Clinical trial NCT04881747
Conditions: Healthy
Sponsor: Eli Lilly and Company
Start date: 2021-05-14; Completion date: 2021-07-24
Enrollment: 47 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The main purpose of this study is to compare the amount of lasmiditan that gets into the blood stream and how long it takes the body to get rid of it, when given as a oral-disintegrating (OD) tablet compared to immediate-release (IR) tablet formulation. The information about any adverse effects experienced will be collected and the tolerability of lasmiditan when administered as OD tablet will also be evaluated.

Screening is required within 28 days prior to the start of the study. For each participant, the total duration of the clinical trial will be about 5 weeks, including screening.

Detailed description:

Arms: arm 1: Participants received 100 mg lasmiditan as IR tablet formulation administered orally. arm 2: Participants received 100 mg lasmiditan as OD tablet formulation administered orally without water. arm 3: Participants received 100 mg lasmiditan as OD tablet formulation administered orally with water.
Interventions: intervention 1: Lasmiditan
Intervention descriptions: intervention 1: Administered orally.

Protocol documents:
Prot_000.pdf: 
Protocol H8H-MC-LAIA 
Bioequivalence of Lasmiditan Oral Disintegrating Tablet Compared to Current Immediate-
Release Tablet Formulation to Support Treatment of Migraine 
NCT04881747 
Approval Date: 8-Sep-2020 


CONFIDENTIAL
Protocol H8H-MC-LAIA
1
Title Page
Confidential Information
The information contained in this document is confidential and is intended for the use of clinical investigators.  It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of lasmiditan (LY573144), 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 (FOIA) Exemption 4 and may not be 
reproduced or otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title: Bioequivalence of Lasmiditan Oral Disintegrating Tablet Compared to Current 
Immediate-Release Tablet Formulation to Support Treatment of Migraine
Protocol Number: H8H-MC-LAIA
Amendment Number: This is the initial protocol
Compound: Lasmiditan (LY573144)
Study Phase: 1
Short Title: Bioequivalence of lasmiditan oral disintegrating tablet compared to current 
immediate-release tablet formulation to support treatment of migraine
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana USA 46285
Regulatory Agency Identifier Number(s)
IND: 103420
Approval Date: Protocol Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 08-Sep-2020 GMT


CONFIDENTIAL
Protocol H8H-MC-LAIA
2
Medical Monitor Name and Contact Information will be provided separately.


CONFIDENTIAL
Protocol H8H-MC-LAIA
3
Table of Contents
1.
Protocol Summary......................................................................................................6
1.1.
Synopsis.......................................................................................................................6
1.2.
Schema.........................................................................................................................9
1.3.
Schedule of Activities (SoA) ......................................................................................10
2.
Introduction..............................................................................................................12
2.1.
Study Rationale ..........................................................................................................12
2.2.
Background ................................................................................................................12
2.3.
Benefit/Risk Assessment ............................................................................................13
3.
Objectives and Endpoints.........................................................................................14
4.
Study Design .............................................................................................................15
4.1.
Overall Design............................................................................................................15
4.2.
Scientific Rationale for Study Design .........................................................................16
4.3.
Justification for Dose..................................................................................................16
4.4.
End of Study Definition..............................................................................................16
5.
Study Population ......................................................................................................17
5.1.
Inclusion Criteria........................................................................................................17
5.2.
Exclusion Criteria.......................................................................................................18
5.3.
Lifestyle Considerations .............................................................................................19
5.3.1.
Meals and Dietary Restrictions ...................................................................................20
5.3.2.
Caffeine, Alcohol, and Tobacco..................................................................................20
5.3.3.
Activity ......................................................................................................................20
5.4.
Screen Failures ...........................................................................................................20
6.
Study Intervention....................................................................................................21
6.1.
Study Interventions Administered...............................................................................21
6.1.1.
Administration Details................................................................................................21
6.2.
Preparation/Handling/Storage/Accountability.............................................................22
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................22
6.4.
Study Intervention Compliance...................................................................................22
6.5.
Concomitant Therapy .................................................................................................23
6.6.
Dose Modification......................................................................................................23
6.7.
Intervention after the End of the Study........................................................................23
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................24
7.1.
Discontinuation of Study Intervention ........................................................................24
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................24
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................25
7.3.
Lost to Follow-up .......................................................................................................25
8.
Study Assessments and Procedures .........................................................................26
8.1.
Efficacy Assessments .................................................................................................26
8.2.
Safety Assessments ....................................................................................................26
8.2.1.
Physical Examinations................................................................................................26
8.2.2.
Vital Signs..................................................................................................................27


CONFIDENTIAL
Protocol H8H-MC-LAIA
4
8.2.3.
Electrocardiograms.....................................................................................................27
8.2.4.
Clinical Safety Laboratory Assessments .....................................................................27
8.2.5.
Safety Monitoring.......................................................................................................28
8.3.
Adverse Events and Serious Adverse Events ..............................................................30
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................30
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................31
8.3.3.
Follow-up of AEs and SAEs.......................................................................................31
8.3.4.
Regulatory Reporting Requirements for SAEs............................................................31
8.3.5.
Pregnancy...................................................................................................................31
8.3.6.
Product Complaints ....................................................................................................32
8.4.
Treatment of Overdose ...............................................................................................33
8.5.
Pharmacokinetics........................................................................................................33
8.5.1.
Bioanalysis .................................................................................................................33
8.6.
Pharmacodynamics.....................................................................................................33
8.7.
Genetics .....................................................................................................................33
8.8.
Biomarkers.................................................................................................................33
8.9.
Immunogenicity Assessments.....................................................................................34
8.10.
Health Economics.......................................................................................................34
8.11.
Product Acceptability and Palatability Assessments....................................................34
9.
Statistical Considerations.........................................................................................35
9.1.
Statistical Hypotheses.................................................................................................35
9.2.
Sample Size Determination.........................................................................................35
9.3.
Populations for Analyses ............................................................................................35
9.3.1.
Study Participant Disposition......................................................................................35
9.3.2.
Study Participant Characteristics.................................................................................35
9.4.
Statistical Analyses.....................................................................................................36
9.4.1.
General Considerations...............................................................................................36
9.4.2.
Pharmacokinetic Analyses ..........................................................................................36
9.4.3.
Safety Analyses ..........................................................................................................37
9.4.4.
Product Acceptability and Palatability Analyses .........................................................37
9.5.
Interim Analyses.........................................................................................................37
9.6.
Data Monitoring Committee (DMC)...........................................................................37
10.
Supporting Documentation and Operational Considerations ................................38
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................38
10.1.1.
Regulatory and Ethical Considerations........................................................................38
10.1.2.
Informed Consent Process ..........................................................................................38
10.1.3.
Data Protection...........................................................................................................39
10.1.4.
Dissemination of Clinical Study Data .........................................................................39
10.1.5.
Data Quality Assurance ..............................................................................................40
10.1.6.
Source Documents......................................................................................................41
10.1.7.
Study and Site Start and Closure.................................................................................41
10.1.8.
Publication Policy.......................................................................................................42
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................43
10.2.1.
Blood Sampling Summary..........................................................................................45


CONFIDENTIAL
Protocol H8H-MC-LAIA
5
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.......................................................46
10.3.1.
Definition of AE.........................................................................................................46
10.3.2.
Definition of SAE.......................................................................................................47
10.3.3.
Recording and Follow-up of AE and/or SAE ..............................................................48
10.3.4.
Reporting of SAEs......................................................................................................49
10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...............................................................................................51
10.4.1.
Definitions..................................................................................................................51
10.4.2.
Contraception Guidance..............................................................................................51
10.4.3.
Contraception Methods...............................................................................................52
10.4.4.
Collection of Pregnancy Information ..........................................................................53
10.5.
Appendix 5: Genetics .................................................................................................54
10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ...............................................................................................................55
10.7.
Appendix 7: Abbreviations .........................................................................................57
11.
References.................................................................................................................59




CONFIDENTIAL
Protocol H8H-MC-LAIA
7
Overall Design
Screening
All participants will be screened within 28 days prior to enrollment. 
Treatment and Assessment Period
Eligible participants will take part in 3 separate dosing periods. In each period, participants will 
be admitted to the clinical research unit (CRU) on Day -1 and remain resident in the CRU until 
discharge on Day 6. 
There will be a washout period of ≥5 days between the day of dosing in 1 period and the day of 
dosing in the subsequent period. Days 5 and 6 of Period 1 and 2 may coincide with Days -1 and 
1 of Period 2 and 3, respectively, provided the required washout between lasmiditan doses is 
observed. 
On Day 1 of Period 1, participants will be equally randomized to receive a 100-mg oral dose in 
1 of 6 dosing sequences in each of 3 dosing periods. 
Pharmacokinetic blood sampling and safety assessments, including vital sign measurements,
physical examinations, clinical laboratory tests, electrocardiograms, and adverse event recording 
will be performed according to the Schedule of Activities.
Follow-up
Day 6 of Period 3 will be considered the final visit of the study. 
Disclosure Statement: This is a Phase 1, open-label, randomized, single-dose, 3-way crossover 
study, with 6 sequences in healthy participants.
Number of Participants: Approximately 48 participants will be enrolled to ensure that 
36 participants, 6 per treatment sequence, complete the study.
Intervention Groups and Duration: Participants will receive single 100-mg doses of lasmiditan 
in each of 3 dosing periods, according to 1 of the randomized sequences detailed below.


CONFIDENTIAL
Protocol H8H-MC-LAIA
8
Dosing Sequences for Protocol H8H-MC-LAIA
Sequence
Period 1
Period 2
Period 3
1
IR (reference)
OD without water (test)
OD with water (test)
2
IR (reference)
OD with water (test)
OD without water (test)
3
OD without water (test)
OD with water (test)
IR (reference)
4
OD without water (test)
IR (reference)
OD with water (test)
5
OD with water (test)
IR (reference)
OD without water (test)
6
OD with water (test)
OD without water (test)
IR (reference)
Abbreviations: IR = immediate release; OD = oral disintegrating.
Screening will occur up to 28 days prior to enrollment. Each participant will take part in 
3 treatment periods. In each period, participants will be admitted to the CRU on Day -1 and 
remain resident in the CRU until discharge on Day 6. At the discretion of the investigator, 
participants may remain resident in the CRU for the entirety of the study, i.e., from admission to 
the CRU on Day -1 of Period 1 until discharge from the CRU on Day 6 of Period 3, after all 
assessments have been completed. 
Data Monitoring Committee: No


CONFIDENTIAL
Protocol H8H-MC-LAIA
9
1.2.
Schema


CONFIDENTIAL
Protocol H8H-MC-LAIA
10
1.3.
Schedule of Activities (SoA)
Study Schedule Protocol H8H-MC-LAIA
Screening
Dosing Periods 1 to 3
Comments
Procedure
-28 to -2 
days prior 
to D1
D-1a
D1a
D2
D3
D4
D5a
D6a
ED
Informed consent
X
Admission to CRU
X
Participants may remain at the CRU throughout the 
duration of the study, at the discretion of the 
investigator, i.e., admission to CRU in Period 1 only.
Discharge from CRU
X
Participants may remain at the CRU throughout the 
duration of the study, at the discretion of the 
investigator, i.e., discharge from CRU in Period 3 only.
Medical history and 
demographics
X
Participant eligibility
X
Confirm participant eligibility against inclusion and 
exclusion criteria (see Section 5).
Lasmiditan 
administration
X
A minimum washout of 5 days between lasmiditan 
doses is required. 
Height
X
Weight
X
Urine drug screen
X
X
On D-1, only required if participant is being admitted to 
CRU.
Alcohol breath test
X
X
On D-1, only required if participant is being admitted to 
CRU.
Pregnancy test
X
X
Serum pregnancy test to be performed at screening. 
Urine pregnancy test to be performed on D-1
(admission to CRU only).
Supine vital signs
(pulse rate, blood 
pressure, and oral 
body temperature)
X
X
P, 1, 2 h
24 h
X
Time points may be added for each period, if warranted 
and agreed up on between Lilly and the investigator.
12-lead ECG
X
P


CONFIDENTIAL
Protocol H8H-MC-LAIA
11
Screening
Dosing Periods 1 to 3
Comments
Procedure
-28 to -2 
days prior 
to D1
D-1a
D1a
D2
D3
D4
D5a
D6a
ED
Clinical laboratory 
tests
X
X
24 h
X
See Appendix 2 (Section 10.2) for details. 
Full physical 
examination
X
Additional symptom-driven physical examinations may 
be performed at the discretion of the investigator.
Pharmacogenetic  
blood sample
P
D1 of Period 1 only.
PK sampling in 
plasma (lasmiditan 
and M8)
P, 0.5, 1, 1.5, 
2, 2.5, 3, 4, 
6, 8, 12 h
24 h
48 h
72 h
96 h
120 h
The 120 h sample may serve as the D1 predose sample 
for subsequent periods, if participants are remaining 
in-house.
Product acceptability 
and palatability 
X
D1 of dosing periods when the OD tablet is 
administered either with or without water. Complete 
questionnaire immediately after OD tablet
administration.
Adverse event review
X
X
X
X
X
X
X
X
X
Concomitant
medication review
X
X
X
X
X
X
X
X
X
Abbreviations: CRU = clinical research unit; ECG = electrocardiogram; D = Day; ED = early discontinuation; h = hour; M8 = metabolite 8; OD = oral 
disintegrating; P = predose; PK = pharmacokinetic(s).  
a
The Day 5 and Day 6 visits of a treatment period may occur at the same time as the Day -1 and Day 1 visits, respectively, of the subsequent treatment period. 
Therefore, assessments that occur on both visits will only be performed once. All results must be reviewed prior to dosing on Day 1 of each treatment period.  
The Day 6 visit of Treatment Period 3 will be considered the final visit.  


CONFIDENTIAL
Protocol H8H-MC-LAIA
12
2.
Introduction
Lasmiditan (LY573144) has been developed by Eli Lilly and Company (Lilly), and approved by 
the Food and Drug Administration (FDA), for the acute treatment of migraine with or without 
aura in adults. Full details of the preclinical and clinical safety and tolerability data are contained 
in the Investigator’s Brochure (IB).  
2.1.
Study Rationale
Previous clinical studies of lasmiditan have used an immediate-release (IR) tablet formulation. 
An oral-disintegrating (OD) tablet has been developed to support pediatric development and for 
more convenient administration in adults, e.g., for those who have difficulty swallowing a tablet.  
This study is intended to determine the bioequivalence, safety, and tolerability of a newly
developed OD tablet of lasmiditan compared to the current IR tablet. Information on the 
acceptability and palatability of the OD tablet will also be collected during the study. 
2.2.
Background
Lasmiditan is a low-molecular-weight agonist of the 5-hydroxytryptamine (5-HT)1F receptor 
with a nonvascular and primarily neural mechanism of action. It has a high affinity for the 
human 5-HT1F receptor and a >440-fold selectivity for the human 5-HT1F receptor relative to the 
5-HT1B receptor. Lasmiditan has high solubility and permeability.
Lasmiditan doses have been evaluated in healthy participants or patients with migraine across 
completed Phase 1, 2, and 3 clinical studies. Across these studies, single intravenous and single 
oral doses of lasmiditan were administered over a range of 0.1 mg to 400 mg. Multiple oral doses 
of 200 mg or 400 mg were administered orally once daily (QD) for 7 days. Cumulatively through 
14 August 2018, approximately 4945 participants have received lasmiditan. The most frequently 
reported lasmiditan adverse events (AEs) in the 2 Phase 3 placebo-controlled studies, in which 
patients treated 1 migraine attack with oral lasmiditan (50, 100, or 200 mg) or placebo, were 
dizziness, paresthesia, somnolence, fatigue, and nausea, and the majority were mild or moderate 
in severity. Safety and tolerability in healthy participants were similar up to the highest dose of 
400 mg administered as a single and multiple (QD for 7 days) dose, with drowsiness, dizziness, 
and paresthesia being the most frequently reported AEs. The majority of these were mild in 
severity, and none were severe.
In previous studies, following single oral dose administration of lasmiditan to healthy 
participants, lasmiditan was absorbed with a median time of maximum observed drug 
concentration (tmax) of 1.8 hours, and rapidly eliminated with a mean terminal half-life (t1/2) of 
approximately 5.7 hours. Lasmiditan exposure increased in a dose-dependent manner that was 
considered to be approximately linear with dose over a clinical dose range of 50 to 200 mg. No 
accumulation of lasmiditan was previously observed with repeated QD dosing of 200 or 400 mg. 
Lasmiditan undergoes extensive hepatic and extrahepatic metabolism with ketone reduction to 
inactive metabolite 8 (M8) as the major biotransformation pathway.  


CONFIDENTIAL
Protocol H8H-MC-LAIA
13
2.3.
Benefit/Risk Assessment
There is no anticipated therapeutic benefit for the healthy participants.
A 100-mg dose of lasmiditan will be used in the current study. Oral doses of lasmiditan up to the 
highest single and multiple oral dose given (400 mg) were well tolerated in healthy participants, 
with no drug-related serious adverse events (SAEs) or withdrawals due to AEs as of 14 August 
2018. Lasmiditan caused no significant QT prolongation either at 100 or 400 mg, and no 
clinically significant changes in clinical laboratory data. Lasmiditan has been associated with a 
mean decrease in heart rate of 5 to 10 bpm compared to 2 to 5 bpm for placebo. Additionally, in 
non-elderly healthy volunteers, a mean increase in blood pressure of approximately 2 to 3 mmHg 
was observed 1 hour after dosing with 200 mg lasmiditan. There were no additional findings on 
vital signs following QD dosing for 7 days. Overall, in previous healthy volunteer studies, these 
changes were well tolerated. Although central nervous system disorders were commonly 
reported as AEs, especially at higher dose levels, they were generally mild or moderate in 
intensity.  
Participants should avoid driving or operating machinery for at least 8 hours following dosing 
with lasmiditan. This risk is mitigated in the current study as participants will be confined to the 
clinical research unit (CRU).
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of lasmiditan may be found in the IB.




CONFIDENTIAL
Protocol H8H-MC-LAIA
15
4.
Study Design
4.1.
Overall Design
Study H8H-MC-LAIA (LAIA) is a Phase 1, open-label, randomized, single-dose, 3-way 
crossover study in healthy participants. Approximately 48 participants will be enrolled such that 
36 participants, 6 per treatment sequence, complete the study.
Screening
All participants will be screened within 28 days prior to enrollment. 
Treatment and Assessment Period
Eligible participants will take part in 3 separate dosing periods. In each period, participants will 
be admitted to the CRU on Day -1 and remain resident in the CRU until discharge on Day 6. At 
the discretion of the investigator, participants may remain resident in the CRU for the entirety of 
the study, i.e., from admission to the CRU on Day -1 of Period 1 until discharge from the CRU 
on Day 6 of Period 3, after all assessments have been completed. 
There will be a washout period of ≥5 days between the day of dosing in 1 period and the day of 
dosing in the subsequent period. Days 5 and 6 of Period 1 and 2 may coincide with Days -1 
and 1 of Period 2 and 3, respectively, provided the required washout between lasmiditan doses is 
observed. 
On Day 1 of Period 1, participants will be equally randomized to receive a 100-mg oral dose in 
1 of 6 dosing sequences in each of 3 dosing periods as shown in Table LAIA.1. 
Table LAIA.1.
Dosing Sequences for Protocol H8H-MC-LAIA
Sequence
Period 1
Period 2
Period 3
1
IR (reference)
OD without water (test)
OD with water (test)
2
IR (reference)
OD with water (test)
OD without water (test)
3
OD without water (test)
OD with water (test)
IR (reference)
4
OD without water (test)
IR (reference)
OD with water (test)
5
OD with water (test)
IR (reference)
OD without water (test)
6
OD with water (test)
OD without water (test)
IR (reference)
Abbreviations: IR = immediate release; OD = oral disintegrating.
Pharmacokinetic blood sampling and safety assessments, including vital sign measurements,
physical examinations, clinical laboratory tests, electrocardiograms (ECGs), and AE recording 
will be performed according to the SoA (Section 1.3).
Follow-up
Day 6 of Period 3 will be considered the final visit of the study. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
16
4.2.
Scientific Rationale for Study Design
In order to minimize any potential period effect and to allow each participant to act as his/her 
own control, a randomized, 3-sequence, crossover design has been selected.
Based on the t1/2 of lasmiditan and its metabolites, at least 5 days between the day of dosing in 
1 period and the day of dosing in the subsequent period is considered sufficient time for the 
study drug to washout.  
Conducting the study in healthy participants mitigates the potential confounding effects of the
disease state and concomitant medications in participants with migraine. A population of healthy 
participants is frequently used in the assessment of the pharmacokinetics (PK) of both small and 
large molecules.
This study will be open label as the study primary endpoint PK measures are objective rather
than subjective.
4.3.
Justification for Dose
An oral dose of 100 mg lasmiditan is a clinically effective dose for the target population, based 
on data obtained from previous completed studies. 
Previous studies in healthy participants have shown single doses of lasmiditan up to 400 mg are 
generally safe and well tolerated. 
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all required 
phases of the study including the last scheduled procedure shown in the SoA (Section 1.3).
The end of the study is defined as the date of the last visit of the last participant in the study.


CONFIDENTIAL
Protocol H8H-MC-LAIA
17
5.
Study Population
Eligibility of participants for enrollment in the study will be based on the results of screening 
medical history, physical examination, vital signs, clinical laboratory tests, and ECG. 
The nature of any conditions present at the time of the physical examination and any preexisting 
conditions will be documented.
The inclusion and exclusion criteria used to determine eligibility should be applied at screening 
only and at the discretion of the investigator through predose Day 1 (Period 1 only) for safety, 
not continuously throughout the trial.
Screening may occur up to 28 days prior to enrollment. Participants who are not enrolled within 
28 days of screening may undergo an additional medical assessment and/or clinical 
measurements to confirm their eligibility. In such instances, repeat the following screening tests 
and procedures: weight, vital signs, ECG, clinical laboratory tests, and pregnancy test (females 
only).  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Participant Characteristics
1. Are males or females from 18 to 65 years of age inclusive, at the time of signing the 
informed consent.
For contraception requirements of this protocol, see Appendix 4 (Section 10.4).
2. Have a body mass index of 19.0 to 35.0 kg/m2, inclusive at the time of screening.
3. Are overtly healthy as determined by medical evaluation including:

medical history

physical examination

laboratory tests

ECG

vital signs.
4. Have clinical laboratory test results within normal reference range for the population or 
CRU, or results within 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.
Informed Consent
6. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1),
which includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.


CONFIDENTIAL
Protocol H8H-MC-LAIA
18
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Have known allergies to lasmiditan, related compounds, or any components of the 
formulation of lasmiditan, or a history of significant atopy.
2. Have a history of clinically significant allergic reactions to medications or food products, 
at the discretion of the investigator.
3. Have an abnormal blood pressure and/or pulse rate, as determined by the investigator.
4. Have clinically significant abnormalities on ECG, as determined by investigator.
5. Have a history or presence of cardiovascular, respiratory, renal, gastrointestinal, 
endocrine, hematological, or neurological disorders capable of significantly altering the 
absorption, metabolism, or elimination of drugs; of constituting a risk when taking the 
study interventions; or of interfering with the interpretation of data. 
Note: Uncomplicated procedures such as appendectomy, splenectomy, and 
cholecystectomy are considered as acceptable, at the discretion of the investigator.
6. Show a history of central nervous system conditions such as strokes, transient ischemic 
attacks, significant head trauma, seizures, central nervous system infections, migraine, 
brain surgery, or any other neurological conditions that, in the opinion of the investigator, 
increase the risk of participating in the study.
7. Have a history or presence of neuropsychiatric disease (e.g., manic depressive illness, 
schizophrenia, depression) considered as clinically significant by the investigator.
Prior/Concomitant Therapy
8. Have used or are intending to use over-the-counter or prescription medication, including 
dietary supplements, within 14 days prior to dosing and until study discharge (apart from 
occasional acetaminophen, hormonal contraception, or hormone-replacement therapy).
Prior/Concurrent Clinical Study Experience
9. Are currently enrolled in any other clinical study involving a study intervention or any 
other type of medical research judged not to be scientifically or medically compatible 
with this study.
10. Have participated, within the past 30 days of admission, in a clinical study involving any 
study intervention. If the previous study intervention has a long half-life, 5 half-lives or 
30 days (whichever is longer) should have passed.
11. Have previously completed or withdrawn from this study or any other study investigating 
lasmiditan, and have previously received the investigational product.
Diagnostic assessments
12. Have positive findings on drug screening.
13. Show evidence of human immunodeficiency virus (HIV) and/or positive HIV antibodies.
14. Show evidence of hepatitis B and/or have a positive hepatitis B surface antigen test result 
at screening.


CONFIDENTIAL
Protocol H8H-MC-LAIA
19
15. Show evidence of hepatitis C and/or have positive hepatitis C antibody test result at 
screening. 
Note: Participants with positive hepatitis C antibody due to prior resolved disease can be 
enrolled if a confirmatory negative hepatitis C RNA test is obtained.
16. Positive hepatitis C RNA test result at screening.
Note: Test is optional and participants with negative hepatitis C antibody test are not 
required to also undergo hepatitis C RNA testing.
Other Exclusions
17. Have donated blood of more than 500 mL within the previous 2 months of screening.
18. Regularly use known drugs of abuse or have a past history of drug abuse.
19. Have an average weekly alcohol intake that exceeds 21 units per week (males) and 
14 units per week (females), or are unwilling to stop alcohol consumption from 24 hours 
prior to admission and whilst resident at the CRU. At all other times, participants must 
agree to consume no more than 3 units per day (males) and 2 units per day (females).
(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).
20. Smoke more than 10 cigarettes or e-cigarettes, or 3 cigars, or 3 pipes, per day and are 
unable to refrain from smoking while resident in the CRU, including the use of any 
nicotine-containing products (e.g., nicotine patches).
21. Consume excessive amounts of coffee, tea, cola, or other caffeinated beverages per day, 
or are unwilling to stop caffeine consumption 24 hours prior to admission and whilst 
resident at the CRU. Excessive amount is defined as greater than 6 servings per day 
(1 serving is approximately equivalent to 120 mg of caffeine). 
22. Are unable to comply with the dietary regimen of the CRU.
23. Are females who have a positive pregnancy test at screening or on admission to CRU 
(Day -1).
24. Are females planning to become pregnant during the study or within 1 month of study 
completion.
25. Are females who are lactating.
26. Are investigative site personnel directly affiliated with this study and/or their immediate 
families. Immediate family is defined as a spouse, biological or legal guardian, child, or 
sibling.
27. Are Lilly or Covance employees.
28. In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study.
5.3.
Lifestyle Considerations
Throughout the study, participants may undergo medical assessments and review of compliance 
with requirements before continuing in the study.  


CONFIDENTIAL
Protocol H8H-MC-LAIA
20
5.3.1.
Meals and Dietary Restrictions
During each confinement period, participants will consume only food and beverages that are 
provided to them by the CRU staff. Standard meals (e.g., breakfast, lunch, dinner, and snack) 
will be provided to the participants while resident at the CRU.
Lasmiditan will be administered after an overnight fast of at least 8 hours. On Day 1 of each 
dosing period, participants will abstain from water at least 1 hour before and after dosing (except 
for water given with the dose). Participants will remain fasting for approximately 4 hours 
postdose, at which time a meal will be served.
5.3.2.
Caffeine, Alcohol, and Tobacco
Participants will abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, 
tea, cola drinks, and chocolate) for 24 hours prior to admission and whist resident in the CRU.
Participants will abstain from alcohol consumption 24 hours prior to admission and while 
resident at the CRU. At all other times, participants must agree to consume no more than 3 units 
per day for males or 2 units per day for females.
Participants who use tobacco products will be instructed that use of nicotine-containing products 
(including nicotine patches) will not be permitted while they are in the CRU.
5.3.3.
Activity
Participants will abstain from strenuous exercise for 48 hours before each blood collection for 
clinical laboratory tests. Participants may participate in light recreational activities during studies 
(e.g., watching television, reading).
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled in the study.
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened. Repeating of laboratory tests during the screening period or repeating screening 
assessments to comply with the protocol-designated screening period does not constitute 
rescreening. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
21
6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
6.1.
Study Interventions Administered
This study involves the comparison of a single 100-mg dose of lasmiditan OD tablet (test) versus 
the current IR tablet formulation (reference). Table LAIA.2 shows the study interventions to be 
administered.
Table LAIA.2.
Study Interventions Administered
Study intervention
Lasmiditan
Lasmiditan
Dosage formulation
Immediate-Release Tablet
Oral-Disintegrating Tablet
Unit dose strength/dosage 
level
100-mg tablet
100-mg tablet
Route of administration
Oral
Oral
Use
Reference
Test
Dosing instructions
1 tablet taken on Day 1 of the treatment
period according to the randomized 
dosing sequence
1 tablet taken on Day 1 of the treatment
period with or without water according to 
the randomized dosing sequence
Sourcing
Provided centrally by the sponsor
Provided centrally by the sponsor
Packaging and labelling
Study intervention will be provided in a 
blister. Each blister will be labeled per 
country requirement
Study intervention will be provided in a 
blister. Each blister will be labeled per 
country requirement
6.1.1.
Administration Details
Participants will be equally randomized to 1 of 6 dosing sequences in each of 3 dosing periods as 
described in Section 4.1.
For each dosing period, participants will receive a single oral dose on the morning of Day 1.  

IR tablet: Participants receiving the IR tablet formulation will swallow the tablet with 
240 mL of room-temperature water.  

OD tablet (without water): Immediately before dose administration participants 
receiving the OD tablet formulation without water will receive 20 mL of room-
temperature water to wet their palettes. Then using a dry hand, participants will place the 
OD tablet on top of the tongue and keep it there until it disintegrates. A gentle pressure 
may be exerted on the tablet by pressing the tongue against the roof of the mouth to 
facilitate disintegration of the tablet. The participants will then fully swallow the saliva 
containing both disintegrated and any un-disintegrated remaining part of the tablet.

OD tablet (with water): Immediately before dose administration participants receiving 
the OD tablet formulation with water will receive 20 mL of room-temperature water to 
wet their palettes. Then using a dry hand, participants will place the OD tablet on top of 
the tongue and keep it there until it disintegrates. A gentle pressure may be exerted on the 


CONFIDENTIAL
Protocol H8H-MC-LAIA
22
tablet by pressing the tongue against the roof of the mouth to facilitate disintegration of 
the tablet. Once the tablet has disintegrated, the participants will then drink 240 mL of 
room-temperature water and swallow with the saliva containing both disintegrated and 
any un-disintegrated remaining part of the tablet.
All doses will be administered in a sitting position and participants will not be allowed to lie 
supine for 2 hours after dosing, unless clinically indicated or for study procedures.
6.2.
Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study intervention 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records).
4. The investigator or designee will return all unused study interventions to Lilly or its 
designee at the end of the study. In some cases, sites may destroy the material if, during 
the CRU selection, the evaluator has verified and documented that the site has 
appropriate facilities and written procedures to dispose of clinical materials.
6.3.
Measures to Minimize Bias: Randomization and Blinding
This is an open-label study; potential bias will be reduced by central randomization.
On Day 1 of Treatment Period 1, participants will be assigned a unique number (randomization 
number). The randomization number encodes the participant’s assignment to 1 of 6 treatment 
sequences, according to the randomization schedule generated prior to the study by the Statistics 
Department at Covance. Each participant will be dispensed study intervention, labeled with 
his/her unique randomization number, throughout the study.
6.4.
Study Intervention Compliance
Participants are dosed at the site and they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose administered 
in the clinic will be recorded in the source documents and recorded in the electronic case report 
form (eCRF). The dose of study intervention and study participant identification will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention. Study site personnel will examine each participant’s mouth 
to ensure that the study intervention was ingested.


CONFIDENTIAL
Protocol H8H-MC-LAIA
23
6.5.
Concomitant Therapy
Participants must abstain from taking prescription or nonprescription drugs (including dietary
supplements) within 14 days prior to dosing and until study discharge, unless, in the opinion of 
the investigator and sponsor, the medication will not interfere with the study.
Acetaminophen, at doses of 3 g/24 hours, is permitted for use at the discretion of the 
investigator for the treatment of headache etc. Contraceptive medication is permitted as per the 
contraception requirements (Section 10.4) and hormone-replacement therapy is also allowed. 
Other concomitant medication may be considered on a case-by-case basis by the investigator in 
consultation with the Lilly clinical pharmacologist (CP)/clinical research physician (CRP), or 
designee.
6.6.
Dose Modification
Dose modification is not permitted in this study.
6.7.
Intervention after the End of the Study
Not applicable. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
24
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
Participants discontinuing from study intervention prematurely for any reason should complete 
AE and other follow-up/early discontinuation procedures as per the SoA (Section 1.3).
Participants discontinuing from the study prematurely for any reason must complete AE and 
follow-up/early discontinuation procedures as per the SoA (Section 1.3).
Discontinuation of specific sites or of the study as a whole is described in Appendix 1 
(Section 10.1.7).
7.1.
Discontinuation of Study Intervention
Discontinuation of the study drug for abnormal liver tests should be considered by the 
investigator when a participant meets 1 of the following conditions after consultation with the 
Lilly-designated medical monitor:

alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of 
normal (ULN)

ALT or AST >3 × ULN sustained for more than 2 weeks

ALT or AST >3 × ULN and total bilirubin level (TBL) >2 × ULN or international 
normalized ratio >1.5

ALT or AST >3 × ULN and the appearance of fatigue, nausea, vomiting, right 
upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%).
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study:

at any time at his/her own request 

at the request of his/her designee (for example, parents or legal guardian)

at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons

if the participant becomes pregnant during the study

if enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study.
Discontinuation is expected to be uncommon.
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA (Section 1.3). See SoA for data to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be completed.
The participant will be permanently discontinued both from the study intervention and from the 
study at that time.


CONFIDENTIAL
Protocol H8H-MC-LAIA
25
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant
withdraws from the study, he/she may request destruction of any samples taken and not tested,
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued from study treatment unless 
there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment. If the investigator and the sponsor CRP agree it is medically 
appropriate to continue, the investigator must obtain documented approval from the sponsor CRP 
to allow the inadvertently enrolled participant to continue in the study with or without treatment 
with investigational product. Safety follow-up is as outlined in Section 1.3 (SoA), Section 8.2
(Safety Assessments), and Section 8.3 (Adverse Events and Serious Adverse Events) of the 
protocol.
7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.


CONFIDENTIAL
Protocol H8H-MC-LAIA
26
8.
Study Assessments and Procedures
Study procedures and their timings are summarized in the SoA (Section 1.3).
Protocol waivers or exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable.
Appendix 2 (Section 10.2) lists the laboratory tests that will be performed for this study.
Appendix 2 (Section 10.2.1) 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.
Assessment collection time
The specifications in this protocol for the timings of safety and sample collection are given as 
targets to be achieved within reasonable limits. Modifications may be made to the time points 
based upon emerging clinical information. The scheduled time points may be subject to minor 
alterations; however, the actual time must be correctly recorded in the eCRF. Failure or being 
late (that is, outside stipulated time allowances) to perform procedures or obtain samples within 
the stipulated time allowances due to legitimate clinical issues (for example, equipment technical 
problems, venous access difficulty) will not be considered protocol deviations. However, the 
CRU is required to notify the sponsor in writing using a file note.
8.1.
Efficacy Assessments
Efficacy is not evaluated in this study.
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.3).
8.2.1.
Physical Examinations
A complete physical examination will include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, and neurological systems. Height and weight will also be measured 
and recorded.
Investigators should pay special attention to clinical signs related to previous illnesses.


CONFIDENTIAL
Protocol H8H-MC-LAIA
27
Additional symptom-driven physical examinations may be performed at the discretion of the 
investigator.
Any clinically significant findings in a physical examination should be reported as AEs.
8.2.2.
Vital Signs
For each participant, vital signs measurements should be conducted according to the SoA
(Section 1.3).
Blood pressure and pulse rate should be measured after at least 5 minutes supine. For each 
individual participant, the same cuff size should be used throughout the study for the 
measurements of blood pressure. The cuff should be attached to the participant’s dominant arm.
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms. Where orthostatic measurements are required, participants should be 
supine for at least 5 minutes and stand for at least 2 minutes, but no longer than 3 minutes. If the 
participant feels unable to stand, supine vital signs only will be collected. 
Additional vital signs may be measured during each dosing period if warranted and agreed upon 
between Lilly and the investigator.
8.2.3.
Electrocardiograms
For each participant, a single 12-lead digital ECG will be collected as outlined in the SoA 
(Section 1.3).
Electrocardiograms must be recorded before collecting any blood samples. Participants must be 
supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake 
during ECG collection. 
Electrocardiograms may be obtained at additional times, when deemed clinically necessary. All 
ECGs recorded should be stored at the investigational site.
Electrocardiograms will be interpreted by 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 
participant is still present, to determine whether the participant meets entry criteria at the relevant 
visits and for immediate participant management, should any clinically relevant findings be 
identified. 
If a clinically significant finding is identified (including, but not limited to, changes in 
QT/corrected QT interval from baseline) after enrollment, the investigator will determine if the 
participant can continue in the study. The investigator, or qualified designee, is responsible for 
determining if any change in participant management is needed, and must document his/her 
review of the ECG printed at the time of collection. Any new clinically relevant finding should 
be reported as an AE.
8.2.4.
Clinical Safety Laboratory Assessments
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and the 
SoA for the timing and frequency.
The laboratory reports must be filed with the source documents. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
28
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or Lilly CP.

If such values do not return to normal/baseline within a period of time judged reasonable 
by the investigator, the etiology should be identified and the sponsor notified.

All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), 
must be conducted in accordance with the laboratory manual and the SoA (Section 1.3).

If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE), then the results 
must be recorded in the eCRF.
8.2.5.
Safety Monitoring
The Lilly CP or CRP will monitor safety data throughout the course of the study.
Lilly will review SAEs within time frames mandated by company procedures (Section 8.3.1). 
The Lilly CP or CRP will periodically review:

trends in safety data

laboratory analytes 

AEs.
When appropriate, the Lilly CP or CRP will consult with the functionally independent Global 
Patient Safety medical physician or clinical research scientist.
8.2.5.1.
Hepatic Safety
Close hepatic monitoring
Laboratory tests (Appendix 6, Section 10.6), including ALT, AST, alkaline phosphatase (ALP), 
and TBL, should be repeated, with the addition of direct bilirubin, gamma-glutamyl transferase, 
and creatine kinase, within 48 to 72 hours to confirm the abnormality and to determine if it is 
increasing or decreasing, if 1 or more of these conditions occur:
If a participant with baseline results of ...
develops the following elevations:
ALT or AST <1.5 × ULN
ALT or AST ≥3 × ULN
ALP <1.5 × ULN
ALP ≥2 × ULN
TBL <1.5 × ULN
TBL ≥2 × ULN (except for participants with Gilbert’s 
syndrome)
ALT or AST ≥1.5 × ULN
ALT or AST ≥2 × baseline
ALP ≥1.5 × ULN
ALP ≥2 × baseline


CONFIDENTIAL
Protocol H8H-MC-LAIA
29
TBL ≥1.5 × ULN
TBL ≥2 × baseline (except for participants with Gilbert’s 
syndrome)
If the abnormality persists or worsens, clinical and laboratory monitoring and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated CP. At a minimum, this evaluation should include physical examination and 
a thorough medical history, including symptoms, recent illnesses (for example, heart failure, 
systemic infection, hypotension, or seizures), recent travel, history of concomitant medications 
(including over-the-counter), herbal and dietary supplements, history of alcohol drinking and 
other substance abuse.
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests.  
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels.
Comprehensive hepatic evaluation  
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur:
If a participant with baseline results of...
develops the following elevations:
ALT or AST <1.5 × ULN
ALT or AST ≥3 × ULN with hepatic signs/symptoms*, or
ALT or AST ≥5 × ULN
ALP <1.5 × ULN
ALP ≥3 × ULN
TBL <1.5 × ULN
TBL ≥2 × ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5 × ULN
ALT or AST ≥2 × baseline with hepatic signs/symptoms*, or
ALT or AST ≥3 × baseline
ALP ≥1.5 × ULN
ALP ≥2 × baseline
TBL ≥1.5 × ULN
TBL ≥1.5 × baseline (except for participants with Gilbert’s 
syndrome) 
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, and/or 
eosinophilia >5%.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-international normalized ratio; 
tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal imaging 
study (for example, ultrasound or computed tomography scan).  
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated CP, including tests for hepatitis D virus, cytomegalovirus, 
Epstein-Barr virus, acetaminophen levels, acetaminophen protein adducts, urine toxicology 
screen, Wilson’s disease, blood alcohol levels, urinary ethyl glucuronide, and serum 
phosphatidylethanol. Based on the circumstances and the investigator’s assessment of the 
participant’s clinical condition, the investigator should consider referring the participant for a 
hepatologist or gastroenterologist consultation, magnetic resonance cholangiopancreatography, 
endoscopic retrograde cholangiopancreatography, cardiac echocardiogram, or a liver biopsy.  


CONFIDENTIAL
Protocol H8H-MC-LAIA
30
Additional hepatic data collection in study participants who have abnormal liver test 
results during the study
Additional safety data collection in hepatic safety eCRF should be performed in study 
participants who meet 1 or more of the following conditions:  

Elevation of serum ALT to ≥5 × ULN on 2 or more consecutive blood tests (if baseline 
ALT <1.5× ULN)
o
In participants with baseline ALT ≥1.5 × ULN, the threshold is ALT ≥3 × 
baseline on 2 or more consecutive tests

Elevated serum TBL to ≥2 × ULN (if baseline TBL <1.5 × ULN) (except for cases of 
known Gilbert’s syndrome)
o
In participants with baseline TBL ≥1.5 × ULN, the threshold should be TBL ≥2 × 
baseline

Elevation of serum ALP to ≥2 × ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5 × ULN)
o
In participants with baseline ALP ≥1.5 × ULN, the threshold is ALP ≥2 × baseline 
on 2 or more consecutive blood tests

Hepatic event considered to be an SAE

Discontinuation of study drug due to a hepatic event.
Note: The interval between the 2 consecutive blood tests should be at least 2 days.
8.3.
Adverse Events and Serious Adverse Events
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or study (see Section 7).
Investigators are responsible for monitoring the safety of participants 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 participant.
The investigator is responsible for the appropriate medical care of participants during the study.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All AEs and SAEs will be collected from the signing of the ICF until participation in study has 
ended.
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the Adverse Event eCRF.
Although all AEs after signing the ICF are recorded by the site in the eCRF, SAE reporting to 
sponsor begins after the participant has signed the ICF and has received study drug. However, if 


CONFIDENTIAL
Protocol H8H-MC-LAIA
31
an SAE occurs after signing the ICF, but prior to receiving lasmiditan, it needs to be reported 
ONLY if it is considered reasonably possibly related to study procedures.
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 3 (Section 10.3). The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
sponsor.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3).
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE
occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is provided in Appendix 10.3.
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRBs)/Independent Ethics Committees 
(IECs), and investigators.
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
8.3.5.
Pregnancy
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study intervention and until study end.


CONFIDENTIAL
Protocol H8H-MC-LAIA
32
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 4 (Section 10.4).
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
Pregnancy (maternal or paternal exposure to study intervention) does not meet the definition of 
an AE. However, to fulfill regulatory requirements, any pregnancy should be reported following 
the SAE process described in Appendix 3 (Section 10.3) to collect data on the outcome for both 
mother and fetus.
8.3.6. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
trial intervention.
Sponsor collects product complaints on investigational products and drug delivery systems used 
in clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Participants will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
Note: AEs/SAEs that are associated with a product complaint will also follow the processes 
outlined in Section 8.3.3 and Appendix 3 (Section 10.3) of the protocol.
8.3.6.1.
Time Period for Detecting Product Complaints
Product complaints that result in an AE will be detected, documented, and reported to the 
sponsor during all periods of the study in which the drug is used.
If the investigator learns of any product complaint at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a drug provided 
for the study, the investigator will promptly notify the sponsor.
8.3.6.2. Prompt Reporting of Product Complaints to Sponsor
Product complaints will be reported to the sponsor within 24 hours after the investigator becomes 
aware of the complaint.
The Product Complaint Form will be sent to the sponsor by email. If email is unavailable, then
fax should be utilized.
8.3.6.3.
Follow-up of Product Complaints
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the product complaint.
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator and submitted to the sponsor.


CONFIDENTIAL
Protocol H8H-MC-LAIA
33
8.4.
Treatment of Overdose
For this study, any dose of lasmiditan greater than 100 mg within a 24-hour time period will be 
considered an overdose.
There is no specific antidote for lasmiditan. 
In the event of an overdose, the investigator/treating physician should:
1. Contact the Lilly CP immediately.
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
intervention can no longer be detected systemically (at least 2 days).
3. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF.
Decisions regarding dose interruptions will be made by the investigator in consultation with the 
Lilly CP based on the clinical evaluation of the participant.
8.5.
Pharmacokinetics
Venous blood samples of approximately 2 mL will be collected for measurement of plasma
concentrations of lasmiditan and M8, as specified in the SoA (Section 1.3).
A maximum of 3 samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor.
Instructions for the collection and handling of biological samples will be provided by the 
sponsor. The actual date and time (24-hour clock time) of each sample will be recorded.
8.5.1.
Bioanalysis
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor.
Concentrations of lasmiditan and M8 will be assayed using a validated liquid chromatography 
with tandem mass spectrometry method.
Bioanalytical samples collected to measure study intervention concentrations will be retained for 
a maximum of 1 year following last participant visit for the study.
8.6.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7.
Genetics
A blood sample for DNA isolation will be collected from participants. 
See Appendix 5 (Section 10.5) for information regarding genetic research.
8.8.
Biomarkers
Biomarkers are not evaluated in this study.


CONFIDENTIAL
Protocol H8H-MC-LAIA
34
8.9.
Immunogenicity Assessments
Immunogenicity is not evaluated in this study.
8.10.
Health Economics
This section is not applicable for this study. 
8.11.
Product Acceptability and Palatability Assessments
The participant will be asked to provide responses to questions designed to assess the 
acceptability and palatability of the OD tablet when administered with and without water. The 
questionnaire will assess the participant’s experience relating to the taste, smell, mouthfeel, 
aftertaste, and the approximate disintegration time of the OD tablet in the oral cavity.
The questionnaire will be completed by the participant immediately after administration of the 
OD tablet both with and without water. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
35
9.
Statistical Considerations
9.1.
Statistical Hypotheses
Bioequivalence of the OD tablet without water versus the current IR tablet will be established if 
the 90% confidence interval (CI) of the ratio of geometric least square means for area under the 
concentration versus time curve (AUC) from time zero to infinity (AUC[(0-∞]), AUC from time 
zero to time t, where t is the last time point with a measurable concentration (AUC[0-tlast]), and 
maximum observed drug concentration (Cmax) is within the testing boundaries of 0.8 and 1.25.
9.2.
Sample Size Determination
A total of 36 participants are required complete the study to establish equivalence between the 
OD tablet formulation without water and the current IR tablet, based on the PK parameters 
measured.
Given the 6×3 design this would mean at least 6 participants would be randomly assigned to each 
of the 6 dosing sequences. The calculated total number of participants assumes 90% power for 
the two one-sided test (TOST) for equivalence with a significance level of 5%, analogous to a 
90% CI. Further, this is based on:

a nominally assigned true mean ratio of 1.05

a coefficient of variation for Cmax of 24.1%

ratio testing boundaries of 0.8 and 1.25.
Assuming that 25% of participants will drop out or fail to provide full study data, approximately 
48 participants should be enrolled to ensure that 36 participants, 6 per treatment sequence, will 
complete the study.
9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Enrolled
All participants randomly assigned to study intervention.
Safety
All enrolled participants who received at least 1 dose of study 
intervention. Participants will be analyzed according to the 
intervention they actually received.
Pharmacokinetic Analysis
All enrolled participants who received at least 1 dose of study 
intervention and have evaluable PK data.
9.3.1.
Study Participant Disposition
A detailed description of participant disposition will be provided at the end of the study.
9.3.2.
Study Participant Characteristics
The participants’ age, sex, weight, height, body mass index, race, and other demographic 
characteristics will be recorded and summarized using descriptive statistics.


CONFIDENTIAL
Protocol H8H-MC-LAIA
36
9.4.
Statistical Analyses
Statistical analysis of this study will be the responsibility of the sponsor or its designee.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the statistical analysis plan (SAP) and the clinical study report. Additional exploratory 
analyses of the data will be conducted as deemed appropriate.
The SAP will be finalized prior to the first participant visit and it will include a more technical 
and detailed description of the statistical analyses described in this section. This section is a 
summary of the planned statistical analyses of the most important endpoints including primary 
and key secondary endpoints.
9.4.1. General Considerations
Data listings will be provided for all data that are databased. Data listings will be provided for all 
participants up to the point of withdrawal, with any participants excluded from the relevant 
population highlighted.
Summary statistics and statistical analysis will only be presented for data where detailed in the 
SAP. Summary statistics and statistical analyses will generally only be performed for 
participants included in the relevant analysis population. For the calculation of summary 
statistics and statistical analysis, unrounded data will be used.
9.4.2.
Pharmacokinetic Analyses
9.4.2.1.
Pharmacokinetic Parameter Estimation
Pharmacokinetic parameter estimates for lasmiditan and M8, based on plasma concentrations,
will be calculated by standard noncompartmental methods of analysis and summarized using 
descriptive statistics.
The primary PK parameters for analysis will be Cmax, AUC(0-∞), and AUC from time zero to 
time t, where t is the last time point with a measurable concentration (AUC[0-tlast]) of
lasmiditan.  
Other noncompartmental parameters, such as half-life, apparent clearance, and apparent volume 
of distribution may be reported.
9.4.2.2.
Pharmacokinetic Statistical Inference
Log-transformed AUC(0-∞), AUC(0-tlast), and Cmax of lasmiditan will be evaluated in a linear 
mixed-effects model with fixed effects for period, sequence, and treatment and a random effect 
for participant within sequence.
All valid PK data will be included, whether or not the participants completed all 3 periods.
Estimates of geometric least square mean ratios together with the corresponding 90% CIs will be 
derived for the comparisons of AUC(0-∞), AUC(0-tlast), and Cmax as follows:

Primary endpoint: lasmiditan OD tablet without water (test) versus lasmiditan IR tablet


CONFIDENTIAL
Protocol H8H-MC-LAIA
37

Secondary endpoint: lasmiditan OD tablet with water (test) versus lasmiditan IR tablet.
The 2 lasmiditan formulations will be considered bioequivalent if the 90% CIs of the ratio of 
geometric least square means falls completely within 0.80 to 1.25.
Values of tmax will be analyzed non-parametrically using the Wilcoxon signed rank test.
Estimates of the median difference between test and reference formulations based on the 
observed medians, 90% CIs, and the p-value from the Wilcoxon test will be calculated.
Additional PK analyses may be conducted if deemed appropriate.
9.4.3.
Safety Analyses
9.4.3.1.
Clinical Evaluation of Safety
All study intervention 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 study intervention as perceived by the investigator. Symptoms reported to occur prior to 
enrollment 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 study intervention-related SAEs will be reported.
9.4.3.2.
Statistical Evaluation of Safety
Safety parameters that will be assessed include safety laboratory parameters and vital signs. The 
parameters will be listed and summarized using standard descriptive statistics. Additional 
analysis will be performed if warranted upon review of the data.
9.4.4.
Product Acceptability and Palatability Analyses
Responses from the product acceptability and palatability questionnaire will be summarized 
categorically (frequency and percentage).
9.5.
Interim Analyses 
No interim analyses are planned for this study. If an unplanned interim analysis is deemed 
necessary for reasons other than a safety concern, the protocol must be amended.
9.6.
Data Monitoring Committee (DMC)
Not applicable to this study. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
38
10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines

Applicable laws and regulations.
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC
before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC

Notifying the IRB of SAEs or other significant safety findings as required by IRB/IEC
procedures

Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations.
Investigator sites are compensated for participation in the study as detailed in the clinical trial
agreement.
10.1.2.
Informed Consent Process
The investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant or his/her legally authorized representative and answer all
questions regarding the study.
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center.


CONFIDENTIAL
Protocol H8H-MC-LAIA
39
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.
Participants must be re-consented to the most current version of the ICF during their 
participation in the study.
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative and is kept on file.
10.1.3.
Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
The sponsor has processes in place to ensure data protection, information security and data 
integrity. These processes include appropriate contingency plan(s) for appropriate and timely 
response in the event of a data security breach.
10.1.4.
Dissemination of Clinical Study Data
Communication of Suspended or Terminated Dosing
If a decision is taken to suspend or terminate dosing in the trial due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, by phone and/or email) 
as soon as possible. It will be a requirement that investigators respond upon receipt to confirm 
that they understand the communication and have taken the appropriate action prior to further 
dosing any participants with study intervention. Any investigator not responding will be 
followed up by Lilly personnel prior to any further planned dosing. If a dose is planned 
imminently, Lilly personnel will immediately, and continually, use all efforts to reach 
investigators until contact is made and instructions verified.
Reports
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
40
Data 
The sponsor does not proactively share data from Phase 1 clinical trials. Requests for access to 
Phase 1 clinical trial data are evaluated on a case-by-case basis taking into consideration the 
ability to anonymize the data and the nature of the data collected.
10.1.5.
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques are provided in the Monitoring Plan.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.
The sponsor assumes accountability for actions delegated to other individuals (e.g., Contract 
Research Organizations).
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the Clinical Trial Agreement (CTA)
unless local regulations or institutional policies require a longer retention period. No records may 
be destroyed during the retention period without the written approval of the sponsor. No records 
may be transferred to another location or party without written notification to the sponsor.
In addition, the sponsor or its representatives will periodically check a sample of the participant
data recorded against source documents at the study site. The study may be audited by sponsor or 
its representatives, and/or regulatory agencies at any time. Investigators will be given notice 
before an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.


CONFIDENTIAL
Protocol H8H-MC-LAIA
41
An electronic data capture (EDC) system will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF.
Data collected via the sponsor-provided data capture system will be stored at a third party. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse.
Data from complaint forms submitted to sponsor will be encoded and stored in the global 
product complaint management system.
10.1.6.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available.
Definition of what constitutes source data can be found in Section 10.1.5.
10.1.7.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development.


CONFIDENTIAL
Protocol H8H-MC-LAIA
42
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and assures
appropriate participant therapy and/or follow-up.
10.1.8.
Publication Policy
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal if the results are deemed to be of significant medical 
importance.


CONFIDENTIAL
Protocol H8H-MC-LAIA
43
10.2.
Appendix 2: Clinical Laboratory Tests
The tests detailed below will be performed by the local laboratory.
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5
of the protocol.
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations.
Pregnancy testing will be conducted as detailed in the SoA (Section 1.3).
Investigators must document their review of each laboratory safety report.


CONFIDENTIAL
Protocol H8H-MC-LAIA
44
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Hematocrit
Sodium
Hemoglobin
Potassium
Erythrocyte count (RBC)
Bicarbonate
Mean cell volume 
Chloride
Mean cell hemoglobin 
Calcium
Mean cell hemoglobin concentration 
Phosphorus/Phosphate
Leukocytes (WBC) 
Glucose (fasting)
Platelets
Blood urea nitrogen
Differential WBC (absolute counts and %) of:
Creatinine
Neutrophils
Uric acid
Lymphocytes
Total protein
Monocytes
Albumin
Eosinophils
Total bilirubina
Basophils
Alkaline phosphatase
Aspartate aminotransferase
Urinalysis
Alanine aminotransferase
Specific gravity
pH
Ethanol testingb
Protein
Urine drug screenb
Glucose
Hepatitis B surface antigenc
Ketones
Hepatitis C antibodyc,d
Bilirubin
HIVc
Urobilinogen
Blood
Serum pregnancy test (all females)c
Nitrite
Urine pregnancy test (all females)e
Microscopic examination of sedimentf
FSH (postmenopausal females only)c
Abbreviations: FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; RBC = red blood cells; 
WBC = white blood cells.
Note: Results of these assays will be validated by the local laboratory at the time of testing. Additional tests may be 
performed or auto-calculated by the laboratory as part of its standard panel that cannot be removed. Some of the 
above parameters are calculated from measured values. Omission of calculated values will not be considered as a 
protocol violation.
a
Direct and indirect bilirubin will be analyzed if total bilirubin is elevated.
b
Performed at screening and admission to the clinical research unit (CRU; Day -1).
c
Performed at screening only.
d
Participants with a positive hepatitis C antibody test result can have a confirmatory hepatitis C RNA test.
e
Performed for all females on admission to CRU (Day -1). A positive urine test will be confirmed with a serum 
pregnancy test. 
f
Test only if dipstick result is abnormal.


CONFIDENTIAL
Protocol H8H-MC-LAIA
45
10.2.1.
Blood Sampling Summary
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study. 
Protocol H8H-MC-LAIA Sampling Summary
Purpose
Blood Volume per 
Sample (mL)
Number of Blood 
Samples
Total Volume 
(mL)
Screening testsa
19.5
1
19.5
Clinical laboratory testsa
12.5
6
75
Pharmacokinetics 
2
51b
102
Pharmacogenetics
10
1
10
Total
206.5
Total for clinical purposes 
210
a
Additional samples may be drawn if needed for safety purposes. 
b Includes additional 3 samples, if required.










CONFIDENTIAL
Protocol H8H-MC-LAIA
50

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE report within the designated reporting time frames.

Contacts for SAE reporting can be found in SAE Report.


CONFIDENTIAL
Protocol H8H-MC-LAIA
51
10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
10.4.1.
Definitions
Females of Childbearing Potential
A female is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Females NOT of Childbearing Potential 
Females in the following categories are considered not of childbearing potential:
1.
Infertile due to surgical sterilization

Documented hysterectomy

Documented bilateral oophorectomy

Document bilateral tubal ligation 
2.
Permanent infertility due to an alternate medical cause other than the above, (e.g., mullerian 
agenesis.)
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
3.
Postmenopausal female defined as either:

a woman at least 40 years of age with an intact uterus, not on hormone therapy, who has 
cessation of menses for at least 12 months without an alternative medical cause, AND a 
follicle-stimulating hormone >40 mIU/L

a woman 55 years or older not on hormone therapy, who has had at least 12 months of 
spontaneous amenorrhea

a woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone-replacement therapy.
10.4.2.
Contraception Guidance
10.4.2.1.
Female Participants
All females must test negative for pregnancy prior to initiation of treatment as indicated by a 
negative serum pregnancy test at the screening visit followed by a negative urine pregnancy test 
within 24 hours prior to exposure. A positive urine test will be confirmed with a serum 
pregnancy test.
Female participants not of childbearing potential are not required to adhere to contraceptive 
requirements.
Female participants of childbearing potential must agree to use either 1 highly effective method 
of contraception (<1% failure rate), or a combination of 2 effective methods of contraception, see 
Section 10.4.3, during the study and until 30 days after the last dose of study medication. 


CONFIDENTIAL
Protocol H8H-MC-LAIA
52
10.4.2.2.
Male Participants
Male participants are not required to adhere to contraceptive requirements.
10.4.3.
Contraception Methods
Abstinence
Participants who are abstinent (if this is complete abstinence, as their preferred and usual 
lifestyle) must agree to remain abstinent without sexual relationships with the opposite sex.
Same-sex relationships
Participants who are in a same-sex relationship (as part of their preferred and usual lifestyle) 
must agree to stay in a same-sex relationship without sexual relationships with the opposite sex. 
Participants who are in exclusively same-sex relationships as their preferred and usual lifestyle 
are not required to use contraception.
Highly effective and effective contraception methods
Highly effective methods of contraception (less than 1% failure rate)
Combined oral contraceptive pill and 
mini-pill
Intrauterine device (such as Mirena® and ParaGard®)
NuvaRing®
Contraceptive patch – ONLY women less than 198 pounds (90 kg)
Implantable contraceptives
Vasectomy – for partners of female participants
Injectable contraceptives (such as 
Depo-Provera®)
Fallopian tube implants (Essure®) if confirmed by 
hysterosalpingogram
Total abstinence
Effective methods of contraception (use 2 forms combined except where noted)
Male condom with spermicidea
Cervical sponge
Female condom with spermicidea
Cervical cap with spermicide
Diaphragm with spermicide
a
Male and female condoms should not be used in combination.
Unacceptable contraception methods
Unacceptable methods of contraception include

periodic abstinence, such as
o
calendar
o
ovulation
o
symptothermal
o
post-ovulation methods

declaration of abstinence just for the duration of the study

withdrawal.


CONFIDENTIAL
Protocol H8H-MC-LAIA
53
10.4.4.
Collection of Pregnancy Information
Male participants with partners who become pregnant

The investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This 
applies only to male participants who receive lasmiditan.

After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported including fetal status 
(presence or absence of anomalies) and indication for the procedure. 
Female Participants who become pregnant

The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the appropriate form and submitted to the sponsor within 24 hours of 
learning of a participant's pregnancy. 

The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the sponsor. Generally, follow-up will not be required 
for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of 
pregnancy will be reported, including fetal status (presence or absence of anomalies) or 
indication for the procedure.

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE. 

A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring 
at ≥20 weeks gestational age) is always considered to be an SAE and will be reported as 
such. 

Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.4. While the investigator is not obligated to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous reporting.

Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention. If the participant is discontinued from the study 
intervention, follow the standard discontinuation process and continue directly to the 
follow-up phase. The follow-up on the pregnancy outcome should continue independent 
of intervention or study discontinuation.   


CONFIDENTIAL
Protocol H8H-MC-LAIA
54
10.5.
Appendix 5: Genetics
Use/Analysis of DNA
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants.
DNA samples will be used for research related to lasmiditan or migraine and related diseases. 
They may also be used to develop tests/assays including diagnostic tests related to lasmiditan
and/or interventions of this drug class and migraine. Genetic research may consist of the analysis 
of one or more candidate genes or the analysis of genetic markers throughout the genome or 
analysis of the entire genome (as appropriate).
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to lasmiditan or study interventions of this class to understand study disease or 
related conditions.
The results of genetic analyses may be reported in the clinical study report or in a separate study 
summary.
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
The samples will be retained while research on lasmiditan continues but no longer than 15 years 
or other period as per local requirements.


CONFIDENTIAL
Protocol H8H-MC-LAIA
55
10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments
See Section 8.2.5.1 for guidance on appropriate test selection.
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing.
Local testing may be performed in addition to central testing when necessary for immediate 
participant management.
Results will be reported if a validated test or calculation is available.
Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs - red blood cells)
Alkaline phosphatase (ALP)
Leukocytes (WBCs - white blood cells)
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
    Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
    Lymphocytes
Creatine kinase (CK)
    Monocytes
Other Chemistry
    Basophils
Acetaminophen
    Eosinophils
Acetaminophen protein adducts
Platelets
Alkaline phosphatase isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl alcohol (EtOH)
Prothrombin time, international normalized ratio (INR)
(PT-INR)
Haptoglobin
Serology
Immunoglobulin IgA (quantitative)
Hepatitis A virus (HAV) testing:
Immunoglobulin IgG (quantitative)
    HAV total antibody
Immunoglobulin IgM (quantitative)
    HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatis B virus (HBV) testing:
Urine Chemistry
    Hepatitis B surface antigen (HBsAg)
Drug screen
    Hepatitis B surface antibody (anti-HBs)
Ethyl glucuronide (EtG)
    Hepatitis B core total antibody (anti-HBc)
Other Serology
    Hepatitis B core IgM antibody
Anti-nuclear antibody (ANA)
    Hepatitis B core IgG antibody
Anti-smooth muscle antibody (ASMA) a


CONFIDENTIAL
Protocol H8H-MC-LAIA
56
    HBV DNA d
Anti-actin antibody b
Hepatitis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNA d
    EBV DNA d
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody
Hepatitis E virus (HEV) testing:
    CMV DNA d
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNA d
    HSV (Type 1 and 2) DNA d
Microbiology c
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
a
Not required if anti-actin antibody is tested.
b
Not required if anti-smooth muscle antibody (ASMA) is tested.
c
Assayed ONLY by investigator-designated local laboratory; no central testing available.
d
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.


CONFIDENTIAL
Protocol H8H-MC-LAIA
57
10.7.
Appendix 7: Abbreviations
Term
Definition
5-HT
5-hydroxytryptamine
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
AUC(0-∞)
area under the concentration versus time curve from time zero to infinity
AUC(0-tlast)
area under the concentration versus time curve from time zero to time t, where t is the 
last time point with a measurable concentration
CFR
Code of Federal Regulations
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 study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CP
clinical pharmacologist
CRF
case report form
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
ECG
electrocardiogram
eCRF
electronic case report form
enroll
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment.
enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.


CONFIDENTIAL
Protocol H8H-MC-LAIA
58
GCP
good clinical practice
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed and dated informed consent form.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IR
immediate-release
IRB
Institutional Review Board
M8
metabolite 8
OD
oral-disintegrating 
participant
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control.
PK
pharmacokinetic(s)
QD
once daily
SAE
serious adverse event
SAP
statistical analysis plan
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SoA
Schedule of Activities
t1/2 
terminal half-life
TBL
total bilirubin
tmax
time of maximum observed drug concentration
ULN
upper limit of normal


CONFIDENTIAL
Protocol H8H-MC-LAIA
59
11.
References
None cited. 


Leo Document ID = b68f9a2b-3e5d-41e9-8785-c9b7a20d5bee
Approver: 
Approval Date & Time: 04-Sep-2020 16:04:48 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 08-Sep-2020 12:00:20 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
Statistical Analysis Plan H8H-MC-LAIA 
 
 
Bioequivalence of Lasmiditan Oral Disintegrating Tablet Compared to Current Immediate-
Release Tablet Formulation to Support Treatment of Migraine 
 
NCT04881747 
 
Approval Date: 10-Mar-2021 
 
 
 


Final v1, 08 March 2021
             Page 1 of 18
STATISTICAL ANALYSIS PLAN
Bioequivalence of Lasmiditan Oral Disintegrating Tablet Compared to Current 
Immediate-Release Tablet Formulation to Support Treatment of Migraine
Statistical Analysis Plan Status: Final v1
Statistical Analysis Plan Date: 08-March-2021
Study Drug: Lasmiditan (LY573144)
Sponsor Reference: H8H-MC-LAIA
Covance CRU Study: 1000071-8447232 
Clinical Phase I
Approval Date: 10-Mar-2021 GMT


Final v1, 08 March 2021
             Page 2 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
1. TABLE OF CONTENTS
1.
TABLE OF CONTENTS ............................................................................................... 2
2.
ABBREVIATIONS........................................................................................................ 3
3.
INTRODUCTION ......................................................................................................... 5
4.
STUDY OBJECTIVES AND ENDPOINTS .................................................................. 5
4.1
Primary Objective and Endpoint.............................................................................. 5
4.2
Secondary Objectives and Endpoints ....................................................................... 6
4.3
Exploratory Objectives and Endpoints..................................................................... 6
5.
STUDY DESIGN........................................................................................................... 6
6.
TREATMENTS............................................................................................................. 7
7.
SAMPLE SIZE JUSTIFICATION ................................................................................. 8
8.
DEFINITION OF ANALYSIS POPULATIONS............................................................ 8
9.
STATISTICAL METHODOLOGY ............................................................................... 9
9.1
General.................................................................................................................... 9
9.2
Demographics, Baseline Characteristics, and Participant Disposition....................... 9
9.3
Pharmacokinetic Assessment................................................................................... 9
9.3.1
Pharmacokinetic Analysis............................................................................... 9
9.3.2
Pharmacokinetic Statistical Methodology ..................................................... 13
9.4
Safety and Tolerability Assessments...................................................................... 14
9.4.1
Adverse events ............................................................................................. 14
9.4.2
Concomitant medication............................................................................... 14
9.4.3
Clinical laboratory parameters...................................................................... 14
9.4.4
Vital signs .................................................................................................... 14
9.4.5
Electrocardiogram ........................................................................................ 15
9.4.6
Product Acceptability and Palatability Analyses ........................................... 15
9.4.7
Hepatic Monitoring ...................................................................................... 15
9.4.8
Other assessments......................................................................................... 17
9.4.9
Safety and Tolerability Statistical Methodology............................................ 17
10. INTERIM ANALYSES ............................................................................................... 17
11. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ...... 17
12. REFERENCES ............................................................................................................ 17
13. DATA PRESENTATION ............................................................................................ 17
13.1 Derived Parameters ............................................................................................... 17
13.2 Missing Data ......................................................................................................... 17
13.3 Insufficient Data for Presentation .......................................................................... 18


Final v1, 08 March 2021
             Page 3 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
2. ABBREVIATIONS
Abbreviations pertain to the Statistical Analysis Plan (SAP) only (not the tables, figures and 
listings [TFLs]).
%AUC(tlast-∞)
Percentage of AUC(0-∞) extrapolated
AE
Adverse event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
AUC
Area under the concentration versus time curve
AUC(0-∞)
Area under the concentration versus time curve from time zero to 
infinity
AUC(0-tlast)
Area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable concentration
BQL
Below the lower limit of quantitation
Cmax
Maximum observed drug concentration
CL/F
Apparent total body clearance of drug calculated after extra vascular 
administration (not M8)
CRF
Case Report Form
CRU
Clinical Research Unit
CSR
Clinical Study Report
ECG
Electrocardiogram
ICH
International Conference on Harmonisation
IR
Immediate release
LS
Least square
M8
Metabolite 8
MedDRA
Medical Dictionary for Regulatory Activities
MR
Metabolic ratio
OD
Oral disintegrating
PK
Pharmacokinetic
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SD
Standard deviation 
TBL
Total bilirubin


Final v1, 08 March 2021
             Page 4 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
TEAE
Treatment-emergent adverse event 
TFLs
Tables, Figures, and Listings
t1/2
Half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
tmax
Time of maximum observed drug concentration
ULN
Upper limit of normal
Vss/F
Apparent volume of distribution at steady state after extra-vascular 
administration (not M8)
Vz/F
Apparent volume of distribution during the terminal phase after 
extra-vascular administration (not M8)
WHO
World Health Organization


Final v1, 08 March 2021
             Page 5 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
3. INTRODUCTION
This SAP has been developed after review of the Clinical Study Protocol (final version dated 
08 September 2020).
This SAP describes the planned analysis of the safety, tolerability, and pharmacokinetic (PK)
data from this study. A detailed description of the planned TFLs to be presented in the clinical 
study report (CSR) is provided in the accompanying TFL shell document.
The intent of this document is to provide guidance for the statistical and PK analyses of data. In
general, the analyses are based on information from the protocol, unless they have been modified 
by agreement with Eli Lilly and Company. A limited amount of information concerning this 
study (e.g., objectives, study design) is given to help the reader’s interpretation. For open-label 
studies, this SAP must be signed off prior to first participant visit for this study. When the SAP 
and TFL shells are agreed upon and finalized, they will serve as the template for this study’s 
CSR.
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon with
Eli Lilly and Company and identified in the CSR. Any minor deviations from the TFLs may not 
be documented in the CSR.
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1 and the ICH E3 Guideline entitled Guidance for Industry: 
Structure and Content of Clinical Study Reports2.
4. STUDY OBJECTIVES AND ENDPOINTS
4.1
Primary Objective and Endpoint
The primary objective of the study is to evaluate the PK of lasmiditan following administration 
of a single 100-mg dose of lasmiditan oral disintegrating (OD) tablet (test) administered without 
water versus the current immediate release (IR) tablet formulation (reference) in healthy 
participants.
The primary endpoints of the study are:

Maximum observed drug concentration (Cmax)

Area under the concentration versus time curve from time zero to infinity [AUC(0-∞)]

Area under the concentration versus time curve from time zero to time t, where t is the 
last time point with a measurable concentration [AUC(0-tlast)]


Final v1, 08 March 2021
             Page 6 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
4.2
Secondary Objectives and Endpoints
The secondary objectives and endpoints of the study are:

To evaluate the PK of lasmiditan following administration of a single 100-mg dose of 
lasmiditan OD tablet (test) administered with water versus the current IR tablet 
formulation (reference) in healthy participants
o
Cmax
o
AUC(0-∞)
o
AUC(0-tlast)

To evaluate the safety and tolerability of lasmiditan following administration of a single 
100-mg dose of lasmiditan OD tablet (test) versus the current IR tablet formulation 
(reference) in healthy participants
o
Incidence of treatment-emergent adverse event (TEAEs) and serious adverse 
events (SAEs)
4.3
Exploratory Objectives and Endpoints
The exploratory objectives and endpoints of the study are:

To characterize the PK of metabolite 8 (M8) following administration of a single 100-mg 
dose of lasmiditan OD tablet (test) or the current IR tablet formulation (reference) in 
healthy participants
o
Cmax
o
AUC(0-∞)
o
AUC(0-tlast)

To assess the product acceptability and palatability of lasmiditan OD tablets
o
Responses to OD tablet acceptability and palatability questionnaire
5. STUDY DESIGN
This study is a Phase 1, open-label, randomized, single-dose, 3-way crossover study in healthy 
participants. Approximately 48 participants will be enrolled such that 36 participants, 6 per 
treatment sequence, complete the study.
Screening
All participants will be screened within 28 days prior to enrollment.


Final v1, 08 March 2021
             Page 7 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
Treatment and Assessment Period
Eligible participants will take part in 3 separate dosing periods. In each period, participants will
be admitted to the clinical research unit (CRU) on Day -1 and remain resident in the CRU until 
discharge on Day 6. At the discretion of the investigator, participants may remain resident in the 
CRU for the entirety of the study, i.e., from admission to the CRU on Day -1 of Period 1 until 
discharge from the CRU on Day 6 of Period 3, after all assessments have been completed.
There will be a washout period of ≥5 days between the day of dosing in 1 period and the day of 
dosing in the subsequent period. Days 5 and 6 of Period 1 and 2 may coincide with Days -1 and 
1 of Period 2 and 3, respectively, provided the required washout between lasmiditan doses is
observed.
On Day 1 of Period 1, participants will be equally randomized to receive a 100-mg oral dose in 1 
of 6 dosing sequences in each of 3 dosing periods.
PK blood sampling and safety assessments, including vital sign measurements, physical 
examinations, clinical laboratory tests, electrocardiograms (ECGs), and adverse event (AE)
recording will be performed.
Follow-up
Day 6 of Period 3 will be considered the final visit of the study.
A general schema for this study can be seen in Figure 1.
Figure 1:  H8H-MC-LAIA Study Schema
6. TREATMENTS
The following is a list of the study treatment sequence labels that will be used in selected TFLs.


Final v1, 08 March 2021
             Page 8 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
Sequence
Study Treatment Sequence*
Treatment order in TFL
1
100 mg Lasmiditan IR (reference) / 100 mg Lasmiditan OD without 
water (test) / 100 mg Lasmiditan OD with water (test)
1
2
100 mg Lasmiditan IR (reference) / 100 mg Lasmiditan OD with 
water (test) / 100 mg Lasmiditan OD without water (test)
2
3
100 mg Lasmiditan OD without water (test) / 100 mg Lasmiditan OD 
with water (test) / 100 mg Lasmiditan IR (reference)
3
4
100 mg Lasmiditan OD without water (test) / 100 mg Lasmiditan IR 
(reference) / 100 mg Lasmiditan OD with water (test)
4
5
100 mg Lasmiditan OD with water (test) / 100 mg Lasmiditan IR 
(reference) / 100 mg Lasmiditan OD without water (test)
5
6
100 mg Lasmiditan OD with water (test) / 100 mg Lasmiditan OD 
without water (test) / 100 mg Lasmiditan IR (reference)
6
*Abbreviations: IR = immediate release; OD = oral disintegrating
The following is a list of the study treatment names that will be used in the PK and remaining 
TFLs.
Study Treatment Name*
Treatment order in TFL
100 mg lasmiditan IR (reference)
1
100 mg lasmiditan OD without water (test)
2
100 mg lasmiditan OD with water (test)
3
*Abbreviations: IR = immediate release; OD = oral disintegrating
7. SAMPLE SIZE JUSTIFICATION
A total of 36 participants are required to complete the study to establish equivalence between the 
OD tablet formulation without water and the current IR tablet, based on the PK parameters 
measured.
Given the 6h3 design, this would mean at least 6 participants would be randomly assigned to 
each of the 6 dosing sequences. The calculated total number of participants assumes 90% power 
for the two one-sided test for equivalence with a significance level of 5%, analogous to a 90% 
confidence interval. Further, this is based on:
•
a nominally assigned true mean ratio of 1.05
•
a coefficient of variation for Cmax of 24.1%
•
ratio testing boundaries of 0.8 and 1.25
Assuming that 25% of participants will drop out or fail to provide full study data, approximately 
48 participants should be enrolled to ensure that 36 participants, 6 per treatment sequence, will 
complete the study.
8. DEFINITION OF ANALYSIS POPULATIONS
The “Enrolled” population will consist of all participants randomly assigned to lasmiditan.
The “Safety” population will consist of all enrolled participants who received at least 1 dose of 
lasmiditan. Participants will be analyzed according to the intervention they actually received.


Final v1, 08 March 2021
             Page 9 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
The “Pharmacokinetic” population will consist of all enrolled participants who received at least 1 
dose of lasmiditan and have evaluable PK data. Participants may be excluded from the PK 
summary statistics and statistical analysis if a participant has an adverse event of vomiting that 
occurs at or before 2 times median time of maximum observed drug concentration (tmax).
All protocol deviations that occur during the study will be considered for their severity/impact 
and will be taken into consideration when participants are assigned to analysis populations.
9. STATISTICAL METHODOLOGY
9.1
General
Data listings will be provided for all data that is databased. Summary statistics and statistical 
analysis will only be presented for data where detailed in this SAP. For continuous data, 
summary statistics will include the arithmetic mean, arithmetic standard deviation (SD), median, 
min, max and N; for log-normal data (e.g. the PK parameters: area under the concentration 
versus time curve (AUC) and Cmax) the geometric mean and geometric coefficient of variation
will also be presented. For categorical data, frequency count and percentages will be presented. 
Data listings will be provided for all participants up to the point of withdrawal, with any 
participants excluded from the relevant population highlighted. Summary statistics and statistical 
analyses will generally only be performed for participants included in the relevant analysis 
population. For the calculation of summary statistics and statistical analysis, unrounded data will 
be used. 
Mean change from baseline is the mean of all individual participants’ change from baseline 
values. Each individual change from baseline will be calculated by subtracting the individual 
participant’s baseline value from the value at the timepoint. The individual participant’s change 
from baseline values will be used to calculate the mean change from baseline using a SAS 
procedure such as PROC UNIVARIATE.
Data analysis will be performed using SAS® Version 9.4 or greater.
9.2
Demographics, Baseline Characteristics, and Participant Disposition
Participant disposition will be summarized and listed. The demographic and baseline 
characteristics variables age, sex, race, ethnicity, country of enrolment, site ID, body weight, 
height and body mass index will be summarized and listed. All other demographic variables will 
be listed only.
9.3
Pharmacokinetic Assessment
9.3.1
Pharmacokinetic Analysis
Noncompartmental methods applied with a validated software program (WinNonlin Phoenix 
v8.1 or later) to the plasma concentrations of LY573144 and its metabolite M8 will be used to 
determine the following PK parameters, when possible:


Final v1, 08 March 2021
             Page 10 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
Parameter
Units
Definition
AUC(0-tlast)
ng*h/mL
area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable concentration
AUC(0-∞)
ng*h/mL
area under the concentration versus time curve from time zero to 
infinity
%AUC(tlast-∞)
%
percentage of AUC(0-∞) extrapolated
Cmax
ng/mL
maximum observed drug concentration
tmax
h
time of maximum observed drug concentration
t1/2
h
half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
CL/F
L/h
apparent total body clearance of drug calculated after extra-vascular 
administration (not M8)
Vz/F
L
apparent volume of distribution during the terminal phase after 
extra-vascular administration (not M8)
Vss/F
L
apparent volume of distribution at steady state after extra-vascular 
administration (not M8)
Additional PK parameters may be calculated, as appropriate. The software and version used for 
the final analyses will be specified in the CSR. Any exceptions or special handling of data will 
be clearly documented within the CSR.
Formatting of tables, figures and abbreviations will follow the Eli Lilly Global PK/PD/TS Tool: 
NON-COMPARTMENTAL PHARMACOKINETIC STYLE GUIDE. The version of the tool 
effective at the time of PK analysis will be followed.
General PK Parameter Rules

Actual sampling times will be used in the final analyses of individual PK parameters, 
except for non-bolus pre-dose sampling times which will be set to zero.

Cmax and tmax will be reported from observed values. If Cmax occurs at more than 
one timepoint, tmax will be assigned to the first occurrence of Cmax. 

AUC parameters will be calculated using a combination of the linear and logarithmic 
trapezoidal methods (linear-log trapezoidal rule). The linear trapezoidal method will be 
applied up to tmax and then the logarithmic trapezoidal method will be used after tmax. The 
minimum requirement for the calculation of AUC will be the inclusion of at least three 
consecutive plasma concentrations above the LLOQ, with at least one of these 
concentrations following Cmax. AUC(0-) values where the percentage of the total area 
extrapolated is more than 20% will be flagged. Any AUC(0-) value excluded from 
summary statistics will be noted in the footnote of the summary table.

Half-life associated with the terminal rate constant (λz) in non-compartmental analysis
(t1/2) will be calculated, when appropriate, based on the apparent terminal log-linear 
portion of the concentration-time curve. The start of the terminal elimination phase for 
each participant will be defined by visual inspection and generally will be the first point 


Final v1, 08 March 2021
             Page 11 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
at which there is no systematic deviation from the log-linear decline in plasma 
concentrations. Half-life will only be calculated when a reliable estimate for this 
parameter can be obtained comprising of at least 3 data points. If t1/2 is estimated over a 
time window of less than 2 half-lives, the values will be flagged in the data listings. Any 
t1/2 value excluded from summary statistics will be documented in the footnote of the 
summary table. 

A uniform weighting scheme will be used in the regression analysis of the terminal log-
linear portion of the concentration-time curve.

The parameters based on observed Clast will be reported.
Individual PK Parameter Rules

Only quantifiable concentrations will be used to calculate PK parameters with the 
exception of special handling of certain concentrations reported below the lower limit of 
quantitation (BQL). Plasma concentrations reported as BQL will be set to a value of zero 
when all of the following conditions are met: 
o
The compound is non-endogenous.
o
The samples are from the initial dose period for a participant or from a subsequent 
dose period following a suitable wash-out period.
o
Predose concentrations > 5% Cmax will be flagged with exclusions to be noted.
o
The time points occur before the first quantifiable concentration.

All other BQL concentrations that do not meet the above criteria will be set to missing. 

Also, where two or more consecutive concentrations are BQL towards the end of a 
profile, the profile will be deemed to have terminated and therefore any further 
quantifiable concentrations will be set to missing for the calculation of the PK parameters 
unless it is considered to be a true characteristic of the profile of the drug.
Individual Concentration vs. Time Profiles

Individual concentrations will be plotted utilizing actual sampling times.

The terminal point selections will be indicated on a semi-logarithmic plot.
Average Concentration vs. Time Profiles

The average concentration profiles will be graphed using scheduled (nominal) sampling 
times. 

The average concentration profiles will be graphed using arithmetic average 
concentrations.


Final v1, 08 March 2021
             Page 12 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA

The pre-dose average concentration for single-dose data from non-endogenous 
compounds will be set to zero. Otherwise, only quantifiable concentrations will be used 
to calculate average concentrations.

Concentrations at a sampling time exceeding the sampling time window specified in the 
protocol, or ± 10%, will be excluded from the average concentration profiles.

Concentrations excluded from the mean calculation will be documented in the CSR.

A concentration average will be plotted for a given sampling time only if 2/3 of the 
individual data at the time point have quantifiable measurements that are within the 
sampling time window specified in the protocol or ± 10%. An average concentration 
estimated with less than 2/3 but more than 3 data points may be displayed on the mean
concentration plot if determined to be appropriate and will be documented within the 
CSR.
Treatment of Outliers during Pharmacokinetic Analysis
Application of this procedure to all PK analyses is not a requirement. Rather, this procedure 
provides justification for exclusion of data when scientifically appropriate. This procedure 
describes the methodology for identifying an individual value as an outlier for potential 
exclusion, but does not require that the value be excluded from analysis. The following 
methodology will not be used to exclude complete profiles from analysis.
Data within an Individual Profile
A value within an individual profile may be excluded from analysis if any of the following 
criteria are met:

For PK profiles during multiple dosing, the concentration of the pre-dose sample exceeds 
all measured concentrations for that individual in the subsequent post-dose samples.

For PK profiles during single dosing of non-endogenous compounds, the concentration in 
a pre-dose sample is quantifiable.

For any questionable datum that does not satisfy the above criteria, the profile will be 
evaluated and results reported with and without the suspected datum. 
Data between Individual Profiles
1.
If n<6, then the dataset is too small to conduct a reliable range test. Data will be analyzed 
with and without the atypical value, and both sets of results will be reported. 
2.
If n6, then an objective outlier test will be used to compare the atypical value to other 
values included in that calculation:
a.
Transform all values in the calculation to the logarithmic domain.


Final v1, 08 March 2021
             Page 13 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
b. Find the most extreme value from the arithmetic mean of the log transformed 
values and exclude that value from the dataset.
c.
Calculate the lower and upper bounds of the range defined by the arithmetic 
mean ±3*SD of the remaining log-transformed values.
d. If the extreme value is within the range of arithmetic mean ±3*SD, then it is 
not an outlier and will be retained in the dataset.
e.
If the extreme value is outside the range of arithmetic mean ±3*SD, then it is 
an outlier and will be excluded from analysis.
If the remaining dataset contains another atypical datum suspected to be an outlier and n ≥ 6 
following the exclusion, then repeat step 2 above. This evaluation may be repeated as many 
times as necessary, excluding only one suspected outlier in each iteration, until all data 
remaining in the dataset fall within the range of arithmetic mean ±3*SD of the log-transformed 
values.
Reporting of Excluded Values
Individual values excluded as outliers will be documented in the CSR. Approval of the CSR will 
connote approval of the exclusion.
9.3.2
Pharmacokinetic Statistical Methodology
Log-transformed AUC (0-∞), AUC(0-tlast), and Cmax of lasmiditan will be evaluated in a linear
mixed-effects model3 with fixed effects for period, sequence, and treatment and a random effect
for participant within sequence.
Example SAS Code:
proc mixed data = xxx;
by parameter;
class treatment period sequence participant;
model log_pk = treatment period sequence / cl residual;
random participant(sequence); 
lsmeans treatment / cl pdiff alpha = 0.1;
ods output lsmeans=lsmeans diffs=diffs;
run;
All valid PK data will be included, whether or not the participants completed all 3 periods.
Estimates of geometric least square (LS) mean ratios together with the corresponding 90% CIs 
will be derived for the comparisons of AUC (0-∞), AUC(0-tlast), and Cmax as follows:

Primary endpoint: lasmiditan OD tablet without water (test) versus lasmiditan IR tablet

Secondary endpoint: lasmiditan OD tablet with water (test) versus lasmiditan IR tablet.


Final v1, 08 March 2021
             Page 14 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
The 2 lasmiditan formulations will be considered bioequivalent if the 90% CIs of the ratio of
geometric LS means of AUC (0-∞), AUC(0-tlast), and Cmax falls completely within 0.80 to 1.25.
Values of tmax will be analyzed non-parametrically using the Wilcoxon signed rank4 test.
Estimates of the median difference between test and reference formulations based on the
observed medians, 90% CIs, and the p-value from the Wilcoxon test will be calculated.
Additional PK analyses may be conducted if deemed appropriate.
9.4
Safety and Tolerability Assessments
9.4.1
Adverse events
Where changes in severity are recorded in the Case Report Form (CRF), each separate severity 
of the AE will be reported in the listings, only the most severe will be used in the summary 
tables. A pre-existing condition is defined as an AE that starts before the participant has provided 
written informed consent and is ongoing at consent. A non-treatment emergent AE is defined as 
an AE which starts after informed consent but prior to the first dose. A TEAE is defined as an 
AE which occurs postdose or which is present prior to dosing and becomes more severe 
postdose. 
All AEs will be listed. TEAEs will be summarized by treatment, severity and relationship to the 
study drug. The frequency (the number of AEs, the number of participants experiencing an AE
and the percentage of participants experiencing an AE) of TEAEs will be summarized by 
treatment, Medical Dictionary for Regulatory Activities (MedDRA) version 23.0 system organ 
class and preferred term. The summary and frequency AE tables will be presented for all 
causalities and those considered related to the study drug by the investigator. Any SAEs will be 
listed. 
Discontinuations due to AEs will be listed.
9.4.2
Concomitant medication
Concomitant medication will be coded using the WHO drug dictionary (Version MAR20B3). 
Concomitant medication will be listed.
9.4.3
Clinical laboratory parameters
All clinical chemistry, hematology, and urinalysis data will be listed. Additionally, clinical 
chemistry, hematology and urinalysis data outside the reference ranges will be listed and flagged 
on individual participant data listings.
9.4.4
Vital signs
Vital signs data will be summarized by treatment together with changes from baseline, where 
baseline is defined as the Day 1 predose assessment within each period. Figures of mean vital 
signs and mean changes from baseline profiles will be presented by treatment. 


Final v1, 08 March 2021
             Page 15 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
Values for individual participants will be listed.
9.4.5
Electrocardiogram
All ECGs will be performed for safety monitoring purposes only and will not be presented. Any 
clinically significant findings from ECGs will be reported as an AE.
9.4.6      Product Acceptability and Palatability Analyses
Participants will be asked to provide responses to questions designed to assess the acceptability 
and palatability of the OD tablet when administered with and without water. The questionnaire 
will be completed by the participant immediately after administration of the OD tablet both with 
and without water, and will assess the participants’ experience relating to the taste, smell, 
mouthfeel, aftertaste, and the approximate disintegration time of the OD tablet in the oral cavity. 
Responses from the product acceptability and palatability questionnaire will be summarized 
categorically (frequency and percentage) by treatment, and listed. 
9.4.7
Hepatic Monitoring
Close hepatic monitoring
If a participant who had normal or near normal baseline alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBL) (i.e., 
<1.5× upper limit of normal [ULN]), experiences elevated ALT≥3× ULN, AST≥3× ULN, 
ALP≥2× ULN, or TBL≥2× ULN, laboratory tests should be repeated within 48 to 72 hours, 
including ALT, AST, ALP, TBL, direct bilirubin, gamma-glutamyltransferase, and creatinine 
kinase to confirm the abnormality and to determine if it is increasing or decreasing.
In participants enrolled with elevated baseline ALT, AST, ALP or TBL (≥1.5× ULN), the 
thresholds for close monitoring are ALT≥2× baseline, AST≥2× baseline, ALP≥2× baseline, or 
TBL≥2× baseline.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, including symptoms, recent illnesses, (for example, heart failure, systemic infection, 
hypotension, or seizures), recent travel, history of concomitant medications (including 
over-the-counter), herbal and dietary supplements, history of alcohol drinking and other 
substance abuse.
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated medical monitor.
Comprehensive hepatic evaluation
If a study participant, who had baseline ALT, AST, ALP, TBL<1.5× ULN, experiences elevated 
ALT≥5× ULN, AST≥5× ULN, ALP ≥3× ULN, TBL ≥2× ULN, or elevated ALT, AST ≥3× ULN 
with hepatic signs/symptoms (severe fatigue, nausea, vomiting, right upper quadrant abdominal 


Final v1, 08 March 2021
             Page 16 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
pain, fever, rash, and/or eosinophilia>5%), a comprehensive evaluation should be performed to 
search for possible causes of liver injury.
In participants who had elevated baseline ALT, AST, ALP, or TBL (≥1.5× ULN), the thresholds 
for performing this evaluation are ALT≥3× baseline, AST≥3× baseline, ALP≥2× baseline, 
TBL≥1.5× baseline, or ALT, AST ≥2× baseline with hepatic signs/symptoms.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-international normalized ratio, 
viral hepatitis A, B, C, E, tests for autoimmune hepatitis, and an abdominal imaging study (for 
example, ultrasound or computed tomography scan).
Additional hepatic data collection in participants who have abnormal liver tests during the 
study
Additional hepatic safety data collection should be performed in participants who meet 1 or more 
of the following 5 conditions:
1. Elevation of serum ALT to ≥5× ULN on 2 or more consecutive blood tests (if baseline 
ALT<1.5x ULN)
In participants with baseline ALT≥1.5× ULN, the threshold is ALT≥3x baseline 
on 2 or more consecutive tests
2. Elevation of TBL to ≥2× ULN (if baseline TBL <1.5× ULN)
In participants with baseline TBL ≥1.5× ULN, the threshold should be TBL ≥2x 
baseline
3. Elevation of serum ALP to ≥2× ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5× ULN)
In participants with baseline ALP≥1.5× ULN, the threshold is ALP ≥2× baseline 
on 2 or more consecutive blood tests
4. Hepatic event considered to be an SAE
5. Discontinuation of the investigational product due to a hepatic event.
Where applicable, the following will be presented. The participants’ liver disease history and 
associated person liver disease history data will be listed. Any concomitant medications that have 
potential for hepatotoxicity, including acetaminophen will be listed. Results from any hepatic 
monitoring procedures, such as a magnetic resonance elastography scan, and biopsy assessments 
will be listed, if performed.
Hepatic risk factor assessment data will be listed. Liver related signs and symptoms data will be 
summarized by treatment and listed. Alcohol and recreational drug use data will also be listed.
All hepatic chemistry, hematology, coagulation, and serology data will be listed. Values outside 
the reference ranges will be flagged on the individual participant data listings.


Final v1, 08 March 2021
             Page 17 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
9.4.8
Other assessments
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed.
9.4.9
Safety and Tolerability Statistical Methodology
No inferential statistical analyses are planned.
10.
INTERIM ANALYSES
No interim statistical analyses are planned.
11.
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES
There were no changes from the protocol specified statistical analyses.
12.
REFERENCES
1. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998.
2. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995.
3. Brown H, Prescott R. Applied Mixed Models in Medicine. Chichester: John Wiley & Sons, 
1999.
4. Lehmann EL. Nonparametrics: Statistical Methods Based on Ranks. San Francisco, CA: 
Holden-Day; 1975.
13.
DATA PRESENTATION
13.1
Derived Parameters
Individual derived parameters (e.g. PK parameters) and appropriate summary statistics will be 
reported to three significant figures. Observed concentration data, e.g. Cmax, should be reported 
as received. Observed time data, e.g. tmax, should be reported as received. N and percentage 
values should be reported as whole numbers. Median values should be treated as an observed 
parameter and reported to the same number of decimal places as minimum and maximum values.
13.2
Missing Data
Missing data will not be displayed in listings.


Final v1, 08 March 2021
             Page 18 of 18
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8447232 
Sponsor Reference H8H-MC-LAIA
13.3
Insufficient Data for Presentation
Some of the TFLs may not have sufficient numbers of participants or data for presentation. If 
this occurs, the blank TFL shell will be presented with a message printed in the center of the 
table, such as, “No serious adverse events occurred for this study.”


Leo Document ID = 2049b77a-30e0-4d19-955c-ed1c7f41d078
Approver: 
Approval Date & Time: 09-Mar-2021 09:41:39 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 09-Mar-2021 12:34:43 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 09-Mar-2021 15:44:48 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 10-Mar-2021 15:20:55 GMT
Signature meaning: Approved
PPD
PPD
PPD
PPD