investigator’s brochure
IEC
independent ethics committee
ICF
informed consent form
ICH
International Council for Harmonisation


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Protocol number J2G-MC-JZJU(b) 
65
informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed and dated informed consent form.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB
institutional review board
NSCLC
Non-small cell lung carcinoma
participant
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control
PC
product complaint
PFOS
powder for oral suspension
PK
pharmacokinetics
QTc
corrected QT interval
QTcB
corrected QT interval using Bazett’s formula
QTcF
corrected QT interval using Fridercia’s formula
QTL
quality tolerance limit
RTU
ready to use
SAE
serious adverse event
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SoA
schedule of assessments
TBL
total bilirubin
ULN
upper limit of normal


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
66
10.8.
Appendix 8: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment [a]: (07-Sep-2021)
This amendment is considered to be nonsubstantial.
Overall Rationale for the Amendment:
The protocol is amended to correct the timepoints for clinical laboratory assessments in the 
Schedule of Activities. Minor editorial changes have been done which is not reflected in the 
below table. The following table describes the change made in amendment (b).
Section # and Name
Description of Change
Brief Rationale
1.3 Schedule of 
Activities (SoA)
Added timepoints for collection 
of PK samples in the table and 
deleted the following 
information in the footnotes 
“Samples will be taken at the 
following timepoints on Days 
1,8 and 15: predose, and 0.5, 
0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 
12, 24, 36, 48, 72, 96, 120, 144 
hours postdose” from footnote of 
Schedule of Activities (SoA) 
table for consistent presentation.
Added PK sample - Selpercatinib 
(plasma) timepoint for early 
discontinuation (ED).
To remove the additional 
PK sampling timepoints 
that were inadvertently 
added in Original Protocol. 
1.3 Schedule of 
Activities (SoA)
Added Single 12-lead ECG 
assessment at ED.
Missing 12-lead ECG 
assessment added.
1.3 Schedule of 
Activities (SoA)
A comment has been added to the 
Taste Assessment Questionnaire 
“To be performed for the RTU 
suspension and PFOS 
formulations only immediately 
after dosing”.
To clarify taste assessment 
will be measured after 
dosing. 
1.3 Schedule of 
Activities (SoA)
Deleted the foot note “Vital signs 
assessments on Days 5 and 14 
should be performed in the 
morning at a time relative to 
To correct the schedule of 
activities for the missing 
vital signs measurement 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
67
Section # and Name
Description of Change
Brief Rationale
predose on Days 1 and 8,
respectively”.
Added “Assessments on Days 5 
12, and 19 should be performed 
in the morning at a time relative 
to predose on Days 1, 8 and 15, 
respectively” to the table.

Timepoints for vital signs 
measurement 
added on Day 9, 12, 16 and 19
deleted on Day 14.
timepoints in the original 
protocol.
10.2.1 Blood 
Sampling Summary
Added Blood sampling Summary 
table.
This summary table was 
missed in Original Protocol.
10.4.2 Contraception 
Guidance
Added Bilateral tubal occlusion.
This procedure was 
inadvertently missed in 
Original Protocol. 


CONFIDENTIAL
Protocol number J2G-MC-JZJU(b) 
68
11.
References
Levey AS, Stevens LA, Schmid CH, et al. A New Equation to Estimate Glomerular Filtration 
Rate. Ann Interim Med. 2009;150(9):604-612.
LOXO-RET-19075 Clinical Study Report: An Open-Label, 3-Period, Fixed Sequence Study to 
Evaluate the Effect of an H2 Antagonist and a Proton Pump Inhibitor on the Single Dose 
Pharmacokinetics of LOXO-292 in Healthy Adult Subjects


Leo Document ID= 226ad363-bc7a-4644-857d-2bbfb8e89309 
Approver: 
PD 
--------------
Approval Date & Time: 22-Nov- 2021 13:37:44 GMT 
Signature meaning: Approved 
Approver: PPD 
----------------
Approval Date & Time: 22-Nov- 2021 19:01:20 GMT 
Signature meaning: Approved 

SAP_001.pdf: 
Statistical Analysis Plan J2G-MC-JZJU Version 1.0
An Open-Label, Randomized Study to Evaluate the Relative Bioavailbility of Selpercatinib in 3 Formulations 
for Pediatric Use
NCT05136404
Approval Date: 09-Nov-2021


Fi nal Versi o n 1. 0, 0 4 N o ve m ber 2 0 2 1
             Pa ge 1 of 1 6
S T A TI S TI C A L A N A L Y SI S P L A N
A n O pe n -L a bel, R a n d o mize d St u d y t o E v al u ate t he Rel ati ve Bi o a v ail a bilit y of
Sel perc ati ni b i n 3 F or m ul ati o ns f or Pe di atric Use
Stati stical A nal ysis Pla n Stat us : Fi nal
Stati stical A nal ysis Pla n Versi o n: 1. 0
Stati stical A nal ysis Pla n Date : 0 4 N o ve m ber 2 0 2 1
I nvest i gati onal Me dici nal Pr o d uct : L Y 3 5 2 7 7 2 3
Pr ot oc ol Refere nce : J 2 G-M C -J ZJ U
La bc or p St u d y : 8 4 4 5 3 2 9
Cli nical P hase I
A p pr o v al D at e: 0 9- N o v- 2 0 2 1 G M T


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1. TABLE OF CONTENTS
1.
TABLE OF CONTENTS ............................................................................................... 2
2.
ABBREVIATIONS........................................................................................................ 3
3.
INTRODUCTION ......................................................................................................... 5
4.
STUDY OBJECTIVES AND ENDPOINTS .................................................................. 5
5.
STUDY DESIGN........................................................................................................... 6
5.1
Screening ................................................................................................................ 6
5.2
Treatment and Assessment Period ........................................................................... 6
6.
TREATMENTS............................................................................................................. 7
7.
SAMPLE SIZE JUSTIFICATION ................................................................................. 7
8.
DEFINITION OF ANALYSIS POPULATIONS............................................................ 7
9.
STATISTICAL METHODOLOGY ............................................................................... 8
9.1
General.................................................................................................................... 8
9.2
Demographics and Participant Disposition............................................................... 8
9.3
Pharmacokinetic Assessment................................................................................... 8
9.3.1
Pharmacokinetic Analysis............................................................................... 8
9.3.2
Pharmacokinetic Statistical Methodology ..................................................... 12
9.4
Safety and Tolerability Assessments...................................................................... 13
9.4.1
Adverse events ............................................................................................. 13
9.4.2
Concomitant medication............................................................................... 13
9.4.3
Clinical laboratory parameters...................................................................... 13
9.4.4
Vital signs .................................................................................................... 13
9.4.5
Electrocardiogram (ECG)............................................................................. 13
9.4.6
Hepatic Monitoring ...................................................................................... 14
9.4.7
Palatability Questionnaires ........................................................................... 14
9.4.8
Other assessments......................................................................................... 14
9.4.9
Safety and Tolerability Statistical Methodology............................................ 14
10. INTERIM ANALYSES ............................................................................................... 14
11. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ...... 14
12. REFERENCES ............................................................................................................ 15
13. DATA PRESENTATION ............................................................................................ 15
13.1 Derived Parameters ............................................................................................... 15
13.2 Missing Data ......................................................................................................... 15
13.3 Insufficient Data for Presentation .......................................................................... 15
14. APPENDICES ............................................................................................................. 16
Appendix 1: Document History...................................................................................... 16


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2. ABBREVIATIONS
Abbreviations pertain to the Statistical Analysis Plan (SAP) only (not the tables, figures and 
listings [TFLs]).
AE
Adverse event
AUC
Area under the concentration versus time curve
AUC(0-∞)
Area under the concentration versus time curve from time zero to 
infinity
AUC(0-tlast)
Area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable concentration
BQL
Below the lower limit of quantitation
CI
Confidence interval
CL/F
Apparent total body clearance of drug calculated after extra-vascular
administration
Clast
Last predicted observed drug concentration
Cmax
Maximum observed drug concentration
CRU
Clinical Research Unit
CSR
Clinical Study Report
CV%
Coefficient of variation
ECG
Electrocardiogram
ICH
International Conference on Harmonisation
MedDRA
Medical Dictionary for Regulatory Activities
PFOS
Powder for oral suspension
PK
Pharmacokinetic
RTU
Ready to use
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SD
Standard deviation 
t1/2
Half-life associated with the terminal rate constant (λz) in non-
compartmental analysis
TEAE
Treatment-emergent adverse event
TFLs
Tables, Figures, and Listings
tmax
Time of maximum observed drug concentration


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Vss/F
Apparent volume of distribution at steady state after extravascular 
administration
Vz/F
Apparent volume of distribution during the terminal phase after 
extra-vascular administration
WHO
World Health Organization


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3. INTRODUCTION
This SAP has been developed after review of the Clinical Study Protocol (final version dated 19 
July 2021), and protocol amendment (a) (final version dated 07 September 2021). 
This SAP describes the planned analysis of the safety, tolerability and pharmacokinetic (PK) data 
from this study. A detailed description of the planned TFLs to be presented in the clinical study 
report (CSR) is provided in the accompanying TFL shell document.
The intent of this document is to provide guidance for the statistical and PK analyses of data. In
general, the analyses are based on information from the protocol, unless they have been modified 
by agreement with Eli Lilly and Company. A limited amount of information concerning this 
study (e.g., objectives, study design) is given to help the reader’s interpretation. For open-label 
studies, this SAP must be signed off prior to first participant visit for this study. When the SAP 
and TFL shells are agreed upon and finalized, they will serve as the template for this study’s 
CSR.
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon with
Eli Lilly and Company and identified in the CSR. Any minor deviations from the TFLs may not 
be documented in the CSR.
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1 and the ICH E3 Guideline entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports2.
4. STUDY OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the relative bioavailability of 
RTU (ready to use) and PFOS (powder for 
oral suspension) suspensions compared to 
the capsule formulation

Maximum observed drug concentration 
(Cmax), area under the concentration 
versus time curve from time zero to 
infinity (AUC[0-∞]), area from under the 
concertation versus time curve from time 
zero to time t (AUC0-tlast), and time to 
maximum observed drug concentration 
(tmax) of selpercatinib
Secondary 

To evaluate the safety and tolerability of a 
single 20-mg oral dose of selpercatinib 
RTU and PFOS suspensions

Summary of the number, severity, and 
type of treatment-emergent adverse events 
(TEAEs) and serious adverse events 
(SAEs)


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
To assess the palatability of selpercatinib 
RTU and PFOS suspensions

Responses to palatability questionnaire 
(RTU suspension only)
5. STUDY DESIGN
Study J2G-MC-JZJU (JZJU) will be an open-label, Phase 1 randomized, 3-formulation, 3-period, 
crossover study in adult heathy male and female participants. The RTU 20-mg suspension and 
the PFOS 20 mg/mL formulation will be compared to the 20 mg capsule formulation.
Figure 1 below illustrates the study design.
Figure 1: J2G-MC-JZJU Study Schema
Safety assessments, including adverse events (AEs), concomitant medications, medical 
assessments, clinical laboratory tests, vital signs, and electrocardiograms (ECGs), and blood 
sampling for PK, will be performed.
5.1
Screening
All participants will be screened within 28 days prior to enrolment.
5.2
Treatment and Assessment Period
Participants will be admitted to the clinical research unit (CRU) on Day -1. On the morning of
Day 1, participants will be randomized to 1 of 3 treatment sequences and will receive single
doses of 20 mg selpercatinib on each of Days 1, 8, and 15 as either the RTU suspension, the
PFOS, or the capsule, and will be dosed according to the randomization sequence following an
overnight fast of at least 10 hours.
The treatment sequences to be used are shown in Figure 2:


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Figure 2: Treatment Sequences for Study J2G-MC-JZJU
There will be a washout of 7 days between doses of selpercatinib. Participants will remain 
resident at the CRU for the full duration of the treatment period (i.e., up to Day 21).
6. TREATMENTS
The following is a list of the study treatment abbreviations that will be used in the TFLs.
Study Treatment Name
Abbreviation
Treatment order in TFL
20 mg selpercatinib capsule 
Capsule 
1
RTU selpercatinib 20 mg Suspension 
RTU 
2
20 mg/mL selpercatinib PFOS 
PFOS 
3
PFOS = powder for oral suspension, RTU = ready to use
7. SAMPLE SIZE JUSTIFICATION
Up to approximately 42 participants will be enrolled to ensure that at least approximately 36 
participants complete the study. The sample size for this study is justified based on a precision 
for the ratio of geometric means and it is represented by the half-width of the 90% confidence 
interval (CI) of the point estimate on the logarithmic scale. Based on an intra-participant
variability of 70% (LOXO-RET-19075), with a probability of 90%, a 90% CI for the ratio of the 
geometric means for Cmax and area under the concentration versus time curve (AUC) will be 
obtained with a precision about 0.288 in the log scale, which corresponds to approximately 0.334 
in the natural scale.
8. DEFINITION OF ANALYSIS POPULATIONS
The “Safety” population will consist of all enrolled participants who received at least one dose of 
selpercatinib, whether or not they completed all protocol requirement. 
The “Pharmacokinetic” population will consist of all participants who received at least one dose 
of selpercatinib and have evaluable PK data. Participants may be excluded from the PK summary 
statistics and statistical analysis if a participant has an AE of vomiting that occurs at or before 2 
times median tmax.


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All protocol deviations that occur during the study will be considered for their severity/impact 
and will be taken into consideration when participants are assigned to analysis populations.
9. STATISTICAL METHODOLOGY
9.1
General
Data listings will be provided for all data that is databased. Summary statistics and statistical 
analysis will only be presented for data where detailed in this SAP. For continuous data, 
summary statistics will include the arithmetic mean, arithmetic standard deviation (SD), median, 
minimum, maximum and n (number of subjects); for log-normal data (e.g. the PK parameters: 
AUCs and Cmax) the geometric mean and geometric coefficient of variation (CV%) will also be 
presented. For categorical data, frequency count and percentages will be presented. Data listings 
will be provided for all participants up to the point of withdrawal, with any participants excluded 
from the relevant population highlighted. Summary statistics and statistical analyses will 
generally only be performed for participants included in the relevant analysis population. For the 
calculation of summary statistics and statistical analysis, unrounded data will be used. 
Mean change from baseline is the mean of all individual participants’ change from baseline 
values. Each individual change from baseline will be calculated by subtracting the individual 
participant’s baseline value from the value at the timepoint. The individual participant’s change 
from baseline values will be used to calculate the mean change from baseline using a SAS 
procedure such as Proc Univariate.
Data analysis will be performed using SAS® Version 9.4 or greater.
9.2
Demographics and Participant Disposition
Participant disposition will be summarized and listed. The demographic variables age, sex, race, 
ethnicity, country of enrolment, site ID, body weight, height and body mass index will be 
summarized and listed. All other demographic variables will be listed only.
9.3
Pharmacokinetic Assessment
9.3.1
Pharmacokinetic Analysis
Noncompartmental methods applied with a validated software program (Phoenix WinNonlin 
Version 8.1 or later) to the plasma concentrations of selpercatinib will be used to determine the 
following PK parameters, when possible: 


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Parameter
Units
Definition
AUC(0-tlast)
ng.h/mL
area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable 
concentration
AUC(0-∞)
ng.h/mL
area under the concentration versus time curve from time zero to 
infinity
Cmax
ng/mL
maximum observed drug concentration
tmax
h
time of maximum observed drug concentration
t1/2
h
half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
CL/F
L/h
apparent total body clearance of drug calculated after 
extra-vascular administration
Vz/F
L
apparent volume of distribution during the terminal phase after 
extra-vascular administration
Vss/F
L
apparent volume of distribution at steady state after extra-vascular 
administration
Additional PK parameters may be calculated, as appropriate.  
The software and version used for the final analyses will be specified in the CSR. Any 
exceptions or special handling of data will be clearly documented within the final CSR.
Formatting of tables, figures and abbreviations will follow the Eli Lilly Global PK/PD/TS Tool: 
NON-COMPARTMENTAL PHARMACOKINETIC STYLE GUIDE. The version of the tool
effective at the time of PK analysis will be followed.
General PK Parameter Rules

Actual sampling times will be used in the final analyses of individual PK parameters, 
except for non-bolus pre-dose sampling times which will be set to zero.

Cmax and tmax will be reported from observed values.  If Cmax occurs at more than one time 
point, tmax will be assigned to the first occurrence of Cmax. 

AUC parameters will be calculated using a combination of the linear and logarithmic 
trapezoidal methods (linear-log trapezoidal rule).  The linear trapezoidal method will be 
applied up to tmax and then the logarithmic trapezoidal method will be used after tmax. The 
minimum requirement for the calculation of AUC will be the inclusion of at least three 
consecutive plasma concentrations above the lower limit of quantification, with at least 
one of these concentrations following Cmax.

The t1/2 will be calculated, when appropriate, based on the apparent terminal log-linear 
portion of the concentration-time curve. The start of the terminal elimination phase for 
each subject will be defined by visual inspection and generally will be the first point at 
which there is no systematic deviation from the log-linear decline in plasma
concentrations.  Half-life will only be calculated when a reliable estimate for this 


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parameter can be obtained comprising of at least 3 data points.  If t1/2 is estimated over a 
time window of less than 2 half-lives, the values will be flagged in the data listings. Any 
t1/2 value excluded from summary statistics will be documented in the footnote of the 
summary table. 

A uniform weighting scheme will be used in the regression analysis of the terminal log-
linear portion of the concentration-time curve.

The parameters based on last predicted observed drug concentration (Clast) will be 
reported (except in bioequivalence and bioavailability studies, where only the observed 
parameters will be reported).
Individual PK Parameter Rules

Only quantifiable concentrations will be used to calculate PK Parameters with the 
exception of special handling of certain concentrations reported below the lower limit of 
quantitation (BQL).  Plasma concentrations reported as BQL will be set to a value of zero
when all of the following conditions are met:
o
The compound is non-endogenous.
o
The samples are from the initial dose period for a subject or from a subsequent 
dose period following a suitable wash-out period.
o
The time points occur before the first quantifiable concentration.

All other BQL concentrations that do not meet the above criteria will be set to missing.

Also, where two or more consecutive concentrations are BQL towards the end of a 
profile, the profile will be deemed to have terminated and therefore any further 
quantifiable concentrations will be set to missing for the calculation of the PK parameters 
unless it is considered to be a true characteristic of the profile of the drug.
Individual Concentration vs. Time Profiles

Individual concentrations will be plotted utilizing actual sampling times.

The terminal point selections will be indicated on a semi-logarithmic plot.
Average Concentration vs. Time Profiles

The average concentration profiles will be graphed using scheduled (nominal) sampling 
times.

The average concentration profiles will be graphed using arithmetic average 
concentrations.


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
The pre-dose average concentration for single-dose data from non-endogenous 
compounds will be set to zero.  Otherwise, only quantifiable concentrations will be used 
to calculate average concentrations.

Concentrations at a sampling time exceeding the sampling time window specified in the 
protocol, or ± 10%, will be excluded from the average concentration profiles.

Concentrations excluded from the mean calculation will be documented in the final CSR.

A concentration average will be plotted for a given sampling time only if 2/3 of the 
individual data at the time point have quantifiable measurements that are within the 
sampling time window specified in the protocol or ± 10%. An average concentration 
estimated with less than 2/3 but more than 3 data points may be displayed on the mean 
concentration plot if determined to be appropriate and will be documented within the 
final CSR.
Treatment of Outliers during Pharmacokinetic Analysis
Application of this procedure to all PK analyses is not a requirement. Rather, this procedure 
provides justification for exclusion of data when scientifically appropriate. This procedure 
describes the methodology for identifying an individual value as an outlier for potential 
exclusion, but does not require that the value be excluded from analysis. The following 
methodology will not be used to exclude complete profiles from analysis.
Data within an Individual Profile
A value within an individual profile may be excluded from analysis if any of the following 
criteria are met:

For PK profiles during multiple dosing, the concentration of the pre-dose sample exceeds 
all measured concentrations for that individual in the subsequent post-dose samples.

For PK profiles during single dosing of non-endogenous compounds, the concentration in 
a pre-dose sample is quantifiable.

For any questionable datum that does not satisfy the above criteria, the profile will be 
evaluated and results reported with and without the suspected datum.
Data between Individual Profiles
1.
If n<6, then the dataset is too small to conduct a reliable range test.  Data will be 
analyzed with and without the atypical value, and both sets of results will be reported.  
2.
If n6, then an objective outlier test will be used to compare the atypical value to other 
values included in that calculation:
a.
Transform all values in the calculation to the logarithmic domain.


Fi nal Versi o n 1. 0, 0 4 N o ve m ber 2 0 2 1
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C O N FI D E N TI A L
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b.
F i n d t he most e xtre m e val ue fr o m t he arit h metic mea n of t he lo g tra nsf or me d
val ues a n d e xcl u de t hat val ue fr o m t he dataset.
c.
Calc ulate t he l o wer a n d u p per b o u n ds of t he ra n ge defi ne d b y t he arit h metic 
mea n ± 3 * S D of t he re m ai ni n g l og- tra nsf or me d val ues.
d.
If t he e xtre me val ue is wit hi n t he ra n ge of arith metic mea n ± 3 * S D, t he n it is 
n ot a n o utlier a n d will be retai ne d i n t he dataset .
e.
If t he e xtre me val ue is o utsi de t he ra n ge of arit h metic mea n ± 3 * S D, t he n it is 
a n o utlier a n d will be e xcl u de d fr o m a nal ysis.
If t he re mai ni n g dataset c o ntai ns a n ot her at ypi c al  d at u m s us pecte d t o be a n o utlier a n d n ≥ 6 
f oll owi n g t he e xcl usi o n, t he n re peat ste p 2 a b o ve. T his e val uat i on ma y be re peate d as ma n y 
ti mes as necessar y, e xcl u di n g o nl y o ne s us pected o utlier i n eac h iterati o n, u nt il all data 
r e mai ni n g i n t he dataset fall wi t hi n t he ra n ge of arit h met ic mea n ± 3 * S D of t he l o g -tra nsf or me d 
val ues.
Re p orti n g of E xcl u de d Val ues
I n di vi d ual val ues e xcl u de d as o utliers will be d oc u me nte d i n t he fi nal C S R .  A p p r o val of t he 
fi nal C S R will c o n n ote a p pr o val of t he e xcl usi o n.
9. 3. 2
P h ar m ac o ki netic St atistic al Met h o d ol o g y
P K para meters will be e val uate d t o esti mate relati ve bi oa vaila bilit y of  t he R T U a n d P F O S 
s us pe nsi o ns c o m pare d t o t he ca ps ule f or m ulat i on. 
L o g -tra nsf or med C ma x, A U C( 0-∞), a n d A U C( 0 -tlast) para meters will be e val uate d i n a li near 
mi xe d effect m o del wit h fi xe d effects f or treat me nt f or m ulat i on, peri o d, se q ue nce, a n d a ra n d o m 
effect f or partici pa nt. T he treat me nt differe nces bet wee n R T U (test) a n d P F O S (test) , a n d t he 
ca ps ule (refere nce) f or m ulat i ons will be bac k -tra nsf or me d t o prese nt t he rati os of ge o metric least 
s q uares mea ns a n d t he c orres p o n di n g 9 0 % CIs.
T he t ma x will be a nal yze d usi n g a Wilc o x o n si g ne d ra n k test. Esti mates of t he me dia n differe nce 
base d o n t he i n di vi d ual paire d differe nces , 9 0 % CIs, a n d p-val ues fr o m t he Wilc o x o n test will be 
calc ulate d.
C CI


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Labcorp Study: 8445329
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9.4
Safety and Tolerability Assessments
9.4.1
Adverse events
Where changes in severity are recorded in the CRF, each separate severity of the AE will be 
reported in the listings, only the most severe will be used in the summary tables. A pre-existing 
condition is defined as a condition that starts before the participant has provided written
informed consent and is ongoing at consent. A non-treatment emergent AE is defined as an AE 
which starts after informed consent but prior to dosing. A TEAE is defined as an AE which 
occurs postdose or which is present prior to dosing and becomes more severe postdose. 
All AEs will be listed. TEAEs will be summarized by treatment, severity and relationship to the 
study drug. The frequency (the number of AEs, the number of participants experiencing an AE
and the percentage of participants experiencing an AE) of TEAEs will be summarized by 
treatment, Medical Dictionary for Regulatory Activities (MedDRA) version 24.0 system organ 
class and preferred term. The summary and frequency AE tables will be presented for all 
causalities and those considered related to the study drug by the investigator. Any SAEs will be 
listed. 
Discontinuations due to AEs will be listed.
9.4.2
Concomitant medication
Concomitant medication will be coded using the WHO drug dictionary (Version March 2021). 
Concomitant medication will be listed.
9.4.3
Clinical laboratory parameters
All clinical chemistry and hematology data will be summarized by parameter and treatment, and 
listed. Urinalysis data will be listed. Additionally, clinical chemistry, hematology and urinalysis 
data outside the reference ranges will be listed and flagged on individual participant data listings.
9.4.4
Vital signs
Vital signs data will be summarized by treatment together with changes from baseline, where 
baseline is defined as the Day 1, Day 8, or Day 15 predose (as appropriate) assessment. Figures 
of mean vital signs and mean changes from baseline profiles will be presented by treatment, for 0 
(predose) to 96 h (Day 5/11/19) postdose.
Values for individual participants will be listed.
9.4.5
Electrocardiogram (ECG)
ECGs will be performed for safety monitoring purposes only and will not be presented. Any 
clinically significant findings from ECGs will be reported as an AE.


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9.4.6
Hepatic Monitoring
If a participant experiences elevated laboratory parameters, as detailed in Section 8.2.6.1 of the 
protocol, additional tests will be performed to confirm the abnormality. Additional safety data 
may be collected if required, as defined in the protocol. Where applicable, the following will be 
presented.
The participants’ liver disease history and associated person liver disease history data will be 
listed. Use of acetaminophen during the study, which has potential for hepatotoxicity, will be 
listed. Results from any hepatic monitoring procedures, such as a magnetic resonance 
elastography scan, and biopsy assessments will be listed, if performed.
Hepatic risk factor assessment data will be listed. Liver related signs and symptoms data will be 
summarized by treatment and listed. Alcohol and recreational drug use data will also be listed.
All hepatic chemistry, hematology, coagulation, and serology data will be listed. Values outside 
the reference ranges will be flagged on the individual participant data listings.
9.4.7
Palatability Questionnaires
The participant will be asked to provide responses to questions designed to assess the
acceptability and palatability of the RTU suspension. The questionnaire will assess the
participant’s experience relating to the taste, smell, and after taste in the oral cavity.
The questionnaire will be completed by the participant immediately after administration of the
RTU suspension and PFOS formulations.
These data will be summarized by treatment, and listed.
9.4.8
Other assessments
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed.
9.4.9
Safety and Tolerability Statistical Methodology
No inferential statistical analyses are planned.
10.
INTERIM ANALYSES
No interim statistical analyses are planned. If an unplanned interim analysis is deemed necessary 
for reasons other than a safety concern, the protocol and SAP must be amended.
11.
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES
There were no changes from the protocol specified statistical analyses.


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12.
REFERENCES
1. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998.
2. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995.
13.
DATA PRESENTATION
13.1
Derived Parameters
Individual derived parameters (e.g. PK parameters) and appropriate summary statistics will be 
reported to three significant figures. Observed concentration data, e.g. Cmax, should be reported 
as received. Observed time data, e.g. tmax, should be reported as received. N and percentage 
values should be reported as whole numbers. Median values should be treated as an observed 
parameter and reported to the same number of decimal places as minimum and maximum values.
13.2
Missing Data
Missing data will not be displayed in listings.
13.3
Insufficient Data for Presentation
Some of the TFLs may not have sufficient numbers of participants or data for presentation. If 
this occurs, the blank TFL shell will be presented with a message printed in the center of the 
table, such as, “No serious adverse events occurred for this study.”


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Labcorp Study: 8445329
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14.
APPENDICES
Appendix 1: Document History
Status and Version
Date of Change
Summary/Reason for Changes
Final Version 1.0
NA
NA; the first version.
NA = not applicable


L e o  D o c u m e n t  I D  =  a 5 a 0 4 a b 0 - 7 a 1 0 - 4 9 4 2 - a f d 2 - 0 f f f d 0 7 b d 4 9 1
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 5 - N o v - 2 0 2 1  1 0 : 4 0 : 0 4  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 8 - N o v - 2 0 2 1  1 0 : 0 4 : 5 8  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 8 - N o v - 2 0 2 1  1 6 : 1 9 : 2 4  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 9 - N o v - 2 0 2 1  1 0 : 1 7 : 4 2  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
P P D
P P D
P P D
P P D