Clinical trial NCT03212638
Conditions: Healthy
Sponsor: Eli Lilly and Company
Start date: 2017-06-27; Completion date: 2017-11-01
Enrollment: 42 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purposes of this study are to determine:

* If there are any differences in the amount of baricitinib in the blood/body when taken in two different forms.
* How a high-fat, high-calorie meal affects the amount of baricitinib in the blood/body.
* The safety and tolerability of baricitinib.

The study has two parts. Individuals will participate in only one part.

Participants will be admitted to the clinical research unit (CRU) and will be discharged from the CRU following the completion of 3 overnight stays.

Each part of this study will last from 8-10 days, not including screening. Follow-up will occur 7 to 14 days after the last dose of baricitinib.

Detailed description:

Arms: arm 1: 4 mg (milligram) baricitinib suspension test formulation (TF) administered orally (PO) without water following a 10 hour fast. (Baricitinib T1) arm 2: 4 mg baricitinib suspension formulation (TF) administered PO prior to 240 mL water following a 10 hour fast (Baricitinib T2) arm 3: 4 mg baricitinib tablet administered PO, taken with 240 mL water following a 10 hour fast (baricitinib R) arm 4: 4 mg baricitinib suspension test formulation (TF) administered after 10 hour fast. (TF fasting) arm 5: 4 mg baricitinib suspension TF administered after a high fat meal.(baricitinib TF Fed)
Interventions: intervention 1: Baricitinib suspension intervention 2: Baricitinib tablet
Intervention descriptions: intervention 1: Administered orally intervention 2: Administered orally

Protocol documents:
Prot_000.pdf: 
Protocol I4V-MC-JAGU A Bioequivalence and Food Effect Study in Healthy Subjects 
Comparing Baricitinib Suspension and Commercial Tablet Formulations 
 
 
NCT03212638 
Approval Date: 28-Sep-2016 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 1
Baricitinib (LY3009104)
Protocol I4V-MC-JAGU
A Bioequivalence and Food Effect Study in Healthy 
Subjects Comparing Baricitinib Suspension and 
Commercial Tablet Formulations
Confidential Information
The information contained in this protocol 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 
baricitinib (LY3009104), 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.  
Baricitinib (LY3009104)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Clinical Pharmacology Protocol Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 28-Sep-2016 GMT


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 2
Baricitinib (LY3009104)
Table of Contents
A Bioequivalence and Food Effect Study in Healthy Subjects 
Comparing Baricitinib Suspension and Commercial Tablet 
Formulations
Section
Page
Protocol I4V-MC-JAGU A Bioequivalence and Food Effect Study in 
Healthy Subjects Comparing Baricitinib Suspension and Commercial 
Tablet Formulations ............................................................................................................1
Table of Contents........................................................................................................................2
1.
Protocol Synopsis................................................................................................................8
2.
Schedule of Activities .......................................................................................................11
3.
Introduction ......................................................................................................................14
3.1.
Study Rationale............................................................................................................14
3.2.
Background..................................................................................................................14
3.3.
Benefit/Risk Assessment..............................................................................................15
4.
Objectives and Endpoints..................................................................................................17
5.
Study Design.....................................................................................................................18
5.1.
Overall Design .............................................................................................................18
5.2.
Number of Participants.................................................................................................20
5.3.
End of Study Definition ...............................................................................................20
5.4.
Scientific Rationale for Study Design...........................................................................20
5.5.
Justification for Dose ...................................................................................................21
6.
Study Population...............................................................................................................22
6.1.
Inclusion Criteria..........................................................................................................22
6.2.
Exclusion Criteria ........................................................................................................23
6.3.
Lifestyle and/or Dietary Requirements .........................................................................24
6.3.1.
Meals and Dietary Restrictions.............................................................................25
6.3.2.
Caffeine, Alcohol, and Tobacco ...........................................................................25
6.3.3.
Activity................................................................................................................25
6.4.
Screen Failures.............................................................................................................26
7.
Treatment..........................................................................................................................27
7.1.
Treatment Administered...............................................................................................27
7.1.1.
Packaging and Labeling .......................................................................................28
7.2.
Method of Treatment Assignment ................................................................................28
7.2.1.
Selection and Timing of Doses.............................................................................28
7.3.
Blinding .......................................................................................................................28


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 3
Baricitinib (LY3009104)
7.4.
Dose Modification........................................................................................................28
7.5.
Preparation/Handling/Storage/Accountability...............................................................28
7.6.
Treatment Compliance .................................................................................................29
7.7.
Concomitant Therapy...................................................................................................29
7.8.
Treatment After the End of the Study...........................................................................29
8.
Discontinuation Criteria ....................................................................................................30
8.1.
Discontinuation from Study Treatment.........................................................................30
8.1.1.
Discontinuation of Inadvertently Enrolled Subjects..............................................30
8.2.
Discontinuation from the Study....................................................................................30
8.3.
Subjects Lost to Follow-up...........................................................................................30
9.
Study Assessments and Procedures ...................................................................................31
9.1.
Efficacy Assessments...................................................................................................31
9.2.
Adverse Events ............................................................................................................31
9.2.1.
Serious Adverse Events........................................................................................32
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................32
9.2.2.
Complaint Handling.............................................................................................33
9.3.
Treatment of Overdose.................................................................................................33
9.4.
Safety...........................................................................................................................33
9.4.1.
Laboratory Tests ..................................................................................................33
9.4.2.
Vital Signs ...........................................................................................................33
9.4.3.
Electrocardiograms ..............................................................................................33
9.4.4.
Safety Monitoring ................................................................................................34
9.5.
Pharmacokinetics .........................................................................................................34
9.5.1.
Bioanalysis...........................................................................................................34
9.6.
Pharmacodynamics ......................................................................................................35
9.7.
Genetics .......................................................................................................................35
9.8.
Biomarkers...................................................................................................................35
9.9.
Health Economics ........................................................................................................35
10.
Statistical Considerations and Data Analysis.....................................................................36
10.1. Sample Size Determination ..........................................................................................36
10.2. Populations for Analyses..............................................................................................36
10.2.1.
Study Participant Disposition ...............................................................................36
10.2.2.
Study Participant Characteristics ..........................................................................36
10.3. Statistical Analyses ......................................................................................................36
10.3.1.
Safety Analyses....................................................................................................37
10.3.1.1.
Clinical Evaluation of Safety..........................................................................37
10.3.1.2.
Statistical Evaluation of Safety.......................................................................37
10.3.2.
Pharmacokinetic Analyses....................................................................................37


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 4
Baricitinib (LY3009104)
10.3.2.1.
Pharmacokinetic Parameter Estimation...........................................................37
10.3.2.2.
Pharmacokinetic Statistical Inference .............................................................37
10.3.3.
Interim Analyses..................................................................................................38
11.
References ........................................................................................................................39


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 5
Baricitinib (LY3009104)
List of Tables
Table
Page
Table JAGU.1.
Objectives and Endpoints .......................................................................17
Table JAGU.2.
Treatment Sequences in Part A of Study I4V-MC-JAGU........................18
Table JAGU.3.
Treatment Sequences in Part B of Study I4V-MC-JAGU........................19
Table JAGU.4.
Treatments Administered in Part A.........................................................27


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 6
Baricitinib (LY3009104)
List of Figures
Figure
Page
Figure JAGU.1.
Illustration of study design for Protocol I4V-MC-JAGU.........................20


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 7
Baricitinib (LY3009104)
List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions ................................................................40
Appendix 2.
Clinical Laboratory Tests........................................................................44
Appendix 3.
Study Governance, Regulatory and Ethical Considerations.....................45
Appendix 4.
Blood Sampling Summary......................................................................48


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 8
Baricitinib (LY3009104)
1. Protocol Synopsis
Title of Study:
A Bioequivalence and Food Effect Study in Healthy Subjects Comparing Baricitinib Suspension and Commercial 
Tablet Formulations
Rationale:  
This study is designed to support development of the baricitinib suspension formulation which is being developed 
for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients from the age of 2 years, 
who have had inadequate responses to previous disease-modifying antirheumatic drugs.  In Part A, single oral 4-mg 
doses of baricitinib suspension formulation administered with and without water will each be compared with a 
single oral dose of 4 mg commercial tablet formulation to determine whether the bioavailability of baricitinib
administered as suspension, under either condition, is equivalent to baricitinib administered as the commercial tablet 
formulation.  Interim analysis of data from Part A will be used to determine the administration of the suspension 
formulation in Part B of the study.
Additionally, in Part B, a single oral dose of the suspension formulation administered under fed conditions will be 
compared to administration under fasted conditions to assess the effects of food on the rate and extent of absorption.  
Objectives/Endpoints:  
Objectives
Endpoints
Primary
To determine if 4 mg of baricitinib administered in a 
single dose of the suspension formulation (2 mL of 
2 mg/mL suspension), with or without water, is 
bioequivalent (with 0.80, 1.25 as the bioequivalence 
boundaries) to 4 mg of baricitinib administered as a 
single 4-mg tablet.
The ratio of geometric least square means between 
each test formulation and the reference formulation for 
maximum observed drug concentration (Cmax), area 
under the concentration versus time curve (AUC) from 
time zero to the last time point with a measurable 
concentration (AUC[0-tlast]), and AUC from time zero 
to infinity (AUC[0-∞]).  
Secondary
The secondary objectives are:

To evaluate the tolerability of baricitinib given 
as a single dose when administered to healthy 
adult subjects.

To compare the relative bioavailability of the 
suspension formulation administered with and 
without water.

To determine the effect of a high-fat, 
high-calorie meal on the pharmacokinetics (PK) 
of baricitinib when administered as a single 
4-mg dose of the suspension formulation.

Incidence of treatment-emergent adverse 
events (TEAEs).

The ratio of geometric least square means 
between administration of suspension 
formulation with and without water for Cmax, 
AUC(0-tlast), AUC(0-∞), and median of 
differences for time of maximum observed 
drug concentration (tmax).

The ratio of geometric least square means 
between the fasted and fed state for Cmax, 
AUC(0-tlast), AUC(0-∞), and median of 
differences for tmax.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 9
Baricitinib (LY3009104)
Summary of Study Design:  
Study I4V-MC-JAGU is a 2-part, single-center, Phase 1, open-label, randomized, crossover study in healthy 
subjects.  
Part A will be a 3-period, randomized, crossover study to evaluate the bioequivalence of 4 mg baricitinib 
administered as a single dose of the suspension formulation, with and without water, and 4 mg of baricitinib 
administered as a single 4-mg tablet with water.  
Part B will be a 2-period, randomized, crossover study to determine the effect of a high-fat, high-calorie meal on the 
PK of baricitinib administered as a single dose of the suspension formulation.  Subjects who participate in Part A of 
the study will not participate in Part B.  
Subjects in each part of the study will be admitted to the clinical research unit (CRU) on Day -1 of each period.  
Following an overnight fast of at least 10 hours, subjects will be administered 4 mg baricitinib according to the 
randomization schedule.  At a minimum, subjects will be resident at the CRU until collection of the 12-hour PK 
sample; all subsequent assessments may be conducted on an outpatient basis at the discretion of the investigator.  
Blood sampling for assessment of baricitinib PK will be performed up to 48 hours postdose (Day 3).  
Safety will be assessed through adverse event (AE) recording, medical review and targeted examination, clinical 
laboratory evaluations, and vital signs.  
Treatment Arms and Duration:  
Part A: Subjects will receive single doses of 4 mg baricitinib as suspension formulation administered without water, 
suspension formulation administered with 240 mL water, and commercial tablet formulation administered with 
240 mL water, with sequence determined by randomization.
Part B:  Subjects will receive a single dose of 4 mg baricitinib suspension in a fasted state and a single dose of 4 mg 
baricitinib suspension after a high-fat, high-calorie meal, with sequence determined by randomization.
Screening will occur up to 28 days prior to dosing in Period 1 and each treatment period will last approximately 
48 hours.  There will be at least 72 hours between dosing in each consecutive period and a follow-up visit will occur 
7 to 14 days after the last dose of baricitinib.  
Number of Subjects:  
Part A:  Twenty-six subjects may be enrolled to ensure that 20 subjects complete Part A of the study.
Part B: It is planned that up to a maximum of 18 subjects may be enrolled so that approximately 14 subjects 
complete Part B of the study but this number may be revised upon interim analysis of data from Part A.
Statistical Analysis:
Safety parameters that will be assessed include TEAEs, clinical laboratory parameters, and vital signs.  The 
parameters will be listed and summarized using standard descriptive statistics, as appropriate.  
Pharmacokinetic parameter estimates for baricitinib will be calculated by standard noncompartmental methods of 
analysis. Pharmacokinetic parameter estimates will be evaluated to delineate effects of baricitinib formulation.  For 
the primary analysis, log-transformed Cmax, AUC(0-tlast), and AUC(0-∞) estimates will be evaluated in a linear 
mixed-effects model with fixed effects for formulation, period, sequence, and a random effect for subject 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 10
Baricitinib (LY3009104)
(sequence).  The treatment differences between each test compared to the reference formulation will be 
back-transformed to present the ratios of geometric least squares means and the corresponding confidence interval 
(CI).  The Holm step-down procedure for an overall 0.1 alpha level will be used.
Bioequivalence between the suspension formulation administered either with or without water and the commercial 
tablet will be concluded if the 95% CI for  Cmax, AUC(0-tlast), and AUC(0-∞) are all completely contained within 
the interval (0.80, 1.25).  Bioequivalence between the suspension formulation using the other administration and the 
commercial tablet will be concluded if the 90% CIs for Cmax, AUC(0-tlast), and AUC(0-∞) are all completely 
contained within the interval (0.80, 1.25).
For secondary analyses, the same model specified above will be used for Cmax, AUC(0-tlast), and AUC(0-∞).  Ratios 
of geometric least squares means and the corresponding 90% CIs will be presented.  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.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 11
Baricitinib (LY3009104)
2. Schedule of Activities


I4V-MC-JAGU Clinical Pharmacology Protocol 
Page 12 
Baricitinib (LY3009104) 
Study Schedule Protocol I4V-MC-JAGU 
 
Screening 
Part A Periods 1,2, and 3 
Part B Periods 1 and 2 
 
Follow-Up/Early 
Discontinuation 
Comments 
Procedure 
≤28 days 
prior to 
Period 1 
dose 
-1 
1 
2 
3 
7 to 14 days after 
last dose 
 
Informed 
Consent 
X 
 
 
 
 
 
 
Subject 
Admission to 
CRU 
 
X 
 
 
 
 
 
Subject 
Discharge from 
CRU 
 
 
X 
 
 
 
Subjects may be discharged after the 12 hour PK 
sample is collected in each period and return for 
all other assessments on an outpatient basis, at the 
discretion of the investigator.   
Outpatient Visit 
 
 
 
X 
X 
 
At the investigator’s discretion, subjects may be 
discharged anytime between 12-hours postdose 
and Day 3 and thus may attend as outpatients for 
collection of the 24-, 36-, and 48-hour PK 
samples.   
Overnight Fast 
 
X 
 
 
 
 
Subjects will be fasted from ≥10 hours prior to 
dosing. 
Study Treatment 
Administration 
 
 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
BMI will be calculated at screening.   
Vital Signs 
(supine) 
X 
 
Predose 
 
 
X 
Supine blood pressure and/or pulse rate may be 
measured as clinically indicated as well as at the 
scheduled times.  Additional scheduled vital signs 
may be measured during each study period, if 
warranted and agreed upon between Lilly and the 
investigator. 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 13
Baricitinib (LY3009104)
Screening
Part A Periods 1,2, and 3
Part B Periods 1 and 2
Follow-Up/Early 
Discontinuation
Comments
Procedure
≤28 days 
prior to 
Period 1 
dose
-1
1
2
3
7 to 14 days after 
last dose
Clinical 
Laboratory
Tests
X
Predose
X
See Appendix 2, Clinical Laboratory Tests, for 
details.  
Pregnancy Test 
X
X
Serum pregnancy test will be performed at 
screening.  A serum or urine pregnancy test will be 
performed at follow-up/early discontinuation and 
may be performed at other times at the 
investigator’s discretion.
Physical 
Exam/Medical 
Assessment
X
Predose
X
X
A complete physical examination to be conducted 
at screening.  All other medical assessment to 
include medical review and targeted examination, 
as appropriate.  Day 2 medical assessment may be 
performed any time prior to discharge if subject 
remains resident in the CRU beyond Day 2.
12-lead ECG
(single)
X
X
Genetic Sample
Predose 
(Period 1 
only)
Single sample for pharmacogenetic analysis.
PK Samples 
(hours) 
Predose, 
0.25, 0.5, 
0.75, 1, 1.5, 
2, 3, 4, 6, 9, 
12
24, 36
48
Sampling times are relative to the time of study 
treatment administration.
Abbreviations:  BMI = body mass index; CRU = clinical research unit; ECG = electrocardiogram; PK = pharmacokinetics.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 14
Baricitinib (LY3009104)
3. Introduction
3.1.
Study Rationale
This study is designed to support development of the baricitinib suspension formulation which is 
being developed for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) in pediatric 
patients from the age of 2 years, who have had inadequate responses to previous 
disease-modifying antirheumatic drugs. In Part A, single oral 4-mg doses of baricitinib 
suspension formulation administered with and without water will each be compared with a single 
oral dose of 4 mg commercial tablet formulation to determine whether the bioavailability of 
baricitinib administered as suspension, under either condition, is equivalent to baricitinib
administered as the commercial tablet formulation.  Interim analysis of data from Part A will be 
used to determine the administration of the suspension formulation in Part B of the study.
Additionally, in Part B, a single oral dose of the suspension formulation administered under fed 
conditions will be compared to administration under fasted conditions to assess the effects of 
food on the rate and extent of absorption.
3.2.
Background
Baricitinib is presently being studied for the treatment of adult patients with rheumatoid arthritis 
(RA) and has completed Phase 2 and 3 trials for the treatment of RA at doses up to 4 mg once 
daily (QD).  Baricitinib represents a selective inhibitor of the Janus kinase (JAK) family of 
protein tyrosine kinases with excellent potency and selectivity for JAK2 and JAK1, and a lower 
potency for JAK3, or tyrosine kinase 2 (Fridman et al. 2010).  Signal transducers and activators 
of transcription (STATs), once phosphorylated by JAKs, become active transcription factors and 
drive the expression of multiple genes important for cell activation, localization, survival, and 
proliferation (Valentino and Pierre 2006).
Chronic inflammatory conditions are associated with aberrant production of cytokines and 
growth factors.  Inhibition of JAK-STAT signaling to target multiple RA-associated cytokine 
pathways has the potential to simultaneously reduce inflammation, cellular activation, and 
proliferation of key immune cells.  Inhibitors of JAK have been demonstrated to have a clinically 
meaningful efficacy in patients with RA (Boy et al. 2009; Kremer et al. 2009).  Nonbiological 
agents, such as baricitinib, that are orally administered and have a shorter half-life may provide 
an alternative to the longer-acting injectable biologic therapies currently available.
For the Phase 3 studies conducted in adults with RA, a tablet formulation of baricitinib was 
developed and is the proposed commercial formulation for RA.
Following oral administration in healthy subjects, the time of maximum observed drug 
concentration (tmax) was approximately 1.5 hours, indicating that baricitinib is rapidly absorbed.  
Dose-proportional increases in exposure across the dose range 1 to 30 mg have been observed.  
There is no indication suggesting the pharmacokinetics (PK) is time-dependent.  The half-life 
associated with the terminal rate constant in noncompartmental analysis (t1/2) of baricitinib is 
approximately 6 to 8 hours in healthy subjects, leading to observation of minimal accumulation 
with QD dosing.  Following a single oral dose of 10 mg baricitinib containing 100 µCi of 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 15
Baricitinib (LY3009104)
[14C]-baricitinib in healthy subjects, a mean (± standard deviation) of 75.2% (± 6.7%) of the 
dose was excreted in urine and 19.9% (± 4.9%) was excreted in feces through the last collection 
interval (see Section 6.1.3.4 of the Investigator’s Brochure [IB] for further information on 
disposition).  
In addition to the commercial tablet formulation, an age appropriate suspension formulation is 
being developed in order to allow potential treatment of pediatric patients with pJIA.  This study 
will be conducted to determine whether the suspension formulation is bioequivalent to the 
commercial tablet formulation when the suspension is administered alone and with water, which 
may increase the amount of drug substance in solution, thus achieving bioequivalence should 
bioavailability of the suspension formulation be decreased.
No clinically meaningful food effect was observed with the tablet formulation of baricitinib; a 
high-fat meal decreased the mean area under the concentration versus time curve (AUC) and 
maximum observed drug concentration (Cmax) of baricitinib by approximately 11% and 18%, 
respectively, and delayed the median tmax by 0.5 hours.  Part B of this study aims to assess the 
effect of a high-fat meal on the bioavailability of the baricitinib suspension formulation.  
3.3.
Benefit/Risk Assessment
Cumulatively, approximately 4332 subjects have received baricitinib during the clinical 
development program (481 healthy subjects, 36 subjects with varying degrees of renal 
impairment, 8 subjects with hepatic dysfunction, and 3807 subjects with RA or other 
inflammatory diseases).  In clinical pharmacology studies, baricitinib was generally safe and well 
tolerated in single doses ranging from 1 to 40 mg and in repeat oral doses ranging from 2 to 
20 mg for up to 10 days, in healthy subjects. One male subject with end stage renal disease died 
of renal failure approximately 22 days after receiving the second of 2 single 5-mg doses of 
baricitinib.  The subject was on dialysis and had a history of type 2 diabetes and hypertension.  
The event was considered by the investigator to be unrelated to study drug.  A serious adverse 
event (SAE) of migraine was reported in 1 healthy adult, after a single 20-mg dose of baricitinib, 
and there was 1 event of maternal exposure during pregnancy following QD dosing of 10 mg 
baricitinib.  Adverse events (AEs) leading to discontinuation of healthy subjects from studies of 
baricitinib include conjunctivitis (5 mg twice-daily dosing and single 10-mg dose), blood 
bilirubin increased (10 mg QD), influenza-like illness (10 mg QD), complicated migraine (single 
20-mg dose), oral herpes (single 10-mg dose), ear infection (10 mg QD), and diarrhea (single 
10-mg dose).
In healthy subjects, the most notable post-treatment drug effect reported was a reduction in 
absolute neutrophil count (ANC).  Mean ANC decreased after dosing in a generally 
dose-dependent manner.  The lowest levels were reached approximately 8 hours postdose, and 
then returned to predose levels by 24 hours after each dose.  The maximum ANC decrease from 
baseline following a single 10-mg dose was 36.5%.  These decreases may be attributed to 
neutrophil margination.  
As this study is enrolling healthy subjects, no clinical benefit is anticipated from study 
participation.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 16
Baricitinib (LY3009104)
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated AEs of baricitinib are to be found in the IB.  


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 17
Baricitinib (LY3009104)
4. Objectives and Endpoints
Table JAGU.1 shows the objectives and endpoints of the study.
Table JAGU.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
To determine if 4 mg of baricitinib administered in a 
single dose of the suspension formulation (2 mL of 
2 mg/mL suspension), with or without water, is 
bioequivalent (with 0.80, 1.25 as the bioequivalence 
boundaries) to 4 mg of baricitinib administered as a 
single 4-mg tablet.
The ratio of geometric least square means between each 
test formulation and the reference formulation for Cmax, 
area under the concentration versus time curve (AUC) 
from time zero to the last time point with a measurable 
concentration (AUC[0-tlast]), and AUC from time zero 
to infinity (AUC[0-∞]).  
Secondary
The secondary objectives are:

To evaluate the tolerability of baricitinib given 
as a single dose when administered to healthy 
adult subjects.

To compare the relative bioavailability of the 
suspension formulation administered with and 
without water.

To determine the effect of a high-fat, 
high-calorie meal on the PK of baricitinib 
when administered as a single 4-mg dose of 
the suspension formulation.

Incidence of treatment-emergent adverse events
(TEAEs).

The ratio of geometric least square means  
between administration of suspension 
formulation with and without water for Cmax, 
AUC(0-tlast), AUC(0-∞), and median of 
differences for tmax..

The ratio of geometric least square means 
between the fasted and fed state for Cmax, 
AUC(0-tlast), AUC(0-∞), and median of 
differences for tmax..


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 18
Baricitinib (LY3009104)
5. Study Design
5.1.
Overall Design
This is a 2-part, single-center, Phase 1, open-label, randomized, crossover study in healthy 
subjects.
Part A will be a 3-period, randomized, crossover study to evaluate the bioequivalence of 4 mg 
baricitinib administered as a single dose of the suspension formulation, with and without water, 
and 4 mg of baricitinib administered as a single 4-mg tablet with water.  
Subjects will be randomly allocated to 1 of 3 treatment sequences (Table JAGU.2).  
Approximately 8 subjects may be allocated to each treatment sequence.  Subjects will receive 
single oral doses of baricitinib on 3 separate occasions, separated by washout periods of at least 
72 hours.  Each subject will receive the following:

a single 4-mg (2 mL × 2 mg/mL) dose of baricitinib suspension formulation administered 
without water (T1), in the fasted state

a single 4-mg (2 mL × 2 mg/mL) dose of baricitinib suspension formulation administered 
with 240 mL water (T2), in the fasted state

a single 4-mg (1 × 4 mg) dose of baricitinib commercial tablet formulation administered 
with 240 mL water (R), in the fasted state
Table JAGU.2.
Treatment Sequences in Part A of Study I4V-MC-JAGU
Sequence
Period 1
Period 2
Period 3
1
T1
T2
R
2
T2
R
T1
3
R
T1
T2
Abbreviations:  R = 4-mg dose of baricitinib commercial tablet formulation administered with 240 mL water; 
T1 = 4-mg dose of baricitinib suspension formulation administered without water; T2 = 4-mg dose of baricitinib 
suspension formulation administered with 240 mL water.  
Part B will be a 2-period, randomized, crossover study to determine the effect of a high-fat,
high-calorie meal on the PK of baricitinib administered as a single dose of the suspension 
formulation. Subjects who participate in Part A of the study will not participate in Part B.  
Subjects will be randomly allocated to 1 of 2 treatment sequences (Table JAGU.3).  Subjects will 
receive single oral doses of baricitinib on 2 separate occasions, separated by a washout period of 
at least 72 hours.  Whether or not these doses are administered with water (ie what the Part B 
suspension test formulation [TF] will be) will be decided after an interim analysis of the data 
from Part A of the study (see Section 10.3.3).  Each subject will receive the following:


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 19
Baricitinib (LY3009104)

a single 4-mg (2 mL × 2 mg/mL) dose of baricitinib TF administered after a high-fat, 
high-calorie meal

a single 4-mg (2 mL × 2 mg/mL) dose of baricitinib TF administered in the fasted state
Table JAGU.3.
Treatment Sequences in Part B of Study I4V-MC-JAGU
Sequence
Period 1
Period 2
1
TFfasted
TFfed
2
TFfed
TFfasted
Abbreviations:  TFfasted = 4-mg dose of baricitinib suspension test formulation administered in the fasted state; 
TFfed = 4-mg dose of baricitinib suspension test formulation administered after a high-fat, high-calorie meal.  
Each subject will provide informed consent for study participation and will undergo a screening 
examination within 28 days prior to the first dose.  
In each study period (of Part A or Part B), subjects will be admitted to the clinical research unit 
(CRU) on Day -1 and will be dosed with baricitinib, following an overnight fast of at least 
10 hours, according to their assigned treatment sequence, on the morning of Day 1.  At a 
minimum, subjects will be resident at the CRU until collection of the 12-hour PK sample; all 
subsequent assessments may be conducted on an outpatient basis at the discretion of the 
investigator.  There will be at least a 72-hour washout period between dosing in 2 consecutive 
study periods.  A follow-up visit will occur 7 to 14 days after the last dose of baricitinib.
In each period, serial blood samples will be collected predose and at prespecified times up to 
48 hours postdose (Day 3) for the determination of plasma concentrations of baricitinib for PK 
assessments.  
Safety will be assessed throughout each part of the study by AE recording, medical review and 
targeted examination, clinical laboratory evaluations, and vital signs.  
Figure JAGU.1 illustrates the study design.




I4V-MC-JAGU Clinical Pharmacology Protocol
Page 21
Baricitinib (LY3009104)
demonstrate bioequivalence to the commercial tablet formulation, it is anticipated that 
administration with water may increase the amount of drug substance in solution, thus aiding 
absorption and the achievement of bioequivalence.  
The administration method for the suspension that demonstrates bioequivalence to the 
commercial tablet formulation in Part A of the study will be used in Part B (see Section 10.3.3).  
Interim analysis of intra-subject variability data in Part A will also inform on required subject 
numbers for Part B of the study.  
This study has been designed to show definitive equivalence between the commercial tablet and 
suspension formulation, potentially facilitating the interchangeability of suspension and tablet 
formulations in future clinical studies with pediatric pJIA patients.
Part B of the study will assess the effect of a high-fat, high-calorie meal on the bioavailability of 
the suspension formulation, in accordance with regulatory guidance for new formulations (US 
Food and Drug Administration [FDA] 2002).  
The washout period of at least 72 hours adequately minimizes the potential PK carryover effects 
of baricitinib, given its median t1/2 of approximately 6 to 8 hours in healthy subjects.  
5.5.
Justification for Dose
The 4 mg commercial tablet formulation to be used as a reference in this study is the highest unit 
dose strength used in Phase 3 trials for RA.  A 4-mg dose of baricitinib has been extensively 
studied in previous Phase 1 studies assessing baricitinib PK and has been well tolerated in 
healthy subjects.  The 2 mg/mL suspension concentration is planned to be used in future clinical 
studies with this formulation.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 22
Baricitinib (LY3009104)
6. Study Population
Eligibility of subjects for study enrollment will be based on the results of screening medical 
history, physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG).
Screening may occur up to 28 days prior to dosing in Period 1.  Subjects who are not dosed
within 28 days of screening may be subjected to an additional medical assessment and/or clinical 
measurements to confirm their eligibility.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Subjects are eligible for inclusion in the study only if they meet all of the following criteria at 
screening and/or enrollment:
[1]
are overtly healthy males or females, as determined by medical history and 
physical examination
[1a] male subjects:
agree to use an effective method of contraception and not donate sperm for 
the duration of the study and for 28 days following the last dose of 
baricitinib
[1b] female subjects:
women not of child-bearing potential may participate, and include those who are:
a) infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal 
ligation), congenital anomaly such as mullerian agenesis; or
b) postmenopausal – postmenopausal is defined as women with an intact uterus 
who have not taken hormones or oral contraceptives within 1 year, who have 
had either cessation of menses for at least 1 year, or 6 to 12 months of 
spontaneous amenorrhea with follicle-stimulating hormone consistent with 
menopause
[2]
are aged 21 to 65 years, inclusive, at the time of screening
[3]
have a body mass index (BMI) of 18.5 to 29.9 kg/m2, inclusive, at screening
[4]
have clinical laboratory test results within normal reference range for the 
investigative site, or results with acceptable deviations that are judged to be 
not clinically significant by the investigator
[5]
have venous access sufficient to allow for blood sampling as per the protocol
[6]
are reliable and willing to make themselves available for the duration of the 
study and are willing to follow study procedures
[7]
have given signed informed consent


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 23
Baricitinib (LY3009104)
6.2.
Exclusion Criteria
Subjects will be excluded from study enrollment if they meet any of the following criteria at 
screening and/or enrollment:
[8] Are investigative site personnel directly affiliated with this study and their 
immediate families.  Immediate family is defined as a spouse, biological or 
legal guardian, child, or sibling.
[9] are Lilly employees
[10] are currently enrolled in a clinical trial involving an investigational product or 
any other type of medical research judged not to be scientifically or medically 
compatible with this study
[11]
have participated, within the last 30 days, in a clinical trial involving an 
investigational product.  If the previous investigational product has a long 
half-life, 3 months or 5 half-lives (whichever is longer) should have passed.
[12]
have previously completed or withdrawn from this study or any other study 
investigating baricitinib, and have previously received the investigational 
product 
[13]
have known allergies to baricitinib, related compounds, or any components of 
the formulation, or history of significant atopy
[14]
have an abnormality in the 12-lead ECG that, in the opinion of the 
investigator, increases the risks associated with participating in the study
[15]
have an abnormal blood pressure as determined by the investigator
[16]
have a history of or current cardiovascular, respiratory, hepatic, 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
[17]
have known or ongoing psychiatric disorders that would interfere with study 
participation as determined by the investigator
[18]
regularly use known drugs of abuse 
[19]
show evidence of human immunodeficiency virus (HIV) infection and/or 
positive HIV antibodies
[20]
show evidence of hepatitis C and/or positive hepatitis C antibody
[21]
show evidence of hepatitis B and/or positive hepatitis B surface antigen
[22]
are women who are pregnant or lactating
[23]
have used or intend to use over-the-counter or prescription medication,
including herbal medications, within 14 days prior to dosing and during the 
study


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 24
Baricitinib (LY3009104)
[24]
have donated blood of more than 450 mL within 3 months of study enrollment
[25]
have an average weekly alcohol intake that exceeds 21 units per week (males) 
and 14 units per week (females), or are unwilling to abide by alcohol 
restrictions as specified in Section 6.3.2 (1 unit = 12 oz or 360 mL of beer; 
5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
[26]
are subjects who currently smoke more than 10 cigarettes per day (or 
equivalent in tobacco or nicotine products) or are unwilling to abide by 
smoking restrictions as specified in Section 6.3.2
[27]
have a current or recent history (<30 days prior to screening and/or <45 days 
prior to Day -1 in Period 1) of a clinically significant bacterial, fungal, 
parasitic, viral (not including rhinopharyngitis), or mycobacterial infection
[28]
have an ANC <2000 cells/µL (2 × 109/L) at screening.  For abnormal values, 
a single repeat will be allowed.  
[29]
have had symptomatic herpes zoster within 3 months of screening
[30]
have received live vaccine(s) within 3 months of screening, or intend to 
during the study
[31]
are unwilling to comply with the dietary requirements/restrictions during the 
study:  (i) consume only the meals provided during inpatient visits (see 
Section 6.3), and (ii) refrain from consuming grapefruit, star fruit, pomelos, or 
products containing these fruits, for at least 14 days prior to the first dose and 
during the study
[32]
have used or intend to use drugs or substances that are known to be strong or 
moderate inhibitors or inducers of cytochrome P450 (CYP) 3A or strong 
inhibitors of organic anion transporter 3 (OAT3; such as probenecid) within 
30 days prior to the first dose and throughout the study
[33]
Have a history of, in the opinion of the investigator, excessive methylxanthine 
use within the previous 6 months, or are unwilling to abide by restrictions as 
specified in Section 6.3.2.  Excessive intake is defined as more than 6 units of 
caffeine per day; one caffeine unit is contained in the following items:  
1 (177 mL) cup of coffee, 1 (355 mL) cup of tea, 2 (355 mL) cans of cola, or 
3 oz (85 g) of chocolate.
[34]
in the opinion of the investigator or sponsor, are unsuitable for inclusion in the 
study
6.3.
Lifestyle and/or Dietary Requirements
Throughout the study, subjects may undergo medical assessments and review of compliance with 
requirements before continuing in the study.  


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 25
Baricitinib (LY3009104)
6.3.1. Meals and Dietary Restrictions
Grapefruit, star fruit, pomelos, or products containing these fruits will not be allowed from 
14 days prior to the first dose and during the study.  
Administration of baricitinib in the fasted state
Following an overnight fast (water only permitted) of at least 10 hours, subjects will be 
administered 4 mg baricitinib with or without approximately 240 mL room temperature water (as 
determined by the randomization schedule [Part A] or based on the results from the interim 
analysis planned for Part A [Part B]).  Water can be allowed as desired except from 1 hour 
before until 2 hours after drug administration.  No food or fluid (except water) will be allowed 
for at least 4 hours postdose.  Lunch will be provided after the 4-hour PK sample is collected.
Administration of baricitinib in the fed state (Part B only)
Following an overnight fast (water only permitted) of at least 10 hours, subjects will start a US 
FDA-defined high-fat, high-calorie meal 30 minutes prior to administration of baricitinib.  It is 
intended that the meal will be ingested in its entirety over an approximate 25-minute period, such 
that it is completed at least 5 minutes before dosing.  A 4-mg dose of baricitinib will be given 
with or without approximately 240 mL room temperature water (as determined by interim 
analysis of data from Part A).  Water can be given as desired except for 1 hour before and 
2 hours after drug administration.  No further food or fluids (except water) will be permitted until 
at least 4 hours postdose and lunch will be provided after collection of the 4-hour PK sample.  
High-fat meal:  The high-fat, high-calorie meal (fat comprises approximately 50% of total 
calorific content) should consist of approximately 800 to 1000 kilocalories in total.  No 
additional food or substitute is allowed.  A typical test meal is 2 eggs fried in butter, 2 strips of 
bacon, 2 slices of toast with butter, 4 ounces of hash brown potatoes, and 8 ounces of whole milk.  
The test meal derives approximately 150, 250, and 500 to 600 kilocalories from protein, 
carbohydrate, and fat, respectively.  
6.3.2. Caffeine, Alcohol, and Tobacco
Alcohol – Alcohol will not be permitted from 48 hours prior to each admission until after 
collection of the 48-hour PK sample in each period and within 48 hours prior to the follow-up 
visit.  During the washout period, alcohol will be restricted to a maximum of 2 units per day.  
Caffeine/methylxanthine – Subjects will be advised not to exceed their usual intake of caffeine-
or methylxanthine-containing food and drinks, such as coffee, tea, cola, and chocolate during the 
study.  
Smoking – Subjects should not smoke or use any nicotine products from 2 hours prior to each 
admission until after collection of the 48-hour PK sample.  
6.3.3. Activity
Subjects should not engage in strenuous physical exercise from 1 week prior to the first dose 
until completion of the follow-up assessments.  


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 26
Baricitinib (LY3009104)
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.  Individuals may be rescreened only once, at the discretion of the investigator.  The 
interval between rescreenings should be at least 1 week.  If rescreening is performed, the 
individual must sign a new informed consent form (ICF) and will be assigned a new 
identification number.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 27
Baricitinib (LY3009104)
7. Treatment
7.1.
Treatment Administered
Part A of this study involves a comparison of baricitinib administered as a 4-mg dose of the 
suspension formulation administered with and without 240 mL water with baricitinib 
administered as a 4-mg dose of the commercial tablet formulation administered with 240 mL 
water.  
Table JAGU.4 shows the treatment regimens for Part A.
Baricitinib will be administered orally as 1 × 4-mg tablet with approximately 240 mL room 
temperature water, as 2 mL × 2 mg/mL suspension administered without water, or as 
2 mL × 2 mg/mL suspension followed immediately by 240 mL of room temperature water, in the 
morning of Day 1 of the appropriate treatment period (as defined by the randomization).  
Subjects will not be allowed to lie supine for 2 hours after dosing, unless clinically indicated or 
for study procedures.
Table JAGU.4.
Treatments Administered in Part A
Treatment name
Baricitinib
Baricitinib
Baricitinib
Dosage formulation
Suspension
Suspension
Commercial Tablet
Dosage level(s)/ Unit 
dose strengths
2 mL × 2 mg/mL
2 mL × 2 mg/mL
1 4-mg
Route of 
administration
Oral
Oral
Oral
Dosing instructionsa
Dose administered
following ≥10-hour fast 
without water
Dose administered 
following ≥10-hour fast 
and immediately prior to
240 mL water
Dose administered 
following ≥10-hour fast 
with 240 mL water
a
Further instructions for the storage and dispensing of the suspension formulation will be provided to the site in a 
separate document.  
Part B of this study involves a comparison of baricitinib administered as a 4 -mg dose of the 
suspension formulation in the fasted state compared to following a high-fat, high-calorie meal.
A 4-mg dose of baricitinib will be administered orally as 2 mL × 2 mg/mL suspension in the 
morning of Day 1 of each treatment period.  Whether the doses are administered alone or 
followed by 240 mL room temperature water will be subject to a decision based on interim 
analysis of data from Part A of the study (see Section 10.3.3).  Subjects will not be allowed to lie 
supine for 2 hours after dosing, unless clinically indicated or for study procedures.
The investigator or designee is responsible for:


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 28
Baricitinib (LY3009104)

explaining the correct use of the investigational products to the site personnel

verifying that instructions are followed properly

maintaining accurate records of investigational product dispensing and collection

and returning all unused medication to Lilly or its designee at the end of the study
Note: In some cases, sites may destroy the material if, during the investigative site selection, the 
evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose of clinical trial materials.  
7.1.1. Packaging and Labeling
Each tablet of baricitinib contains 4 mg of active ingredient, and is provided as bulk supply in 
high-density polyethylene bottles.  
Baricitinib suspension formulation contains 2 mg/mL baricitinib and is provided as bulk supply 
in polyethylene terephthalate bottles.  
Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.2.
Method of Treatment Assignment
Subjects will be randomized to treatment sequences using a computer-generated allocation 
schedule.
7.2.1. Selection and Timing of Doses
This study will use a fixed dose of 4 mg baricitinib.  A dose of 4 mg is selected as it is the 
primary dose studied in Phase 3 clinical studies and is the recommended commercial dose in 
patients with RA.  
The doses will be administered at approximately the same times on each day.  The actual time of 
all dose administrations will be recorded in the subject’s electronic case report form (eCRF).
7.3.
Blinding
This will be an open-label study.  
7.4.
Dose Modification
Dose reductions or adjustments will not be allowed during this study.  
7.5.
Preparation/Handling/Storage/Accountability
Only participants enrolled in the study may receive investigational product and only authorized 
site staff may supply or administer study treatment. All study treatments should be stored in an
environmentally controlled and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the investigator and authorized site staff.
Baricitinib tablets and suspension will be stored at room temperature.  


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 29
Baricitinib (LY3009104)
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance (such as
receipt, reconciliation, and final disposition records).
7.6.
Treatment Compliance
The investigational product will be administered at the clinical site, and documentation of 
treatment administration will occur at the site.
7.7.
Concomitant Therapy
Over-the–counter or prescription medications, including herbal medications, are to be avo ided 
within 14 days prior to dosing and during the study.  Drugs that are known to be strong or 
moderate inhibitors or inducers of CYP3A or strong inhibitors of OAT3 (such as probenecid) are 
not allowed within 30 days prior to the first dose and throughout the study.  Additional drugs are 
to be avoided during the study unless required to treat an AE or for the treatment of an ongoing 
medical problem.
If the need for concomitant medication arises, inclusion or continuation of the subject may be at 
the discretion of the investigator after consultation with a Lilly clinical pharmacologist (CP) or 
clinical research physician (CRP).  Any additional medication used during the course of the 
study must be documented.
7.8.
Treatment After the End of the Study
This section is not applicable for this study.  


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 30
Baricitinib (LY3009104)
8. Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
Subjects who discontinue the investigational product early will have early discontinuation 
procedures performed as shown in the Schedule of Activities (Section 2).
8.1.1. Discontinuation of Inadvertently Enrolled Subjects
If the sponsor or investigator identifies a subject who did not meet enrollment criteria and was 
inadvertently enrolled, the subject will be discontinued from the study and early discontinuation 
assessments will be performed as shown in the Schedule of Activities (Section 2).
8.2.
Discontinuation from the Study
Subjects will be discontinued in the following circumstances:

enrollment in any other clinical trial involving an investigational product or enrollment in 
any other type of medical research judged not to be scientifically or medically compatible 
with this study

participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

investigator decision
o
the investigator decides that the subject should be discontinued from the study

subject decision
o
the subject requests to be withdrawn from the study
Subjects who discontinue the study early will have early discontinuation procedures performed 
as shown in the Schedule of Activities (Section 2).
8.3.
Subjects Lost to Follow-up
A subject 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 are expected to make 
diligent attempts to contact subjects who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 31
Baricitinib (LY3009104)
9. Study Assessments and Procedures
Section 2 lists the Schedule of Activities, detailing the study procedures and their timing.
Appendix 2 lists the laboratory tests that will be performed for this study.
Appendix 4 provides a summary of the maximum number and volume of invasive samples, for 
all sampling, during the study.
Unless otherwise stated in subsections below, all samples collected for specified laboratory tests 
will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may be 
retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
Investigators must document their review of each laboratory safety report.
9.1.
Efficacy Assessments
This section is not applicable for this study.
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of subjects who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the subject.
The investigator is responsible for the appropriate medical care of subjects during the study.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the subject to discontinue the investigational product before 
completing the study.  The subject should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
After the ICF is signed, study site personnel will record, via eCRF, the occurrence and nature of 
each subject’s preexisting conditions.  Additionally, site personnel will record any change in the 
condition(s) and the occurrence and nature of any AEs.  
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, or a study procedure, taking into account concomitant 
treatment or pathologies.  
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product and/or study procedure and the AE.
Planned surgeries should not be reported as AEs unless the underlying medical condition has 
worsened during the course of the study.
If a subject’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 32
Baricitinib (LY3009104)
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following:

death

initial or prolonged inpatient hospitalization

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

events considered significant by the investigator based upon appropriate medical 
judgment
Study site personnel must alert Lilly, or its designee, of any SAE within 24 hours of investigator 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.
Although all AEs are recorded in the eCRF after signing informed consent, SAE reporting begins 
after the subject has signed informed consent and has received investigational product.  
However, if an SAE occurs after signing informed consent, but prior to receiving investigational 
product, AND is considered reasonably possibly related to a study procedure then it MUST be 
reported.
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued from and/or completed the study (the subject summary eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly .  
Pregnancy (maternal or paternal exposure to investigational product) does not meet the definition 
of an AE.  However, to fulfill regulatory requirements any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 Code of Federal Regulations 312.32 and European Union Clinical 
Trial Directive 2001/20/EC and the associated detailed guidances or national regulatory 
requirements in participating countries require the reporting of SUSARs.  Lilly has procedures 
that will be followed for the recording and expedited reporting of SUSARs that are consistent 
with global regulations and the associated detailed guidances.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 33
Baricitinib (LY3009104)
9.2.2. Complaint Handling
Lilly collects product complaints on investigational products used in clinical trials in order to 
ensure the safety of study participants, monitor quality, and to facilitate process and product 
improvements.
Subjects should 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.
9.3.
Treatment of Overdose
For the purposes of this study, an overdose of baricitinib is considered any dose higher than the 
dose assigned.
The IB contains information on the highest single doses administered to healthy subjects.  There 
is no specific antidote for baricitinib.  In the event of an overdose, the subject should receive 
appropriate supportive care and any AEs should be documented.  
9.4.
Safety
9.4.1. Laboratory Tests
For each subject, laboratory tests detailed in Appendix 2 should be conducted according to the 
Schedule of Activities (Section 2).  
9.4.2. Vital Signs
For each subject, vital signs measurements should be conducted according to the Schedule of 
Activities (Section 2).  
Blood pressure and pulse rate should be measured after at least 5 minutes supine.
Additional vital signs may be assessed as clinically indicated as well as at the scheduled times.  
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms.  If orthostatic measurements are required, subjects should be supine 
for at least 5 minutes and stand for at least 3 minutes.  If the subject feels unable to stand, supine 
vital signs only will be recorded.  
Additional vital signs may be measured during each study period if warranted and agreed upon 
between the sponsor and investigator.
9.4.3. Electrocardiograms
For each subject, ECGs should be collected according to the Schedule of Activities (Section 2).  
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
subject receives the first dose of the investigational product should be reported to Lilly, or its 
designee, as an AE via eCRF.  
For each subject, a single 12-lead digital ECG will be collected according to the Schedule of 
Activities (Section 2).  Electrocardiograms must be recorded before collecting any blood for 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 34
Baricitinib (LY3009104)
safety or PK tests.  Subjects 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 a qualified physician (the investigator or qualified 
designee) at the site as soon after the time of ECG collection as possible, and ideally while the 
subject is still present, to determine whether the subject meets entry criteria at the relevant 
visit(s) and for immediate subject management, should any clinically relevant findings be 
identified.  
If a clinically significant finding is identified (including, but not limited to, changes in QT/QT
corrected for heart rate interval from baseline) after enrollment, the investigator will determine if 
the subject can continue in the study.  The investigator, or qualified designee, is responsible for 
determining if any change in subject 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.
9.4.4. Safety Monitoring
The Lilly CP or CRP/clinical research 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 consult with the functionally independent Global Patient Safety therapeutic area 
physician or clinical research scientist when appropriate, and periodically review:

trends in safety data

laboratory analytes

AEs
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
of approximately 3 mL each will be collected to determine the plasma concentrations of 
baricitinib.  A maximum of 5 samples may be collected at additional time points during each part 
of the study if warranted and agreed upon between both the investigator and sponsor.  
Instructions for the collection and handling of blood samples will be provided by the sponsor.  
The actual date and time (24-hour clock time) of each sampling will be recorded.
9.5.1. Bioanalysis
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor.
Concentrations of baricitinib will be assayed using a validated liquid chromatography with 
tandem mass spectrometric detection method.  


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 35
Baricitinib (LY3009104)
Bioanalytical samples collected to measure investigational product concentrations will be 
retained for a maximum of 1 year following last subject visit for the study.  
9.6.
Pharmacodynamics
This section is not applicable for this study.
9.7.
Genetics
A blood sample will be collected for pharmacogenetic analysis as specified in the Schedule of 
Activities (Section 2), where local regulations allow.  
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to baricitinib and to 
investigate genetic variants thought to play a role in inflammatory disease.  Assessment of 
variable response may include evaluation of AEs or differences in efficacy.  
All samples will be coded with the subject number.  These samples and any data generated can 
be linked back to the subject only by the investigative site personnel.  
Samples will be retained for a maximum of 15 years after the last subject visit, or for a shorter 
period if local regulations and/or ethical review boards (ERBs) impose shorter time limits, for 
the study at a facility selected by Lilly or its designee.  This retention period enables use of new 
technologies, response to regulatory questions, and investigation of variable response that may 
not be observed until later in the development of baricitinib or after baricitinib is commercially 
available.  
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, multiplex assays, and candidate gene studies.  
Regardless of technology utilized, data generated will be used only for the specific research 
scope described in this section.  
9.8.
Biomarkers
This section is not applicable for this study.  
9.9.
Health Economics
This section is not applicable for this study.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 36
Baricitinib (LY3009104)
10.
Statistical Considerations and Data Analysis
10.1. Sample Size Determination
In Part A, 26 subjects may be enrolled to ensure that 20 complete the study.  
For Cmax, assuming an intra-subject coefficient of variation of 16%, 20 subjects provide 90% 
power to show bioequivalence for a 95% confidence interval (CI) using 0.8 and 1.25 as the lower 
and upper bioequivalence limits, respectively.  A 95% CI was used to calculate the power for this 
study to assure both comparisons of the suspension formulation (with and without water) versus 
the commercial tablet had adequate power using the Holm’s step-down procedure.  This 
procedure adjusts for multiplicity maintaining the family-wise type 1 error rate.  
For AUC(0-∞) and AUC(0-tlast), assuming an intra-subject coefficient of variation of 7.8% and 
7.6%, respectively, 20 subjects provide greater than 99% power to show bioequivalence for a 
95% CI using 0.8 and 1.25 as the lower and upper bioequivalence limits, respectively.
In Part B, it is planned that up to a maximum of 18 subjects will be enrolled in order that 
14 complete the study; however, this number may be revised based on interim analysis of the 
intra-subject variation in PK parameters of baricitinib suspension formulation i n Part A of the 
study.  
Subjects who are randomized and discontinue the study prior to completion of all study periods 
in their assigned study part may be replaced to ensure that a minimum of 20 subjects complete 
Part A of the study and 14 complete Part B.  Replacement subjects will complete all 3 periods 
(Part A) or 2 periods (Part B), following the sequence of the withdrawn subject.  
10.2. Populations for Analyses
10.2.1. Study Participant Disposition
A detailed description of subject disposition will be provided at the end of the study.  
10.2.2. Study Participant Characteristics
The subject’s age, sex, weight, height, BMI, race, and other demographic characteristics will be 
recorded and summarized using descriptive statistics.
10.3. Statistical Analyses
Statistical analysis of this study will be the responsibility of Eli Lilly and Company or its 
designee.
Pharmacokinetic analyses will be conducted on the full and completer analysis sets.  For each 
study part (Part A or Part B), the full analysis set includes all data from all subjects receiving at 
least 1 dose of baricitinib in that study part, with evaluable PK data, according to the treatment 
the subjects actually received.  The completer analysis set for each study part includes data from 
subjects who receive all doses of baricitinib for that study part and have evaluable PK data, 
according to the treatment the subjects actually received.  Safety analyses will be conducted for 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 37
Baricitinib (LY3009104)
all enrolled subjects, whether or not they completed all protocol requirements.  Additional 
exploratory analyses of the data will be conducted as deemed appropriate.  Study results may be 
pooled with the results of other studies for population PK analysis purposes to avoid issues with 
post-hoc analyses and incomplete disclosures of analyses.  
10.3.1. Safety Analyses
10.3.1.1. Clinical Evaluation of Safety
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.
The incidence of symptoms for each treatment will be presented by severity and by association 
with investigational product as perceived by the investigator.  Symptoms reported to occur prior 
to study entry will be distinguished from those reported as new or increased in severity during 
the study.  Each symptom will be classified by the most suitable term from the medical 
regulatory dictionary.
The number of investigational product-related SAEs will be reported.
10.3.1.2. Statistical Evaluation of Safety
Safety parameters that will be assessed include TEAEs, clinical laboratory parameters, and vital 
signs.  The parameters will be listed, and summarized using standard descriptive statistics, as 
appropriate.  Additional analysis will be performed if warranted upon review of the data.
10.3.2. Pharmacokinetic Analyses
10.3.2.1. Pharmacokinetic Parameter Estimation
Pharmacokinetic parameter estimates for baricitinib will be calculated by standard 
noncompartmental methods of analysis.
The primary parameters for analysis will be Cmax, AUC(0-tlast), and AUC(0-∞).  The tmax will 
be observed from the data.  Other noncompartmental parameters may be reported.
10.3.2.2. Pharmacokinetic Statistical Inference
Pharmacokinetic parameter estimates will be evaluated to delineate effects of baricitinib 
formulation.  For the primary analysis, log-transformed Cmax, AUC(0-tlast), and AUC(0-∞)
estimates will be evaluated in a linear mixed-effects model with fixed effects for formulation, 
period, sequence, and a random effect for subject (sequence).  The treatment differences between 
each test compared to the reference formulation will be back-transformed to present the ratios of 
geometric least squares means and the corresponding CIs.  The Holm step-down procedure for 
an overall 0.1 alpha level will be used.
Bioequivalence between the suspension formulation administered either with or without water
and the commercial tablet will be concluded if the 95% CI for Cmax, AUC(0-tlast), and 
AUC(0-∞) are all completely contained within the interval (0.80, 1.25).  Bioequivalence between 
the suspension formulation using the other administration and the commercial tablet will be 


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 38
Baricitinib (LY3009104)
concluded if the 90% CIs for  Cmax, AUC(0-tlast), and AUC(0-∞) are all completely contained 
within the interval (0.80, 1.25).
For secondary analyses, the same model specified above will be used for Cmax, AUC(0-tlast), and 
AUC(0-∞).  Ratios of geometric least squares means and the corresponding 90% CIs will be 
presented.  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.  
10.3.3. Interim Analyses
A formal interim analysis will be performed after completion of Part A of the study.  This is an 
open-label study.  Pharmacokinetic data will be analyzed after all PK data are available for 
Part A of the study. Statistical analysis will be conducted to test the baricitinib suspension 
formulation, administered with and without water, for bioequivalence with the commercial tablet 
formulation.  The administration method for the suspension formulation that is bioequivalent to 
the commercial tablet formulation will be used in Part B of the study.  If both administration 
methods are bioequivalent to the commercial tablet formulation, suspension will be administered
without water in Part B of the study, for ease of administration.  If the suspension formulation is 
not bioequivalent to the commercial tablet formulation using either administration method, all 
available data will be used to assess the most appropriate way to administer the drug in Part B.  
Intra-subject variability estimates of PK parameters will be used to determine the number of 
subjects required to complete Part B of the study.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 39
Baricitinib (LY3009104)
11.
References
Boy MG, Wang C, Wilkinson BE, Chow VF, Clucas AT, Krueger JG, Gaweco AS, Zwillich SH, 
Changelian PS, Chan G. Double-blind, placebo-controlled, dose-escalation study to evaluate 
the pharmacologic effect of CP-690,550 in patients with psoriasis. J Invest Dermatol. 
2009;129(9):2299-2302.
[FDA 2002] US Department of Health and Human Services Food and Drug Administration 
Center for Drug Evaluation and Research. Guidance for Industry. Food-Effect Bioavailability 
and Fed Bioequivalence Studies. 2002.
Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Tho mas B, Collier P, 
Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis 
G, Newton RC, Metcalf B, Friedman SM, Vaddi K. Selective inhibition of JAK1 and JAK2 is 
efficacious in rodent models of arthritis: preclinical characterization of INCB028050. 
J Immunol. 2010;184(9):5298-5307.
Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, Krishnaswami S, 
Burgos-Vargas R, Wilkinson B, Zerbini CA, Zwillich SH. The safety and efficacy of a JAK 
inhibitor in patients with active rheumatoid arthritis: results of a double-blind, 
placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. 
Arthritis Rheum. 2009;60(7):1895-1905.
Valentino L, Pierre J. JAK/STAT signal transduction: regulators and implication in 
hematological malignancies. Biochem Pharmacol. 2006;71(6):713-721.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 40
Baricitinib (LY3009104)
Appendix 1.
Abbreviations and Definitions


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 41
Baricitinib (LY3009104)
Term
Definition
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
ANC
absolute neutrophil count
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 the last time point with a 
measurable concentration
BMI
body mass index
CI
confidence interval
Cmax
maximum observed drug concentration
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 the trial-related requirements, good clinical practice (GCP) requirements, 
and the applicable regulatory requirements.
confirmation
A process used to confirm that laboratory test results meet the quality requirements defined 
by the laboratory generating the data and that Lilly is confident that results are accurate.  
Confirmation will either occur immediately after initial testing or will require that samples 
be held to be retested at some defined time point, depending on the steps required to obtain 
confirmed results.
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.
CRU
clinical research unit
CYP
cytochrome P450
ECG
electrocardiogram
eCRF
electronic case report form
enroll
The act of assigning a subject to a treatment.  Subjects who are enrolled in the trial are those 
who have been assigned to a treatment.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 42
Baricitinib (LY3009104)
enter
Subjects entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
ERB
ethical review board
FDA
Food and Drug Administration
GCP
good clinical practice
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
informed consent
A process by which a subject voluntarily confirms his or her willingness to participate in a 
particular trial, after having been informed of all aspects of the trial that are relevant to the 
subject’s decision to participate.  Informed consent is documented by means of a written, 
signed, and dated informed consent form.  
interim analysis
An interim analysis is an analysis of clinical trial data, separated into treatment groups, that 
is conducted before the final reporting database is created/locked.
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.
investigator
A person responsible for the conduct of the clinical trial at a trial site.  If a trial is conducted 
by a team of individuals at a trial site, the investigator is the responsible leader of the team 
and may be called the principal investigator.
JAK
Janus kinase
OAT3
organic anion transporter 3
open-label
A study in which there are no restrictions on knowledge of treatment allocation, therefore 
the investigator and the study participant are aware of the drug therapy received during the 
study.
pJIA
polyarticular juvenile idiopathic arthritis
PK
pharmacokinetic
QD
once daily
R
4-mg dose of baricitinib commercial tablet formulation administered with 240 mL water
RA
rheumatoid arthritis
SAE
serious adverse event


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 43
Baricitinib (LY3009104)
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 trial.  
STAT
signal transducer and activator of transcription
SUSARs
suspected unexpected serious adverse reactions 
t1/2
half-life associated with the terminal rate constant in noncompartmental analysis
T1
4-mg dose of baricitinib suspension formulation administered without water
T2
4-mg dose of baricitinib suspension formulation administered with 240 mL water
TEAE
treatment-emergent adverse event:  Any untoward medical occurrence that emerges during 
a defined treatment period, having been absent pretreatment, or worsens relative to the 
pretreatment state, and does not necessarily have to have a causal relationship with this 
treatment 
TF
test formulation
TFfasted
4-mg dose of baricitinib suspension test formulation administered in the fasted state
TFfed
4-mg dose of baricitinib suspension test formulation administered after a high-fat, 
high-calorie meal
tmax
time of maximum observed drug concentration


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 44
Baricitinib (LY3009104)
Appendix 2.
Clinical Laboratory Tests
Laboratory Tests
Hematologya
Clinical Chemistrya
Hematocrit
Sodium
Hemoglobin
Potassium
Erythrocyte count (RBC)
Chloride 
Mean cell volume 
Calcium 
Mean cell hemoglobin 
Glucose (fasting)
Mean cell hemoglobin concentration 
Urea
Leukocytes (WBC)
Total cholesterol 
Absolute counts of:
Total protein
Neutrophils
Albumin
Lymphocytes
Total bilirubin
Monocytes
Alkaline phosphatase (ALP)
Eosinophils
Aspartate aminotransferase (AST)
Basophils
Alanine aminotransferase (ALT)
Platelets
Creatinine
Urinalysisa
Gamma-glutamyl transferase (GGT)
Specific gravity
Creatine kinase
pH
Protein
Hepatitis B surface antigenb
Glucose
Hepatitis C antibodyb
Ketones
HIVb
Bilirubin
Pregnancy test (females)c
Urobilinogen
FSH (females, if applicable)b,d
Blood
Nitrite
Leukocytes
Microscopic examination of sedimente
Abbreviations:  FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; RBC = red blood cells; 
WBC = white blood cells.
a
Results will be validated by local laboratory at the time of initial testing.
b
Performed at screening only.  Hepatitis B surface antigen, Hepatitis C antibody, and HIV tests will only be 
performed if results have not been obtained for the subject in the last 6 months.
c
Serum pregnancy test to be performed at screening.  A serum or urine pregnancy test will be performed at 
follow-up/early discontinuation and may be performed at other times at the investigator’s discretion.  
d
Postmenopausal women only; analyzed in serum.
e
Test only if dipstick result is abnormal and per investigator’s discretion.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 45
Baricitinib (LY3009104)
Appendix 3.
Study Governance, Regulatory and Ethical 
Considerations
Informed Consent
The investigator is responsible for:

ensuring that the subject understands the potential risks and benefits of participating in 
the study

Ensuring that informed consent is given by each subject or legal representative.  This 
includes obtaining the appropriate signatures and dates on the ICF prior to the 
performance of any protocol procedures and prior to the administration of investigational 
product.

answering any questions the subject may have throughout the study and sharing in a 
timely manner any new information that may be relevant to the subject’s willingness to 
continue his or her participation in the trial
Ethical Review
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site.  Lilly or its representatives must approve the ICF 
before it is used at the investigative site.  All ICFs must be compliant with the International 
Conference on Harmonisation (ICH) guideline on GCP.
The study site’s ERB should be provided with the following:

the current IB and updates during the course of the study

ICF 

relevant curricula vitae
Regulatory Considerations
This study will be conducted in accordance with:
1) consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines 
2) applicable ICH GCP Guidelines 
3) applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third party organization.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 46
Baricitinib (LY3009104)
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.  
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Final Report Signature
The investigator or designee will sign the clinical study report for this study, indicating 
agreement with the analyses, results, and conclusions of the report.
The sponsor’s responsible medical officer and statistician will sign/approve the final clinical 
study report for this study, confirming that, to the best of his or her knowledge, the report 
accurately describes the conduct and results of the study.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

Provide training to instruct the investigators and study coordinators.  This training will 
give instruction on the protocol, the completion of the eCRFs, and study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by mail, 
telephone, and/or fax

review and evaluate eCRF data and/or use standard computer edits to detect errors in data 
collection

conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the subject data 
recorded against source documents at the study site.  The study may be audited by Lilly and/or 
regulatory agencies at any time.  Investigators will be given notice before an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to the original source 
documents.
Data Collection Tools/Source Data
An electronic data capture system will be used in this study.  The site must define and retain all 
source records and must maintain a record of any data where source data are directly entered into 
the data capture system.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 47
Baricitinib (LY3009104)
Study and Site Closure
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.


I4V-MC-JAGU Clinical Pharmacology Protocol
Page 48
Baricitinib (LY3009104)
Appendix 4.
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 each part of the
study.  Fewer venipunctures and blood draws may actually occur, but this will not require a 
protocol amendment.
Protocol I4V-MC-JAGU Part A Sampling Summary
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
17
1
17
Clinical laboratory testsa
11
4
44
Pharmacokinetics 
3
50b
150
Blood discard for cannula patency
0.3
50b
15
Pharmacogenetics
10
1
10
Total
236
Total for clinical purposes [rounded up to nearest 10 mL] 
240
a
Additional samples may be drawn if needed for safety purposes.
b
Including 5 additional samples, if needed.
Protocol I4V-MC-JAGU Part B Sampling Summary
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
17
1
17
Clinical laboratory testsa
11
3
33
Pharmacokinetics 
3
35b
105
Blood discard for cannula patency
0.3
35b
10.5
Pharmacogenetics
10
1
10
Total
175.5
Total for clinical purposes [rounded up to nearest 10 mL] 
180
a
Additional samples may be drawn if needed for safety purposes.
b
Including 5 additional samples, if needed.


Leo Document ID = 0b0d5583-0ce1-4fb4-9bbb-bb09ae9715bb
Approver: 
Approval Date & Time: 27-Sep-2016 13:59:29 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 28-Sep-2016 13:11:11 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
Statistical Analysis Plan 14V-MC-JAGU A Bioequivalence and Food Effect Study in Healthy Subjects 
Comparing Baricitinib Suspension and Commercial Tablet Formulations 
NCT03212638
Approval Date: 05-Jul-2017