Clinical trial NCT03040479
Conditions: Migraine
Sponsor: Eli Lilly and Company
Start date: 2017-03-14; Completion date: 2017-07-17
Enrollment: 24 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, open-label, non-randomized, parallel-group, single dose study. This study will enroll up to 24 participants and will include 2 hepatic impaired participant groups and one group of control participants with normal hepatic function.

Detailed description:
This study will enroll up to 24 participants and will include 2 hepatic impaired participant groups and one group of control participants with normal hepatic function. Approximately four participants with mild hepatic impairment will be enrolled first (Group 1). To ensure participant safety, following dosing of these first four participants, a safety meeting will take place to review the safety data prior to dosing additional participants. After safety and pharmacokinetic (PK) results from the first four participants have been reviewed, an additional four participants with mild hepatic impairment (remainder of Group 1) will be enrolled concurrently with the moderate hepatic impairment group (Group 2). Thereafter, matched participants with normal hepatic function (Group 3) will be enrolled. All participants will participate in one treatment period and will receive a single dose of lasmiditan in the fasting state.

Arms: arm 1: lasmiditan 200 mg single dose arm 2: lasmiditan 200 mg single dose arm 3: lasmiditan 200 mg single dose
Interventions: intervention 1: lasmiditan 200 mg
Intervention descriptions: intervention 1: single dose

Protocol documents:
Prot_000.pdf: 
Protocol H8H-CD-LAHF  
 
 
A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral 
Lasmiditan in Subjects with Normal and Impaired Hepatic Function 
 
NCT03040479 
 
Approval Date: 09-Jan-2016 
 
 
 


Clinical Study Report  
Project No COL MIG-114/H8H-CD-LAHF 
16.1 
STUDY INFORMATION 
16.1.1 
Protocol and Protocol Amendments 
Original Protocol CUD-P9-453 (COL MIG-114) 


 
A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study 
of Oral Lasmiditan in Subjects with Normal and Impaired Hepatic Function 
Protocol Number: 
CUD-P9-453 (COL MIG-114) 
Investigational Product: 
Lasmiditan 
Sponsor: 
CoLucid Pharmaceuticals, Inc. 
222 Third Street 
Suite 1320 
Cambridge, MA, USA, 02142 
Sponsor’s contact person: 
 
 
Tel. 
 
Cell. 
 
Email. 
 
Protocol Version 
Date 
1.0 
Original 
2017/01/09 
COMPLIANCE 
The study will be conducted in accordance with standards of Good Clinical Practice, as defined 
by the International Conference on Harmonisation and all applicable federal and local 
regulations. 
CONFIDENTIALITY STATEMENT 
The information provided in this document is strictly confidential and is available for review to investigator(s) 
and to the appropriate Independent Ethics Committee (IEC) or Institutional Review Board (IRB). It may not be 
used, divulged, published or otherwise disclosed without the written authorization from Algorithme Pharma or 
the Sponsor. 
Algorithme Pharma 
Head Office 
575 Armand-Frappier  
Blvd. 
Laval (Quebec) H7V 4B3 
Canada 
www.algopharm.com 
Tel. : 
 
Fax : 
 
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TABLE OF CONTENTS 
1.
INTRODUCTION .............................................................................................................................................. 14 
1.1. Background ................................................................................................................................................... 14 
1.2. Nonclinical Studies ....................................................................................................................................... 14 
1.3. Pharmacokinetics .......................................................................................................................................... 14 
1.4. Clinical Information ...................................................................................................................................... 15 
1.5. Study Rationale ............................................................................................................................................. 15 
2.
STUDY OBJECTIVES ...................................................................................................................................... 15 
2.1. Primary Objective ......................................................................................................................................... 15 
2.2. Secondary Objectives .................................................................................................................................... 15 
3.
STUDY DESIGN ................................................................................................................................................ 15 
3.1. General Study Design .................................................................................................................................... 15 
3.2. Number of Centers and Subjects ................................................................................................................... 16 
3.3. Schedule of Drug Administration .................................................................................................................. 16 
4.
SUBJECT SELECTION .................................................................................................................................... 17 
4.1. Study Population ........................................................................................................................................... 17 
4.2. Inclusion Criteria ........................................................................................................................................... 17 
4.3. Exclusion Criteria .......................................................................................................................................... 18 
4.4. Withdrawal Criteria ....................................................................................................................................... 21 
5.
STUDY TREATMENTS .................................................................................................................................... 22 
5.1. Description and Handling of Study Treatments ............................................................................................ 22 
5.1.1. Formulation of Test Product .................................................................................................................. 22 
5.1.2. Packaging and Labeling ......................................................................................................................... 22 
5.1.3. Storage and Handling ............................................................................................................................. 23 
5.2. Method of Assigning Subjects to Treatment Groups .................................................................................... 23 
5.3. Blinding ......................................................................................................................................................... 23 
5.4. Dosing and Administration ........................................................................................................................... 23 
5.4.1. Dispensing .............................................................................................................................................. 23 
5.4.2. Administration Instructions .................................................................................................................... 23 
5.4.3. Treatment Compliance ........................................................................................................................... 24 
5.4.4. Study Drug Accountability..................................................................................................................... 24 
5.5. Prior and Concomitant Medication ............................................................................................................... 24 
5.6. Study-Specific Restrictions ........................................................................................................................... 25 
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6.
STUDY PROCEDURES AND GUIDELINES................................................................................................. 25 
6.1. Study Procedures ........................................................................................................................................... 30 
6.1.1. Physical Examination ............................................................................................................................. 30 
6.1.2. C-SSRS Questionnaire ........................................................................................................................... 30 
6.1.3. Vital Signs .............................................................................................................................................. 30 
6.1.4. Laboratory Evaluations .......................................................................................................................... 30 
6.1.4.1. Pregnancy Tests .............................................................................................................................. 31 
6.1.5. 12-Lead Electrocardiogram .................................................................................................................... 31 
6.1.6. Follow-up Call ....................................................................................................................................... 31 
6.1.7. Pharmacokinetic Sampling ..................................................................................................................... 31 
6.1.7.1. Sample processing, storage and shipping ........................................................................................ 32 
6.2. Bioanalytical Methods ................................................................................................................................... 32 
6.2.1. Aberrant values and retested samples .................................................................................................... 32 
6.2.2. Incurred sample reproducibility ............................................................................................................. 32 
6.3. Pharmacokinetic Measurements .................................................................................................................... 32 
7.
ADVERSE EVENTS .......................................................................................................................................... 33 
7.1. Definitions ..................................................................................................................................................... 33 
7.1.1. Severity Assessment ............................................................................................................................... 34 
7.1.2. Causality Assessment ............................................................................................................................. 35 
7.2. Routine Reporting ......................................................................................................................................... 35 
7.3. Serious Adverse Event Reporting ................................................................................................................. 36 
8.
STATISTICAL ANALYSIS .............................................................................................................................. 37 
8.1. Analysis Sets ................................................................................................................................................. 37 
8.1.1. Safety Analysis Set ................................................................................................................................ 37 
8.1.2. Pharmacokinetic Analysis Set ................................................................................................................ 37 
8.2. Sample Size Determination ........................................................................................................................... 38 
8.3. Statistical Analysis ........................................................................................................................................ 38 
8.3.1. Descriptive Analysis .............................................................................................................................. 38 
8.3.1.1. Safety Analyses ............................................................................................................................... 38 
8.3.1.2. Pharmacokinetic Endpoint Analyses ............................................................................................... 38 
8.3.2. Statistical Methodology ......................................................................................................................... 38 
8.3.2.1. Interim Analysis .............................................................................................................................. 39 
9.
ETHICS ............................................................................................................................................................... 39 
9.1. Institutional Review Board (IRB) ................................................................................................................. 39 
9.2. Ethical Conduct of the Study ......................................................................................................................... 39 
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9.3. Participant Information and Consent ............................................................................................................. 39 
9.4. Subject Confidentiality .................................................................................................................................. 40 
10. DATA COLLECTION, RETENTION, AND MONITORING ...................................................................... 40 
10.1. Case Report Forms ........................................................................................................................................ 40 
10.2. Data Management and Processing ................................................................................................................. 40 
10.3. Quality Assurance ......................................................................................................................................... 40 
10.4. Record Retention ........................................................................................................................................... 41 
10.5. Monitoring of the Study ................................................................................................................................ 41 
11. ADMINISTRATIVE PROCEDURES .............................................................................................................. 41 
11.1. Adherence to Protocol ................................................................................................................................... 41 
11.2. Investigator Responsibilities ......................................................................................................................... 41 
11.3. Delegation of Investigator Duties .................................................................................................................. 41 
11.4. Premature Termination or Suspension of a Study ......................................................................................... 42 
11.5. Clinical Trial Application (CTA) .................................................................................................................. 42 
11.6. Exemption Application for Controlled Substances ....................................................................................... 42 
11.7. Publications ................................................................................................................................................... 42 
12. REFERENCES ................................................................................................................................................... 43 
13. Appendix A ......................................................................................................................................................... 44 
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LIST OF IN-TEXT TABLES 
Table 1: Formulation of Lasmiditan, 200 mg Tablets .................................................................. 22
Table 2. Schedule of Assessments for All Subjects ...................................................................... 27
Table 3. Schedule of Pharmacokinetic Assessments .................................................................... 29
Table 4. Pharmacokinetic Parameters ........................................................................................... 33
Table 5. Adverse Event Relationship to Study Drug .................................................................... 35
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STUDY SYNOPSIS 
Name of Sponsor/Company: 
CoLucid Pharmaceuticals, Inc. 
Name of product: 
Lasmiditan 
Title of Study: 
A Phase I, Multicenter, Open-Label, Parallel-Group, 
Pharmacokinetic Single Dose Study of Oral Lasmiditan in Subjects 
with Normal and Impaired Hepatic Function 
Study Development Phase: 
Phase I 
Objectives: 
The primary objective of this study is to evaluate the 
pharmacokinetic profile of lasmiditan following a single oral 
200 mg dose in subjects with mild and moderate hepatic function 
relative to matched, healthy control subjects with normal hepatic 
function. 
The secondary objective of this study is to assess the safety and 
tolerability of a single oral 200 mg dose of lasmiditan in subjects 
with normal, mild and moderate hepatic function. 
Test product: 
Lasmiditan 200 mg tablets 
Dose and Mode of 
Administration: 
Single dose of 200 mg of lasmiditan administered orally. 
Study Design: 
This is a multicenter, open-label, non-randomized, parallel-group, 
single dose study. 
This study will enroll up to 24 subjects and will include 
2 hepatic-impaired subject groups and one group of control subjects 
with normal hepatic function. 
Approximately four subjects with mild hepatic impairment will be 
enrolled first (Group 1). To ensure subject safety, following dosing 
of these first four subjects, a safety meeting will take place to 
review the safety data prior to dosing additional subjects. After 
safety and PK results from the first four subjects have been 
reviewed, an additional four subjects with mild hepatic impairment 
(remainder of Group 1) will be enrolled concurrently with the 
moderated hepatic impairment group (Group 2). Thereafter, 
matched subjects with normal hepatic function (Group 3) will be 
enrolled. 
All subjects will participate in one treatment period and will receive 
a single dose of lasmiditan in the fasting state. 
Subjects will be confined to the clinic from at least 10 hours prior to 
dosing until 36 hours after drug administration. 
Duration of Study: 
Up to 35 days including Screening. 
Study Population: 
Male and female adult subjects with normal hepatic function and 
male and female adult patients with mild or moderate hepatic 
impairment. Hepatic impairment will be classified using Child-
Pugh scores as follows: 
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5 to 6 points = Class A, mild hepatic impairment (Group 1); 
7 to 9 points = Class B, moderate hepatic impairment (Group 2); 
Normal hepatic function will be included in Group 3. 
Planned Number of Subjects: 
The study is planned to enroll up to 24 subjects: 8 subjects with 
mild hepatic impairment, 8 subjects with moderate hepatic 
impairment, and 8 healthy subjects with normal hepatic function. 
Subjects with moderate hepatic impairment will be enrolled as 
determined by review of safety data from the previously dosed 
group. 
Main Criteria for Inclusion: 
Male or female aged  ≥ 18 years 
Body mass index  ≥ 18.50 kg/m2 
Non clinical significant findings on 12-lead electrocardiogram 
(ECG) 
For females, negative result on a pregnancy test 
Group 1 (Mild Hepatic Impairment) 
Presence of mild hepatic impairment (Child-Pugh Class A) 
Group 2 (Moderate Hepatic Impairment) 
Presence of moderate hepatic impairment (Child-Pugh Class B) 
Group 3 (Normal Hepatic Function) 
Subjects will be matched by age (±10 years), weight (±20%), and 
gender to the pooled mean values of subjects with hepatic 
impairment. 
Hepatic function will be classified once at the Screening Visit, 
using the Child-Pugh score for each subject. 
Procedures and Assessments 
Safety evaluations including vital signs (body temperature, pulse 
rate and blood pressure), physical exams, safety laboratory tests 
(clinical chemistry, hematology, endocrinology, urinalysis, 
pregnancy test, drug, and alcohol screen), ECGs, adverse event 
(AE) collection, and concomitant medication recording will be 
conducted prior to and during the treatment period. 
Pharmacokinetic (PK) blood samples will be collected at predose 
and for 36 hours after dosing on Day 1; 18 PK blood samples will 
be obtained from each patient/subject. 
Criteria for Evaluation: 
Safety: 
Safety will be evaluated by assessment of 12-lead safety ECGs, 
measurements of vital signs, physical examination and clinical 
laboratory tests at baseline and at various time points during the 
study, and by the documentation of adverse events/concomitant 
medication. 
Pharmacokinetics: 
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The following plasma PK parameters of lasmiditan will be 
calculated: Cmax, Tmax, AUC0-T, AUC0-∞, AUC0-T/∞, λz, Thalf, ClTOT/F 
and VD/F. 
Statistical Analyses: 
Safety data will be listed by subject and summarized by hepatic 
function group using frequency of event/abnormality or descriptive 
statistical summaries, as appropriate. 
PK parameters will be listed and summarized by hepatic function 
group using descriptive statistics. Mean and individual plasma 
concentration-time profiles will be presented graphically. 
A regression analysis in which the Child-Pugh classification and the 
pharmacokinetic parameters are treated as continuous variables will 
be used to evaluate the relationship between hepatic function and 
the estimated pharmacokinetic parameters of lasmiditan. 
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LIST OF ABBREVIATIONS 
Term 
Definition 
AE 
Adverse event 
ANOVA 
Analysis of variance 
AUC 
Area under the curve 
BLQ 
Below the limit of quantification 
Cmax 
Maximum observed concentration 
CL 
Clearance 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CV 
Coefficient of variation 
EOI 
End of infusion 
GeoCV% 
Percent geometric coefficient of variation 
GeoMean 
Geometric mean 
λZ 
Apparent terminal elimination rate constant 
LLOQ 
Lower limit of quantification 
MTD 
Maximum tolerated dose 
Min 
Minimum 
Max 
Maximum 
n 
Number of Observations 
NCA 
Noncompartmental analysis 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
QA 
Quality assurance 
QC 
Quality control 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SEM 
Standard error of the mean 
SOP 
Standard Operating Procedure 
Thalf 
Apparent terminal elimination half-life 
Tmax 
Time to peak concentration 
U.S. 
United States 
 
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FACILITIES 
AUTHOR OF THE PROTOCOL: 
 
 
Algorithme Pharma 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
COORDINATING PRINCIPAL INVESTIGATOR: 
 
 
Algorithme Pharma 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
Phone: 
 
PRINCIPAL INVESTIGATOR: 
 
New Orleans Center for Clinical Research 
1928 Alcoa Highway, Suite 107  
Knoxville, TN 37920 
 
 
Orlando Clinical Research Center 
5055 South Orange Ave. 
Orlando, FL 32809 
 
MEDICAL LABORATORY*: 
Dynacare Solutions Santé 
4850 Dobrin St. 
Montreal, Quebec, Canada 
H4R 2P8 
Orlando Regional Medical Center Clinical Lab 
1414 Kuhl Ave  
Orlando FL 32809 
Laboratory Corporation of America (LapCorp) 
1924 Alcoa Highway 
Knoxville, TN 37920 
*Samples may be outsourced to affiliated accredited laboratory facilities, if necessary. 
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BIOANALYTICAL FACILITY:  
Covance Laboratories 
3301 Kinsman Blvd, 
Madison, WI 53704, USA 
 
SCIENTIFIC AND REGULATORY FACILITY: 
 
Algorithme Pharma 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
PROJECT MANAGEMENT: 
 
Algorithme Pharma 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
STATISTICAL FACILITY: 
 
 
Algorithme Pharma 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
DATA MANAGEMENT FACILITY: 
 
Algorithme Pharma 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
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Research Protocol N° CUD-P9-453 
Sponsor Project N° COL MJG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9-453 
Sponsor Project No COL-MIG-114 
.., Altasciences 
~ CLINICAL RESEARCH 
'-,!. ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDIT AN IN SUBJECTS 
WITH NORMAL AND IMP 
AIRED HEPATIC FUNCTION 
We have read this study protocol and agree that it contains all necessary information required to 
conduct this study. We agree to conduct the study according to this protocol and in accordance 
with Good Clinical Practices and the applicable regulatory requirements: 
 
Coordinating Principal Investigator 
Altascieoces Company Inc. ( 
doing business as Algorithme Pharma) 
 
Principal Investigator 
New Orleans Center for ClinfoaJ Research 
 
Principal Investigator 
Orlando Clinical Research Center 
Al'"" ciences Company Inc. (doing business as AJgorithme Pharma) 
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Research Protocol N° CUD-P9-453 
Sponsor Project N1 COL MIG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9-453 
Sponsor Project No COL-MIG-114 
-, Altasciences 
~ CLINICAL RESEARCH 
u ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDITAN IN SUBJECTS 
WITH NORMAL AND IMPAIRED HEPATIC FUNCTION 
We have read this study protocol and agree that it contains all necessary information required to 
conduct this study. We agree to conduct the study according to this protocol and in accordance 
with Good Clinical Practices and the applicable regulatory requirements: 
 
,
Coordinating Principal Investigator 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
 
Principal Investigator 
New Orleans Center for Clinical Research 
 
Principal Investigator 
Orlando Clinical Research Center 
 
 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
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Research Protocol N° CUD-P9-453 
Sponsor Project f
f
 
COL.MIG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9-453 
Sponsor Project No COL-MIG-114 
Altasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDIT AN IN SUBJECTS 
WITH NORMAL AND IIYIPAIRED HEPATIC FUNCTION 
We have read this study protocol and agree that it contains all necessary information required to 
conduct this study. We agree to conduct the study according to this protocol and in accordance 
with Good Clinical Practices and the applicable regulatory requirements: 
 
 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
New Orleans Center for Clinical Research 
 
 
Orlando Clinical Research Center 
 
 
Altasciences Company Inc. (doing business as Algorithme Pharma) 
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Research Protocol N° CUD-P9-453 
Sponsor Project N' COLMIG-114 
PROTOCOL APPROVAL 
RESEARCH PROTOCOL NUMBER: CUD-P9--453 
Sponsor Project No COL-MIG-114 
-, A 
ltasciences 
CLINICAL RESEARCH 
ALGORITHME PHARMA 
TITLE: A PHASE I, MULTICENTER, OPEN-LABEL, PARALLEL-GROUP, 
PHARMACOKINETIC SINGLE DOSE STUDY OF ORAL LASMIDIT AN IN SUBJECTS 
WITH NORMAL AND IMP 
AIRED HEPA TIC FUNCTION 
On behalf of the Sponsor, I am aware of, and agree to comply with, all of the procedures 
contained within this protocol: 
Digitally signed by Bernice Kuca 
ON: cn=Bernlce 
Kuca, o=CoLucld 
Pharmaceuticals, Inc, ou, 
email=bkuca@colucid.com, e=US 
Oate:2017.01.3117:51:15-05'00' 
 
Date (yyyy/mm/dd) 
 
CoLucid Pharmaceuticals, Inc. 
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1. INTRODUCTION 
1.1. Background 
CoLucid Pharmaceuticals, Inc. (CoLucid) is developing lasmiditan (COL-144), a small molecule 
5-HT1F receptor agonist. The chemical name of lasmiditan (COL-144) is 2,4,6-trifluoro-N-[6-(1-
methylpiperidine-4-carbonyl)pyridine-2-yl]benzamide hemisuccinate. 
Triptans, which are 5-HT1B/1D receptor agonists, are well established as an acute therapy for 
migraine, though they are not effective in all patients or attacks. Triptans were developed as 
cerebral vasoconstrictors, mediated via their affinity for 5-HT1B receptors located on vascular 
smooth muscle. Inherent in this mechanism of action is a liability for coronary vasoconstriction, 
and therefore, triptans are contraindicated in patients with cardiovascular disease. 
1.2. Nonclinical Studies 
Unlike triptans, lasmiditan is a highly selective and potent agonist at the 5-HT1F receptor with 
>470-fold higher affinity for the 5-HT1F receptor than for 5-HT1B/1D receptors. In preclinical 
models (rodent) of relevance to migraine, agonists selective for 5-HT1F receptors inhibited 
trigeminal nociceptive processing without affecting blood vessel tone. Unlike triptans, lasmiditan 
did not constrict rabbit saphenous vein, an assay predictive of human coronary artery 
constriction. Lasmiditan is under development as a neurally acting treatment for migraine 
without the vasoconstrictor liability of triptans. 
Safety pharmacology studies (central nervous system [CNS] respiratory, cardiovascular, and 
renal) employing single intravenous (IV) administration of lasmiditan indicated that 
administration of lasmiditan at the intended clinically effective exposure levels is unlikely to 
produce adverse effects on cardiovascular, respiratory or renal function. Based on observations 
in mice, the neural mechanism of action of lasmiditan may, with exposure to high doses, produce 
CNS effects such as increased sensitivity to auditory stimuli, analgesia, reduced activity, 
hypothermia, and anticonvulsant activity. However, there have been no comparable observations 
in clinical studies, apart from alleviation of headache pain. 
1.3. Pharmacokinetics 
Cmax and AUC for subjects dosed orally (200 mg) were also measured in a fed/fasted study (COL 
MIG-104). During fed conditions (394.7 ng/mL and 2244 ng*h/mL, respectively) PK parameters 
were slightly increased compared to the fasted condition (322.8 ng/mL and 1892 ng*h/mL, 
respectively). Hence, food had a minor effect on the PK of lasmiditan. 
The plasma clearance (~59 L/h IV and 160 L/h oral), and the high total volume of distribution 
(~300 L for IV and 1016 L for oral), indicated extensive distribution. There were no significant 
effects of gender or body weight on PK parameters. 
In vitro and in vivo metabolism studies have shown that the metabolic pathways of lasmiditan 
include N-oxidation, N-dealkylation, carbonyl oxidation, desaturation of the piperidine moiety, 
ketoreduction, or a combination of each. Up to 12 metabolites have been detected in human 
hepatocytes, of which none were unique to human. When examined in vivo using LC-MS/MS 
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analysis of human plasma samples from subjects receiving oral lasmiditan, three major 
metabolites (M7, M8, and (S,R)-M18) were detected. The relative proportions of metabolites to 
intact lasmiditan remained reasonably constant throughout the oral dose range studied and their 
PK were approximately linear. 
The half-life of the metabolites fell into two categories; the non-reduced metabolites with a half-
life similar to or only slightly longer than intact lasmiditan (~4.5 h), and the reduced metabolites 
with a half-life distinctly longer (>12 h) than that of lasmiditan. 
1.4. 
Clinical Information  
Five Phase 1 studies of lasmiditan have been completed in Europe using IV, sublingual, and oral 
formulations of lasmiditan in 213 healthy subjects. Two European Phase 2 studies have been 
completed with lasmiditan in the acute treatment of migraine. COL MIG-301 (SAMURAI) the 
first of two, Phase 3 randomized, double-blind, placebo controlled trials has completed in the 
United States. The second confirmatory study, COL MIG-302 (SPARTAN), is ongoing in the 
US, UK and Germany along with COL MIG-305, the open-label year long dosing study. 
Further information on the lasmiditan formulation, animal studies, and human studies can be 
found in the current Investigator’s Brochure. 
1.5. Study Rationale 
Lasmiditan is excreted through the kidneys and seems to have significant extrahepatic 
metabolism. This study was designed to evaluate the effects of impaired hepatic function on 
lasmiditan PK parameters, and on its safety. 
Results of this study may provide information on lasmiditan dosing recommendations in patients 
with hepatic impairment. 
2. STUDY OBJECTIVES 
2.1. Primary Objective 
The primary objective of this study is to evaluate the pharmacokinetic profile of lasmiditan 
following a single oral 200 mg dose in subjects with mild and moderate hepatic function relative 
to matched, healthy controls with normal hepatic function. 
2.2. Secondary Objectives 
The secondary objective of this study is to assess the safety and tolerability of a single oral 
200 mg dose of lasmiditan in subjects with normal, mild and moderate hepatic function. 
3. STUDY DESIGN 
3.1. General Study Design 
This is a multi-center, open-label, non-randomized, parallel-group, single dose study.  
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This study will enroll up to 24 subjects and will include 2 hepatic impaired subject groups and 
one group of control subjects with normal hepatic function. 
Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion 
criteria and none of the exclusion criteria will be entered in the study. 
Approximately four subjects with mild hepatic impairment will be enrolled first (Group 1). To 
ensure subject safety, following dosing of these first four subjects, a safety meeting will take 
place to review the safety data prior to dosing additional subjects. After safety and PK results 
from the first four subjects have been reviewed, an additional four subjects with mild hepatic 
impairment (remainder of Group 1) will be enrolled concurrently with the moderated hepatic 
impairment group (Group 2). Thereafter, matched subjects with normal hepatic function (Group 
3) will be enrolled. There will be up to 8 subjects in each of the following groups, based on 
hepatic function at screening: 
 Group 1: Mild hepatic impairment subjects (Child-Pugh Class A: 5 to 6 points) 
 Group 2: Moderate hepatic impairment subjects (Child-Pugh Class B: 7 to 9 points) 
 Group 3: Healthy subjects with normal hepatic function 
 
All subjects will participate in one treatment period and will receive a single dose of lasmiditan 
in the fasting state.  
Subjects will be confined to the clinic from at least 10 hours prior to dosing until 36 hours after 
drug administration. 
The total duration of each subject’s participation in the study will be 3 days (Day –1 through the 
last PK sample taken on Day 2), not including the screening and follow-up phone call. 
3.2. Number of Centers and Subjects 
The study is planned to enroll up to 24 subjects in 3 centers. Up to eight subjects will be enrolled 
in each group. Subjects who withdraw from the study may be replaced. Replacement subjects 
will be not enrolled for subjects who discontinue the study due to treatment-related AEs. 
An effort will be made to include subjects with high BMI, moreover, an effort will be made to 
enroll more females than males (for an approximate ratio of 60%/40%) or at least 50%/50%. 
3.3. Schedule of Drug Administration 
The following treatment regimen will be used: 
 Experimental treatment: Lasmiditan 200 mg 
The total duration of the study is expected to be 35 days, including screening. 
The study may be stopped or interrupted at any time for safety, PK, or administrative reasons. 
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4. SUBJECT SELECTION 
4.1. Study Population 
Subjects who meet all the inclusion criteria and none of the exclusion criteria will be eligible for 
participation in this study. A signed copy of the informed consent form will be provided to each 
subject. 
4.2. Inclusion Criteria 
All subjects: 
1. Availability for the entire study period 
2. Motivated volunteer and absence of intellectual problems likely to limit the validity of 
consent to participate in the study or the compliance with protocol requirements; ability 
to cooperate adequately; ability to understand and observe the instructions of the 
physician or designee 
3. Male or female volunteer 
4. A female volunteer must meet one of the following criteria: 
- 
If of childbearing potential – agrees to use one of the accepted contraceptive regimens 
from at least 28 days prior to the drug administration, during the study and for at least 
60 days after the dose. An acceptable method of contraception includes one of the 
following: 
 Abstinence from heterosexual intercourse 
 Systemic contraceptives (birth control pills, injectable/implant/insertable 
hormonal birth control products, transdermal patch) 
 Intrauterine device (with or without hormones) 
 Condom with spermicide or condom with intra-vaginally applied spermicide 
- 
If of non-childbearing potential – should be surgically sterile (i.e. has undergone 
complete hysterectomy, bilateral oophorectomy, or tubal ligation) or in a menopausal 
state (at least one year without menses) 
5. A male volunteer with sexual partners who are pregnant, possibly pregnant, or who could 
become pregnant must meet the following criteria: 
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- 
Participant is unable to procreate, defined as surgically sterile (i.e. has undergone a 
vasectomy within the last 6 months) 
- 
Participant is apt to procreate and agrees to use one of the accepted contraceptive 
regimens from first drug administration until 3 months after the drug administration. 
An acceptable method of contraception includes one of the following: 
 Abstinence from heterosexual intercourse. 
 Condom with spermicide or condom with intra-vaginally applied spermicide 
6. A male volunteer agrees to refrain from sperm donation from drug administration until 
90 days after the drug administration 
7. Volunteer aged of at least 18 years 
8. Volunteer with a body mass index (BMI) ≥18.5 kg/m2 
9. Light-, non- or ex-smokers. A light smoker is defined as someone smoking 10 cigarettes 
or less per day for at least 3 months before Day 1 of this study. An ex-smoker is defined 
as someone who completely stopped smoking for at least 6 months before Day 1 of this 
study 
10. Willingness to adhere to the protocol requirements as evidenced by the informed consent 
form (ICF) duly read, signed and dated by the volunteer 
Subjects with Normal Hepatic Function: 
11. Clinical laboratory values within the laboratory's stated normal range; if not within this 
range, these must be without any clinical significance 
12. Have no clinically significant diseases captured in the medical history or evidence of 
clinically significant findings on physical examination and/or clinical laboratory 
evaluations (hematology, general biochemistry, endocrinology, electrocardiogram [ECG], 
and urinalysis) 
13. Must match by gender, as well as to the pooled mean values for age (± 10 years) and 
weight (± 20%) of subjects with hepatic impairment 
Hepatic Impaired Subjects: 
14. Considered clinically stable in the opinion of the Investigator 
15. Presence of mild hepatic impairment (Child-Pugh Class A: 5-6 points) or moderate 
hepatic impairment (Child-Pugh Class B: 7-9 points) at screening (Appendix A) 
4.3. Exclusion Criteria 
All Subjects: 
1. Females who are pregnant or are lactating 
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2. History of significant hypersensitivity to lasmiditan or any related products (including 
excipients of the formulations) as well as severe hypersensitivity reactions (like 
angioedema) to any drugs 
3. Suicidal tendency, history of or disposition to seizures, state of confusion, clinically 
relevant psychiatric diseases 
4. Subject is at imminent risk of suicide (positive response to question 4 or 5 on the C-
SSRS) or had a suicide attempt within 6 months prior to the screening visit 
5. Presence or history of any disorder (including Parkinson disease) that could interfere with 
completion of the study based on the opinion of the Principal Investigator 
6. Any history of tuberculosis and/or prophylaxis for tuberculosis 
7. Positive results to HIV Ag/Ab Combo tests (and HIV I & II screen at OCRC site) 
8. Females who are pregnant according to a positive pregnancy test 
9. Volunteers who took lasmiditan in the previous 28 days before Day 1 of this study 
10. Volunteers who took an Investigational Product (in another clinical trial) in the previous 
28 days before day 1 of this study 
11. Volunteers who have already participated in this clinical study 
12. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical 
studies, etc.) in the previous 56 days before day 1 of this study 
Subjects with Normal Hepatic Function: 
13. Seated pulse rate less than or equal 50 Beats per Minute (bpm) or more than 100 bpm at 
screening 
14. Seated blood pressure below 90/60 mmHg or higher than 140/90 mmHg at screening 
15. Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions 
known to interfere with the absorption, distribution, metabolism, or excretion of drugs or 
known to potentiate or predispose to undesired effects 
16. History of significant gastrointestinal, liver or kidney disease that may affect drug 
bioavailability 
17. Presence of significant cardiovascular, pulmonary, hematologic, neurological, 
psychiatric, endocrine, immunologic or dermatologic disease 
18. Presence of out-of-range cardiac interval (PR < 110 msec, PR > 220 msec, QRS < 60 
msec, QRS >119 msec and QTc > 450 msec for males and > 460 msec for females) on 
the screening ECG or other clinically significant ECG abnormalities 
19. Maintenance therapy with any drug or significant history of drug dependency or alcohol 
abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) 
20. Positive screening of alcohol and/or drugs of abuse 
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21. Positive results to Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C 
Virus (HCV (C)) tests 
22. Any clinically significant illness in the previous 28 days before day 1 of this study 
23. Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 
(CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, 
fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP 
enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and 
St John’s Wort), in the previous 28 days before day 1 of this study 
24. Volunteers who donated 50 mL or more of blood in the previous 28 days before day 1 of 
this study 
Hepatic Impaired Subjects: 
25. Seated pulse rate less than 40 bpm or more than 110 bpm at screening 
26. Seated blood pressure below 90/50 mmHg or higher than 170/100 mmHg at screening 
27. History of hepatic transplant 
28. Acute exacerbation of hepatic disease within 14 days of study drug administration 
29. History or presence, in the opinion of the Investigator, of significant clinically unstable 
respiratory, cardiovascular, pulmonary, renal, hematologic, gastrointestinal, endocrine, 
immunologic, dermatologic, neurologic, or psychiatric disease  
30. Have poorly controlled Type 1 or Type 2 diabetes as defined by Hemoglobin A1c  10% 
31. Evidence of hepatocellular carcinoma present or acute hepatic disease from infection or 
drug toxicity at the time of screening 
32. Presence of severe encephalopathy 
33. Presence of surgically-created or transjugular intrahepatic portal systemic shunts 
34. History of any major surgery within 6 months before Day 1 
35. History of bariatric surgery or any other gastrointestinal surgery that may induce 
malabsorption 
36. Estimated creatinine clearance by Cockcroft-Gault equation  40 mL/min/1.73 m2 at 
screening 
37. Presence of clinically significant physical, laboratory, or electrocardiogram (ECG) 
finding that, in the opinion of the Investigator and/or Sponsor, may interfere with any 
aspect of study conduct or interpretation of results 
38. Subjects with acute, unstable, or untreated significant medical conditions. Subjects 
requiring treatment for hepatic impairment or other chronic disease (e.g., well-controlled 
diabetes, hypertension) must be on a stable treatment plan (medicines, doses, and 
regimens) for at least 2 weeks (except insulin) prior to Day 1 and during the entire study.  
Small adjustments in the dosages of some concomitant medications may be permitted 
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during the study, and will be discussed on a case-by-case basis.  In all cases, the subjects’ 
treatment history must be reviewed and their enrollment must be agreed to by both the 
investigator and the Sponsor’s medical monitor 
39. Positive screening of alcohol and/or drugs of abuse unless results can be explained by a 
prescription medication 
40. Volunteers who donated 100 mL or more of blood in the previous 28 days before day 1 
of this study 
4.4. Withdrawal Criteria 
Subjects may voluntarily withdraw from the study, or be removed from the study at the 
discretion of the Investigator or Sponsor at any time. The Investigator may withdraw a subject at 
any time if it is determined that continuing the study would result in a significant safety risk to 
the subject. 
If such withdrawal occurs, or if the subject fails to return for visits, the Investigator should 
determine the primary reason for a subject’s premature withdrawal from the study and record the 
reason in the respective subject’s study documents. Attempts should be made to have the subject 
complete the Post-Study tests or Early Termination study procedures.  
Premature withdrawal may occur for any of the following reasons: 
 A subject who experiences emesis within 5 hours following drug administration will be 
removed from the study period. 
 Noncompliance with the protocol requirements 
 Difficulties with blood collection 
 Pregnancy 
 Adverse event (AE) 
 Subject request 
 Investigator request 
 Sponsor request 
 Unanticipated event that could result in an inadequately characterized pharmacokinetic 
profile, such as a missed blood draw, an adverse event, meal deviations or concomitant 
medications. 
 Subjects who are prematurely withdrawn from the study for reasons other than safety 
may be replaced by an equal number of newly enrolled subjects at the Sponsor’s 
discretion. 
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5. STUDY TREATMENTS 
5.1. Description and Handling of Study Treatments 
5.1.1. Formulation of Test Product 
Lasmiditan is a 5-HT1F receptor agonists, developed by CoLucid Pharmaceuticals, Inc. for the 
acute treatment of migraine. Oral doses of lasmiditan 50 mg, 100 mg and 200 mg are being 
investigated in Phase 3 clinical trials. The Test product used in this study will be provided by the 
Sponsor as a single 200 mg oral tablet. See Table 1 for the formulation of lasmiditan. 
Table 1: Formulation of Lasmiditan, 200 mg Tablets 
Component 
Function 
Amount 
200mg Tablet 
Intragranular Components 
Lasmiditan hemisuccinate 
a, b 
Active 
Ingredient 
231.28 mg 
Microcrystalline cellulose 
PH102 b 
Filler 
123.47 mg 
Starch 1500 
Binder 
30.0 mg 
Croscarmellose sodium 
Disintegrant 
22.5 mg 
Sodium lauryl sulfate 
Wetting Agent 
2.25 mg 
Purified water c 
Granulating 
Medium  
Qs 
Extragranular Components 
Croscarmellose sodium 
Disintegrant 
31.5 mg 
Magnesium stearate 
(Non-bovine) 
Lubricant 
9.0 mg 
Totals 
450 mg 
Film Coating Materials 
Opadry II White 
(85F18422) 
d 
Film Coat 
11.25 mg 
Purified water 
e 
Suspending 
Agent 
(45.00 mg)  
a 
A salt correction factor for the hemisuccinate is assigned as 0.865 
b 
Note that the amount of lasmiditan hemisuccinate may be adjusted for purity and moisture content.  An 
adjustment will be made to the amount of microcrystalline cellulose used to maintain tablet weight.  
c 
Water for granulation is removed upon drying of the wet mass. 
d 
Opadry II White (85F18422) is prepared as a suspension at 20% w/w in Sterile Water for Injection and 
applied to a target of 2.5% weight gain. 
e 
The amount of water may be adjusted to facilitate suspension of the coating agent.  This water is removed 
during processing and does not appear in the final product. 
5.1.2. Packaging and Labeling 
The Sponsor will be responsible for ensuring that the treatment is manufactured in accordance 
with applicable Good Manufacturing Practice regulations and requirements. All labels for study 
drugs will meet applicable requirements of the protocol and the Canadian Health Products and 
the US Food and Drug Administration (FDA). 
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5.1.3. Storage and Handling 
Lasmiditan tablets should be stored by the study site at controlled room temperature of 25°C 
(77°F); excursions are permitted to +/- 15°C (59°F-104°F). 
5.2. Method of Assigning Subjects to Treatment Groups 
No randomization will be performed for this study. Instead subjects will be categorized into 
either the control group of healthy volunteers with normal hepatic function, or into one of the 
two groups of subjects with varying degrees of hepatic impairment (mild or moderate hepatic 
impairment). 
Once a subject number has been assigned to a subject, it will not be reassigned to another 
subject. Subjects who withdraw from the study may be replaced. Replacement subjects will not 
be enrolled for subjects who discontinue the study due to treatment-related toxicity. A new 
unique subject number will be assigned to the replacement subject. 
5.3. Blinding 
No unblinding procedure is required, as this is an open-label study. 
5.4. Dosing and Administration 
5.4.1. Dispensing 
Designated site staff will dispense study drug in tablet form. 
Study drugs will be administered to the subjects under supervision of the study center personnel. 
5.4.2. Administration Instructions 
The study drug will be administered orally in the morning.  
Dosing will be performed by trained personnel and supervised by the Principal Investigator or 
physician in charge.  
Subjects will be asked to fast overnight (no food or drink, except water) prior to dosing, for a 
minimum of 10 hours, at Day -1. Fasting will continue for at least 4 hours following drug 
administration, after which a standardized lunch will be served. A supper, a light snack and other 
meals will also be served at appropriate times thereafter, but not before 9 hours after dosing. 
Fluid intake other than water will be controlled during the housing period and for all subjects. 
Water will be provided ad libitum until 1 hour pre-dose. The drug will be given with about 
240 mL (8 oz.) of water at room temperature. Water will be allowed ad libitum beginning 1 hour 
after the administration of the drug. 
The tablet must be swallowed whole and must not be chewed or broken. 
Study medications will be administered to each subject consecutively, and at adequate intervals, 
for the purpose of accurate sampling time. The date and time of each dose must be recorded. 
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The physician in charge will remain at the clinical site for at least the first 4 hours following drug 
administration, and will remain available at all times during the study. 
5.4.3. Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
 All doses will be administered under the supervision of the Investigator (or designee). 
 A mouth and hand check of all subjects will be carried out to ensure that all tablets have 
been swallowed. 
5.4.4. Study Drug Accountability 
Complete and accurate records of all study drugs must be kept. This includes acknowledgment of 
receipt of each shipment of study product (quantity and condition), subject dispensing records, 
and returned or destroyed study product. 
At the conclusion of the study, all unused investigational products and all medication containers 
will be returned to the Sponsor unless the Sponsor has approved other arrangements. Drug 
accountability will be performed at the completion of the trial. 
5.5. Prior and Concomitant Medication 
Hepatic-impaired subjects will be permitted to continue taking any prescription or OTC 
medication necessary for the management of their hepatic disease or other concurrent illness. 
The dosing schedules for such medications must be stable for 2 weeks before day 1 of the study 
(except for insulin) and maintained throughout the study. Minor dose changes consistent with 
treatment practices may be permitted at the discretion of the Investigator. All medications taken 
during the 14 days prior to dosing will be recorded in the subject’s CRF and reviewed by the 
Investigator. When concomitant medications are administered, the indication, name, dose, route, 
and frequency will be recorded in each subject’s CRF. 
For healthy subjects, beside enzyme-modifying drugs that are not allowed for 28 days (refer to 
exclusion criteria), subjects will be requested to abstain from taking any prescription medications 
used with the intention to treat a condition for 28 days prior to dosing and during the study, 
unless judged differently by the Principal Investigator or designee. Systemic contraceptives and 
hormone replacement therapy will be permitted. Subjects will also be requested to abstain from 
taking any over-the-counter (OTC) products for 7 days prior to dosing and during the study. 
They will be specifically reminded that this includes cold preparations (containing ASA), 
acetylsalicylic acid (ASA), vitamins and natural products used for therapeutic benefits and 
antacid preparations. Vitamins used as nutritional supplements in non-therapeutic doses (as 
judged by the Principal  Investigator or designee) may be accepted, but they must be stopped at 
least 48 hours prior to dosing and during the study. 
If a medication (including OTC) other than those specified in the protocol is used after dosing or 
at any time before the end of the study, the Principal Investigator or designee and/or the Sponsor 
will decide whether the subject will be permitted to remain in the study, depending on the drug 
used, the time of drug intake, etc. The drug and dose will be noted. 
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5.6. Study-Specific Restrictions 
 Subjects will be requested to abstain from alcohol for 48 hours prior to dosing and during 
the study period. Throughout the study (including the return visits), in case of any doubt 
about alcohol consumption, a test for alcohol may be performed to confirm the 
physician's judgment. 
 During the study, subjects who are light-smokers should not smoke more than 
10 cigarettes per day. They will also be instructed to abstain from smoking for 2 hours 
prior to and until 4 hours after drug administration. 
 Subjects will be requested to avoid food or beverages containing xanthines (i.e. tea, 
coffee, cola drinks, energy drinks or chocolate) for 48 hours prior to dosing and during 
study period. 
 Subjects will be instructed to avoid food or beverages containing grapefruit and/or 
pomelo for 7 days prior to dosing and during study period. 
 Subjects will remain seated for the first 4 hours following drug administration, avoiding 
both vigorous exertion and complete rest. However, should adverse events occur at any 
time, subjects may be placed in an appropriate position. Subjects will not engage in 
strenuous activity at any time during the confinement. 
 Female volunteers of childbearing potential will have to take appropriate measures to 
prevent pregnancy for at least 28 days prior to the administration of the study drug, 
during the study and for at least 60 days after the drug administration, as described in 
Section 4.2. 
 Male subjects who are apt to procreate will be expected to use an acceptable 
contraceptive regimen from day 1 of this study, throughout the duration of the entire 
study, and until at least 3 months after the drug administration, as described in Section 
4.2. Condoms with spermicide will be provided to subjects upon departure from the 
clinical site. In addition to the use of condoms with spermicide, subjects will be informed 
that it is strongly recommended that their female partner uses one of the two methods 
listed below: 
- 
Systemic contraceptives (birth control pills, injectable/ implantable/ insertable 
hormonal birth control products, transdermal patch). 
- 
Intrauterine device. 
 Male subjects must refrain from sperm donation from the screening and until at least 
3 months after the drug administration. 
6. STUDY PROCEDURES AND GUIDELINES 
Unless otherwise stated in this protocol, clinical site standard operating procedures (SOPs), 
which are available for all activities relevant to the quality of the study, will be followed during 
this study. The different parts of this study are summarized in Table 2 and explained in the 
following sections. The list of assessments for each study part is indicated with an "X" when the 
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assessments have to be performed. Any deviation from protocol should be noted in the Case 
Report Forms (CRFs) and the Sponsor should be notified. 
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Table 2. Schedule of Assessments for All Subjects 
Examination 
Screening 
Days 
 
 
Post-
Study 
Tests or 
ETa 
End of Study 
Day 28 to – 1 
-1 
1 
2 
2 
7 (±3) 
Review Inc/Exclusion Criteria & 
MedicalHistory 
X 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
Check-in 
 
X 
 
 
 
 
Dosing 
 
 
X 
 
 
 
Clinic Confinement 
 
X 
X 
X 
 
 
Discharge 
 
 
 
X 
 
 
Demographics 
X 
 
 
 
 
 
C-SSRS questionnaire 
X 
 
 
 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
 
 
X 
 
Vital Signsb 
X 
 
X 
 
X 
 
Height, Weight, and BMI 
X 
 
 
 
 
 
12-lead ECGc 
X 
 
X 
 
X 
 
HIV Ag/Ab Combo, HBsAg (B) (Hepatitis 
B) and HCV (C) Tests 
X 
 
 
 
 
 
Drug and Alcohol Screen 
X 
X 
 
 
 
 
Pregnancy test (females) 
X 
X 
 
 
X 
 
Clinical Laboratory Evaluationsd 
X 
X 
 
 
X 
 
PK Blood Samplee 
 
 
X 
X 
 
 
Follow-up Call 
 
 
 
 
 
X 
Adverse Events Recording 
X 
X 
X 
X 
X 
X 
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a  Early Termination (ET).  
b Vital signs will be measured prior to dosing and approximately 2 and 4 hours after study drug administration, including orthostatic blood pressure. 
c  12-lead ECG will be performed prior to dosing and approximately 2 hours after study drug administration. 
d  Clinical laboratory tests (hematology, biochemistry, coagulation (screening only), endocrinology (screening only) and urinalysis) will be performed. On 
Day -1, these will be done in the evening prior to drug administration. 
e  PK blood samples will be collected according to schedule of PK assessments in Table 3. 
 
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Table 3. Schedule of Pharmacokinetic Assessments 
PK Blood Sampling 
Prior to dosing 
0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 
36 hours postdose 
 
Time of PK sampling and dosing must be recorded. 
 
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6.1. Study Procedures 
Safety assessments will include physical examination, vital signs (blood pressure, heart rate, and 
body temperature), 12-lead ECG, laboratory tests (hematology, biochemistry, and urinalysis), 
and continuous adverse event (AE) monitoring. Body weight and height will be measured at 
Screening and BMI will be calculated. 
Clinically significant physical examination findings prior to the administration of study drug will 
be recorded as a medical history; clinically significant findings after the drug administration will 
be recorded as an AE. 
The laboratory tests will be carried out according to the standard operating procedures of the 
licensed medical laboratory. Abnormal results will be verified to rule out laboratory error. 
Persistent relevant abnormal values should be followed up until the cause is determined or until 
the values return to the pre-medication value. 
After the ICF is signed, information about all local and systemic clinical events, whether 
volunteered by the subject, discovered by Investigator questioning, or detected through other 
means, will be collected, recorded and followed as appropriate. 
6.1.1. Physical Examination 
A complete physical examination will be performed by a medically qualified and licensed 
individual as scheduled in Table 2. The physical examination will include a review of the 
following: head and neck, heart, lungs, abdomen and general appearance. 
Demographic data (age, gender, race, body weight adjusted for indoor clothing, height, BMI), 
and alcohol and smoking habits will be recorded. 
During study days not requiring a complete physical examination, a symptom-targeted physical 
exam should be done if a new AE is reported, if medically indicated. 
6.1.2. C-SSRS Questionnaire 
A Columbia Suicide Severity Rating Scale will be performed as scheduled in Table 2. 
6.1.3. Vital Signs 
Vital sign measurements (body temperature, pulse rate, blood pressure and orthostatic blood 
pressure) are specified in Table 2. Vital signs can also be monitored during the study when 
judged necessary by the physician in charge or designee. Vital signs are to be performed prior to 
blood draws. 
6.1.4. Laboratory Evaluations 
Laboratory evaluations will be performed as scheduled in Table 2. The physician in charge or 
designee will assess each abnormal value to determine if it is clinically significant. Postdose 
clinically significant laboratory values will be reported as adverse events. 
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 General biochemistry: Sodium, potassium, chloride, glucose, blood urea nitrogen (BUN), 
creatinine, ClCr, eGFR, total bilirubin, alkaline phosphatase, uric acid (screening only), 
AST, ALT and albumin 
 Hematology: White cell count with differential (absolute values of neutrophil, 
lymphocyte, monocyte, eosinophil, and basophil), red cell count, hemoglobin, 
hemoglobin A1c, hematocrit, mean corpuscular volume (MCV), and platelets count 
 Coagulation: PT/INR and PTT levels (screening only) 
 Urinalysis: Color, appearance, specific gravity, pH, leukocyte, protein, glucose, ketones, 
bilirubin, blood, nitrite, urobilinogen. Microscopic examination will only be performed if 
the dipstick test is outside of the reference range for leukocyte, blood, nitrite or protein 
 Endocrinology: Ferritin (screening only) 
 Serology: HIV Ag/Ab Combo, HBsAg and HCV 
 Drug Screen: Alcohol, amphetamines, barbiturates, cannabinoids (THC), cocaine, opiates 
and phencyclidine (PCP) 
6.1.4.1. 
Pregnancy Tests 
A pregnancy test will be performed on female subjects as specified in Table 2. 
6.1.5. 12-Lead Electrocardiogram 
Twelve-lead ECGs will be performed as specified in Table 2. On the study days where ECGs are 
conducted, they should be scheduled prior to blood draws that occur for that day, as the blood 
draws can impact the ECG reading. Subjects must be in a supine position for 10 minutes prior to 
ECG recording. 
6.1.6. Follow-up Call 
A symptom-directed follow-up telephone call will be made to all subjects following drug 
application as specified in Table 2. 
6.1.7. Pharmacokinetic Sampling 
Blood samples will be collected by direct venipuncture. However, as an option to the volunteer 
or if judged necessary by the clinical staff, blood samples may be collected from an indwelling 
cannula (stylet catheter that requires no flushing), which will be placed in the forearm vein of the 
subject. Blood samples will be kept in an ice-water bath pending processing. Blood samples will 
be collected in one tube of 6 mL each. 
The complete schedule for each part is presented in Table 3. The time of blood sample collection 
will be calculated according to the drug administration schedule. The clock time of all blood 
draws will be recorded and reported for all subjects in the CRF. For postdose samples, all 
deviations from the scheduled sampling time of 2 minutes or more will be reported in the final 
report. 
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The total volume of blood withdrawn, including ~47 mL required for screening and poststudy 
tests, should not exceed 155 mL per subject.  
6.1.7.1. 
Sample processing, storage and shipping 
Blood samples will be processed, split, stored, and shipped according to the sample processing 
instructions supplied by the bioanalytical facility. 
6.2. Bioanalytical Methods 
Plasma lasmiditan concentrations will be measured according to a validated bioanalytical 
method.  
Samples from all subjects who received the investigational product will be assayed. 
6.2.1. Aberrant values and retested samples 
Unacceptable values attributable to bioanalytical reasons will be determined according to the 
bioanalytical Facility’s SOPs. The method of re-assay and the acceptance criteria for selecting 
which value to report for the re-assayed samples will follow the bioanalytical Facility’s SOPs. 
All cases of re-assay will be reported in the final report. 
No samples will be repeated for pharmacokinetic reasons. 
6.2.2. Incurred sample reproducibility 
In order to establish the reproducibility of the assay with incurred samples, at least 10% of the 
total analyzable study samples will be selected and re-assayed. The replicate measurement is not 
to be averaged with the original one, but both values will be presented in the bioanalytical report 
with the initial value being used for PK calculations. The concentrations of the original and 
replicate samples will be tabulated, along with the percent difference between the two values. 
6.3. Pharmacokinetic Measurements 
The PK parameters are presented in Table 4. Below limit of quantitation concentrations (coded 
BLQ) will be treated as zero for all PK analyses. All reported sampling time deviations (see 
Section 6.1.7) will be taken into consideration for evaluation of plasma PK parameters. 
The pharmacokinetic parameters will be estimated using a non-compartmental approach with a 
log-linear terminal phase assumption. The trapezoidal rule will be used to estimate the area under 
the curve, and the terminal phase will be estimated by maximizing the coefficient of 
determination estimated from the log-linear regression model. Disposition parameters (AUC0-∞, 
AUC0-T/∞, λZ, Thalf, ClTOT/F and VD/F) will not be estimated for individual concentration-time 
profiles where the terminal log-linear phase cannot be reliably characterized. 
In the case where less than 3 consecutive measurable plasma concentrations of lasmiditan are 
observed, the AUC parameters will not be estimated. 
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Table 4. Pharmacokinetic Parameters 
PK Parameter 
Definition 
Cmax  
Maximum observed plasma concentration 
Tmax 
Time of maximum observed plasma concentration; if it occurs at more than 
one time point, Tmax is defined as the first time point with this value 
AUC0-T 
Cumulative area under the plasma concentration time curve calculated from 0 
to TLQC using the linear trapezoidal method, where TLQC represents time of last 
observed quantifiable plasma concentration 
AUC0-∞ 
Area under the plasma concentration time curve extrapolated to infinity, 
calculated as AUCT + CLQC/λZ, where CLQC is the measured concentration at 
time TLQC  
AUC0-T/ 
Relative percentage of AUC0-T with respect to AUC0-∞ 
λZ 
Apparent elimination rate constant, estimated by linear regression of the 
terminal linear portion of the log concentration versus time curve 
Thalf 
Terminal elimination half-life, calculated as ln(2)/λZ 
ClTOT/F 
Apparent Total Plasma Clearance, calculated as dose /AUC0-∞ 
VD/F 
Apparent Volume of Distribution, calculated as dose / λZ*AUC0-∞ 
 
Additional pharmacokinetic parameters may be calculated if deemed appropriate. 
Pharmacokinetic analyses will be generated using Phoenix® WinNonlin® Version 6.3 (or higher). 
7. ADVERSE EVENTS 
7.1. Definitions 
An AE is defined as any untoward medical occurrence in a subject administered a medicinal 
product and which does not necessarily have to have a causal relationship with this treatment. 
AEs occurring after the initiation of the treatment are referred to as treatment emergent adverse 
events (TEAEs). An AE can therefore be any unfavorable and unintended sign (for example, an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to this medicinal product. 
A suspected adverse reaction is any adverse event for which there is a reasonable possibility that 
the drug caused the adverse event. ‘Reasonable possibility’ means there is evidence to suggest a 
causal relationship between the drug and the adverse event. A suspected adverse reaction implies 
a lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug. 
An AE may be: 
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 A new illness, 
 Worsening of a concomitant illness, 
 An effect of the study medication; it could be an abnormal laboratory value as well as a 
significant shift from baseline within normal range which the Principal Investigator or 
medical qualified designate considers to be clinically important. 
Surgical procedures themselves are not AEs. They are therapeutic measures for conditions that 
required surgery. The condition for which the surgery is required is an AE, if it occurs or is 
detected during the study period. Planned surgical measures permitted by the clinical study 
protocol and the conditions(s) leading to these measures are not AEs, if the condition(s) was 
(were) known before the start of study treatment. In the latter case, the condition should be 
reported as medical history. 
A serious adverse event (SAE) or reaction is any untoward medical occurrence that at any dose: 
 Results in death, 
 Is life-threatening, 
 Requires inpatient hospitalization or prolongation of existing hospitalization, 
 Results in persistent or significant disability or incapacity (defined as a substantial 
disruption of a person’s ability to conduct normal life functions), 
 Is a congenital anomaly or birth defect, 
Is an important medical event (including development of drug dependence or drug abuse) that 
may jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed above (according to medical judgment of the Principal Investigator). 
7.1.1. Severity Assessment 
All adverse events will be graded as mild, moderate, or severe according to the following 
definitions: 
Mild: 
Causing no limitation of usual activities; the subject may experience slight 
discomfort. 
Moderate: 
Causing some limitation of usual activities; the subject may experience annoying 
discomfort. 
Severe: 
Causing inability to carry out usual activities; the subject may experience 
intolerable discomfort or pain. 
Every effort will be made to obtain an adequate evaluation of the severity. 
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7.1.2. Causality Assessment 
The Principal Investigator or a medical qualified designate will determine the relationship of any 
adverse event to study drug using the following guidelines in Table 5. 
Table 5. Adverse Event Relationship to Study Drug 
Relationship to Drug 
Comment 
Reasonable Possibility 
A temporal relationship exists between the AE onset and 
administration of the investigational product that cannot be readily 
explained by the subject’s clinical state or concomitant therapies. 
Furthermore, the AE appears with some degree of certainty to be 
related, based on the known therapeutic and pharmacologic actions or 
adverse event profile of the investigational product. 
In case of cessation or reduction of the dose, the AE may abate or 
resolve and it may reappear upon rechallenge. 
No Reasonable Possibility 
Evidence exists that the AE has an etiology other than the 
investigational product. 
For SAEs, an alternative causality must be provided (eg, pre-existing 
condition, underlying disease, intercurrent illness, or concomitant 
medication). 
7.2. Routine Reporting 
For the purposes of this study, the period of observation of adverse events extends from the 
screening visit until the follow-up call. During this period, all adverse events spontaneously 
reported by the subject, observed by the clinical staff, or elicited by general questioning will be 
recorded and reported in the CRF. 
Any AE which remains unresolved as of the last visit will require an evaluation and follow-up 
until the AE has been resolved or a reasonable explanation for its persistence found, or is deemed 
mild and safely resolving. 
In the case of AEs deemed related to the Investigational Product, every effort will be made to 
determine the final outcome. 
It is the Investigator’s responsibility to ensure subjects experiencing AE receive appropriate 
follow-up, treatment where required, and that every action is well documented. 
Subjects will be questioned on their health status at the beginning of study period and before 
departure from the clinical site. Open-ended questions will be asked. 
Subjects will be questioned on their health status at the beginning of the study period and before 
the departure from the clinical site. Open-ended questions will be asked. 
Classification will be performed by System Organ Class (SOC) and Preferred Term (PT) using 
the Medical Dictionary for Regulatory Activities (MedDRA), version 19.0 or higher. 
In general, AEs occurring secondary to other events (eg, clinical sequelae or a cascade of events) 
should be identified by their primary cause. For example, if severe vomiting is known to result in 
dehydration, it is sufficient to record only vomiting as SAE or AE in the CRF. However, 
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medically significant AEs occurring secondary to an initiating event that are separated in time 
should be recorded as independent events on the CRF. 
Pregnancy in a female subject on the study shall be reported to the Sponsor within 24 hours of 
the knowledge of its occurrence by the Principal Investigator or designee (for pregnancies 
occurring during the course of the study or immediately following the end of the study). Because 
of the possibility that the fetus/embryo could have been exposed to the study drug through the 
parent and for the subject’s safety, the pregnancy will be followed up to determine its outcome, 
including spontaneous or voluntary termination, details of birth, presence or absence of any birth 
defects, congenital anomalies, or maternal and/or newborn complications. 
The pregnancy will be recorded and reported by the Principal Investigator or designee to the 
Sponsor. Pregnancy follow-up will also be properly recorded to ensure quality and completeness 
of the data belonging to the study drug and will include an assessment of the possible causal 
relation between the study drug and any pregnancy outcome. Any SAE experienced during 
pregnancy will be reported on a SAE Report Form. 
7.3. Serious Adverse Event Reporting 
Algorithme Pharma will notify any SAE to the Sponsor, without regard to causality, within 
24 hours after becoming aware of its occurrence.  
If, during follow-up, any non-serious AE worsens and eventually meets the criteria for an SAE, 
that AE should be recorded as a new SAE. 
The initial SAE report must be as complete as possible, including details of the current illness 
and SAE, and an assessment of the causal relationship between the event and the investigational 
product(s). Information not available at the time of the initial report (e.g., an end date for the AE, 
laboratory values received after the report, or hospital discharge summary) must be documented. 
All follow-up information must be reported as soon as the relevant info is available. 
The notification should be directed to the following Sponsor representative: 
Bernice Kuca, Head Clinical/Regulatory Operations 
CoLucid Pharmaceuticals, Inc. 
Tel. 
 
Fax. 
 
Email:
 
An SAE will be considered “unexpected” if the AE is not listed in the investigator brochure or is 
not listed at the specificity or severity that has been observed; or, if an investigator brochure is 
not required or available, is not consistent with the risk information described in the general 
investigational plan or elsewhere in the current application. "Unexpected," as used in this 
definition, also refers to AEs that are mentioned in the investigator brochure as occurring with a 
class of drugs or as anticipated from the pharmacological properties of the drug, but are not 
specifically mentioned as occurring with the particular drug under investigation. 
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Algorithme Pharma will determine whether any serious unexpected related adverse event must 
be reported to the IRB. If so, the event will be reported via fax or email within 15 calendar days 
of the investigator or staff becoming aware of the event. 
The Sponsor will determine whether the SAE must be reported in an expedited manner to the 
FDA and to the Health Canada Therapeutic Products Directorate (TPD). If so, Algorithme 
Pharma Inc, on the behalf of the Sponsor will report the event to the FDA, TPD, and all 
participating investigators. 
During a clinical trial conducted in Canada, it is required to inform Health Canada of any 
serious, unexpected adverse drug reaction that has occurred inside or outside Canada: 
 Where it is neither fatal nor life-threatening, within 15 days after becoming aware of the 
information; 
 Where it is fatal or life-threatening, immediately where possible and, in any event, within 
7 days after becoming aware of the information; and 
 Within 8 days after having informed Health Canada of the ADR, submit as complete a 
report as possible which includes an assessment of the importance and implication of any 
findings. 
If reports of any new and unexpected AEs become available to the Sponsor during the clinical 
portion of this study (related or not to the present study), the Sponsor has to advise 
Algorithme Pharma, through its Clinical Investigator, of those events. If required by the Sponsor, 
Algorithme Pharma may advise the Canadian authorities. 
8. STATISTICAL ANALYSIS 
8.1. Analysis Sets 
8.1.1. Safety Analysis Set 
The safety population will include all subjects who received the investigational product under 
study. 
8.1.2. Pharmacokinetic Analysis Set 
All subjects who received lasmiditan, had no major protocol deviations, and completed the 
period with evaluable (sufficient and interpretable) data will be included in the PK analysis. 
Concentration data of the remaining subjects will be presented separately. 
If some subjects do not complete the sampling schedule resulting in an inadequately 
characterized AUC and elimination parameters, samples of these subjects could be included in 
the statistical pharmacokinetic analysis for only the Cmax and Tmax parameters. This decision is to 
be documented by the SRA department and approved by the Sponsor before the start of the 
sample analysis by the bioanalytical facility. 
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8.2. Sample Size Determination 
There is no formal statistical sample size calculation for this study. A sample size of 24; 
including 8 subjects/patients for each hepatic function group (8 subjects with normal hepatic 
function, 8 patients with mildly impaired hepatic function and 8 patients with moderately 
impaired hepatic function) was chosen because it is considered typical for studies evaluating the 
effect of hepatic function on the pharmacokinetics of a drug. 
8.3. Statistical Analysis 
A detailed statistical analysis plan (SAP) describing the methodology to be used will be prepared 
prior to the completion of the clinical phase of the study. The sections below summarize the data 
analysis to be undertaken. 
8.3.1. Descriptive Analysis 
8.3.1.1. 
Safety Analyses 
Data to be listed by subject and summarized by group will include demographic data, AEs, vital 
signs, ECG parameters, and clinical laboratory evaluations. All values outside the clinical 
reference ranges will be flagged on the data listings. Other data to be listed by subject will 
include urinary drug screen, serology results, physical examination findings and concomitant 
medications. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA Version 19.0 or higher). Concomitant medications will be coded using the World 
Health Organisation drug dictionary (WHO-DDE March 1st, 2016). 
8.3.1.2. 
Pharmacokinetic Endpoint Analyses 
Descriptive statistics will be calculated for plasma concentrations at each individual time point 
and for all PK parameters. The individual plasma concentration/time profiles will be presented 
using the actual sampling times whereas the mean plasma concentration/time profiles will be 
presented using the theoretical sampling times. 
8.3.2. Statistical Methodology 
The natural logarithmic transformation of Cmax, AUC0-T, AUC0-∞, λZ, ClTOT/F and VD/F as well as 
the rank-transformation of Tmax will be used for all statistical inference. 
Statistical analyses will be generated using validated SAS® (version 9.4 or higher). 
Regression Analysis  
The Child-Pugh classification at baseline will be used the primary measure of hepatic function 
for a regression analysis to evaluate the relationships between estimated hepatic function and PK 
parameters. Hepatic function in affected subjects will be entered in separate regression models as 
the following: 
 Individual Child-Pugh scores; 
 Hepatic Impairment Group:  
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o 1: Child-Pugh classification A;  
o 2: Child-Pugh classification B;  
o 3: Subject with normal hepatic function 
For each PK parameter, a regression analysis will be performed to assess the impact of impaired 
Hepatic Function, using a regression model of the form α + β*(Hepatic Function) + ε where the 
errors (ε) will be assumed to be independent and normally distributed with mean zero and 
variance σ2. The parameter β represents the correlation between the relevant PK parameter and 
the Hepatic Function which will be treated as a continuous variable. 
The hypothesis of the slope of trend being different from zero will be assumed if the two-sided 
test of the nullity of the parameter β is statistically significant at the 5% level. 
8.3.2.1. 
Interim Analysis 
Approximately four subjects with mild hepatic impairment will be enrolled first (Group 1). To 
ensure subject safety, following dosing of these first four subjects, a safety meeting will take 
place to review the safety data prior to dosing additional subjects. After safety and PK results 
from the first four subjects have been reviewed, an additional four subjects with mild hepatic 
impairment (remainder of Group 1) will be enrolled concurrently with the moderated hepatic 
impairment group (Group 2). Thereafter, matched subjects with normal hepatic function 
(Group 3) will be enrolled. 
Interim PK analysis of subjects with mild hepatic function will be performed as described in 
Section 6.3. 
9. ETHICS 
9.1. Institutional Review Board (IRB) 
This protocol and the ICF will be submitted to IRBs (or IECs) (one for each study center) prior 
to initiation of the study and the study will not start until the Board has approved the documents. 
Notification of the Board’s approval will be appended to the final report. 
9.2. Ethical Conduct of the Study 
This study will be conducted in compliance with the study protocol, the ethical principles in the 
latest version of the Declaration of Helsinki, the ICH Guideline E6 for GCP, the FDA GCP Code 
of Federal Regulations (CFR) Title 21, part 56, European regulation EU 536/2014 and the 
Tri-Council Policy Statement (Canada). 
9.3. Participant Information and Consent 
Before inclusion in the study, each prospective subject will be given a full explanation of the 
purpose of the study, the procedures to be carried out and the potential hazards. Once this 
essential information is provided to the volunteer and once the physician in charge or designee 
has the conviction that the volunteer understands the implications of participating in the study, 
the volunteers will be required to read, sign and date a properly executed written informed 
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consent form prior to enrollment. Subjects will be assured that they may withdraw from the study 
at any time without jeopardizing their medical care. They will be given a copy of their informed 
consent form. 
If an amended or revised ICF is introduced during the study, each subject’s further consent 
should be obtained. 
9.4. Subject Confidentiality 
The Investigators and the Sponsor will preserve the confidentiality of all subjects taking part in 
the study, in accordance with GCP and local regulations. Subjects should be identified by a 
unique subject identifier on all study documents provided to the Sponsor. In compliance with 
Federal regulations/ICH GCP Guidelines, it is required that the Investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and IRB access to 
review the subject’s original medical records for verification of study-related procedures and 
data. The investigator is obligated to inform the subject that his/her study-related records will be 
reviewed by the above named representatives without violating the confidentiality of the subject. 
10. DATA COLLECTION, RETENTION, AND MONITORING 
10.1. Case Report Forms 
A CRF is a gathering of all pertinent data collected for each subject included (i.e., who received 
an Investigational Product treatment) in a clinical trial. Once all CRF forms (including 
multi-subject CRF forms) are completed and reviewed. At Algorithme Pharma, the complete 
CRF will be approved and signed by the Study Manager, who received a signature delegation 
from the Principal Investigator. At the clinical sites, the complete CRF will be approved and 
signed by the Principal Investigator. 
The original source documents and a copy of the corresponding CRFs will be retained by the 
Investigator. Copies of the CRFs will be provided to the Sponsor. 
10.2. Data Management and Processing 
Data entry will be performed according to clinical site facility procedures. Information will be 
entered into a Medrio database, which will be used for developing tables and listings for the final 
study report. Appropriately trained and designated individuals will be given access to the 
database and will perform entry of the data from the CRFs. The data management process will 
comply with all regulatory standards and will use from the clinical sites for generating the final 
locked database. 
10.3. Quality Assurance 
Designated personnel from Algorithme Pharma will be responsible for maintaining quality 
assurance (QA) and quality control (QC) systems to ensure that the trial is conducted and 
clinical/PK/statistical data are generated, documented and reported in compliance with the 
protocol and ICH Guideline E6 for Good Clinical Practices. 
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All parts of the bioanalytical phase of the study and all its documentation will be subject to 
inspection by the quality assurance unit of the bioanalytical facility to ensure that the data are 
generated, documented and reported in compliance with the protocol and applicable 
requirements as outlined in the FDA and OECD Principles of GLP. 
10.4. Record Retention 
All essential documents and records will be maintained by the study centers for a period of 
25 years. These documents may be retained for a longer period if required by the applicable 
regulatory requirement(s) (FDA CFR 312.57 (C)) or if needed by the Sponsor. 
10.5. Monitoring of the Study 
The Sponsor or its representative may visit the study facilities at any time in order to maintain 
current and personal knowledge of the study through review of the records, comparison with 
source documents, observation and discussion of the conduct and progress of the study. 
Algorithme Pharma will permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s) by providing direct access to source data/documents. 
11. ADMINISTRATIVE PROCEDURES 
11.1. Adherence to Protocol 
Excluding an emergency situation in which proper treatment is required for the protection, safety 
and well-being of the study subjects, the study will be conducted as described in the approved 
protocol and performed according to ICH/GCP and FDA guidelines. Any deviation from the 
protocol will be recorded and explained. 
If amendments to the protocol and/or amendments or revisions to the ICF are required, the 
modifications will be documented and submitted to an IRB for approval. 
11.2. Investigator Responsibilities 
The form “Qualified Investigator Undertaking” will be signed by the Investigator responsible for 
the medical decisions and care provided to the subjects (being also referred to as the “Qualified 
Investigator”) at each site prior to the commencement of his responsibilities with respect to the 
clinical trial, as required by the Food and Drug Regulations. The undertaking form will be 
maintained with the trial records and will be made available upon request. 
In addition, the FDA 1572 form, Statement of Investigator [Title 21, CFR Part 312], duly signed 
by the Principal Investigator and/or the Principal Investigator (if in charge of clinical assessment) 
as a condition for conducting the clinical investigation will be kept on file and will be available 
upon request. 
11.3. Delegation of Investigator Duties 
The Principal Investigator will ensure that all personnel involved in the trial are adequately 
qualified and informed about the protocol, any amendments to the protocol, the study treatments, 
and their trial-related duties and functions. 
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The Principal Investigator will maintain a list of sub-investigator and other appropriately-
qualified persons to whom he delegates significant trial-related duties. 
Should the Principal Investigator delegate the supervision of the investigational product 
administration to a designated person, this individual must have the appropriate medical 
qualifications to effectively conduct or supervise any potential resuscitation procedures. 
11.4. Premature Termination or Suspension of a Study 
The Sponsor or its representative may terminate the study at any time for scientific or corporate 
reasons. 
If the trial is prematurely terminated or suspended for any reason, Algorithme Pharma or the 
Principal Investigator should promptly inform the trial subjects, should assure appropriate 
therapy and follow-up for the subjects and should inform the regulatory authority (ies) when 
required. All procedures should be done according to clinical site procedures. 
11.5. Clinical Trial Application (CTA) 
A CTA must be submitted to Health Canada prior to the study, and a “No Objection Letter” 
(NOL) must be obtained before any drug administration. 
11.6. Exemption Application for Controlled Substances 
This trial does not involve a controlled substance. 
11.7. Publications 
The preparation and submission for publication of a manuscript containing the study results shall 
be in accordance with a process determined by mutual written agreement among the study 
Sponsor and participating institutions.  The publication or presentation of any study results shall 
comply with all applicable privacy laws. 
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12. REFERENCES 
Investigational Brochure, Lasmiditan (COL-144), version 8.0, February 23, 2016 
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13. APPENDIX A 
Child-Pugh Scores 
The score employs five clinical measures of liver disease. Each measure is scored 1-3, with 3 
indicating most severe derangement. 
 
1 Point 
2 Points 
3 Points 
Bilirubin, total, μmol (mg/dL) 
<34 (<2)  
34-50 (2-3) 
>50 (>3) 
Albumin, mg/L 
>35 
28-35 
<28 
INR 
<1.7 
1.71-2.20 
>2.20 
Ascites 
None 
Suppressed with medication 
Refractory 
Hepatic encephalopathy 
None 
Grade I-II  
(or suppressed with medication) 
Grade III-IV  
(or refractory) 
Class A=5-6 points; class B=7-9 points 
INR=International Normalized Ratio 
Source: http://www.doctorslounge.com/gastroenterology/scores/child.htm 
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SAP_001.pdf: 
Statistical Analysis Plan H8H-CD-LAHF 
 
 
A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral 
Lasmiditan in Subjects with Normal and Impaired Hepatic Function 
 
 
NCT03040479  
 
Approval Date: 24-Oct-2017 
 
 
 


Clinical Study Report  
Project No COL MIG-114/H8H-CD-LAHF 
16.1.9 
Documentation of Statistical Methods 
16.1.9.1. Statistical analysis plan (SAP)  
16.1.9.2 Documentation of statistical analysis – SAS® output 


Clinical Study Report  
Project No COL MIG-114/H8H-CD-LAHF 
16.1.9.1. Statistical analysis plan (SAP)  
The statistical analysis plan (SAP) is presented next. 


STATISTICAL ANALYSIS PLAN 
For: 
CoLucid Pharmaceuticals, Inc. 
SPONSOR PROTOCOL No. COL MIG-114 
A Phase I, Multicenter, Open-Label, Parallel-Group, Pharmacokinetic 
Single Dose Study of Oral Lasmiditan in Subjects with Normal and 
Impaired Hepatic Function 
Algorithme Project No. CUD-P9-453 
Prepared by: 
Algorithme Pharma 
575 Armand-Frappier 
Laval, Quebec 
Canada, H7V 4B3 
Version: Final 1.0 
Date: 2017/10/24 


..., Altasciences 
~ CliNICAL RESEARCH 
~ ALGORITHME PHARMA 
We have carefully read this statistical Analysis Plan and agree it 
contains the necessary information required to handle the 
statistical analysis 
of study data. 
 
 
 
On behalf of the Sponsor· 
:Jorl-/Jr 
10 5 
Date 
Date 
Research Protocol No CUD-PS-4531 
Sponsor Project No COL MIG-1141 Version tOj 
2017110/24 
PPD
2 
PPD
PPD
PPD


 
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VERSION CONTROL 
 
Version 
Number 
Version Date Author 
Description of Significant Changes 
from  
Previous Approved Version 
DRAFT 0.1 2017/08/11 
  
 
 
Not App
l
icab
le – F
irst Vers
ion 
DRAFT 0.2 2017/09/29 
  
 
 
Not  App
l
icab
le  –  Second  Vers
ion  after 
the f
irst round of comments 
DRAFT 0.3 2017/10/16 
  
 
 
Not App
l
icab
le – Th
ird Vers
ion after the 
second round of comments 
DRAFT 0.4 2017/10/24 
  
 
 
Not  App
l
icab
le  –  Fourth  Vers
ion  after 
the th
ird round of comments 
FINAL 1.0 
2017/10/28 
  
  / 
 
F
ina
l vers
ion 
 
PPD
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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CONTENTS 
2 
3 
STATISTICAL ANALYSIS PLAN APPROVAL 
VERSION CONTROL 
ABBREVIATIONS 
6 
7 
8 
8 
8 
9 
9 
9 
10 
10 
10 
10 
11 
12 
12 
12 
13 
13 
13 
14 
14 
14 
14 
14 
15 
15 
15 
17 
17 
17 
17 
18 
18 
18 
18 
18 
19 
20 
21 
1.
INTRODUCTION
2.
STUDY OBJECTIVES
Primary Objectives
Secondary Objective
3.
STUDY DESIGN
General Description
Randomization and Unblinding Procedure
4.
STUDY ENDPOINTS
Pharmacokinetic Endpoints
Safety Endpoints
Sample Size Determination
5.
ANALYSIS POPULATIONS
6.
STATISTICAL METHODOLOGY
Analysis Time Points
Methods for Handling Missing Data
7.
STUDY SUBJECTS
Disposition
Protocol Deviations
8.
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic and Background Characteristics
Lifestyle
Medical/Social history
Prior Medication
9.
PHARMACOKINETICS AND STATISTICS
Pharmacokinetic Analysis
Statistical Analysis
10.
SAFETY
Adverse Events
Concomitant Medications
Extent of Exposure
Clinical Laboratory Evaluations
Vital Signs
Electrocardiogram
Physical Examination Findings
Columbia-Suicide Severity Rating Scale (C-SSRS)
11.
INTERIM ANALYSES AND DATA SAFETY MONITORING
12.
CHANGES TO PROTOCOL-SPECIFIED ANALYSES
13.
GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
PLANNED TABLES 
23 


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25 
26 
PLANNED LISTINGS 
APPENDIX A 
APPENDIX B 
27 
Pharmacokinetic Parameters 
27 
APPENDIX C 
28 
TABLE SHELLS 
28 
APPENDIX D 
42 
42 
PHARMACOKINETIC OUTPUTS SHELLS 
PHARMACOKINETIC FIGURES SHELLS 
49 
APPENDIX E 
55 
LISTING SHELLS 
55 


 
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ABBREVIATIONS 
AE 
Adverse Event 
ANOVA 
Analysis of Variance 
ATC 
AUC 
Anatomical/Therapeutic/Chemical 
Area Under Curve 
BMI 
Body Mass Index 
CI 
Confidence Interval 
CLCR 
Creatinine Clearance 
CNS 
Central Nervous System 
CRF 
Case Report Form 
CS 
Clinically Significant 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CSR 
Clinical Study Report 
eGRF 
Estimated Glomerular Filtration Rate 
EOS 
End of Study 
ICF 
Informed Consent Form 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCS 
Not Clinically Significant 
PK 
Pharmacokinetic(s) 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SE 
Standard Error 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TFLs 
Tables, Figures, and Listings 
WHO-DDE 
WHO Drug Dictionary Enhanced 
 
 


 
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1. 
INTRODUCTION 
 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and procedures to be implemented 
for the analyses of data from Protocol No. COL MIG-114. The analyses described in the SAP are based upon the final protocol 
(Fully signed) dated 2017/01/09.   
 
 


 
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2. 
STUDY OBJECTIVES 
Primary Objectives 
The primary objective of this study is to evaluate the pharmacokinetic profile of lasmiditan following a single oral 200 mg dose in 
subjects with mild and moderate hepatic function relative to matched, healthy controls with normal hepatic function. 
 
Secondary Objective 
The secondary objective of this study is to assess the safety and tolerability of a single oral 200 mg dose of lasmiditan in subjects 
with normal, mild and moderate hepatic function.  
 


 
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3. 
STUDY DESIGN  
General Description 
This is a multi-center, open-label, non-randomized, parallel-group, single dose study. This study will enroll up to 24 subjects and 
will include 2 hepatic impaired subject groups and one group of control subjects with normal hepatic function. 
Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion 
criteria will be entered in the study.  
Approximately four subjects with mild hepatic impairment will be enrolled first (Group 1). To ensure subject safety, following 
dosing of these first four subjects, a safety meeting will take place to review the safety data prior to dosing additional subjects. 
After safety and PK results from the first four subjects have been reviewed, an additional four subjects with mild hepatic 
impairment (remainder of Group 1) will be enrolled concurrently with the moderated hepatic impairment group (Group 2). 
Thereafter, matched subjects with normal hepatic function (Group 3) will be enrolled. There will be up to 8 subjects in each of the 
following groups, based on hepatic function at screening: 
x 
Group 1: Mild hepatic impairment subjects (Child-Pugh Class A: 5 to 6 points) 
x 
Group 2: Moderate hepatic impairment subjects (Child-Pugh Class B: 7 to 9 points) 
x 
Group 3: Healthy subjects with normal hepatic function 
All subjects will participate in one treatment period and will receive a single dose of lasmiditan in the fasting state. Subjects will 
be confined to the clinic from at least 10 hours prior to dosing until 36 hours after drug administration. The total duration of each 
subject’s participation in the study will be 3 days (Day –1 through the last PK sample taken on Day 2), not including the 
screening and follow-up phone call. Study procedures 
For complete details on the study assessments to be performed for the study, refer to Appendix A.  
Randomization and Unblinding Procedure 
No randomization will be performed for this study 
No unblinding procedure is required, as this in an open-label study. 
 
  
 


 
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4. 
STUDY ENDPOINTS 
Pharmacokinetic Endpoints 
The following plasma PK parameters of lasmiditan will be calculated: Cmax, Tmax, AUC(0-tlast), AUC(0-∞), %AUC(tlast-f), λz, T1/2, 
CL/F, Vz/F. 
Safety Endpoints 
Safety endpoints include: 
x 
Adverse Events  
x 
Clinical Laboratory Tests (hematology, chemistry, urinalysis) 
x 
Vital Signs 
x 
Physical examination  
x 
Concomitant medication 
x 
12 Lead ECGs 
x 
C-SSRS 
The details of the safety endpoints’ assessment are presented in Section 10. 
Sample Size Determination 
There is no formal statistical sample size calculation for this study. A sample size of 24; including 8 subjects/patients for each 
hepatic function group (8 subjects with normal hepatic function, 8 patients with mildly impaired hepatic function and 8 patients 
with moderately impaired hepatic function) was chosen because it is considered typical for studies evaluating the effect of 
hepatic function on the pharmacokinetics of a drug.. 
 


 
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5. 
ANALYSIS POPULATIONS 
 
Safety Population: 
All subjects who received a dose of study medication will be included in the safety population. This population will be used for all 
demography and safety analyses.  
Pharmacokinetics (PK) Population: 
All subjects who received lasmiditan, had no major protocol deviations, and completed the period with evaluable (sufficient and 
interpretable) data will be included in the PK population. 
If some subjects do not complete the sampling schedule resulting in an inadequately characterized some PK parameters (e.g. 
AUC, VZ/F, λZ), samples of these subjects could be included in the statistical pharmacokinetic analysis for only the evaluable 
parameters 
 
 


 
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6. 
STATISTICAL METHODOLOGY 
 
All analyses will be conducted using the SAS software, version 9.4, or higher. Descriptive statistics of the PK data will be 
performed by  Phoenix® WinNonlin® version 6.3 or higher, Phoenix® ConnectTM version 1.3.1 or higher). 
Adverse events and medical history will be classified using the standard MedDRA terminology version 19.1.  
Prior and concomitant medications will be coded with the WHO-DDE dictionary version March 01, 2016. 
In general, all summary tables will be presented for safety population. Summaries will be presented by hepatic function group.  
In general, the data listings will include all enrolled subjects up to the point of study completion or discontinuation; exceptions will 
be listings pertaining to a subset of subjects only (e.g., subjects with blood sampling time deviations) or a subset of 
records/events (e.g., abnormal laboratory values). 
Categorical variables will be summarized using the PROC FREQ procedure. Continuous variables will be summarized using the 
PROC UNIVARIATE procedure. For log-transformed endpoints, geometric mean, and coefficient of variation will also be 
presented. 
The following general comments also apply to all statistical analyses and data presentations: 
x 
Duration variables in days will be calculated using the general formula: (end date - start date) +1. 
x 
Individual subject listings of all data represented on the CRFs will be provided to facilitate the investigation of 
tabulated values and to allow for the clinical review of all efficacy and safety parameters. 
x 
When assessments are repeated for a given timepoint, only the result which is closes to the dosing time will 
be included in the summary tables. 
The analyses described in this plan are considered a priori, that they have been defined prior to database lock.  Any analyses 
performed subsequent to database lock will be considered post hoc and exploratory.  Post hoc analyses will be labeled as such 
in the corresponding statistical output and identified in the CSR. 
Analysis Time Points  
Unless otherwise specified, the baseline value will be defined as the last non-missing evaluation prior to the first dose of study 
medication. 
Methods for Handling Missing Data  
No imputations of values for missing data will be performed. All data recorded on the case report form will be included in the 
listings that will accompany the clinical study report.   
 
 


 
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7. 
STUDY SUBJECTS 
Disposition 
The subject disposition will be summarized for all subjects enrolled in this study, including: 
x 
The number of subjects enrolled; 
x 
The number of screen failure subjects; 
x 
The number of subjects screened; 
x 
The number and percentage of subjects who completed the study; 
x 
The number and percentage of subjects discontinued from the study by primary reason for discontinuation and overall; 
x 
The number and percentage of subjects included in each of the safety and PK populations. 
The percentages will be calculated using the number of subjects randomized as denominator. 
A listing of subject’s disposition will be provided. A listing of subjects included in each of the analysis populations will also be 
provided. Screen failure subjects will also be presented in a listing. 
Protocol Deviations 
Inclusion/exclusion criteria violations will be presented in a listing. 
All deviations from the scheduled PK sampling time of 2 minutes or more for post dose samples will be taken into consideration 
for the evaluation of PK parameters. 
 
 
 


 
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8. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic and Background Characteristics 
Demographic data and baseline characteristics will be presented in a data listing and summarized by hepatic function group in a 
table. Quantitative assessments to be summarized are age, height, body weight and body mass index (BMI) at screening. 
Subject demographics include sex, age, ethnicity, race and country. Baseline characteristics include height, weight, and BMI. 
Lifestyle 
Alcohol and smoking intake history will be recorded and presented in separate listings. 
Medical/Social history  
Any medical history findings will be recorded and presented in a listing. The listing will include the coding terms (e.g., SOC and 
Preferred Term).  
Prior Medication 
Any medications taken including prescription, nonprescription, OTC (cold and antacid medications), dietary supplements, 
vitamins or herbal medications from screening to the first dose of the study drug will be recorded and presented as prior 
medications in a listing. The listing will include the coding terms (e.g., ATC and Preferred Term).   
 
 
 


 
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9. 
PHARMACOKINETICS AND STATISTICS 
Pharmacokinetic Analysis 
The PK parameters are presented in Section 4 and Appendix B. All reported sampling time deviations (see Section 7) will be 
taken into consideration for evaluation of plasma PK parameters. 
Only quantifiable concentrations will be used to calculate PK parameters. An exception to this rule is made for concentrations 
below the quantification limit (BQL), which will be set to zero when all of the following conditions are met: 
The time points occur before the first quantifiable concentration. All other BQL concentrations will be treated as missing sample. 
The pharmacokinetic parameters will be estimated using a non-compartmental approach with a log-linear terminal phase 
assumption. The trapezoidal rule will be used to estimate the area under the curve, and the terminal phase will be estimated by 
maximizing the coefficient of determination estimated from the log-linear regression model. These parameters (AUC(0-∞), 
%AUC(tlast-∞), λZ, T1/2, CL/F and Vz/F) will be estimated for individual concentration-time profiles only when the terminal log-
linear phase cannot be reliably characterized using the following criteria: 
x 
Phoenix® WinNonlin® Best fit range selection: 
 
x 
R2 of at least 80%  
In the case where less than 3 consecutive measurable plasma concentrations of lasmiditan are observed, the AUC parameters 
will not be estimated. 
Additional pharmacokinetic parameters may be calculated if deemed appropriate. 
Pharmacokinetic analyses and associated descriptive statistics will be generated using Phoenix® WinNonlin® Version 6.3 (or 
higher). 
Statistical Analysis  
The natural logarithmic transformation of Cmax, AUC(0-tlast), AUC(0-∞), λZ, CL/F and VZ/F will be used for all statistical inference. 
Statistical analyses will be generated using validated SAS® (version 9.4 or higher) using the Reg (and Mixed, if applicable) 
procedure(s). 
Regression Analysis 
The Child-Pugh classification at baseline will be used as the primary measure of hepatic function for a regression analysis to 
evaluate the relationships between estimated hepatic function and PK parameters. Hepatic function in affected subjects will be 
entered in separate regression models as the following: 
x 
Individual Child-Pugh scores; 
x 
Hepatic Impairment Group: 
1. 
Child-Pugh classification A; 
2. 
Child-Pugh classification B; 
3. 
Subject with normal hepatic function 
For each PK parameter except Tmax, a regression analysis will be performed to assess the impact of impaired Hepatic Function, 
using a regression model of the form α + β*(Hepatic Function) + ε where the errors (ε) will be assumed to be independent and 
normally distributed with mean zero and variance σ2. The parameter β represents the correlation between the relevant PK 
parameter and the Hepatic Function which will be treated as a continuous variable. 
Non-parametric methods based on the Wilcoxon rank sum test will be used to analyze differences in Tmax  between Hepatic 
Impairment Groups. The rank-transformed Tmax will be used as the dependent variable in a regression model to analyze the 
relationship between Individual Child-Pugh score and Tmax. 


 
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  The following is the SAS code for the regression model including the individual Child-Pugh scores as Hepatic Function:  
Proc Reg;  
Model PKparam = HepaticFunction; 
Run; 
Where HepaticFunction is individual Child-Pugh scores and PKparam is the value of the non-log-transformed or log transformed 
PK parameter. 
The following is the SAS code for the regression model including the Hepatic Impairment Group as Hepatic Function:  
Proc Reg;  
Model PKparam = GrpA GrpB; 
Run; 
Where HepaticFunction is Individual Child-Pugh scores in the first regression model and Hepatic Impairment Group in the 
second regression model and PKparam is the value of the non-log-transformed or log transformed PK parameter. 
The hypothesis of the slope of trend being different from zero will be assumed if the two-sided test of the nullity of the parameter 
β is statistically significant at the 5% level. 
Analysis of Variance 
The effect on the pharmacokinetic parameters of the hepatic function will be done including the measurement of the hepatic 
function and using an analysis of variance (ANOVA). The ANOVA model will include the 3 groups of subjects (2 Child-Pugh 
classification groups and healthy volunteers) entered as fixed effects. 
Pairwise comparisons of the 3 groups will be generated using the Tukey-Kramer’s procedure of adjustment for multiple 
comparisons and statistical significance will be assessed at the two-sided 5% level. Heterogeneity of variance among groups will 
be assumed. Individual contrasts as well as the corresponding 90% confidence interval comparing each group will be computed. 
Proc Mixed;  
Class FunctionGroup;  
Model PKparam = FunctionGroup; 
Repeated / Group = FunctionGroup;  
LSmeans FunctionGroup/ Pdiff=All CL Alpha=0.1 Adjust=Tukey;  
Run; 
Where FunctionGroup is the Hepatic Impairment Group and PKparam is the value of the non-log-transformed Cmax, AUC(0-tlast), 
AUC(0-∞) or the log transformed Cmax, AUC(0-tlast), AUC(0-∞). 
 
Non-parametric methods will be used to analyze differences in Tmax between the Mild and Moderate groups and the Normal 
group. In addition to the group-specific medians and ranges, the Hodges-Lehmann median, 90% CIs and p-values for the 
difference based on the Wilcoxon rank sum test statistic will be presented. 
 
 
 


 
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10. 
SAFETY 
Adverse Events 
An AE is defined as any untoward medical occurrence in a subject administered a medicinal product and which does not 
necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(for example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to this medicinal product. 
A suspected adverse reaction is any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event. ‘Reasonable possibility’ means there is evidence to suggest a causal relationship between the drug and the adverse 
event. A suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any 
adverse event caused by a drug. 
AEs occurring after the initiation of the treatment are referred to as treatment emergent adverse events (TEAEs). 
 
As an overall summary of AEs, the following will be presented by hepatic function group and overall: 
x 
Number of reported AEs;  
x 
Number of reported TEAEs;  
x 
Number and percentage of subjects experiencing TEAEs;  
x 
Number and percentage of subjects experiencing a drug-related TEAE (i.e. those with a relationship classified as 
reasonable possibility) 
x 
Number and percentage of TEAEs by relationship to study treatment (i.e. reasonable possibility, no reasonable 
possibility);  
x 
Number and percentage of TEAEs by severity;  
x 
Number of reported SAEs (serious adverse events);  
x 
Number and percentage of subjects experiencing SAEs;  
x 
Number and percentage of subjects experiencing drug-related SAEs; 
x 
Number and percentage of TEAEs leading to withdrawal; and 
x 
SAEs with an outcome of death.  
Frequency tables will be presented hepatic function group, system organ class and preferred term that summarize all Treatment 
Emergent Adverse Events (TEAEs) and all drug-related TEAEs.  
Subject listings of all Adverse Events (AEs) including severity and relationship to study drug will be provided. AEs leading to 
withdrawal and SAEs will also be presented in separate listings. 
Concomitant Medications 
Medications taken after the first dose of study drug until after discharge from the study will be recorded. Concomitant 
medications will be presented in a listing. The medication name, active ingredient, dose, units, formulation, route, indication or 
reason taken, code, date and time taken will be presented. The listing will also include the coding terms (e.g., ATC and Preferred 
Term). 
Extent of Exposure 
Details of drug dosing (actual treatment received, actual date and time of administration, dose administered, and route of 
administration) will be listed by subject. 
 
 


 
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Clinical Laboratory Evaluations 
Planned laboratory analyses include: 
x 
General Biochemistry: Sodium, potassium, chloride, glucose, blood urea nitrogen (BUN), creatinine, ClCr, eGFR, total 
bilirubin, alkaline phosphatase, Uric Acid at screening, AST, ALT and albumin; 
x 
Hematology: White cell count with differential (absolute values of neutrophil, lymphocyte, monocyte, eosinophil, and 
basophil), red cell count, hemoglobin, hemoglobin A1c, hematocrit, mean corpuscular volume (MCV), and platelets 
count; 
x 
Urinalysis: Color, appearance, specific gravity, pH, leukocyte, protein, glucose, ketones, bilirubin, blood, nitrite, 
urobilinogen. Microscopic examination will only be performed if the dipstick test is outside of the reference range for 
leukocyte, blood, nitrite or protein 
x 
Other: serology, Endocrinology, urine drug screen and serum pregnancy. 
Hematology, chemistry and quantitative urinalysis laboratory test results will be summarized by hepatic function group, 
parameter and visit and will also be presented in a listing 
Separate listings of for serology, Endocrinology, urine drug screen and serum pregnancy will also be provided. 
Subject listings of abnormal on-study laboratory values will be provided. Similarly, clinically significant on-study laboratory data 
will be presented in a second listing.   
Vital Signs 
Vital signs will include the measurement of blood pressure, pulse rate, body temperature, and orthostatic blood pressure.  
For all vital signs, raw values, at each time point will be summarized by hepatic function group, parameter and visit. Vital signs 
data will also be presented in a listing. 
Subject listing of abnormal on-study vital signs values (Out-of-Range – Not Clinically Significant (NCS) or Clinically Significant 
(CS)) will be provided. Similarly, CS on-study vital signs values (Out-of-Range – CS) will be presented in a second listing. 
Electrocardiogram 
A 12-lead ECG will be obtained throughout the study. In some cases, repeat abnormal ECGs may be obtained. 
Raw values at each time point will be summarized by hepatic function group, parameter and visit and will also be presented in a 
listing. Overall safety assessment will also be presented in the listing. 
A subject listing of abnormal on-study ECG assessments (Abnormal – NCS or Abnormal – CS) will be provided. Similarly, CS on-
study ECG assessments (Abnormal – CS) will be presented in a second listing. 
Physical Examination Findings 
A physical examination will be conducted and will be presented in a listing. 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a suicidal ideation rating scale. The scale identifies behaviors and 
thoughts that are associated with an increased risk of suicidal actions in the future.  
Subjects who answer ‘Yes’ to any of the questions on the C-SSRS questionnaire will be presented in a listing. 
 
 
 


 
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11. 
INTERIM ANALYSES AND DATA SAFETY MONITORING 
 
Approximately four subjects with mild hepatic impairment will be enrolled first (Group 1). To ensure subject safety, following 
dosing of these first four subjects, a safety meeting will take place to review the safety data prior to dosing additional subjects. 
After safety and PK results from the first four subjects have been reviewed, an additional four subjects with mild hepatic 
impairment (remainder of Group 1) will be enrolled concurrently with the moderated hepatic impairment group (Group 2). 
Thereafter, matched subjects with normal hepatic function (Group 3) will be enrolled. 
 
 


 
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CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
 
There is no change from the planned analysis described in the protocol. 
 
 


 
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GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
 
Safety  
 
All programs used to generate statistical analyses will be validated according to Algorithme Pharma’s standard operating 
procedures. 
TFLs will be displayed on letter size paper, 8 ½ inches by 11 inches, using the Courier New font.     
In general, summary statistics for raw variables (i.e., variables measured at the study site or central laboratory) will be displayed 
as follows: if required minima, maxima, means, quartiles, standard deviations and confidence limits will be displayed to the same 
number of decimal places as the raw data; if required medians will be displayed to one additional decimal place.   
Percentages will be displayed to one decimal place. Percentages between 0 and 0.1 (exclusive) will be displayed as ‘<0.1’.  P-
values will be displayed to 3 decimal places. P-values that are less than 0.001 will be displayed as ‘<0.001’.   
The numbers of decimal places for summary statistics of derived variables (i.e., variables that are not measured by the study site 
but are calculated for analysis based on other measured variables) will be determined on a case by case basis.  In general, 
minima and maxima will be displayed to the commonly used unit of precision for the parameter. Means, medians, quartiles, and 
confidence limits will be displayed to one additional decimal place and standard deviations will be displayed to two additional 
decimal places. 
The formats and layouts of TFLs are provided in subsequent sections.  Actual formats and layouts may be altered slightly from 
those presented in the templates as necessary to accommodate actual data or statistics.  Minor format changes will not require 
updates to the SAP. 
The tables and listings listed below are common data displays. Their numbering and general content follow the ICH E3 
guidelines.  Some of the tables and listings may not be applicable/appropriate/necessary for a particular study.  Additional tables 
and listings may be included, provided the numbering scheme remains consistent with ICH E3. 
PK Data 
 
All programs used to generate statistical analyses will be validated according to Algorithme Pharma’s standard operating 
procedures. 
 TFLs will be displayed on letter size paper, 8 ½ inches by 11 inches, using the Courier New font.     
Raw variables (i.e., variables measured at the study site or central laboratory) will be displayed with the same number of decimal 
places as received as per bioanalytical laboratory. Derived variables (i.e., variables that are not measured by the study site but 
are calculated for analysis based on other measured variables) will be displayed as follow: 
 
x 
All calculated pharmacokinetic parameter values should be reported to three significant digits. 
x 
Observed concentration data, e.g. Cmax, should be reported as received.  
x 
Observed time data, e.g. Tmax, should be reported as received. 
x 
N should be reported as whole numbers 
x 
Percentage values should be reported with whole numbers, except for the %AUC(tlast-∞). 
x 
Median values should be treated as an observed parameter and reported to the same number of decimal places 
as minimum and maximum values.   
 
Summary statistics of raw variables: minima, mean, geometric mean, median, maxima, and standard deviation, coefficient of 
variation will be displayed with the same number of decimal places as the raw data; 
 


 
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22 
x 
The following summary statistics will be listed for all variables except Tmax and T1/2, arithmetic mean, SD, and CV; 
geometric mean and CV; N, minimum, maximum, and median. 
x 
Summary statistics for Tmax, and other discrete parameters, will be limited to N, minimum, maximum, and median.  
Report not calculated (NC) for other statistics 
x 
Summary statistics for T1/2 will be limited to geometric mean and CV; N, minimum, maximum, and median. Report not 
calculated (NC) for other statistics. 
 
Summary statistics of derived variables will be displayed with the same number of decimal places as the derived variable. 


 
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PLANNED TABLES 
 
Demographic Data 
Table 14.1.1 
Subject Disposition – All Subjects 
Table 14.1.2.1 
Summary of Demographic Characteristics (Safety Population) 
Table 14.1.2.2 
Summary of Demographic Characteristics (Pharmacokinetic Population) 
 
Pharmacokinetic Data  
Table 14.2.1 
Statistical Analysis – SAS output 
 
Safety Data 
Tables in this section are based on the safety population unless otherwise stated. 
Table 14.3.1.1 
Summary of Adverse Events  
Table 14.3.1.2 
Summary of Treatment Emergent Adverse Events by System Organ Class and MedDRA 
Preferred Term 
Table 14.3.1.3 
Summary of Drug-Related Treatment Emergent Adverse Events by System Organ Class and 
MedDRA Preferred Term 
Table 14.3.2.1 
Listing of Deaths, Other Serious and Significant Adverse Events 
Table 14.3.2.2 
Listing of Treatment Emergent Adverse Events Leading to Withdrawal 
Table 14.3.4.1 
Listing of Abnormal On-Study Laboratory Values 
Table 14.3.4.2 
Listing of Clinically Significant On-Study Laboratory Values 
Table 14.3.4.3 
Summary of Blood Chemistry 
Table 14.3.4.4 
Summary of Hematology 
Table 14.3.4.5 
Summary of Quantitative Urinalysis 
Table 14.3.5.1 
Listing of Abnormal On-Study Vital Signs Values 
Table 14.3.5.2 
Listing of Clinically Significant On-Study Vital Signs Values 
Table 14.3.5.3 
Summary of Vital Signs 
Table 14.3.6.1 
Listing of Abnormal On-Study ECG Assessments 
Table 14.3.6.2 
Listing of Clinically Significant On-Study ECG Assessments 
Table 14.3.6.3 
Summary of ECG Assessments 
 
In text Tables: 
PK Parameters of Lasmiditan 
Summary of Statistical Analysis of Lasmiditan 
In text Figures: 
Linear Profile of the Mean for Lasmiditan  
Logarithmic Profile of the Mean for Lasmiditan 
Linear Regression of ln-Transformed Cmax vs Child-Pugh scores 
Linear Regression of ln-Transformed AUC(0-∞) vs Child-Pugh scores 
In text Figures (Section 14): 
Linear Regression of ln-Transformed AUC(0-tlast) vs Child-Pugh scores 


 
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Linear Regression of ln-Transformed CL/F vs Child-Pugh scores 
 
Appendix 16.2.6.1 
PK Tables – Plasma 
- 
Table X. Measured Human Plasma Concentrations  
- 
Table X. Cumulative Area Under the Curve  
- 
Table X. Pharmacokinetic Parameters X. Elimination Parameters  
- 
Table X. Actual Sampling Time 
Appendix 16.2.6.2 
PK – Figures  
- 
Figure x: Linear Profile of the Mean 
- 
Figure x: Logarithmic Profile of the Mean  
- 
Figure x: Individual Linear Profile of Subject x 
- 
Figure x: Individual Logarithmic Profile of Subject 
- 
Figure x: Individual Elimination Profiles 
 
 


 
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PLANNED LISTINGS 
 
Listing 16.2.1 
Listing of Study Disposition 
Listing 16.2.2.1 
Listing of PK Blood Sampling Time Deviations 
Listing 16.2.2.2 
Listing of Protocol Deviations 
Listing 16.2.3 
Listing of Analysis Populations 
Listing 16.2.4.1 
Listing of Demographic Characteristics 
Listing 16.2.4.2 
Listing of Screen Failure Subjects 
Listing 16.2.5 
Listing of Investigational Product Administration 
Listing 16.2.7 
Listing of Adverse Events  
Listing 16.2.8.1 
Listing of Blood Chemistry 
Listing 16.2.8.2 
Listing of Hematology 
Listing 16.2.8.3 
Listing of Urinalysis 
Listing 16.2.8.4 
Listing of Urine Drug Screen 
Listing 16.2.8.5 
Listing of Pregnancy Test 
Listing 16.2.8.6 
Listing of Serology 
Listing 16.2.8.7 
Listing of Endocrinology 
Listing 16.2.9.1 
Listing of Alcohol Habits 
Listing 16.2.9.2 
Listing of Smoking Habits 
Listing 16.2.9.3 
Listing of Prior Medication 
Listing 16.2.9.4 
Listing of Concomitant Medication 
Listing 16.2.9.5 
Listing of Physical Examination 
Listing 16.2.9.6 
Listing of Vital Signs 
Listing 16.2.9.7 
Listing of ECG Assessments 
Listing 16.2.9.8 
Listing of Inclusion/Exclusion Criteria Summary  
Listing 16.2.9.9 
Listing of Medical History 
Listing 16.2.9.10 
Listing of Columbia-Suicide Severity Rating Scale (C-SSRS) 
 
 
 
 


 
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APPENDIX A 
STUDY SCHEDULE 
 
 
 
a Early Termination (ET).  
b Vital signs will be measured prior to dosing and approximately 2 and 4 hours after study drug administration. 
c 12-lead ECG will be performed prior to dosing and approximately 2 hours after study drug administration. 
d Clinical laboratory tests (hematology, biochemistry, endocrinology (screening only) and urinalysis) will be performed. On Day -1, these will be done in the evening prior to drug 
administration. 
e PK blood and urine samples will be collected according to schedule of PK assessments 
 
 
 


 
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APPENDIX B 
Pharmacokinetic Parameters 
PK Parameter 
Definition 
Cmax  
Maximum observed plasma concentration 
Tmax 
Time of maximum observed plasma concentration; if it occurs at more than 
one time point, Tmax is defined as the first time point with this value 
AUC(0-tlast) 
Cumulative area under the plasma concentration time curve calculated from 0 
to TLQC using the linear trapezoidal method, where TLQC represents time of last 
observed quantifiable plasma concentration 
AUC(0-∞) 
Area under the plasma concentration time curve extrapolated to infinity, 
calculated as AUC(0-tlast) + ĈLQC/λZ, where ĈLQC is the estimated concentration 
at time TLQC  
%AUC(tlast-f) 
Relative percentage of AUC(0-tlast) with respect to AUC(0-∞) 
%




)
-
AUC(0
t
-
0
AUC
)
-
AUC(0
 
100
 
)
-
AUC(t
last
last
f

f
u
 
f
 
λZ 
Apparent elimination rate constant, estimated by linear regression of the 
terminal linear portion of the log concentration versus time curve 
T1/2 
Terminal elimination half-life, calculated as ln(2)/λZ 
CL/F 
Apparent Total Plasma Clearance, calculated as dose /AUC(0-∞ 
Vz/F 
Apparent Volume of Distribution, calculated as dose / λZ*AUC(0-∞ 
 
 
 


 
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APPENDIX C 
TABLE SHELLS 
CoLucid Pharmaceuticals, Inc. 
Algorithme Pharma 
Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Table 14.1.1 
Subject Disposition 
(All Subjects) 
 
   
   
Healthy 
Hepatic  
Function 
(N=XX) 
Mild 
Hepatic  
Function 
(N=XX) 
Moderate 
Hepatic  
Function 
(N=XX) 
Overall 
(N=XX) 
  
  
 
 
 
 
Subjects Enrolled 
 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
Screen Fail Subjects 
 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
Subjects Screened [N] 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Subjects Completed the Study [n(%)] 
YES 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
NO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
If No, Reason of Study Discontinuation [n(%)] 
Reason 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Reason 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Reason 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Number of Subjects Included in Each Analysis 
Population [n(%)] 
Safety Population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Pharmacokinetic Population 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
Note: The percentages are based on the number of subjects screened. 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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     Page 1 of x 
 
Table 14.1.2.1 
Summary of Demographic Characteristics 
(Safety Population) 
 
   
   
Healthy Hepatic  
Function 
(N=XX) 
Mild Hepatic  
Function 
(N=XX) 
Moderate 
Hepatic  
Function 
(N=XX) 
Overall 
(N=XX) 
 
  
  
 
 
 
 
 Age (years) 
N 
xx 
xx 
xx 
xx 
  
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
Median 
xx.x 
xx.x 
xx.x 
xx.x 
  
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
 
 
 
 Gender [n(%)] 
MALE 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
FEMALE 
 
 
 
 
  
 
 
 
 
 
 Ethnicity [n(%)] 
HISPANIC/LATINO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
NOT HISPANIC/NOT LATINO 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 Race [n(%)] 
RACE1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
RACE2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
 
 
 
 
 
 Weight (kg) 
N 
xx 
xx 
xx 
xx 
  
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
Median 
xx.x 
xx.x 
xx.x 
xx.x 
  
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
 
 
 
 Height (cm) 
N 
xx 
xx 
xx 
xx 
  
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
Median 
xx.x 
xx.x 
xx.x 
xx.x 
  
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
 
 
 
 Body Mass Index(kg/m2) 
N 
xx 
xx 
xx 
xx 
  
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  
Median 
xx.x 
xx.x 
xx.x 
xx.x 
  
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
  
 
 
  
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
Similar Table: 
 
Table 14.1.2.2 Summary of Demographic Characteristics (Pharmacokinetic Population) 


 
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Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
Table 14.3.1.1 
Summary of Adverse Events  
(Safety Population) 
 
   
 
 
 
 
 
Healthy Hepatic  
Function 
(N=XX) 
Mild Hepatic  
Function 
(N=XX) 
Moderate 
Hepatic  
Function 
(N=XX) 
Overall 
(N=XX) 
 
 
  
  
 
 
 
 
 Adverse Events (AEs) Reported [n] 
 
 
 
xx 
 
 
 
 
 
 
 
 
 Treatment Emergent Adverse Events (TEAEs) Reported [n] 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
Subjects With At Least One TEAE [n(%)]  [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Subjects With At Least One Drug-Related TEAE [n(%)] [1] 
[3] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
TEAEs Relationship  [2] 
 
 
 
 
 
Related [n(%)] [3] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not Related [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
TEAEs Severity/Intensity  [2] 
 
 
 
 
 
Mild [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Moderate [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Severe [n(%)]   
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 Life-Threatening [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 Serious Adverse Events (SAEs) Reported [n] [2] 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Subjects With At Least One SAE [n(%)][1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Subject With an TEAE Leading to Withdrawal [n(%)] [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Death [n(%)]  [1] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
  
 
 
 
 
  
 
[1] Percentages are based on the number of subjects in the Safety population in each treatment group. 
[2] Percentages are based on the total number of treatment emergent adverse events reported in each treatment group. 
[3] TEAE that was reported with a relationship of “reasonable possibility”. 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 


 
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Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Table 14.3.1.2 
Summary of Treatment Emergent Adverse Events by System Organ Class and MedDRA Preferred Term 
(Safety Population) 
 
   
   
 
 
 
  SOC 
   MedDRA Preferred Term 
Healthy Hepatic  
Function 
(N=XX) 
Mild Hepatic Function 
(N=XX) 
Moderate Hepatic Function 
(N=XX) 
 
 
  
  
 
 
 
 
 
 
 
 
 
 Subjects With At Least One TEAE [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 System Organ Class 1 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 11 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 12 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 13 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 System Organ Class 2 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 21 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 22 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   MedDRA Term 23 [n(%)] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
   Etc. 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
Note: Each treatment emergent adverse event is counted only once for each subject within each System Organ Class and MedDRA 
Preferred Term. 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
Similar Table: Table 14.3.1.3 Summary of Drug-Related Treatment Emergent Adverse Events by System Organ Class and MedDRA Preferred Term 
 
 
 
 


 
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     Page 1 of x 
 
Table 14.3.2.1 
Listing of Deaths, Other Serious and Significant Adverse Events 
(Safety Population) 
 
Subject ID 
Visit/ 
Group/ 
AE # 
SOC 
  MedDRA 
Preferred Term 
    Description 
of AE 
Onset Date  
Time 
(Time since 
Last Dose) 
Resolution 
Date Time 
(Duration) 
S: Severity 
R: Relationship 
to Study Drug 
O: Outcome 
S: Serious AE 
D: AE Leading To 
Discontinuation 
Action Taken With Study 
Treatment 
/ 
Other 
Action(s) 
Taken 
/ 
Concomitant Given 
 
 
 
 
 
 
 
 
 
 
xxx 
xxxxx 
xxxxx 
xxxxxxxxxxxx 
  xxxxxxxxxxxx 
     
xxxxxxxxxxxx 
YYYY-MM-DD/ 
HH:MM 
(DD:HH:MM) 
YYYY-MM-
DD/ 
HH:MM 
(DD:HH:MM) xxxxxx 
xxxxx 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
Similar Tables:  
14.3.2.2  Listing of Treatment Emergent Adverse Events Leading to Withdrawal 
 
 


 
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Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Table 14.3.4.1 
Listing of Abnormal On-Study Laboratory Values 
(Safety Population) 
 
Category/ 
Parameter (Unit) 
Reference 
Range 
Subject ID 
Visit 
 
 
Date / Time 
 
Value 
 
Out-of-Range 
Flag 
Assessment [1] 
 
 
 
  
 
 
 
 
 
 
Lab Category 1 
 
 
 
 
  
  
 
  Lab Test 11 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
  Lab Test 12 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lab Category 2 
 
 
 
 
 
 
 
 
 
  Lab Test 21 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
  Lab Test 22 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
  Etc. 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
[1] NCS: Not Clinically Significant   /   CS: Clinically Significant /  TBC: To Be Controlled. 
Note(s): Abnormal values are determined by applying the reference ranges to the results as reported by the external laboratory 
analysis. 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Table 14.3.4.2 
Listing of Clinically Significant On-Study Laboratory Values 
(Safety Population) 
 
Category/ 
Parameter (Unit) 
Reference Range 
Subject ID 
Visit 
 
 
Date / Time 
 
Value 
 
Out-of-
Range Flag  Assessment [1] 
 
 
 
  
 
 
 
 
 
 
Lab Category 1 
 
 
 
 
  
  
 
  Lab Test 11 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
  Lab Test 12 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lab Category 2 
 
 
 
 
 
 
 
 
 
  Lab Test 21 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
  Lab Test 22 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
  Etc. 
xxx-xxx 
xxx 
xxxxxx 
xxxxxx 
 
xxx 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
[1] CS: Clinically Significant / TBC: To Be Controlled.  
Note(s): Abnormal values are determined by applying the reference ranges to the results as reported by the external laboratory 
analysis. 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Table 14.3.4.3 
Summary of Blood Chemistry 
(Safety Population) 
 
   
 
 
   
 
 
 
 
Parameter (unit) 
Visit Name 
 
Statistic   
Healthy Hepatic  
Function 
(N=XX) 
Mild Hepatic  
Function 
(N=XX) 
Moderate Hepatic  
Function 
(N=XX) 
 
 
 
 
 
 
 
 
 
xxx (xxx) 
Screening 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
Day -1 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
Etc. 
 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
Similar Tables:  
14.3.4.4  Summary of Hematology 
14.3.4.5 
Summary of Quantitative Urinalysis 
 
 
 


 
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Table 14.3.5.1 
Listing of Abnormal On-Study Vital Signs Values 
(Safety Population) 
Assessment (Units) Subject ID 
Visit 
 
 
 
Position 
Date / Time 
 Value 
Safety Review 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Vital Sign Test 1 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Sign Test 2 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
Etc. 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
Table 14.3.5.2 
Listing of Clinically Significant On-Study Vital Signs Values 
(Safety Population) 
Assessment (Units) Subject ID 
Visit 
 
 
 
Position 
Date / Time 
 Value 
Safety Review 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Vital Sign Test 1 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Sign Test 2 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
Etc. 
xxx 
xxxxxx 
 
 
xxxxxx 
YYYY-MM-DD:XX:XX 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Algorithme Pharma 
Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
Table 14.3.5.3 
Summary of Vital Signs 
(Safety Population) 
 
 
 
 
 
 
 
 
 
 
Parameter (unit) 
 
Visit 
Timepoint 
 
Statistic 
Healthy Hepatic 
Function 
(N=XX) 
Mild Hepatic  
Function 
(N=XX) 
Moderate 
Hepatic  
Function 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Sign Test 1 
 
 
 
 
 
 
 
 
Screening 
 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
Day 1 
2 Hours 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
4 Hours 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAMMING NOTE:  All visits outlined in Appendix A will be included.  
  
 
  
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Table 14.3.6.1 
Listing of Abnormal On-Study ECG Assessments 
(Safety Population) 
 
Subject ID 
Visit 
Time Point 
Date / Time 
  Position 
Safety Review Parameter (Unit) 
Value 
 
 
 
 
  
 
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM   xxxxxx 
xxxxxx 
 
 
 
 
 
 
   
 
 
 
 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM   xxxxxx 
xxxxxx 
 
 
 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM   xxxxxx 
xxxxxx 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM   xxxxxx 
xxxxxx 
 
 
 
 
 
 
   
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM   xxxxxx 
xxxxxx 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Project #  COL MIG-114/CUD-P9-453 
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Table 14.3.6.2 
Listing of Clinically On-Study ECG Assessments 
(Safety Population) 
 
Subject ID 
Visit 
Time Point 
Date / Time 
  
Position 
Safety Review Parameter (Unit) 
Value 
 
 
 
 
 
 
 
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
 
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
 
 
 
 
xxxxx 
xxxxxx 
xxx 
YYYY-MM-DD: HH:MM 
  
xxxxxx 
xxxxxx 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Project #  COL MIG-114/CUD-P9-453 
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Table 14.3.6.3 
Summary of ECG Assessments 
(Safety Population) 
 
 
 
 
 
 
 
 
 
 
Parameter (unit) 
 
Visit 
Timepoint 
 
Statistic 
Healthy Hepatic 
Function 
(N=XX) 
Mild Hepatic  
Function 
(N=XX) 
Moderate 
Hepatic  
Function 
(N=XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG Assessment Test 1 
 
 
 
 
 
 
 
 
Screening 
 
Value 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Day -1 
 
Value 
 
 
 
 
 
 
 
 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
Day 1 
Pre-dose 
Value 
 
 
 
 
 
 
 
 
N 
xx 
xx 
xx 
 
 
 
 
Mean (SD) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Median 
xx.x 
xx.x 
xx.x 
 
 
 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
Etc. 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROGRAMMING NOTE:  All visits outlined in Appendix A will be included.  
  
 
  
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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APPENDIX D 
PHARMACOKINETIC OUTPUTS SHELLS  
Measured Human Plasma Concentrations of Lasmiditan, Normal Hepatic Function, CUD-P9-453 
 
Time 
(h)  
0.00 
0.25 
0.50 
1.00 
… 
… 
… 
… 
… 
36.00 
Hepatic Function 
Subject 
Concentration 
(ng/mL)  
Normal 
101 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
108 
 
 
 
 
 
 
 
 
 
 
N 
 
 
 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
 
 
 
SD  
 
 
 
 
 
 
 
 
 
 
 
Min  
 
 
 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
 
 
 
 
CV% 
 
 
 
 
 
 
 
 
 
 
Geometric Mean 
 
 
 
 
 
 
 
 
 
 
Geometric CV% 
 
 
 
 
 
 
 
 
 
 
BLQ : Below Limit of Quantitation 
NC: Not Calculated 


 
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Similar tables will be presented for all hepatic groups  


 
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Cumulative Area Under the Curve of Lasmiditan, Normal Hepatic Function, CUD-P9-453 
 
Time 
(h)  
0.00 
0.25 
0.50 
1.00 
… 
… 
… 
… 
… 
36.00 
Hepatic Function 
Subject 
Cumulative AUC 
(ng*h/mL)  
Normal 
101 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
108 
 
 
 
 
 
 
 
 
 
 
N 
 
 
 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
 
 
 
SD  
 
 
 
 
 
 
 
 
 
 
Min  
 
 
 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
 
 
 
 
 
CV% 
 
 
 
 
 
 
 
 
 
 
Geometric Mean 
 
 
 
 
 
 
 
 
 
 
Geometric CV% 
 
 
 
 
 
 
 
 
 
 
NC: Not Calculated 
 
Similar tables will be presented for all hepatic groups and for urine data by intervals. 
 


 
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Pharmacokinetic Parameters of Lasmiditan, Normal Hepatic Function, CUD-P9-453 
Hepatic Function 
Subject 
Cmax 
(ng/mL)  
Tmax 
(h)  
AUC(0-Tlast) 
(ng*h/mL)  
AUC(0-∞) 
(ng*h/mL)  
%AUC(tlast-
-∞) (%) 
T1/2 
(h) 
CL/F 
(L/h)  
VZ/F 
(L)  
Normal 
101 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
108 
 
 
 
 
 
 
 
 
N 
 
 
 
 
 
 
 
 
Mean 
 
NC 
 
 
 
NC 
 
 
SD  
 
NC 
 
 
 
NC 
 
 
Min  
 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
 
 
CV% 
 
NC 
 
 
 
NC 
 
 
 
Geometric Mean 
 
NC 
 
 
 
 
 
 
Geometric CV% 
 
NC 
 
 
 
 
 
 
Similar tables will be presented for all hepatic groups and for urine parameters. 
 
 


 
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Elimination Parameters of Lasmiditan, Normal Hepatic Function, CUD-P9-453 
Hepatic Function 
Subject 
TLIN 
(h)  
TLQC 
(h)  
Number of Points 
R2 
λz 
(1/h)  
Normal 
101 
 
 
 
 
 
… 
 
 
 
 
 
… 
 
 
 
 
 
… 
 
 
 
 
 
… 
 
 
 
 
 
… 
 
 
 
 
 
… 
 
 
 
 
 
108 
 
 
 
 
 
N 
 
 
 
 
 
Mean 
 
 
 
 
 
SD  
 
 
 
 
 
Min  
 
 
 
 
 
 
Median 
 
 
 
 
 
Max 
 
 
 
 
 
CV% 
 
 
 
 
 
Geometric Mean 
 
 
 
 
 
Geometric CV% 
 
 
 
 
 
A similar table will be presented for all hepatic groups. 


 
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Actual Sampling Time of Lasmiditan, Normal Hepatic Function, CUD-P9-453 
 
Time 
(h)  
0.00 
0.25 
0.50 
1.00 
… 
… 
… 
… 
… 
… 
… 
… 
… 
36.00 
Hepatic Function 
Subject 
Actual Time 
(h)  
Normal 
101 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
108 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Min  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CV% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Geometric Mean 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Geometric CV% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NC: Not Calculated 
A similar table will be presented for all hepatic groups. 


 
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Pairwise Comparisons of Lasmiditan, CUD-P9-453 
Parameters 
Geometric LSmeansa 
Comparison 
Adjusted p-
value 
Ratio 
(%) 
90% Confidence Limits (%) 
Group 
 
Lower  
Upper 
Cmax 
Mild (n=x) 
 
Mild vs Moderate 
 
 
 
 
Moderate (n=x) 
 
Mild vs Normal 
 
 
 
 
Normal (n=x) 
 
Moderate vs Normal 
 
 
 
 
AUC(0-tlast) 
Mild (n=x) 
 
Mild vs Moderate 
 
 
 
 
Moderate (n=x) 
 
Mild vs Normal 
 
 
 
 
Normal (n=x) 
 
Moderate vs Normal 
 
 
 
 
AUC(0-∞) 
Mild (n=x) 
 
Mild vs Moderate 
 
 
 
 
Moderate (n=x) 
 
Mild vs Normal 
 
 
 
 
Normal (n=x) 
 
Moderate vs Normal 
 
 
 
 
a Cmax is presented in ng/mL, AUC(0-tlast) and AUC(0-∞) are presented in ng*h/mL 
 
Paired Comparisons of Tmax, Lasmiditan, CUD-P9-453 
Parameter 
Median (Range) 
Comparison 
P-value for 
Difference 
from Control 
Hodges-
Lehmann 
Median for 
Difference 
from Control 
 
90% Confidence Limits for 
Difference from Control 
Group 
 
Lower  
Upper 
Tmax 
Mild (n=x) 
 
Mild vs Moderate 
 
 
 
 
Moderate (n=x) 
 
Mild vs Normal 
 
 
 
 
Normal (n=x) 
 
Moderate vs Normal 
 
 
 
 
Tmax was analyzed using the Wilcoxon rank sum test 
 


 
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PHARMACOKINETIC FIGURES SHELLS  
Figure 1: Linear Profile of the Mean of Lasmiditan in Plasma 
 
 
The figure does not reflect the actual data of the study 
0
100
200
300
400
Concentration (ng/mL)
0
200
400
600
800
Time (h)
Moderate
Normal
Severe


 
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Figure 2: Logarithmic Profile of the Mean of Lasmiditan in Plasma 
 
 
The figure does not reflect the actual data of the study 
 
 
1
10
100
1000
Concentration (ng/mL)
0
200
400
600
800
Time (h)
Moderate
Normal
Severe


 
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Figures 2+1 to (2+1)+N: Individual Linear Profile of Lasmiditan in Plasma 
 
The figure does not reflect the actual data of the study 
 
 
0
100
200
300
400
500
Concentration (ng/mL)
0
200
400
600
800
Time (h)
SubjectNumber=101, RenalGroup=Normal


 
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Figure X: Individual Logarithmic Profile of Lasmiditan in Plasma 
 
 The figure does not reflect the actual data of the study 
 
1
10
100
1000
Concentration (ng/mL)
0
200
400
600
800
Time (h)
SubjectNumber=101, RenalGroup=Normal


 
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Figure N: Individual Elimination Profiles 
 
The figure does not reflect the actual data of the study. 


 
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In Text Figure: 
Figure 
1: 
Linear 
Regression 
of 
ln-Transformed 
Cmax 
vs 
Child-Pugh 
scores
 
The figure does not reflect the actual data of the study. Same graph will be presented for AUC(0-tlast),AUC(0-∞) and CL/F. 
 
 


 
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APPENDIX E 
LISTING SHELLS  
 
 
 


 
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CoLucid Pharmaceuticals, Inc. 
Algorithme Pharma 
Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Listing 16.2.1 
Listing of Study Disposition 
 
 
Subject ID 
Date of Completion or 
Discontinuation 
Subject Status 
Specify 
AE # 
Date of Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.2.1 
Listing of PK Blood Sampling Time Deviations 
 
 
Group 
 Elapsed 
Time (h) 
 Subject ID 
Scheduled 
Date/Time 
Actual 
Date/Time 
Deviation (min) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.3 
Listing of Analysis Populations 
 
Subject ID 
Safety 
Population PK Population  Reason if Excluded from one Population 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.4.1 
Listing of Demographic Characteristics 
 
 
Subject ID 
Age Date of Birth Gender 
Ethnicity Race 
Other Race  
 
Weight (kg)  
Height (cm) 
BMI (kg/m2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.4.2 
Listing of Screen Failures  
 
 
Subject ID 
Date 
 
Specify Primary Reason 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.5 
Listing of Investigational Product Administration 
 
 
 
 
Subject ID 
Visit 
Start 
Date/Time 
 
Treatment 
Dose 
Administered (mg) 
Route 
 
If Any Dosing Issues, 
Specify 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
  
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.7  
Listing of Adverse Events 
 
 
Subject ID 
Visit/ 
Group/ 
AE # 
SOC 
  MedDRA 
Preferred Term 
    Description 
of AE 
Onset Date  
Time 
(Time since 
Last Dose) 
Resolution 
Date Time 
(Duration) 
S: Severity 
R: Relationship 
to Study 
Drug 
O: Outcome 
S: Serious AE 
D: AE Leading To 
Discontinuation 
Action Taken With 
Study Treatment / 
Other Action(s) Taken 
/ Concomitant Given 
 
 
 
  
  
 
 
 
 
 
xxx 
xxxxx 
xxxxx 
xxxxxxxxxxxx 
  xxxxxxxxxxxx 
     
xxxxxxxxxxxx 
YYYY-MM-DD/ 
HH:MM 
(DD:HH:MM) 
YYYY-MM-DD/ 
HH:MM 
(DD:HH:MM) 
xxxxxx 
xxxxx 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 


 
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Listing 16.2.8.1 
Listing of Blood Chemistry 
 
 
Subject ID 
Lab Test Name (Units) 
Reference Range 
Visit 
Date / Time   Value 
 
Out-of-Range 
Flag 
Assessment 
[1] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
[1] NCS: Not Clinically Significant   /   CS: Clinically Significant  /  TBC: To Be Controlled. 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
Similar listing(s): 
 
L16.2.8.2 
 
Listing of Hematology 
L16.2.8.3 
 
Listing of Urinalysis 
L16.2.8.4 
 
Listing of Urine Drug Screen 
L16.2.8.5 
 
Listing of Pregnancy Test 
L16.2.8.6 
 
Listing of Serology 
L16.2.8.7 
 
Listing of Endocrinology 
 
 


 
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Listing 16.2.9.1 
Listing of Alcohol Habits 
 
 
Subject ID 
Intake Status 
Quantity 
Frequency 
Start Date 
End Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
  
 
 


 
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     Page 1 of x 
 
Listing 16.2.9.2 
Listing of Smoking Habits 
 
 
Subject ID 
Intake Status 
Quantity 
Frequency 
Start Date 
End Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.3 
Listing of Prior Medication  
 
 
Subject ID 
#CM  
Related to 
AE#/MH# 
ATC / 
PT / 
Medication 
Name 
Indication 
Dose 
(unit) 
Frequency Formulation 
Total 
Daily 
Dose 
Route 
Start 
Date/ 
Time 
End  
Date/ 
Time 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
Similar Listing:  
 
Listing 16.2.9.4 Listing of Concomitant Medication 
 
 


 
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Listing 16.2.9.5 
Listing of Physical Examination 
 
 
Subject ID 
Visit  
 Date / Time 
 Body System Examined 
Result  (Abnormal Findings) 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.6 
Listing of Vital Signs  
 
 
Subject ID 
Visit 
 
 
Timepoint 
 
Position 
Date / Time 
 
Assessment 
(Units)  
Value  
Safety 
Review  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.7 
Listing of ECG Assessments 
 
 
Subject ID 
Visit 
Time Point 
 Date / Time 
Position 
Safety Review Parameter (Unit) Value 
 
 
 
 
 
 
 
 
 
xxxxx 
xxxxxx 
 
 YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
 
 
 
 
  
 
 
 
 
 
 
 
 YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
 
 
 
 
 YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
xxxxx 
xxxxxx 
 
 YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
 
 
 
 
  
 
 
 
 
xxxxx 
xxxxxx 
 
 YYYY-MM-DD: HH:MM 
xxxxxx 
xxxxxx 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.8 
Listing of Inclusion/Exclusion Criteria Summary 
 
 
Subject ID 
Has the participant met all 
screening eligibility criteria? 
Inclusion/Exclusion 
Failed Criterion Number 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
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Listing 16.2.9.9 
Listing of Medical History 
 
 
Subject ID 
MH # System Organ Class 
MedDRA Preferred Term 
Description of Medical 
History 
Start Date 
End Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
          
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 


 
Research Protocol No CUD-P9-453 | Sponsor Project No COL MIG-114 | Version 1.0| 2017/10/24 
72 
CoLucid Pharmaceuticals, Inc. 
CONFIDENTIAL 
Project #  COL MIG-114/CUD-P9-453 
     Page 1 of x 
 
Listing 16.2.9.10 
Listing of Columbia-Suicide Severity Rating Scale (C-SSRS) 
 
 
Subject ID 
Visit 
Category 
Question 
Answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: VERSION – YYYY-MM-DD 
Data Source: XXXX 
Program Source:  XXXXX.sas 
 
 
 
 


 
Research Protocol No CUD-P9-453 | Sponsor Project No COL MIG-114 | Version 1.0| 2017/10/24 
73 
 
 
 
 
 
contact@altasciences.com 
altasciences.com 
 
 
10103 Metcalf Ave.  
Overland Park, KS 66212 
United States 
913 696-1601 
vinceandassociates.com 
575 Armand-Frappier Blvd. 
Laval, Quebec  
Canada H7V 4B3 
450 973-6077 
algopharm.com 
4837 Amber Valley Parkway 
Fargo, ND 58104 
United States 
701 551-3737 
algopharm.com 


Clinical Study Report  
Project No COL MIG-114/H8H-CD-LAHF 
 
16.1.9.2 Documentation of statistical analysis – SAS® output 
Legend:  
AUCinf= AUC0−∞ 
AUCT=AUC0-Tlast 
LambdaZ = λZ 
Vz_F = Vz/F 
CL_F = CL/F 
lCmax= ln(Cmax) 
lAUCT= ln(AUC0-Tlast) 
lAUCinf= ln(AUC0−∞) 
lVz_F = ln(Vz/F) 
lCL_F = ln (CL/F) 
RkTmax= Rank of Tmax 
 


14:27 Thursday, February 8, 2018
1
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
RAW DATA
--------------------- SUMMARY REPORT ---------------------
14:27 Thursday, February 8, 2018
1
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
RAW DATA
--------------------- SUMMARY REPORT ---------------------
Hepatic Function Group=Mild
Obs Subject
ID
Cmax
Tmax
AUCT
AUCinf
Vz_F
Cl_F
LambdaZ log{Cmax} log{AUCT}
 1 01401
159.00000 2.00000 1229.31750 1261.85792 1586.25544 158.49645 0.09992
5.06890
7.11421
 2 01402
350.00000 0.75000 1629.60250 1673.31600 1370.20933 119.52315 0.08723
5.85793
7.39609
 3 01404
125.00000 2.00000
978.55250 1007.61169 1257.71336 198.48916 0.15782
4.82831
6.88607
 4 01408
518.00000 0.75000 2019.77500 2033.41542
507.28430
98.35668 0.19389
6.24998
7.61074
 5 04101
255.00000 2.50000 2212.32550 2264.40458
855.45252
88.32344 0.10325
5.54126
7.70180
 6 04102
258.00000 2.50000 1603.91250 1635.53001
744.38302 122.28452 0.16428
5.55296
7.38020
 7 04105
220.00000 3.00000 1952.02000 2002.86802 1017.88226
99.85680 0.09810
5.39363
7.57662
 8 04106
416.00000 1.50000 3229.05750 3318.46597
590.96250
60.26881 0.10198
6.03069
8.07995
Obs log{AUCinf} log{CLF} log{LambdaZ} log{Vz_F} Rank{Tmax}
Child-Pugh
classification
Individual Child-Pugh
scores
 1 
7.14034
5.06573
-2.30340
7.36913
14.0
A
5
 2 
7.42256
4.78351
-2.43921
7.22272
2.0
A
5
 3 
6.91534
5.29073
-1.84632
7.13705
14.0
A
5
 4 
7.61747
4.58860
-1.64047
6.22907
2.0
A
6
 5 
7.72507
4.48101
-2.27063
6.75163
18.0
A
5
 6 
7.39972
4.80635
-1.80621
6.61256
18.0
A
5
 7 
7.60234
4.60374
-2.32174
6.92548
21.5
A
5
 8 
8.10726
4.09881
-2.28294
6.38175
8.0
A
5


14:27 Thursday, February 8, 2018
2
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
RAW DATA
--------------------- SUMMARY REPORT ---------------------
14:27 Thursday, February 8, 2018
2
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
RAW DATA
--------------------- SUMMARY REPORT ---------------------
Hepatic Function Group=Moderate
Obs Subject
ID
Cmax
Tmax
AUCT
AUCinf
Vz_F
Cl_F
LambdaZ log{Cmax} log{AUCT}
 9 01403
207.00000 1.25000
960.51333 1008.11653 1898.74936 198.38976 0.10448
5.33272
6.86747
 10 01405
259.00000 1.25000 1831.00000 1870.55382 1134.00305 106.92021 0.09429
5.55683
7.51262
 11 01407
388.00000 1.50000 3600.06667 3810.94140
675.54883
52.48047 0.07769
5.96101
8.18871
 12 01409
221.00000 1.00000 1883.79000 2010.53704 1368.73641
99.47591 0.07268
5.39816
7.54104
 13 04104
359.00000 2.00000 2689.72500 2780.70989
806.74296
71.92408 0.08915
5.88332
7.89719
 14 04107
419.00000 0.75000 3096.65500 3231.82927
774.07373
61.88446 0.07995
6.03787
8.03808
 15 04108
143.00000 1.75000
971.09000
986.38429 1925.20006 202.76073 0.10532
4.96284
6.87842
 16 04110
565.00000 1.50000 3696.07500 3825.60443
573.48982
52.27932 0.09116
6.33683
8.21503
Obs log{AUCinf} log{CLF} log{LambdaZ} log{Vz_F} Rank{Tmax}
Child-Pugh
classification
Individual Child-Pugh
scores
 9 
6.91584
5.29023
-2.25872
7.54895
5.5
B
7
 10 
7.53399
4.67208
-2.36143
7.03351
5.5
B
8
 11 
8.24563
3.96044
-2.55508
6.51553
8.0
B
8
 12 
7.60616
4.59992
-2.62173
7.22164
4.0
B
8
 13 
7.93046
4.27561
-2.41739
6.69301
14.0
B
7
 14 
8.08080
4.12527
-2.52640
6.65167
2.0
B
7
 15 
6.89405
5.31203
-2.25076
7.56279
10.5
B
7
 16 
8.24947
3.95660
-2.39514
6.35174
8.0
B
7


14:27 Thursday, February 8, 2018
3
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
RAW DATA
--------------------- SUMMARY REPORT ---------------------
14:27 Thursday, February 8, 2018
3
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
RAW DATA
--------------------- SUMMARY REPORT ---------------------
Hepatic Function Group=Healthy
Obs Subject
ID
Cmax
Tmax
AUCT
AUCinf
Vz_F
Cl_F
LambdaZ log{Cmax} log{AUCT}
 17 00102
199.00000 4.00000 1902.08500 1922.96133
816.67119 104.00625 0.12735
5.29330
7.55071
 18 00103
307.00000 1.75000 1863.04750 1870.37367
703.84229 106.93050 0.15192
5.72685
7.52997
 19 00104
216.00000 2.00000 1812.21750 1831.52555
887.40804 109.19859 0.12305
5.37528
7.50231
 20 00111
270.00000 2.00000 1729.46000 1767.45418
770.47408 113.15711 0.14687
5.59842
7.45556
 21 00114
189.00000 2.50000 1112.41750 1131.26315 1168.42476 176.79353 0.15131
5.24175
7.01429
 22 00115
288.00000 2.53333 2136.05833 2146.74786
652.50784
93.16418 0.14278
5.66296
7.66672
 23 00116
149.00000 3.00000
886.38500
916.53880 1680.43024 218.21226 0.12985
5.00395
6.78715
 24 00119
192.00000 4.00000 1706.38150 1724.86484
957.16011 115.95111 0.12114
5.25750
7.44213
Obs log{AUCinf} log{CLF} log{LambdaZ} log{Vz_F} Rank{Tmax}
Child-Pugh
classification
Individual Child-Pugh
scores
 17 
7.56162
4.64445
-2.06079
6.70524
23.5
 18 
7.53389
4.67218
-1.88438
6.55655
10.5
 19 
7.51290
4.69317
-2.09514
6.78830
14.0
 20 
7.47730
4.72878
-1.91823
6.64701
14.0
 21 
7.03109
5.17498
-1.88843
7.06341
18.0
 22 
7.67171
4.53436
-1.94646
6.48082
20.0
 23 
6.82060
5.38547
-2.04134
7.42681
21.5
 24 
7.45290
4.75317
-2.11080
6.86397
23.5


14:27 Thursday, February 8, 2018
4
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
DESCRIPTIVE RESULTS (OVERALL)
--------------------- SUMMARY REPORT ---------------------
14:27 Thursday, February 8, 2018
4
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
DESCRIPTIVE RESULTS (OVERALL)
--------------------- SUMMARY REPORT ---------------------
Parameter Hepatic
Function
Group
n
Min
Mean
Geometric
Mean
Median
Max
Range
Standard
Deviation
Coefficient
of
Variation
Cmax
Mild 8
125.00000
287.62500
261.24477
256.50000
518.00000
393.00000
132.53025
46.0774
Cmax
Moderate 8
143.00000
320.12500
294.03456
309.00000
565.00000
422.00000
138.14634
43.1539
Cmax
Healthy 8
149.00000
226.25000
220.30221
207.50000
307.00000
158.00000
55.57942
24.5655
Tmax
Mild 8
0.75000
1.87500
1.67942
2.00000
3.00000
2.25000
0.82375
43.9336
Tmax
Moderate 8
0.75000
1.37500
1.32021
1.37500
2.00000
1.25000
0.40089
29.1558
Tmax
Healthy 8
1.75000
2.72292
2.60613
2.51667
4.00000
2.25000
0.87962
32.3042
AUCT
Mild 8
978.55250 1856.82038 1751.47050 1790.81125 3229.05750 2250.50500
689.27918
37.1215
AUCT
Moderate 8
960.51333 2341.11438 2084.57232 2286.75750 3696.07500 2735.56167 1093.20227
46.6958
AUCT
Healthy 8
886.38500 1643.50654 1585.41976 1770.83875 2136.05833 1249.67333
423.04366
25.7403
AUCinf
Mild 8 1007.61169 1899.68370 1792.31256 1838.09201 3318.46597 2310.85427
706.91779
37.2124
AUCinf
Moderate 8
986.38429 2440.58459 2169.06192 2395.62347 3825.60443 2839.22013 1147.32299
47.0102
AUCinf
Healthy 8
916.53880 1663.96617 1608.01033 1799.48986 2146.74786 1230.20906
418.78659
25.1680
Vz_F
Mild 8
507.28430
991.26784
923.96469
936.66739 1586.25544 1078.97114
386.04048
38.9441
Vz_F
Moderate 8
573.48982 1144.56803 1040.39245
970.37300 1925.20006 1351.71024
537.99098
47.0038
Vz_F
Healthy 8
652.50784
954.61482
912.79750
852.03962 1680.43024 1027.92241
334.69340
35.0606
CL_F
Mild 8
60.26881
118.19988
111.58768
109.68998
198.48916
138.22035
43.20623
36.5535
CL_F
Moderate 8
52.27932
105.76437
92.20576
85.69999
202.76073
150.48141
61.87438
58.5021
CL_F
Healthy 8
93.16418
129.67669
124.37731
111.17785
218.21226
125.04808
43.83200
33.8010
LambdaZ
Mild 8
0.08723
0.12581
0.12077
0.10262
0.19389
0.10666
0.03990
31.7121
LambdaZ
Moderate 8
0.07268
0.08934
0.08863
0.09016
0.10532
0.03264
0.01204
13.4733
LambdaZ
Healthy 8
0.12114
0.13679
0.13626
0.13632
0.15192
0.03078
0.01281
9.3622
lCmax
Mild 8
4.82831
5.56546
5.54711
6.24998
1.42166
0.47671
8.5655
lCmax
Moderate 8
4.96284
5.68370
5.72008
6.33683
1.37398
0.44868
7.8942
lCmax
Healthy 8
5.00395
5.39500
5.33429
5.72685
0.72290
0.24766
4.5906
lAUCT
Mild 8
6.88607
7.46821
7.48636
8.07995
1.19387
0.36606
4.9016
lAUCT
Moderate 8
6.86747
7.64232
7.71912
8.21503
1.34756
0.54237
7.0969
lAUCT
Healthy 8
6.78715
7.36860
7.47894
7.66672
0.87957
0.30297
4.1117
lAUCinf
Mild 8
6.91534
7.49126
7.51245
8.10726
1.19192
0.36456
4.8664
lAUCinf
Moderate 8
6.89405
7.68205
7.76831
8.24947
1.35543
0.54720
7.1231
lAUCinf
Healthy 8
6.82060
7.38275
7.49510
7.67171
0.85110
0.29491
3.9946
lCLF
Mild 8
4.09881
4.71481
4.69362
5.29073
1.19192
0.36456
7.7322
lCLF
Moderate 8
3.95660
4.52402
4.43776
5.31203
1.35543
0.54720
12.0955
lCLF
Healthy 8
4.53436
4.82332
4.71097
5.38547
0.85110
0.29491
6.1143
lLambdaZ
Mild 8
-2.43921
-2.11386
-2.27678
-1.64047
0.79874
0.29964
-14.1749
lLambdaZ
Moderate 8
-2.62173
-2.42333
-2.40627
-2.25076
0.37097
0.13569
-5.5994
lLambdaZ
Healthy 8
-2.11080
-1.99319
-1.99390
-1.88438
0.22643
0.09391
-4.7114
lVz_F
Mild 8
6.22907
6.82867
6.83856
7.36913
1.14006
0.40774
5.9709
lVz_F
Moderate 8
6.35174
6.94735
6.86326
7.56279
1.21104
0.46548
6.7001
lVz_F
Healthy 8
6.48082
6.81651
6.74677
7.42681
0.94598
0.30656
4.4973
RkTmax
Mild 8
2.00000
12.18750
9.01672
14.00000
21.50000
19.50000
7.42552
60.9274
RkTmax
Moderate 8
2.00000
7.18750
6.23253
6.75000
14.00000
12.00000
3.80730
52.9711
RkTmax
Healthy 8
10.50000
18.12500
17.50009
19.00000
23.50000
13.00000
4.85320
26.7763


14:27 Thursday, February 8, 2018
5
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
14:27 Thursday, February 8, 2018
5
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=1 Param=Cmax
Model Information
 Data Set 
WORK.KINDATA
 Dependent Variable 
Value
 Covariance Structure 
Variance Components
 Group Effect 
FunctionGroup
 Estimation Method 
REML
 Residual Variance Method 
None
 Fixed Effects SE Method 
Model-Based
 Degrees of Freedom Method Between-Within
Class Level Information
Class
Levels Values
 FunctionGroup 
3 1 2 3
Dimensions
 Covariance Parameters 
3
 Columns in X 
4
 Columns in Z 
0
 Subjects 
24
 Max Obs per Subject 
1
Number of Observations
 Number of Observations Read 
24
 Number of Observations Used 
24
 Number of Observations Not Used 
0
Iteration History
Iteration Evaluations -2 Res Log Like Criterion
      0 
1
265.15407978
      1 
1
259.49486652 0.00000000
Convergence criteria met.
Covariance Parameter Estimates
Cov Parm
Group
Estimate
 Residual FunctionGroup 1
17564
 Residual FunctionGroup 2
19084
 Residual FunctionGroup 3
3089.07
Fit Statistics
 -2 Res Log Likelihood 
259.5
 AIC (Smaller is Better) 
265.5
 AICC (Smaller is Better) 266.9
 BIC (Smaller is Better) 
269.0
Null Model Likelihood
Ratio Test
DF Chi-Square Pr > ChiSq
2
5.66
0.0590
Type 3 Tests of Fixed Effects
Effect
Num
DF
Den
DF
F Value Pr > F
 FunctionGroup 
2
21
2.05 0.1536


14:27 Thursday, February 8, 2018
6
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=1 Param=Cmax
Least Squares Means
Effect
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t| Alpha
Lower
Upper
 FunctionGroup 1
287.62
46.8565 21
6.14
<.0001
0.1 207.00 368.25
 FunctionGroup 2
320.13
48.8421 21
6.55
<.0001
0.1 236.08 404.17
 FunctionGroup 3
226.25
19.6503 21
11.51
<.0001
0.1 192.44 260.06
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t|
Adjustment
Adj P Alpha
Lower
Upper
 FunctionGroup 1
2
-32.5000
67.6837 21
-0.48
0.6361 Tukey-Kramer 0.8814
0.1
-148.97 83.9663
 FunctionGroup 1
3
61.3750
50.8101 21
1.21
0.2405 Tukey-Kramer 0.4617
0.1 -26.0561
148.81
 FunctionGroup 2
3
93.8750
52.6468 21
1.78
0.0890 Tukey-Kramer 0.1995
0.1
3.2834
184.47
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Adj
Lower
Adj
Upper
 FunctionGroup 1
2
-179.37 114.37
 FunctionGroup 1
3
-48.8797 171.63
 FunctionGroup 2
3
-20.3652 208.12


14:27 Thursday, February 8, 2018
7
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
14:27 Thursday, February 8, 2018
7
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=3 Param=AUCT
Model Information
 Data Set 
WORK.KINDATA
 Dependent Variable 
Value
 Covariance Structure 
Variance Components
 Group Effect 
FunctionGroup
 Estimation Method 
REML
 Residual Variance Method 
None
 Fixed Effects SE Method 
Model-Based
 Degrees of Freedom Method Between-Within
Class Level Information
Class
Levels Values
 FunctionGroup 
3 1 2 3
Dimensions
 Covariance Parameters 
3
 Columns in X 
4
 Columns in Z 
0
 Subjects 
24
 Max Obs per Subject 
1
Number of Observations
 Number of Observations Read 
24
 Number of Observations Used 
24
 Number of Observations Not Used 
0
Iteration History
Iteration Evaluations -2 Res Log Like Criterion
      0 
1
345.79800104
      1 
1
339.95357919 0.00000000
Convergence criteria met.
Covariance Parameter Estimates
Cov Parm
Group
Estimate
 Residual FunctionGroup 1
475106
 Residual FunctionGroup 2
1195091
 Residual FunctionGroup 3
178966
Fit Statistics
 -2 Res Log Likelihood 
340.0
 AIC (Smaller is Better) 
346.0
 AICC (Smaller is Better) 347.4
 BIC (Smaller is Better) 
349.5
Null Model Likelihood
Ratio Test
DF Chi-Square Pr > ChiSq
2
5.84
0.0538
Type 3 Tests of Fixed Effects
Effect
Num
DF
Den
DF
F Value Pr > F
 FunctionGroup 
2
21
1.51 0.2436


14:27 Thursday, February 8, 2018
8
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=3 Param=AUCT
Least Squares Means
Effect
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t| Alpha
Lower
Upper
 FunctionGroup 1
1856.82
243.70 21
7.62
<.0001
0.1 1437.48 2276.16
 FunctionGroup 2
2341.11
386.51 21
6.06
<.0001
0.1 1676.04 3006.19
 FunctionGroup 3
1643.51
149.57 21
10.99
<.0001
0.1 1386.14 1900.88
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t|
Adjustment
Adj P Alpha
Lower
Upper
 FunctionGroup 1
2
-484.29
456.92 21
-1.06
0.3012 Tukey-Kramer 0.5486
0.1 -1270.53
301.95
 FunctionGroup 1
3
213.31
285.94 21
0.75
0.4639 Tukey-Kramer 0.7393
0.1
-278.71
705.33
 FunctionGroup 2
3
697.61
414.44 21
1.68
0.1071 Tukey-Kramer 0.2348
0.1 -15.5299 1410.75
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Adj
Lower
Adj
Upper
 FunctionGroup 1
2
-1475.78
507.19
 FunctionGroup 1
3
-407.15
833.77
 FunctionGroup 2
3
-201.69 1596.91


14:27 Thursday, February 8, 2018
9
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
14:27 Thursday, February 8, 2018
9
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=4 Param=AUCinf
Model Information
 Data Set 
WORK.KINDATA
 Dependent Variable 
Value
 Covariance Structure 
Variance Components
 Group Effect 
FunctionGroup
 Estimation Method 
REML
 Residual Variance Method 
None
 Fixed Effects SE Method 
Model-Based
 Degrees of Freedom Method Between-Within
Class Level Information
Class
Levels Values
 FunctionGroup 
3 1 2 3
Dimensions
 Covariance Parameters 
3
 Columns in X 
4
 Columns in Z 
0
 Subjects 
24
 Max Obs per Subject 
1
Number of Observations
 Number of Observations Read 
24
 Number of Observations Used 
24
 Number of Observations Not Used 
0
Iteration History
Iteration Evaluations -2 Res Log Like Criterion
      0 
1
347.35488834
      1 
1
340.84221814 0.00000000
Convergence criteria met.
Covariance Parameter Estimates
Cov Parm
Group
Estimate
 Residual FunctionGroup 1
499733
 Residual FunctionGroup 2
1316350
 Residual FunctionGroup 3
175382
Fit Statistics
 -2 Res Log Likelihood 
340.8
 AIC (Smaller is Better) 
346.8
 AICC (Smaller is Better) 348.3
 BIC (Smaller is Better) 
350.4
Null Model Likelihood
Ratio Test
DF Chi-Square Pr > ChiSq
2
6.51
0.0385
Type 3 Tests of Fixed Effects
Effect
Num
DF
Den
DF
F Value Pr > F
 FunctionGroup 
2
21
1.74 0.1991


14:27 Thursday, February 8, 2018
10
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=4 Param=AUCinf
Least Squares Means
Effect
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t| Alpha
Lower
Upper
 FunctionGroup 1
1899.68
249.93 21
7.60
<.0001
0.1 1469.61 2329.75
 FunctionGroup 2
2440.58
405.64 21
6.02
<.0001
0.1 1742.58 3138.59
 FunctionGroup 3
1663.97
148.06 21
11.24
<.0001
0.1 1409.19 1918.75
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t|
Adjustment
Adj P Alpha
Lower
Upper
 FunctionGroup 1
2
-540.90
476.46 21
-1.14
0.2691 Tukey-Kramer 0.5037
0.1 -1360.76
278.96
 FunctionGroup 1
3
235.72
290.50 21
0.81
0.4262 Tukey-Kramer 0.7002
0.1
-264.16
735.59
 FunctionGroup 2
3
776.62
431.82 21
1.80
0.0865 Tukey-Kramer 0.1944
0.1
33.5712 1519.67
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Adj
Lower
Adj
Upper
 FunctionGroup 1
2
-1574.78
492.98
 FunctionGroup 1
3
-394.65
866.08
 FunctionGroup 2
3
-160.40 1713.64


14:27 Thursday, February 8, 2018
11
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
14:27 Thursday, February 8, 2018
11
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=8 Param=lCmax
Model Information
 Data Set 
WORK.KINDATA
 Dependent Variable 
Value
 Covariance Structure 
Variance Components
 Group Effect 
FunctionGroup
 Estimation Method 
REML
 Residual Variance Method 
None
 Fixed Effects SE Method 
Model-Based
 Degrees of Freedom Method Between-Within
Class Level Information
Class
Levels Values
 FunctionGroup 
3 1 2 3
Dimensions
 Covariance Parameters 
3
 Columns in X 
4
 Columns in Z 
0
 Subjects 
24
 Max Obs per Subject 
1
Number of Observations
 Number of Observations Read 
24
 Number of Observations Used 
24
 Number of Observations Not Used 
0
Iteration History
Iteration Evaluations -2 Res Log Like Criterion
      0 
1
27.77835282
      1 
1
24.70196938 0.00000000
Convergence criteria met.
Covariance Parameter Estimates
Cov Parm
Group
Estimate
 Residual FunctionGroup 1
0.2273
 Residual FunctionGroup 2
0.2013
 Residual FunctionGroup 3
0.06134
Fit Statistics
 -2 Res Log Likelihood 
24.7
 AIC (Smaller is Better) 
30.7
 AICC (Smaller is Better) 
32.1
 BIC (Smaller is Better) 
34.2
Null Model Likelihood
Ratio Test
DF Chi-Square Pr > ChiSq
2
3.08
0.2148
Type 3 Tests of Fixed Effects
Effect
Num
DF
Den
DF
F Value Pr > F
 FunctionGroup 
2
21
1.42 0.2630


14:27 Thursday, February 8, 2018
12
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=8 Param=lCmax
Least Squares Means
Effect
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t| Alpha
Lower
Upper
 FunctionGroup 1
5.5655
0.1685 21
33.02
<.0001
0.1 5.2754 5.8555
 FunctionGroup 2
5.6837
0.1586 21
35.83
<.0001
0.1 5.4107 5.9567
 FunctionGroup 3
5.3950
0.08756 21
61.61
<.0001
0.1 5.2443 5.5457
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t|
Adjustment
Adj P Alpha
Lower
Upper
 FunctionGroup 1
2
-0.1182
0.2315 21
-0.51
0.6148 Tukey-Kramer 0.8669
0.1
-0.5165 0.2800
 FunctionGroup 1
3
0.1705
0.1899 21
0.90
0.3796 Tukey-Kramer 0.6478
0.1
-0.1564 0.4973
 FunctionGroup 2
3
0.2887
0.1812 21
1.59
0.1260 Tukey-Kramer 0.2704
0.1 -0.02309 0.6005
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Adj
Lower
Adj
Upper
 FunctionGroup 1
2
-0.6205 0.3840
 FunctionGroup 1
3
-0.2417 0.5826
 FunctionGroup 2
3
-0.1045 0.6819


14:27 Thursday, February 8, 2018
13
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
14:27 Thursday, February 8, 2018
13
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=9 Param=lAUCT
Model Information
 Data Set 
WORK.KINDATA
 Dependent Variable 
Value
 Covariance Structure 
Variance Components
 Group Effect 
FunctionGroup
 Estimation Method 
REML
 Residual Variance Method 
None
 Fixed Effects SE Method 
Model-Based
 Degrees of Freedom Method Between-Within
Class Level Information
Class
Levels Values
 FunctionGroup 
3 1 2 3
Dimensions
 Covariance Parameters 
3
 Columns in X 
4
 Columns in Z 
0
 Subjects 
24
 Max Obs per Subject 
1
Number of Observations
 Number of Observations Read 
24
 Number of Observations Used 
24
 Number of Observations Not Used 
0
Iteration History
Iteration Evaluations -2 Res Log Like Criterion
      0 
1
29.02854090
      1 
1
26.48128492 0.00000000
Convergence criteria met.
Covariance Parameter Estimates
Cov Parm
Group
Estimate
 Residual FunctionGroup 1
0.1340
 Residual FunctionGroup 2
0.2942
 Residual FunctionGroup 3
0.09179
Fit Statistics
 -2 Res Log Likelihood 
26.5
 AIC (Smaller is Better) 
32.5
 AICC (Smaller is Better) 
33.9
 BIC (Smaller is Better) 
36.0
Null Model Likelihood
Ratio Test
DF Chi-Square Pr > ChiSq
2
2.55
0.2798
Type 3 Tests of Fixed Effects
Effect
Num
DF
Den
DF
F Value Pr > F
 FunctionGroup 
2
21
0.80 0.4626


14:27 Thursday, February 8, 2018
14
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=9 Param=lAUCT
Least Squares Means
Effect
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t| Alpha
Lower
Upper
 FunctionGroup 1
7.4682
0.1294 21
57.70
<.0001
0.1 7.2455 7.6909
 FunctionGroup 2
7.6423
0.1918 21
39.85
<.0001
0.1 7.3124 7.9723
 FunctionGroup 3
7.3686
0.1071 21
68.79
<.0001
0.1 7.1843 7.5529
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t|
Adjustment
Adj P Alpha
Lower
Upper
 FunctionGroup 1
2
-0.1741
0.2313 21
-0.75
0.4600 Tukey-Kramer 0.7354
0.1 -0.5722 0.2240
 FunctionGroup 1
3
0.09961
0.1680 21
0.59
0.5596 Tukey-Kramer 0.8254
0.1 -0.1895 0.3887
 FunctionGroup 2
3
0.2737
0.2196 21
1.25
0.2264 Tukey-Kramer 0.4402
0.1 -0.1042 0.6517
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Adj
Lower
Adj
Upper
 FunctionGroup 1
2
-0.6761 0.3279
 FunctionGroup 1
3
-0.2649 0.4642
 FunctionGroup 2
3
-0.2029 0.7503


14:27 Thursday, February 8, 2018
15
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
14:27 Thursday, February 8, 2018
15
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=10 Param=lAUCinf
Model Information
 Data Set 
WORK.KINDATA
 Dependent Variable 
Value
 Covariance Structure 
Variance Components
 Group Effect 
FunctionGroup
 Estimation Method 
REML
 Residual Variance Method 
None
 Fixed Effects SE Method 
Model-Based
 Degrees of Freedom Method Between-Within
Class Level Information
Class
Levels Values
 FunctionGroup 
3 1 2 3
Dimensions
 Covariance Parameters 
3
 Columns in X 
4
 Columns in Z 
0
 Subjects 
24
 Max Obs per Subject 
1
Number of Observations
 Number of Observations Read 
24
 Number of Observations Used 
24
 Number of Observations Not Used 
0
Iteration History
Iteration Evaluations -2 Res Log Like Criterion
      0 
1
29.00237589
      1 
1
26.17053116 0.00000000
Convergence criteria met.
Covariance Parameter Estimates
Cov Parm
Group
Estimate
 Residual FunctionGroup 1
0.1329
 Residual FunctionGroup 2
0.2994
 Residual FunctionGroup 3
0.08697
Fit Statistics
 -2 Res Log Likelihood 
26.2
 AIC (Smaller is Better) 
32.2
 AICC (Smaller is Better) 
33.6
 BIC (Smaller is Better) 
35.7
Null Model Likelihood
Ratio Test
DF Chi-Square Pr > ChiSq
2
2.83
0.2427
Type 3 Tests of Fixed Effects
Effect
Num
DF
Den
DF
F Value Pr > F
 FunctionGroup 
2
21
0.96 0.3987


14:27 Thursday, February 8, 2018
16
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
--------------------- SUMMARY REPORT ---------------------
The Mixed Procedure
Order=10 Param=lAUCinf
Least Squares Means
Effect
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t| Alpha
Lower
Upper
 FunctionGroup 1
7.4913
0.1289 21
58.12
<.0001
0.1 7.2695 7.7130
 FunctionGroup 2
7.6821
0.1935 21
39.71
<.0001
0.1 7.3491 8.0150
 FunctionGroup 3
7.3828
0.1043 21
70.81
<.0001
0.1 7.2033 7.5622
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Estimate Standard
Error
DF t Value Pr > |t|
Adjustment
Adj P Alpha
Lower
Upper
 FunctionGroup 1
2
-0.1908
0.2325 21
-0.82
0.4210 Tukey-Kramer 0.6946
0.1
-0.5908 0.2092
 FunctionGroup 1
3
0.1085
0.1658 21
0.65
0.5199 Tukey-Kramer 0.7919
0.1
-0.1768 0.3938
 FunctionGroup 2
3
0.2993
0.2198 21
1.36
0.1877 Tukey-Kramer 0.3783
0.1 -0.07888 0.6775
Differences of Least Squares Means
Effect
Hepatic
Function
Group
Hepatic
Function
Group
Adj
Lower
Adj
Upper
 FunctionGroup 1
2
-0.6952 0.3137
 FunctionGroup 1
3
-0.2512 0.4683
 FunctionGroup 2
3
-0.1776 0.7762


14:27 Thursday, February 8, 2018
17
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
Geometric LSmeans
--------------------- SUMMARY REPORT ---------------------
14:27 Thursday, February 8, 2018
17
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
Geometric LSmeans
--------------------- SUMMARY REPORT ---------------------
Obs Parameters
Group
GeoLSmeans
 1 lCmax
Mild
261.24
 2 lCmax
Moderate
294.03
 3 lCmax
Normal
220.30
 4 lAUCT
Mild
1751.47
 5 lAUCT
Moderate
2084.57
 6 lAUCT
Normal
1585.42
 7 lAUCinf
Mild
1792.31
 8 lAUCinf
Moderate
2169.06
 9 lAUCinf
Normal
1608.01


14:27 Thursday, February 8, 2018
18
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
RATIO ESTIMATE BASED ON ln-TRANSFORMED PARAMETERS
--------------------- SUMMARY REPORT ---------------------
14:27 Thursday, February 8, 2018
18
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
ANOVA analysis
RATIO ESTIMATE BASED ON ln-TRANSFORMED PARAMETERS
--------------------- SUMMARY REPORT ---------------------
Obs Parameters Group vs Group
Adj
P-value
Ratio
(%)
L90
U90
 1 lCmax
1
2
0.8669
88.848 53.769 146.815
 2 lCmax
1
3
0.6478 118.585 78.531 179.068
 3 lCmax
2
3
0.2704 133.469 90.079 197.759
 4 lAUCT
1
2
0.7354
84.021 50.859 138.804
 5 lAUCT
1
3
0.8254 110.474 76.725 159.067
 6 lAUCT
2
3
0.4402 131.484 81.636 211.770
 7 lAUCinf
1
2
0.6946
82.631 49.896 136.842
 8 lAUCinf
1
3
0.7919 111.462 77.784 159.720
 9 lAUCinf
2
3
0.3783 134.891 83.728 217.318


14:27 Thursday, February 8, 2018
19
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
19
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCT
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1
1007220 1007220
1.21 0.2893
 Error 
14 11622321
830166
 Corrected Total 15 12629542
 Root MSE 
911.13435  R-Square 0.0798
 Dependent Mean 2098.96738  Adj R-Sq 0.0140
 Coeff Var 
43.40870    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t| 95% Confidence Limits
 Intercept 
1 791.05592 1209.05488
0.65
0.5235 -1802.10890 3384.22073
 indiv 
1 209.26583
189.98465
1.10
0.2893
-198.21071
616.74237


14:27 Thursday, February 8, 2018
20
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
20
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCT
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
1229
1837
329.0631 -608.0676
849.6
-0.716  |     *|      | 
0.038
        2 
1630
1837
329.0631 -207.7826
849.6
-0.245  |      |      | 
0.004
        3 
978.5525
1837
329.0631 -858.8326
849.6
-1.011  |    **|      | 
0.077
        4 
2020
2047
232.6827
-26.8759
880.9
-0.0305  |      |      | 
0.000
        5 
2212
1837
329.0631
374.9404
849.6
0.441  |      |      | 
0.015
        6 
1604
1837
329.0631 -233.4726
849.6
-0.275  |      |      | 
0.006
        7 
1952
1837
329.0631
114.6349
849.6
0.135  |      |      | 
0.001
        8 
3229
1837
329.0631
1392
849.6
1.638  |      |***   | 
0.201
        9 
960.5133
2256
268.6789
-1295
870.6
-1.488  |    **|      | 
0.105
       10 
1831
2465
403.0183 -634.1826
817.2
-0.776  |     *|      | 
0.073
       11 
3600
2465
403.0183
1135
817.2
1.389  |      |**    | 
0.235
       12 
1884
2465
403.0183 -581.3926
817.2
-0.711  |     *|      | 
0.062
       13 
2690
2256
268.6789
433.8082
870.6
0.498  |      |      | 
0.012
       14 
3097
2256
268.6789
840.7382
870.6
0.966  |      |*     | 
0.044
       15 
971.0900
2256
268.6789
-1285
870.6
-1.476  |    **|      | 
0.104
       16 
3696
2256
268.6789
1440
870.6
1.654  |      |***   | 
0.130
       17 
1902
                 
       18 
1863
                 
       19 
1812
                 
       20 
1729
                 
       21 
1112
                 
       22 
2136
                 
       23 
886.3850
                 
       24 
1706
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
11622321
 Predicted Residual SS (PRESS) 15048631


14:27 Thursday, February 8, 2018
21
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
21
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCinf
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1
1254768 1254768
1.39 0.2579
 Error 
14 12628107
902008
 Corrected Total 15 13882875
 Root MSE 
949.74084  R-Square 0.0904
 Dependent Mean 2170.13414  Adj R-Sq 0.0254
 Coeff Var 
43.76415    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t| 95% Confidence Limits
 Intercept 
1 710.31943 1260.28482
0.56
0.5819 -1992.72268 3413.36153
 indiv 
1 233.57035
198.03465
1.18
0.2579
-191.17173
658.31244


14:27 Thursday, February 8, 2018
22
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
22
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCinf
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
1262
1878
343.0061 -616.3133
885.6
-0.696  |     *|      | 
0.036
        2 
1673
1878
343.0061 -204.8552
885.6
-0.231  |      |      | 
0.004
        3 
1008
1878
343.0061 -870.5595
885.6
-0.983  |     *|      | 
0.072
        4 
2033
2112
242.5419
-78.3261
918.2
-0.0853  |      |      | 
0.000
        5 
2264
1878
343.0061
386.2334
885.6
0.436  |      |      | 
0.014
        6 
1636
1878
343.0061 -242.6412
885.6
-0.274  |      |      | 
0.006
        7 
2003
1878
343.0061
124.6968
885.6
0.141  |      |      | 
0.001
        8 
3318
1878
343.0061
1440
885.6
1.626  |      |***   | 
0.198
        9 
1008
2345
280.0633
-1337
907.5
-1.473  |    **|      | 
0.103
       10 
1871
2579
420.0949 -708.3284
851.8
-0.832  |     *|      | 
0.084
       11 
3811
2579
420.0949
1232
851.8
1.446  |      |**    | 
0.254
       12 
2011
2579
420.0949 -568.3452
851.8
-0.667  |     *|      | 
0.054
       13 
2781
2345
280.0633
435.3980
907.5
0.480  |      |      | 
0.011
       14 
3232
2345
280.0633
886.5174
907.5
0.977  |      |*     | 
0.045
       15 
986.3843
2345
280.0633
-1359
907.5
-1.497  |    **|      | 
0.107
       16 
3826
2345
280.0633
1480
907.5
1.631  |      |***   | 
0.127
       17 
1923
                 
       18 
1870
                 
       19 
1832
                 
       20 
1767
                 
       21 
1131
                 
       22 
2147
                 
       23 
916.5388
                 
       24 
1725
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
12628107
 Predicted Residual SS (PRESS) 16386093


14:27 Thursday, February 8, 2018
23
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
23
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=CL_F
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 1572.52895 1572.52895
0.57 0.4644
 Error 
14
38913 2779.46872
 Corrected Total 15
40485
 Root MSE 
52.72067  R-Square 
0.0388
 Dependent Mean 111.98212  Adj R-Sq -0.0298
 Coeff Var 
47.07954    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 163.66128 69.95914
2.34
0.0347
13.61384 313.70872
 indiv 
1
-8.26867 10.99302
-0.75
0.4644 -31.84635
15.30902


14:27 Thursday, February 8, 2018
24
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
24
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=CL_F
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
158.4964
122.3180
19.0405
36.1785
49.162
0.736  |      |*     | 
0.041
        2 
119.5232
122.3180
19.0405
-2.7948
49.162
-0.0568  |      |      | 
0.000
        3 
198.4892
122.3180
19.0405
76.1712
49.162
1.549  |      |***   | 
0.180
        4 
98.3567
114.0493
13.4636 -15.6926
50.973
-0.308  |      |      | 
0.003
        5 
88.3234
122.3180
19.0405 -33.9945
49.162
-0.691  |     *|      | 
0.036
        6 
122.2845
122.3180
19.0405
-0.0334
49.162
-0.0007  |      |      | 
0.000
        7 
99.8568
122.3180
19.0405 -22.4611
49.162
-0.457  |      |      | 
0.016
        8 
60.2688
122.3180
19.0405 -62.0491
49.162
-1.262  |    **|      | 
0.119
        9 
198.3898
105.7806
15.5465
92.6091
50.376
1.838  |      |***   | 
0.161
       10 
106.9202
97.5120
23.3197
9.4082
47.283
0.199  |      |      | 
0.005
       11 
52.4805
97.5120
23.3197 -45.0315
47.283
-0.952  |     *|      | 
0.110
       12 
99.4759
97.5120
23.3197
1.9640
47.283
0.0415  |      |      | 
0.000
       13 
71.9241
105.7806
15.5465 -33.8565
50.376
-0.672  |     *|      | 
0.022
       14 
61.8845
105.7806
15.5465 -43.8962
50.376
-0.871  |     *|      | 
0.036
       15 
202.7607
105.7806
15.5465
96.9801
50.376
1.925  |      |***   | 
0.176
       16 
52.2793
105.7806
15.5465 -53.5013
50.376
-1.062  |    **|      | 
0.054
       17 
104.0063
                 
       18 
106.9305
                 
       19 
109.1986
                 
       20 
113.1571
                 
       21 
176.7935
                 
       22 
93.1642
                 
       23 
218.2123
                 
       24 
115.9511
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
38913
 Predicted Residual SS (PRESS) 48950


14:27 Thursday, February 8, 2018
25
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
25
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Cmax
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 8057.83696 8057.83696
0.45 0.5149
 Error 
14
252708
18051
 Corrected Total 15
260766
 Root MSE 
134.35239  R-Square 
0.0309
 Dependent Mean 303.87500  Adj R-Sq -0.0383
 Coeff Var 
44.21305    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 186.89130 178.28262
1.05
0.3123 -195.48688 569.26948
 indiv 
1
18.71739
28.01441
0.67
0.5149
-41.36754
78.80233


14:27 Thursday, February 8, 2018
26
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
26
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Cmax
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
159.0000
280.4783
48.5224 -121.4783
125.3
-0.970  |     *|      | 
0.071
        2 
350.0000
280.4783
48.5224
69.5217
125.3
0.555  |      |*     | 
0.023
        3 
125.0000
280.4783
48.5224 -155.4783
125.3
-1.241  |    **|      | 
0.116
        4 
518.0000
299.1957
34.3105
218.8043
129.9
1.684  |      |***   | 
0.099
        5 
255.0000
280.4783
48.5224
-25.4783
125.3
-0.203  |      |      | 
0.003
        6 
258.0000
280.4783
48.5224
-22.4783
125.3
-0.179  |      |      | 
0.002
        7 
220.0000
280.4783
48.5224
-60.4783
125.3
-0.483  |      |      | 
0.017
        8 
416.0000
280.4783
48.5224
135.5217
125.3
1.082  |      |**    | 
0.088
        9 
207.0000
317.9130
39.6184 -110.9130
128.4
-0.864  |     *|      | 
0.036
       10 
259.0000
336.6304
59.4275
-77.6304
120.5
-0.644  |     *|      | 
0.050
       11 
388.0000
336.6304
59.4275
51.3696
120.5
0.426  |      |      | 
0.022
       12 
221.0000
336.6304
59.4275 -115.6304
120.5
-0.960  |     *|      | 
0.112
       13 
359.0000
317.9130
39.6184
41.0870
128.4
0.320  |      |      | 
0.005
       14 
419.0000
317.9130
39.6184
101.0870
128.4
0.787  |      |*     | 
0.030
       15 
143.0000
317.9130
39.6184 -174.9130
128.4
-1.362  |    **|      | 
0.088
       16 
565.0000
317.9130
39.6184
247.0870
128.4
1.925  |      |***   | 
0.176
       17 
199.0000
                 
       18 
307.0000
                 
       19 
216.0000
                 
       20 
270.0000
                 
       21 
189.0000
                 
       22 
288.0000
                 
       23 
149.0000
                 
       24 
192.0000
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
252708
 Predicted Residual SS (PRESS) 316352


14:27 Thursday, February 8, 2018
27
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
27
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=LambdaZ
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.00349
0.00349
3.50 0.0824
 Error 
14 0.01398 0.00099868
 Corrected Total 15 0.01748
 Root MSE 
0.03160  R-Square 0.2000
 Dependent Mean 
0.10757  Adj R-Sq 0.1428
 Coeff Var 
29.37706    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
0.18461
0.04194
4.40
0.0006
0.09467 0.27456
 indiv 
1
-0.01233
0.00659
-1.87
0.0824 -0.02646 0.00181


14:27 Thursday, February 8, 2018
28
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
28
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=LambdaZ
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
0.0999
0.1230
0.0114
-0.0231
0.0295
-0.783  |     *|      | 
0.046
        2 
0.0872
0.1230
0.0114
-0.0358
0.0295
-1.213  |    **|      | 
0.110
        3 
0.1578
0.1230
0.0114
0.0348
0.0295
1.182  |      |**    | 
0.105
        4 
0.1939
0.1107
0.008070
0.0832
0.0306
2.724  |      |***** | 
0.259
        5 
0.1032
0.1230
0.0114
-0.0197
0.0295
-0.670  |     *|      | 
0.034
        6 
0.1643
0.1230
0.0114
0.0413
0.0295
1.401  |      |**    | 
0.147
        7 
0.0981
0.1230
0.0114
-0.0249
0.0295
-0.844  |     *|      | 
0.053
        8 
0.1020
0.1230
0.0114
-0.0210
0.0295
-0.713  |     *|      | 
0.038
        9 
0.1045
0.0983
0.009319
0.006156
0.0302
0.204  |      |      | 
0.002
       10 
0.0943
0.0860
0.0140
0.008283
0.0283
0.292  |      |      | 
0.010
       11 
0.0777
0.0860
0.0140 -0.008316
0.0283
-0.293  |      |      | 
0.010
       12 
0.0727
0.0860
0.0140
-0.0133
0.0283
-0.470  |      |      | 
0.027
       13 
0.0892
0.0983
0.009319 -0.009175
0.0302
-0.304  |      |      | 
0.004
       14 
0.0799
0.0983
0.009319
-0.0184
0.0302
-0.609  |     *|      | 
0.018
       15 
0.1053
0.0983
0.009319
0.006991
0.0302
0.232  |      |      | 
0.003
       16 
0.0912
0.0983
0.009319 -0.007169
0.0302
-0.237  |      |      | 
0.003
       17 
0.1274
                 
       18 
0.1519
                 
       19 
0.1231
                 
       20 
0.1469
                 
       21 
0.1513
                 
       22 
0.1428
                 
       23 
0.1299
                 
       24 
0.1211
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
0.01398
 Predicted Residual SS (PRESS) 0.01726


14:27 Thursday, February 8, 2018
29
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
29
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=RkTmax
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 152.63315 152.63315
4.91 0.0437
 Error 
14 434.80435
31.05745
 Corrected Total 15 587.43750
 Root MSE 
5.57292  R-Square 0.2598
 Dependent Mean 
9.68750  Adj R-Sq 0.2070
 Coeff Var 
57.52693    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
25.78804
7.39514
3.49
0.0036
9.92704 41.64905
 indiv 
1
-2.57609
1.16203
-2.22
0.0437 -5.06840 -0.08377


14:27 Thursday, February 8, 2018
30
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
30
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=RkTmax
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
14.0000
12.9076
2.0127
1.0924
5.197
0.210  |      |      | 
0.003
        2 
2.0000
12.9076
2.0127 -10.9076
5.197
-2.099  |  ****|      | 
0.330
        3 
14.0000
12.9076
2.0127
1.0924
5.197
0.210  |      |      | 
0.003
        4 
2.0000
10.3315
1.4232
-8.3315
5.388
-1.546  |   ***|      | 
0.083
        5 
18.0000
12.9076
2.0127
5.0924
5.197
0.980  |      |*     | 
0.072
        6 
18.0000
12.9076
2.0127
5.0924
5.197
0.980  |      |*     | 
0.072
        7 
21.5000
12.9076
2.0127
8.5924
5.197
1.653  |      |***   | 
0.205
        8 
8.0000
12.9076
2.0127
-4.9076
5.197
-0.944  |     *|      | 
0.067
        9 
5.5000
7.7554
1.6434
-2.2554
5.325
-0.424  |      |      | 
0.009
       10 
5.5000
5.1793
2.4650
0.3207
4.998
0.0642  |      |      | 
0.001
       11 
8.0000
5.1793
2.4650
2.8207
4.998
0.564  |      |*     | 
0.039
       12 
4.0000
5.1793
2.4650
-1.1793
4.998
-0.236  |      |      | 
0.007
       13 
14.0000
7.7554
1.6434
6.2446
5.325
1.173  |      |**    | 
0.065
       14 
2.0000
7.7554
1.6434
-5.7554
5.325
-1.081  |    **|      | 
0.056
       15 
10.5000
7.7554
1.6434
2.7446
5.325
0.515  |      |*     | 
0.013
       16 
8.0000
7.7554
1.6434
0.2446
5.325
0.0459  |      |      | 
0.000
       17 
23.5000
                 
       18 
10.5000
                 
       19 
14.0000
                 
       20 
14.0000
                 
       21 
18.0000
                 
       22 
20.0000
                 
       23 
21.5000
                 
       24 
23.5000
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
434.80435
 Predicted Residual SS (PRESS) 554.34864


14:27 Thursday, February 8, 2018
31
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
31
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Vz_F
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1
17826
17826
0.08 0.7823
 Error 
14 3145409 224672
 Corrected Total 15 3163235
 Root MSE 
473.99586  R-Square 
0.0056
 Dependent Mean 1067.91793  Adj R-Sq -0.0654
 Coeff Var 
44.38505    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 893.92274 628.98190
1.42
0.1771 -455.10926 2242.95473
 indiv 
1
27.83923
98.83497
0.28
0.7823 -184.14070
239.81916


14:27 Thursday, February 8, 2018
32
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
32
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Vz_F
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
1586
1033
171.1872
553.1365
442.0
1.251  |      |**    | 
0.117
        2 
1370
1033
171.1872
337.0904
442.0
0.763  |      |*     | 
0.044
        3 
1258
1033
171.1872
224.5945
442.0
0.508  |      |*     | 
0.019
        4 
507.2843
1061
121.0476 -553.6738
458.3
-1.208  |    **|      | 
0.051
        5 
855.4525
1033
171.1872 -177.6664
442.0
-0.402  |      |      | 
0.012
        6 
744.3830
1033
171.1872 -288.7359
442.0
-0.653  |     *|      | 
0.032
        7 
1018
1033
171.1872
-15.2366
442.0
-0.0345  |      |      | 
0.000
        8 
590.9625
1033
171.1872 -442.1564
442.0
-1.000  |    **|      | 
0.075
        9 
1899
1089
139.7738
809.9520
452.9
1.788  |      |***   | 
0.152
       10 
1134
1117
209.6606
17.3665
425.1
0.0409  |      |      | 
0.000
       11 
675.5488
1117
209.6606 -441.0878
425.1
-1.038  |    **|      | 
0.131
       12 
1369
1117
209.6606
252.0998
425.1
0.593  |      |*     | 
0.043
       13 
806.7430
1089
139.7738 -282.0544
452.9
-0.623  |     *|      | 
0.018
       14 
774.0737
1089
139.7738 -314.7236
452.9
-0.695  |     *|      | 
0.023
       15 
1925
1089
139.7738
836.4027
452.9
1.847  |      |***   | 
0.162
       16 
573.4898
1089
139.7738 -515.3075
452.9
-1.138  |    **|      | 
0.062
       17 
816.6712
                 
       18 
703.8423
                 
       19 
887.4080
                 
       20 
770.4741
                 
       21 
1168
                 
       22 
652.5078
                 
       23 
1680
                 
       24 
957.1601
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
3145409
 Predicted Residual SS (PRESS) 3941589


14:27 Thursday, February 8, 2018
33
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
33
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCT
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.17827 0.17827
0.85 0.3725
 Error 
14 2.94011 0.21001
 Corrected Total 15 3.11839
 Root MSE 
0.45827  R-Square 
0.0572
 Dependent Mean 7.55526  Adj R-Sq -0.0102
 Coeff Var 
6.06552    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
7.00502
0.60811
11.52
<.0001
5.70075 8.30928
 indiv 
1
0.08804
0.09556
0.92
0.3725 -0.11691 0.29299


14:27 Thursday, February 8, 2018
34
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
34
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCT
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
7.1142
7.4452
0.1655
-0.3310
0.427
-0.775  |     *|      | 
0.045
        2 
7.3961
7.4452
0.1655
-0.0491
0.427
-0.115  |      |      | 
0.001
        3 
6.8861
7.4452
0.1655
-0.5591
0.427
-1.308  |    **|      | 
0.128
        4 
7.6107
7.5333
0.1170
0.0775
0.443
0.175  |      |      | 
0.001
        5 
7.7018
7.4452
0.1655
0.2566
0.427
0.600  |      |*     | 
0.027
        6 
7.3802
7.4452
0.1655
-0.0650
0.427
-0.152  |      |      | 
0.002
        7 
7.5766
7.4452
0.1655
0.1314
0.427
0.307  |      |      | 
0.007
        8 
8.0799
7.4452
0.1655
0.6347
0.427
1.485  |      |**    | 
0.165
        9 
6.8675
7.6213
0.1351
-0.7538
0.438
-1.722  |   ***|      | 
0.141
       10 
7.5126
7.7093
0.2027
-0.1967
0.411
-0.479  |      |      | 
0.028
       11 
8.1887
7.7093
0.2027
0.4794
0.411
1.166  |      |**    | 
0.165
       12 
7.5410
7.7093
0.2027
-0.1683
0.411
-0.409  |      |      | 
0.020
       13 
7.8972
7.6213
0.1351
0.2759
0.438
0.630  |      |*     | 
0.019
       14 
8.0381
7.6213
0.1351
0.4168
0.438
0.952  |      |*     | 
0.043
       15 
6.8784
7.6213
0.1351
-0.7429
0.438
-1.696  |   ***|      | 
0.137
       16 
8.2150
7.6213
0.1351
0.5937
0.438
1.356  |      |**    | 
0.088
       17 
7.5507
                 
       18 
7.5300
                 
       19 
7.5023
                 
       20 
7.4556
                 
       21 
7.0143
                 
       22 
7.6667
                 
       23 
6.7872
                 
       24 
7.4421
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
2.94011
 Predicted Residual SS (PRESS) 3.74168


14:27 Thursday, February 8, 2018
35
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
35
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCinf
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.20718 0.20718
0.98 0.3394
 Error 
14 2.96475 0.21177
 Corrected Total 15 3.17193
 Root MSE 
0.46018  R-Square 
0.0653
 Dependent Mean 7.58666  Adj R-Sq -0.0014
 Coeff Var 
6.06568    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
6.99347
0.61065
11.45
<.0001
5.68375 8.30319
 indiv 
1
0.09491
0.09595
0.99
0.3394 -0.11089 0.30071


14:27 Thursday, February 8, 2018
36
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
36
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCinf
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
7.1403
7.4680
0.1662
-0.3277
0.429
-0.764  |     *|      | 
0.044
        2 
7.4226
7.4680
0.1662
-0.0455
0.429
-0.106  |      |      | 
0.001
        3 
6.9153
7.4680
0.1662
-0.5527
0.429
-1.288  |    **|      | 
0.124
        4 
7.6175
7.5629
0.1175
0.0545
0.445
0.123  |      |      | 
0.001
        5 
7.7251
7.4680
0.1662
0.2570
0.429
0.599  |      |*     | 
0.027
        6 
7.3997
7.4680
0.1662
-0.0683
0.429
-0.159  |      |      | 
0.002
        7 
7.6023
7.4680
0.1662
0.1343
0.429
0.313  |      |      | 
0.007
        8 
8.1073
7.4680
0.1662
0.6392
0.429
1.490  |      |**    | 
0.166
        9 
6.9158
7.6578
0.1357
-0.7420
0.440
-1.687  |   ***|      | 
0.136
       10 
7.5340
7.7527
0.2036
-0.2188
0.413
-0.530  |     *|      | 
0.034
       11 
8.2456
7.7527
0.2036
0.4929
0.413
1.194  |      |**    | 
0.173
       12 
7.6062
7.7527
0.2036
-0.1466
0.413
-0.355  |      |      | 
0.015
       13 
7.9305
7.6578
0.1357
0.2726
0.440
0.620  |      |*     | 
0.018
       14 
8.0808
7.6578
0.1357
0.4230
0.440
0.962  |      |*     | 
0.044
       15 
6.8940
7.6578
0.1357
-0.7638
0.440
-1.737  |   ***|      | 
0.144
       16 
8.2495
7.6578
0.1357
0.5916
0.440
1.345  |      |**    | 
0.086
       17 
7.5616
                 
       18 
7.5339
                 
       19 
7.5129
                 
       20 
7.4773
                 
       21 
7.0311
                 
       22 
7.6717
                 
       23 
6.8206
                 
       24 
7.4529
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
2.96475
 Predicted Residual SS (PRESS) 3.77644


14:27 Thursday, February 8, 2018
37
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
37
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCLF
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.20718 0.20718
0.98 0.3394
 Error 
14 2.96475 0.21177
 Corrected Total 15 3.17193
 Root MSE 
0.46018  R-Square 
0.0653
 Dependent Mean 4.61942  Adj R-Sq -0.0014
 Coeff Var 
9.96191    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
5.21260
0.61065
8.54
<.0001
3.90289 6.52232
 indiv 
1
-0.09491
0.09595
-0.99
0.3394 -0.30071 0.11089


14:27 Thursday, February 8, 2018
38
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
38
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCLF
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
5.0657
4.7381
0.1662
0.3277
0.429
0.764  |      |*     | 
0.044
        2 
4.7835
4.7381
0.1662
0.0455
0.429
0.106  |      |      | 
0.001
        3 
5.2907
4.7381
0.1662
0.5527
0.429
1.288  |      |**    | 
0.124
        4 
4.5886
4.6431
0.1175
-0.0545
0.445
-0.123  |      |      | 
0.001
        5 
4.4810
4.7381
0.1662
-0.2570
0.429
-0.599  |     *|      | 
0.027
        6 
4.8064
4.7381
0.1662
0.0683
0.429
0.159  |      |      | 
0.002
        7 
4.6037
4.7381
0.1662
-0.1343
0.429
-0.313  |      |      | 
0.007
        8 
4.0988
4.7381
0.1662
-0.6392
0.429
-1.490  |    **|      | 
0.166
        9 
5.2902
4.5482
0.1357
0.7420
0.440
1.687  |      |***   | 
0.136
       10 
4.6721
4.4533
0.2036
0.2188
0.413
0.530  |      |*     | 
0.034
       11 
3.9604
4.4533
0.2036
-0.4929
0.413
-1.194  |    **|      | 
0.173
       12 
4.5999
4.4533
0.2036
0.1466
0.413
0.355  |      |      | 
0.015
       13 
4.2756
4.5482
0.1357
-0.2726
0.440
-0.620  |     *|      | 
0.018
       14 
4.1253
4.5482
0.1357
-0.4230
0.440
-0.962  |     *|      | 
0.044
       15 
5.3120
4.5482
0.1357
0.7638
0.440
1.737  |      |***   | 
0.144
       16 
3.9566
4.5482
0.1357
-0.5916
0.440
-1.345  |    **|      | 
0.086
       17 
4.6445
                 
       18 
4.6722
                 
       19 
4.6932
                 
       20 
4.7288
                 
       21 
5.1750
                 
       22 
4.5344
                 
       23 
5.3855
                 
       24 
4.7532
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
2.96475
 Predicted Residual SS (PRESS) 3.77644


14:27 Thursday, February 8, 2018
39
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
39
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCmax
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.11320 0.11320
0.54 0.4751
 Error 
14 2.94268 0.21019
 Corrected Total 15 3.05588
 Root MSE 
0.45847  R-Square 
0.0370
 Dependent Mean 5.62458  Adj R-Sq -0.0317
 Coeff Var 
8.15113    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
5.18611
0.60837
8.52
<.0001
3.88127 6.49094
 indiv 
1
0.07016
0.09560
0.73
0.4751 -0.13488 0.27519


14:27 Thursday, February 8, 2018
40
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
40
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCmax
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
5.0689
5.5369
0.1656
-0.4680
0.428
-1.095  |    **|      | 
0.090
        2 
5.8579
5.5369
0.1656
0.3211
0.428
0.751  |      |*     | 
0.042
        3 
4.8283
5.5369
0.1656
-0.7086
0.428
-1.657  |   ***|      | 
0.206
        4 
6.2500
5.6070
0.1171
0.6429
0.443
1.450  |      |**    | 
0.073
        5 
5.5413
5.5369
0.1656 0.004380
0.428
0.0102  |      |      | 
0.000
        6 
5.5530
5.5369
0.1656
0.0161
0.428
0.0376  |      |      | 
0.000
        7 
5.3936
5.5369
0.1656
-0.1433
0.428
-0.335  |      |      | 
0.008
        8 
6.0307
5.5369
0.1656
0.4938
0.428
1.155  |      |**    | 
0.100
        9 
5.3327
5.6772
0.1352
-0.3445
0.438
-0.786  |     *|      | 
0.029
       10 
5.5568
5.7473
0.2028
-0.1905
0.411
-0.463  |      |      | 
0.026
       11 
5.9610
5.7473
0.2028
0.2137
0.411
0.520  |      |*     | 
0.033
       12 
5.3982
5.7473
0.2028
-0.3492
0.411
-0.849  |     *|      | 
0.088
       13 
5.8833
5.6772
0.1352
0.2061
0.438
0.471  |      |      | 
0.011
       14 
6.0379
5.6772
0.1352
0.3607
0.438
0.823  |      |*     | 
0.032
       15 
4.9628
5.6772
0.1352
-0.7143
0.438
-1.631  |   ***|      | 
0.127
       16 
6.3368
5.6772
0.1352
0.6596
0.438
1.506  |      |***   | 
0.108
       17 
5.2933
                 
       18 
5.7268
                 
       19 
5.3753
                 
       20 
5.5984
                 
       21 
5.2417
                 
       22 
5.6630
                 
       23 
5.0039
                 
       24 
5.2575
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
2.94268
 Predicted Residual SS (PRESS) 3.71153


14:27 Thursday, February 8, 2018
41
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
41
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lLambdaZ
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.28942 0.28942
4.76 0.0466
 Error 
14 0.85103 0.06079
 Corrected Total 15 1.14045
 Root MSE 
0.24655  R-Square 0.2538
 Dependent Mean 
-2.26860  Adj R-Sq 0.2005
 Coeff Var 
-10.86800    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
-1.56749
0.32717
-4.79
0.0003 -2.26920 -0.86579
 indiv 
1
-0.11218
0.05141
-2.18
0.0466 -0.22244 -0.00191


14:27 Thursday, February 8, 2018
42
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
42
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lLambdaZ
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
-2.3034
-2.1284
0.0890
-0.1750
0.230
-0.761  |     *|      | 
0.043
        2 
-2.4392
-2.1284
0.0890
-0.3108
0.230
-1.352  |    **|      | 
0.137
        3 
-1.8463
-2.1284
0.0890
0.2821
0.230
1.227  |      |**    | 
0.113
        4 
-1.6405
-2.2406
0.0630
0.6001
0.238
2.517  |      |***** | 
0.221
        5 
-2.2706
-2.1284
0.0890
-0.1422
0.230
-0.619  |     *|      | 
0.029
        6 
-1.8062
-2.1284
0.0890
0.3222
0.230
1.401  |      |**    | 
0.147
        7 
-2.3217
-2.1284
0.0890
-0.1934
0.230
-0.841  |     *|      | 
0.053
        8 
-2.2829
-2.1284
0.0890
-0.1546
0.230
-0.672  |     *|      | 
0.034
        9 
-2.2587
-2.3527
0.0727
0.0940
0.236
0.399  |      |      | 
0.008
       10 
-2.3614
-2.4649
0.1091
0.1035
0.221
0.468  |      |      | 
0.027
       11 
-2.5551
-2.4649
0.1091
-0.0902
0.221
-0.408  |      |      | 
0.020
       12 
-2.6217
-2.4649
0.1091
-0.1568
0.221
-0.709  |     *|      | 
0.061
       13 
-2.4174
-2.3527
0.0727
-0.0647
0.236
-0.274  |      |      | 
0.004
       14 
-2.5264
-2.3527
0.0727
-0.1737
0.236
-0.737  |     *|      | 
0.026
       15 
-2.2508
-2.3527
0.0727
0.1020
0.236
0.433  |      |      | 
0.009
       16 
-2.3951
-2.3527
0.0727
-0.0424
0.236
-0.180  |      |      | 
0.002
       17 
-2.0608
                 
       18 
-1.8844
                 
       19 
-2.0951
                 
       20 
-1.9182
                 
       21 
-1.8884
                 
       22 
-1.9465
                 
       23 
-2.0413
                 
       24 
-2.1108
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
0.85103
 Predicted Residual SS (PRESS) 1.06423


14:27 Thursday, February 8, 2018
43
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
43
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lVz_F
 Number of Observations Read 
24
 Number of Observations Used 
16
 Number of Observations with Missing Values 
8
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
1 0.00686 0.00686
0.04 0.8539
 Error 
14 2.72991 0.19499
 Corrected Total 15 2.73676
 Root MSE 
0.44158  R-Square 
0.0025
 Dependent Mean 6.88801  Adj R-Sq -0.0687
 Coeff Var 
6.41085    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
6.78010
0.58597
11.57
<.0001
5.52332 8.03687
 indiv 
1
0.01727
0.09208
0.19
0.8539 -0.18022 0.21475


14:27 Thursday, February 8, 2018
44
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
44
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Individual Child-Pugh Scores at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lVz_F
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
7.3691
6.8664
0.1595
0.5027
0.412
1.221  |      |**    | 
0.112
        2 
7.2227
6.8664
0.1595
0.3563
0.412
0.865  |      |*     | 
0.056
        3 
7.1371
6.8664
0.1595
0.2706
0.412
0.657  |      |*     | 
0.032
        4 
6.2291
6.8837
0.1128
-0.6546
0.427
-1.533  |   ***|      | 
0.082
        5 
6.7516
6.8664
0.1595
-0.1148
0.412
-0.279  |      |      | 
0.006
        6 
6.6126
6.8664
0.1595
-0.2539
0.412
-0.617  |     *|      | 
0.029
        7 
6.9255
6.8664
0.1595
0.0590
0.412
0.143  |      |      | 
0.002
        8 
6.3818
6.8664
0.1595
-0.4847
0.412
-1.177  |    **|      | 
0.104
        9 
7.5490
6.9010
0.1302
0.6480
0.422
1.536  |      |***   | 
0.112
       10 
7.0335
6.9182
0.1953
0.1153
0.396
0.291  |      |      | 
0.010
       11 
6.5155
6.9182
0.1953
-0.4027
0.396
-1.017  |    **|      | 
0.126
       12 
7.2216
6.9182
0.1953
0.3034
0.396
0.766  |      |*     | 
0.071
       13 
6.6930
6.9010
0.1302
-0.2080
0.422
-0.493  |      |      | 
0.012
       14 
6.6517
6.9010
0.1302
-0.2493
0.422
-0.591  |     *|      | 
0.017
       15 
7.5628
6.9010
0.1302
0.6618
0.422
1.569  |      |***   | 
0.117
       16 
6.3517
6.9010
0.1302
-0.5492
0.422
-1.302  |    **|      | 
0.081
       17 
6.7052
                 
       18 
6.5566
                 
       19 
6.7883
                 
       20 
6.6470
                 
       21 
7.0634
                 
       22 
6.4808
                 
       23 
7.4268
                 
       24 
6.8640
                 
 Sum of Residuals 
0
 Sum of Squared Residuals 
2.72991
 Predicted Residual SS (PRESS) 3.43815


14:27 Thursday, February 8, 2018
45
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
45
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCT
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2
2044534 1022267
1.66 0.2144
 Error 
21 12944140
616388
 Corrected Total 23 14988674
 Root MSE 
785.10359  R-Square 0.1364
 Dependent Mean 1947.14710  Adj R-Sq 0.0542
 Coeff Var 
40.32071    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 1643.50654 277.57604
5.92
<.0001 1066.25558 2220.75751
 GrpA 
1
213.31383 392.55179
0.54
0.5926 -603.04231 1029.66998
 GrpB 
1
697.60783 392.55179
1.78
0.0900 -118.74831 1513.96398


14:27 Thursday, February 8, 2018
46
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
46
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCT
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
1229
1857
277.5760 -627.5029
734.4
-0.854  |     *|      | 
0.035
        2 
1630
1857
277.5760 -227.2179
734.4
-0.309  |      |      | 
0.005
        3 
978.5525
1857
277.5760 -878.2679
734.4
-1.196  |    **|      | 
0.068
        4 
2020
1857
277.5760
162.9546
734.4
0.222  |      |      | 
0.002
        5 
2212
1857
277.5760
355.5051
734.4
0.484  |      |      | 
0.011
        6 
1604
1857
277.5760 -252.9079
734.4
-0.344  |      |      | 
0.006
        7 
1952
1857
277.5760
95.1996
734.4
0.130  |      |      | 
0.001
        8 
3229
1857
277.5760
1372
734.4
1.869  |      |***   | 
0.166
        9 
960.5133
2341
277.5760
-1381
734.4
-1.880  |   ***|      | 
0.168
       10 
1831
2341
277.5760 -510.1144
734.4
-0.695  |     *|      | 
0.023
       11 
3600
2341
277.5760
1259
734.4
1.714  |      |***   | 
0.140
       12 
1884
2341
277.5760 -457.3244
734.4
-0.623  |     *|      | 
0.018
       13 
2690
2341
277.5760
348.6106
734.4
0.475  |      |      | 
0.011
       14 
3097
2341
277.5760
755.5406
734.4
1.029  |      |**    | 
0.050
       15 
971.0900
2341
277.5760
-1370
734.4
-1.866  |   ***|      | 
0.166
       16 
3696
2341
277.5760
1355
734.4
1.845  |      |***   | 
0.162
       17 
1902
1644
277.5760
258.5785
734.4
0.352  |      |      | 
0.006
       18 
1863
1644
277.5760
219.5410
734.4
0.299  |      |      | 
0.004
       19 
1812
1644
277.5760
168.7110
734.4
0.230  |      |      | 
0.003
       20 
1729
1644
277.5760
85.9535
734.4
0.117  |      |      | 
0.001
       21 
1112
1644
277.5760 -531.0890
734.4
-0.723  |     *|      | 
0.025
       22 
2136
1644
277.5760
492.5518
734.4
0.671  |      |*     | 
0.021
       23 
886.3850
1644
277.5760 -757.1215
734.4
-1.031  |    **|      | 
0.051
       24 
1706
1644
277.5760
62.8750
734.4
0.0856  |      |      | 
0.000
 Sum of Residuals 
0
 Sum of Squared Residuals 
12944140
 Predicted Residual SS (PRESS) 16906632


14:27 Thursday, February 8, 2018
47
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
47
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=AUCT
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 1022267
1.66 0.2144
 Denominator 
21
616388


14:27 Thursday, February 8, 2018
48
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
48
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCinf
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2
2536727 1268364
1.91 0.1728
 Error 
21 13940255
663822
 Corrected Total 23 16476982
 Root MSE 
814.75252  R-Square 0.1540
 Dependent Mean 2001.41149  Adj R-Sq 0.0734
 Coeff Var 
40.70890    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 1663.96617 288.05852
5.78
<.0001 1064.91569 2263.01665
 GrpA 
1
235.71753 407.37626
0.58
0.5690 -611.46778 1082.90284
 GrpB 
1
776.61841 407.37626
1.91
0.0704
-70.56690 1623.80373


14:27 Thursday, February 8, 2018
49
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
49
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=AUCinf
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
1262
1900
288.0585 -637.8258
762.1
-0.837  |     *|      | 
0.033
        2 
1673
1900
288.0585 -226.3677
762.1
-0.297  |      |      | 
0.004
        3 
1008
1900
288.0585 -892.0720
762.1
-1.170  |    **|      | 
0.065
        4 
2033
1900
288.0585
133.7317
762.1
0.175  |      |      | 
0.001
        5 
2264
1900
288.0585
364.7209
762.1
0.479  |      |      | 
0.011
        6 
1636
1900
288.0585 -264.1537
762.1
-0.347  |      |      | 
0.006
        7 
2003
1900
288.0585
103.1843
762.1
0.135  |      |      | 
0.001
        8 
3318
1900
288.0585
1419
762.1
1.862  |      |***   | 
0.165
        9 
1008
2441
288.0585
-1432
762.1
-1.880  |   ***|      | 
0.168
       10 
1871
2441
288.0585 -570.0308
762.1
-0.748  |     *|      | 
0.027
       11 
3811
2441
288.0585
1370
762.1
1.798  |      |***   | 
0.154
       12 
2011
2441
288.0585 -430.0475
762.1
-0.564  |     *|      | 
0.015
       13 
2781
2441
288.0585
340.1253
762.1
0.446  |      |      | 
0.009
       14 
3232
2441
288.0585
791.2447
762.1
1.038  |      |**    | 
0.051
       15 
986.3843
2441
288.0585
-1454
762.1
-1.908  |   ***|      | 
0.173
       16 
3826
2441
288.0585
1385
762.1
1.817  |      |***   | 
0.157
       17 
1923
1664
288.0585
258.9952
762.1
0.340  |      |      | 
0.005
       18 
1870
1664
288.0585
206.4075
762.1
0.271  |      |      | 
0.003
       19 
1832
1664
288.0585
167.5594
762.1
0.220  |      |      | 
0.002
       20 
1767
1664
288.0585
103.4880
762.1
0.136  |      |      | 
0.001
       21 
1131
1664
288.0585 -532.7030
762.1
-0.699  |     *|      | 
0.023
       22 
2147
1664
288.0585
482.7817
762.1
0.633  |      |*     | 
0.019
       23 
916.5388
1664
288.0585 -747.4274
762.1
-0.981  |     *|      | 
0.046
       24 
1725
1664
288.0585
60.8987
762.1
0.0799  |      |      | 
0.000
 Sum of Residuals 
0
 Sum of Squared Residuals 
13940255
 Predicted Residual SS (PRESS) 18207680


14:27 Thursday, February 8, 2018
50
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
50
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=AUCinf
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 1268364
1.91 0.1728
 Denominator 
21
663822


14:27 Thursday, February 8, 2018
51
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
51
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=CL_F
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF
Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 2288.42227 1144.21114
0.45 0.6432
 Error 
21
53315 2538.82052
 Corrected Total 23
55604
 Root MSE 
50.38671  R-Square 
0.0412
 Dependent Mean 117.88031  Adj R-Sq -0.0502
 Coeff Var 
42.74396    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 129.67669 17.81439
7.28
<.0001
92.62963 166.72375
 GrpA 
1 -11.47681 25.19335
-0.46
0.6534 -63.86926
40.91564
 GrpB 
1 -23.91232 25.19335
-0.95
0.3533 -76.30477
28.48013


14:27 Thursday, February 8, 2018
52
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
52
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=CL_F
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
158.4964
118.1999
17.8144
40.2966
47.132
0.855  |      |*     | 
0.035
        2 
119.5232
118.1999
17.8144
1.3233
47.132
0.0281  |      |      | 
0.000
        3 
198.4892
118.1999
17.8144
80.2893
47.132
1.703  |      |***   | 
0.138
        4 
98.3567
118.1999
17.8144 -19.8432
47.132
-0.421  |      |      | 
0.008
        5 
88.3234
118.1999
17.8144 -29.8764
47.132
-0.634  |     *|      | 
0.019
        6 
122.2845
118.1999
17.8144
4.0846
47.132
0.0867  |      |      | 
0.000
        7 
99.8568
118.1999
17.8144 -18.3431
47.132
-0.389  |      |      | 
0.007
        8 
60.2688
118.1999
17.8144 -57.9311
47.132
-1.229  |    **|      | 
0.072
        9 
198.3898
105.7644
17.8144
92.6254
47.132
1.965  |      |***   | 
0.184
       10 
106.9202
105.7644
17.8144
1.1558
47.132
0.0245  |      |      | 
0.000
       11 
52.4805
105.7644
17.8144 -53.2839
47.132
-1.131  |    **|      | 
0.061
       12 
99.4759
105.7644
17.8144
-6.2885
47.132
-0.133  |      |      | 
0.001
       13 
71.9241
105.7644
17.8144 -33.8403
47.132
-0.718  |     *|      | 
0.025
       14 
61.8845
105.7644
17.8144 -43.8799
47.132
-0.931  |     *|      | 
0.041
       15 
202.7607
105.7644
17.8144
96.9964
47.132
2.058  |      |****  | 
0.202
       16 
52.2793
105.7644
17.8144 -53.4850
47.132
-1.135  |    **|      | 
0.061
       17 
104.0063
129.6767
17.8144 -25.6704
47.132
-0.545  |     *|      | 
0.014
       18 
106.9305
129.6767
17.8144 -22.7462
47.132
-0.483  |      |      | 
0.011
       19 
109.1986
129.6767
17.8144 -20.4781
47.132
-0.434  |      |      | 
0.009
       20 
113.1571
129.6767
17.8144 -16.5196
47.132
-0.350  |      |      | 
0.006
       21 
176.7935
129.6767
17.8144
47.1168
47.132
1.000  |      |*     | 
0.048
       22 
93.1642
129.6767
17.8144 -36.5125
47.132
-0.775  |     *|      | 
0.029
       23 
218.2123
129.6767
17.8144
88.5356
47.132
1.878  |      |***   | 
0.168
       24 
115.9511
129.6767
17.8144 -13.7256
47.132
-0.291  |      |      | 
0.004
 Sum of Residuals 
0
 Sum of Squared Residuals 
53315
 Predicted Residual SS (PRESS) 69636


14:27 Thursday, February 8, 2018
53
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
53
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=CL_F
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 1144.21114
0.45 0.6432
 Denominator 
21 2538.82052


14:27 Thursday, February 8, 2018
54
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
54
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Cmax
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2
36362
18181
1.37 0.2753
 Error 
21
278164
13246
 Corrected Total 23
314526
 Root MSE 
115.09091  R-Square 0.1156
 Dependent Mean 278.00000  Adj R-Sq 0.0314
 Coeff Var 
41.39961    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 226.25000 40.69078
5.56
<.0001 141.62889 310.87111
 GrpA 
1
61.37500 57.54545
1.07
0.2983 -58.29732 181.04732
 GrpB 
1
93.87500 57.54545
1.63
0.1177 -25.79732 213.54732


14:27 Thursday, February 8, 2018
55
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
55
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Cmax
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
159.0000
287.6250
40.6908 -128.6250
107.7
-1.195  |    **|      | 
0.068
        2 
350.0000
287.6250
40.6908
62.3750
107.7
0.579  |      |*     | 
0.016
        3 
125.0000
287.6250
40.6908 -162.6250
107.7
-1.511  |   ***|      | 
0.109
        4 
518.0000
287.6250
40.6908
230.3750
107.7
2.140  |      |****  | 
0.218
        5 
255.0000
287.6250
40.6908
-32.6250
107.7
-0.303  |      |      | 
0.004
        6 
258.0000
287.6250
40.6908
-29.6250
107.7
-0.275  |      |      | 
0.004
        7 
220.0000
287.6250
40.6908
-67.6250
107.7
-0.628  |     *|      | 
0.019
        8 
416.0000
287.6250
40.6908
128.3750
107.7
1.192  |      |**    | 
0.068
        9 
207.0000
320.1250
40.6908 -113.1250
107.7
-1.051  |    **|      | 
0.053
       10 
259.0000
320.1250
40.6908
-61.1250
107.7
-0.568  |     *|      | 
0.015
       11 
388.0000
320.1250
40.6908
67.8750
107.7
0.630  |      |*     | 
0.019
       12 
221.0000
320.1250
40.6908
-99.1250
107.7
-0.921  |     *|      | 
0.040
       13 
359.0000
320.1250
40.6908
38.8750
107.7
0.361  |      |      | 
0.006
       14 
419.0000
320.1250
40.6908
98.8750
107.7
0.918  |      |*     | 
0.040
       15 
143.0000
320.1250
40.6908 -177.1250
107.7
-1.645  |   ***|      | 
0.129
       16 
565.0000
320.1250
40.6908
244.8750
107.7
2.275  |      |****  | 
0.246
       17 
199.0000
226.2500
40.6908
-27.2500
107.7
-0.253  |      |      | 
0.003
       18 
307.0000
226.2500
40.6908
80.7500
107.7
0.750  |      |*     | 
0.027
       19 
216.0000
226.2500
40.6908
-10.2500
107.7
-0.0952  |      |      | 
0.000
       20 
270.0000
226.2500
40.6908
43.7500
107.7
0.406  |      |      | 
0.008
       21 
189.0000
226.2500
40.6908
-37.2500
107.7
-0.346  |      |      | 
0.006
       22 
288.0000
226.2500
40.6908
61.7500
107.7
0.574  |      |*     | 
0.016
       23 
149.0000
226.2500
40.6908
-77.2500
107.7
-0.718  |     *|      | 
0.025
       24 
192.0000
226.2500
40.6908
-34.2500
107.7
-0.318  |      |      | 
0.005
 Sum of Residuals 
0
 Sum of Squared Residuals 
278164
 Predicted Residual SS (PRESS) 363317


14:27 Thursday, February 8, 2018
56
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
56
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=Cmax
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2
18181
1.37 0.2753
 Denominator 
21
13246


14:27 Thursday, February 8, 2018
57
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
57
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=LambdaZ
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.00987
0.00494
7.79 0.0029
 Error 
21 0.01330 0.00063354
 Corrected Total 23 0.02318
 Root MSE 
0.02517  R-Square 0.4259
 Dependent Mean 
0.11731  Adj R-Sq 0.3713
 Coeff Var 
21.45595    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
0.13679
0.00890
15.37
<.0001
0.11828
0.15529
 GrpA 
1
-0.01098
0.01259
-0.87
0.3929 -0.03715
0.01520
 GrpB 
1
-0.04745
0.01259
-3.77
0.0011 -0.07362 -0.02127


14:27 Thursday, February 8, 2018
58
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
58
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=LambdaZ
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
0.0999
0.1258
0.008899
-0.0259
0.0235
-1.100  |    **|      | 
0.058
        2 
0.0872
0.1258
0.008899
-0.0386
0.0235
-1.639  |   ***|      | 
0.128
        3 
0.1578
0.1258
0.008899
0.0320
0.0235
1.360  |      |**    | 
0.088
        4 
0.1939
0.1258
0.008899
0.0681
0.0235
2.892  |      |***** | 
0.398
        5 
0.1032
0.1258
0.008899
-0.0226
0.0235
-0.958  |     *|      | 
0.044
        6 
0.1643
0.1258
0.008899
0.0385
0.0235
1.634  |      |***   | 
0.127
        7 
0.0981
0.1258
0.008899
-0.0277
0.0235
-1.177  |    **|      | 
0.066
        8 
0.1020
0.1258
0.008899
-0.0238
0.0235
-1.012  |    **|      | 
0.049
        9 
0.1045
0.0893
0.008899
0.0151
0.0235
0.643  |      |*     | 
0.020
       10 
0.0943
0.0893
0.008899
0.004947
0.0235
0.210  |      |      | 
0.002
       11 
0.0777
0.0893
0.008899
-0.0117
0.0235
-0.495  |      |      | 
0.012
       12 
0.0727
0.0893
0.008899
-0.0167
0.0235
-0.708  |     *|      | 
0.024
       13 
0.0892
0.0893
0.008899 -0.000185
0.0235
-0.0079  |      |      | 
0.000
       14 
0.0799
0.0893
0.008899 -0.009393
0.0235
-0.399  |      |      | 
0.008
       15 
0.1053
0.0893
0.008899
0.0160
0.0235
0.679  |      |*     | 
0.022
       16 
0.0912
0.0893
0.008899
0.001821
0.0235
0.0773  |      |      | 
0.000
       17 
0.1274
0.1368
0.008899 -0.009431
0.0235
-0.401  |      |      | 
0.008
       18 
0.1519
0.1368
0.008899
0.0151
0.0235
0.643  |      |*     | 
0.020
       19 
0.1231
0.1368
0.008899
-0.0137
0.0235
-0.583  |     *|      | 
0.016
       20 
0.1469
0.1368
0.008899
0.0101
0.0235
0.428  |      |      | 
0.009
       21 
0.1513
0.1368
0.008899
0.0145
0.0235
0.617  |      |*     | 
0.018
       22 
0.1428
0.1368
0.008899
0.005993
0.0235
0.255  |      |      | 
0.003
       23 
0.1299
0.1368
0.008899 -0.006930
0.0235
-0.294  |      |      | 
0.004
       24 
0.1211
0.1368
0.008899
-0.0156
0.0235
-0.664  |     *|      | 
0.021
 Sum of Residuals 
0
 Sum of Squared Residuals 
0.01330
 Predicted Residual SS (PRESS) 0.01738


14:27 Thursday, February 8, 2018
59
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
59
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=LambdaZ
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2
0.00494
7.79 0.0029
 Denominator 
21 0.00063354


14:27 Thursday, February 8, 2018
60
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
60
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Vz_F
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2
162471
81235
0.44 0.6481
 Error 
21 3853369 183494
 Corrected Total 23 4015840
 Root MSE 
428.36169  R-Square 
0.0405
 Dependent Mean 1030.15023  Adj R-Sq -0.0509
 Coeff Var 
41.58245    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence Limits
 Intercept 
1 954.61482 151.44873
6.30
<.0001
639.65995 1269.56969
 GrpA 
1
36.65302 214.18085
0.17
0.8658 -408.76043
482.06648
 GrpB 
1 189.95321 214.18085
0.89
0.3852 -255.46025
635.36666


14:27 Thursday, February 8, 2018
61
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
61
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=Vz_F
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
1586
991.2678
151.4487
594.9876
400.7
1.485  |      |**    | 
0.105
        2 
1370
991.2678
151.4487
378.9415
400.7
0.946  |      |*     | 
0.043
        3 
1258
991.2678
151.4487
266.4455
400.7
0.665  |      |*     | 
0.021
        4 
507.2843
991.2678
151.4487 -483.9835
400.7
-1.208  |    **|      | 
0.069
        5 
855.4525
991.2678
151.4487 -135.8153
400.7
-0.339  |      |      | 
0.005
        6 
744.3830
991.2678
151.4487 -246.8848
400.7
-0.616  |     *|      | 
0.018
        7 
1018
991.2678
151.4487
26.6144
400.7
0.0664  |      |      | 
0.000
        8 
590.9625
991.2678
151.4487 -400.3053
400.7
-0.999  |     *|      | 
0.048
        9 
1899
1145
151.4487
754.1813
400.7
1.882  |      |***   | 
0.169
       10 
1134
1145
151.4487
-10.5650
400.7
-0.0264  |      |      | 
0.000
       11 
675.5488
1145
151.4487 -469.0192
400.7
-1.171  |    **|      | 
0.065
       12 
1369
1145
151.4487
224.1684
400.7
0.559  |      |*     | 
0.015
       13 
806.7430
1145
151.4487 -337.8251
400.7
-0.843  |     *|      | 
0.034
       14 
774.0737
1145
151.4487 -370.4943
400.7
-0.925  |     *|      | 
0.041
       15 
1925
1145
151.4487
780.6320
400.7
1.948  |      |***   | 
0.181
       16 
573.4898
1145
151.4487 -571.0782
400.7
-1.425  |    **|      | 
0.097
       17 
816.6712
954.6148
151.4487 -137.9436
400.7
-0.344  |      |      | 
0.006
       18 
703.8423
954.6148
151.4487 -250.7725
400.7
-0.626  |     *|      | 
0.019
       19 
887.4080
954.6148
151.4487
-67.2068
400.7
-0.168  |      |      | 
0.001
       20 
770.4741
954.6148
151.4487 -184.1407
400.7
-0.460  |      |      | 
0.010
       21 
1168
954.6148
151.4487
213.8099
400.7
0.534  |      |*     | 
0.014
       22 
652.5078
954.6148
151.4487 -302.1070
400.7
-0.754  |     *|      | 
0.027
       23 
1680
954.6148
151.4487
725.8154
400.7
1.811  |      |***   | 
0.156
       24 
957.1601
954.6148
151.4487
2.5453
400.7
0.00635  |      |      | 
0.000
 Sum of Residuals 
0
 Sum of Squared Residuals 
3853369
 Predicted Residual SS (PRESS) 5032971


14:27 Thursday, February 8, 2018
62
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
62
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=Vz_F
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2
81235
0.44 0.6481
 Denominator 
21 183494


14:27 Thursday, February 8, 2018
63
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
63
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCT
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.30708 0.15354
0.89 0.4272
 Error 
21 3.63967 0.17332
 Corrected Total 23 3.94675
 Root MSE 
0.41631  R-Square 
0.0778
 Dependent Mean 7.49304  Adj R-Sq -0.0100
 Coeff Var 
5.55601    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
7.36860
0.14719
50.06
<.0001
7.06251 7.67470
 GrpA 
1
0.09961
0.20816
0.48
0.6372 -0.33328 0.53249
 GrpB 
1
0.27371
0.20816
1.31
0.2027 -0.15917 0.70660


14:27 Thursday, February 8, 2018
64
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
64
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCT
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
7.1142
7.4682
0.1472
-0.3540
0.389
-0.909  |     *|      | 
0.039
        2 
7.3961
7.4682
0.1472
-0.0721
0.389
-0.185  |      |      | 
0.002
        3 
6.8861
7.4682
0.1472
-0.5821
0.389
-1.495  |    **|      | 
0.106
        4 
7.6107
7.4682
0.1472
0.1425
0.389
0.366  |      |      | 
0.006
        5 
7.7018
7.4682
0.1472
0.2336
0.389
0.600  |      |*     | 
0.017
        6 
7.3802
7.4682
0.1472
-0.0880
0.389
-0.226  |      |      | 
0.002
        7 
7.5766
7.4682
0.1472
0.1084
0.389
0.278  |      |      | 
0.004
        8 
8.0799
7.4682
0.1472
0.6117
0.389
1.571  |      |***   | 
0.118
        9 
6.8675
7.6423
0.1472
-0.7749
0.389
-1.990  |   ***|      | 
0.189
       10 
7.5126
7.6423
0.1472
-0.1297
0.389
-0.333  |      |      | 
0.005
       11 
8.1887
7.6423
0.1472
0.5464
0.389
1.403  |      |**    | 
0.094
       12 
7.5410
7.6423
0.1472
-0.1013
0.389
-0.260  |      |      | 
0.003
       13 
7.8972
7.6423
0.1472
0.2549
0.389
0.654  |      |*     | 
0.020
       14 
8.0381
7.6423
0.1472
0.3958
0.389
1.016  |      |**    | 
0.049
       15 
6.8784
7.6423
0.1472
-0.7639
0.389
-1.962  |   ***|      | 
0.183
       16 
8.2150
7.6423
0.1472
0.5727
0.389
1.471  |      |**    | 
0.103
       17 
7.5507
7.3686
0.1472
0.1821
0.389
0.468  |      |      | 
0.010
       18 
7.5300
7.3686
0.1472
0.1614
0.389
0.414  |      |      | 
0.008
       19 
7.5023
7.3686
0.1472
0.1337
0.389
0.343  |      |      | 
0.006
       20 
7.4556
7.3686
0.1472
0.0870
0.389
0.223  |      |      | 
0.002
       21 
7.0143
7.3686
0.1472
-0.3543
0.389
-0.910  |     *|      | 
0.039
       22 
7.6667
7.3686
0.1472
0.2981
0.389
0.766  |      |*     | 
0.028
       23 
6.7872
7.3686
0.1472
-0.5815
0.389
-1.493  |    **|      | 
0.106
       24 
7.4421
7.3686
0.1472
0.0735
0.389
0.189  |      |      | 
0.002
 Sum of Residuals 
0
 Sum of Squared Residuals 
3.63967
 Predicted Residual SS (PRESS) 4.75386


14:27 Thursday, February 8, 2018
65
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
65
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=lAUCT
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 0.15354
0.89 0.4272
 Denominator 
21 0.17332


14:27 Thursday, February 8, 2018
66
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
66
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCinf
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.36734 0.18367
1.06 0.3639
 Error 
21 3.63514 0.17310
 Corrected Total 23 4.00248
 Root MSE 
0.41606  R-Square 0.0918
 Dependent Mean 7.51869  Adj R-Sq 0.0053
 Coeff Var 
5.53361    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
7.38275
0.14710
50.19
<.0001
7.07685 7.68866
 GrpA 
1
0.10851
0.20803
0.52
0.6074 -0.32411 0.54113
 GrpB 
1
0.29930
0.20803
1.44
0.1650 -0.13332 0.73191


14:27 Thursday, February 8, 2018
67
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
67
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lAUCinf
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
7.1403
7.4913
0.1471
-0.3509
0.389
-0.902  |     *|      | 
0.039
        2 
7.4226
7.4913
0.1471
-0.0687
0.389
-0.177  |      |      | 
0.001
        3 
6.9153
7.4913
0.1471
-0.5759
0.389
-1.480  |    **|      | 
0.104
        4 
7.6175
7.4913
0.1471
0.1262
0.389
0.324  |      |      | 
0.005
        5 
7.7251
7.4913
0.1471
0.2338
0.389
0.601  |      |*     | 
0.017
        6 
7.3997
7.4913
0.1471
-0.0915
0.389
-0.235  |      |      | 
0.003
        7 
7.6023
7.4913
0.1471
0.1111
0.389
0.285  |      |      | 
0.004
        8 
8.1073
7.4913
0.1471
0.6160
0.389
1.583  |      |***   | 
0.119
        9 
6.9158
7.6821
0.1471
-0.7662
0.389
-1.969  |   ***|      | 
0.185
       10 
7.5340
7.6821
0.1471
-0.1481
0.389
-0.380  |      |      | 
0.007
       11 
8.2456
7.6821
0.1471
0.5636
0.389
1.448  |      |**    | 
0.100
       12 
7.6062
7.6821
0.1471
-0.0759
0.389
-0.195  |      |      | 
0.002
       13 
7.9305
7.6821
0.1471
0.2484
0.389
0.638  |      |*     | 
0.019
       14 
8.0808
7.6821
0.1471
0.3988
0.389
1.025  |      |**    | 
0.050
       15 
6.8940
7.6821
0.1471
-0.7880
0.389
-2.025  |  ****|      | 
0.195
       16 
8.2495
7.6821
0.1471
0.5674
0.389
1.458  |      |**    | 
0.101
       17 
7.5616
7.3828
0.1471
0.1789
0.389
0.460  |      |      | 
0.010
       18 
7.5339
7.3828
0.1471
0.1511
0.389
0.388  |      |      | 
0.007
       19 
7.5129
7.3828
0.1471
0.1302
0.389
0.334  |      |      | 
0.005
       20 
7.4773
7.3828
0.1471
0.0945
0.389
0.243  |      |      | 
0.003
       21 
7.0311
7.3828
0.1471
-0.3517
0.389
-0.904  |     *|      | 
0.039
       22 
7.6717
7.3828
0.1471
0.2890
0.389
0.742  |      |*     | 
0.026
       23 
6.8206
7.3828
0.1471
-0.5621
0.389
-1.444  |    **|      | 
0.099
       24 
7.4529
7.3828
0.1471
0.0702
0.389
0.180  |      |      | 
0.002
 Sum of Residuals 
0
 Sum of Squared Residuals 
3.63514
 Predicted Residual SS (PRESS) 4.74794


14:27 Thursday, February 8, 2018
68
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
68
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=lAUCinf
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 0.18367
1.06 0.3639
 Denominator 
21 0.17310


14:27 Thursday, February 8, 2018
69
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
69
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCLF
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.36734 0.18367
1.06 0.3639
 Error 
21 3.63514 0.17310
 Corrected Total 23 4.00248
 Root MSE 
0.41606  R-Square 0.0918
 Dependent Mean 4.68738  Adj R-Sq 0.0053
 Coeff Var 
8.87606    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
4.82332
0.14710
32.79
<.0001
4.51741 5.12923
 GrpA 
1
-0.10851
0.20803
-0.52
0.6074 -0.54113 0.32411
 GrpB 
1
-0.29930
0.20803
-1.44
0.1650 -0.73191 0.13332


14:27 Thursday, February 8, 2018
70
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
70
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCLF
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
5.0657
4.7148
0.1471
0.3509
0.389
0.902  |      |*     | 
0.039
        2 
4.7835
4.7148
0.1471
0.0687
0.389
0.177  |      |      | 
0.001
        3 
5.2907
4.7148
0.1471
0.5759
0.389
1.480  |      |**    | 
0.104
        4 
4.5886
4.7148
0.1471
-0.1262
0.389
-0.324  |      |      | 
0.005
        5 
4.4810
4.7148
0.1471
-0.2338
0.389
-0.601  |     *|      | 
0.017
        6 
4.8064
4.7148
0.1471
0.0915
0.389
0.235  |      |      | 
0.003
        7 
4.6037
4.7148
0.1471
-0.1111
0.389
-0.285  |      |      | 
0.004
        8 
4.0988
4.7148
0.1471
-0.6160
0.389
-1.583  |   ***|      | 
0.119
        9 
5.2902
4.5240
0.1471
0.7662
0.389
1.969  |      |***   | 
0.185
       10 
4.6721
4.5240
0.1471
0.1481
0.389
0.380  |      |      | 
0.007
       11 
3.9604
4.5240
0.1471
-0.5636
0.389
-1.448  |    **|      | 
0.100
       12 
4.5999
4.5240
0.1471
0.0759
0.389
0.195  |      |      | 
0.002
       13 
4.2756
4.5240
0.1471
-0.2484
0.389
-0.638  |     *|      | 
0.019
       14 
4.1253
4.5240
0.1471
-0.3988
0.389
-1.025  |    **|      | 
0.050
       15 
5.3120
4.5240
0.1471
0.7880
0.389
2.025  |      |****  | 
0.195
       16 
3.9566
4.5240
0.1471
-0.5674
0.389
-1.458  |    **|      | 
0.101
       17 
4.6445
4.8233
0.1471
-0.1789
0.389
-0.460  |      |      | 
0.010
       18 
4.6722
4.8233
0.1471
-0.1511
0.389
-0.388  |      |      | 
0.007
       19 
4.6932
4.8233
0.1471
-0.1302
0.389
-0.334  |      |      | 
0.005
       20 
4.7288
4.8233
0.1471
-0.0945
0.389
-0.243  |      |      | 
0.003
       21 
5.1750
4.8233
0.1471
0.3517
0.389
0.904  |      |*     | 
0.039
       22 
4.5344
4.8233
0.1471
-0.2890
0.389
-0.742  |     *|      | 
0.026
       23 
5.3855
4.8233
0.1471
0.5621
0.389
1.444  |      |**    | 
0.099
       24 
4.7532
4.8233
0.1471
-0.0702
0.389
-0.180  |      |      | 
0.002
 Sum of Residuals 
0
 Sum of Squared Residuals 
3.63514
 Predicted Residual SS (PRESS) 4.74794


14:27 Thursday, February 8, 2018
71
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
71
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=lCLF
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 0.18367
1.06 0.3639
 Denominator 
21 0.17310


14:27 Thursday, February 8, 2018
72
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
72
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCmax
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.33702 0.16851
1.03 0.3737
 Error 
21 3.42932 0.16330
 Corrected Total 23 3.76634
 Root MSE 
0.40410  R-Square 0.0895
 Dependent Mean 5.54805  Adj R-Sq 0.0028
 Coeff Var 
7.28373    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
5.39500
0.14287
37.76
<.0001
5.09788 5.69212
 GrpA 
1
0.17046
0.20205
0.84
0.4084 -0.24973 0.59065
 GrpB 
1
0.28870
0.20205
1.43
0.1678 -0.13149 0.70889


14:27 Thursday, February 8, 2018
73
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
73
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lCmax
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
5.0689
5.5655
0.1429
-0.4966
0.378
-1.314  |    **|      | 
0.082
        2 
5.8579
5.5655
0.1429
0.2925
0.378
0.774  |      |*     | 
0.029
        3 
4.8283
5.5655
0.1429
-0.7371
0.378
-1.950  |   ***|      | 
0.181
        4 
6.2500
5.5655
0.1429
0.6845
0.378
1.811  |      |***   | 
0.156
        5 
5.5413
5.5655
0.1429
-0.0242
0.378
-0.0640  |      |      | 
0.000
        6 
5.5530
5.5655
0.1429
-0.0125
0.378
-0.0331  |      |      | 
0.000
        7 
5.3936
5.5655
0.1429
-0.1718
0.378
-0.455  |      |      | 
0.010
        8 
6.0307
5.5655
0.1429
0.4652
0.378
1.231  |      |**    | 
0.072
        9 
5.3327
5.6837
0.1429
-0.3510
0.378
-0.929  |     *|      | 
0.041
       10 
5.5568
5.6837
0.1429
-0.1269
0.378
-0.336  |      |      | 
0.005
       11 
5.9610
5.6837
0.1429
0.2773
0.378
0.734  |      |*     | 
0.026
       12 
5.3982
5.6837
0.1429
-0.2855
0.378
-0.755  |     *|      | 
0.027
       13 
5.8833
5.6837
0.1429
0.1996
0.378
0.528  |      |*     | 
0.013
       14 
6.0379
5.6837
0.1429
0.3542
0.378
0.937  |      |*     | 
0.042
       15 
4.9628
5.6837
0.1429
-0.7209
0.378
-1.907  |   ***|      | 
0.173
       16 
6.3368
5.6837
0.1429
0.6531
0.378
1.728  |      |***   | 
0.142
       17 
5.2933
5.3950
0.1429
-0.1017
0.378
-0.269  |      |      | 
0.003
       18 
5.7268
5.3950
0.1429
0.3318
0.378
0.878  |      |*     | 
0.037
       19 
5.3753
5.3950
0.1429
-0.0197
0.378
-0.0522  |      |      | 
0.000
       20 
5.5984
5.3950
0.1429
0.2034
0.378
0.538  |      |*     | 
0.014
       21 
5.2417
5.3950
0.1429
-0.1533
0.378
-0.405  |      |      | 
0.008
       22 
5.6630
5.3950
0.1429
0.2680
0.378
0.709  |      |*     | 
0.024
       23 
5.0039
5.3950
0.1429
-0.3911
0.378
-1.035  |    **|      | 
0.051
       24 
5.2575
5.3950
0.1429
-0.1375
0.378
-0.364  |      |      | 
0.006
 Sum of Residuals 
0
 Sum of Squared Residuals 
3.42932
 Predicted Residual SS (PRESS) 4.47911


14:27 Thursday, February 8, 2018
74
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
74
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=lCmax
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 0.16851
1.03 0.3737
 Denominator 
21 0.16330


14:27 Thursday, February 8, 2018
75
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
75
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lLambdaZ
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.78760 0.39380
10.10 0.0008
 Error 
21 0.81910 0.03900
 Corrected Total 23 1.60669
 Root MSE 
0.19750  R-Square 0.4902
 Dependent Mean -2.17680  Adj R-Sq 0.4416
 Coeff Var 
-9.07279    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
-1.99319
0.06983
-28.55
<.0001 -2.13840 -1.84798
 GrpA 
1
-0.12067
0.09875
-1.22
0.2353 -0.32603
0.08469
 GrpB 
1
-0.43014
0.09875
-4.36
0.0003 -0.63549 -0.22478


14:27 Thursday, February 8, 2018
76
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
76
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lLambdaZ
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
-2.3034
-2.1139
0.0698
-0.1895
0.185
-1.026  |    **|      | 
0.050
        2 
-2.4392
-2.1139
0.0698
-0.3253
0.185
-1.761  |   ***|      | 
0.148
        3 
-1.8463
-2.1139
0.0698
0.2675
0.185
1.448  |      |**    | 
0.100
        4 
-1.6405
-2.1139
0.0698
0.4734
0.185
2.562  |      |***** | 
0.313
        5 
-2.2706
-2.1139
0.0698
-0.1568
0.185
-0.849  |     *|      | 
0.034
        6 
-1.8062
-2.1139
0.0698
0.3077
0.185
1.665  |      |***   | 
0.132
        7 
-2.3217
-2.1139
0.0698
-0.2079
0.185
-1.125  |    **|      | 
0.060
        8 
-2.2829
-2.1139
0.0698
-0.1691
0.185
-0.915  |     *|      | 
0.040
        9 
-2.2587
-2.4233
0.0698
0.1646
0.185
0.891  |      |*     | 
0.038
       10 
-2.3614
-2.4233
0.0698
0.0619
0.185
0.335  |      |      | 
0.005
       11 
-2.5551
-2.4233
0.0698
-0.1318
0.185
-0.713  |     *|      | 
0.024
       12 
-2.6217
-2.4233
0.0698
-0.1984
0.185
-1.074  |    **|      | 
0.055
       13 
-2.4174
-2.4233
0.0698 0.005937
0.185
0.0321  |      |      | 
0.000
       14 
-2.5264
-2.4233
0.0698
-0.1031
0.185
-0.558  |     *|      | 
0.015
       15 
-2.2508
-2.4233
0.0698
0.1726
0.185
0.934  |      |*     | 
0.042
       16 
-2.3951
-2.4233
0.0698
0.0282
0.185
0.153  |      |      | 
0.001
       17 
-2.0608
-1.9932
0.0698
-0.0676
0.185
-0.366  |      |      | 
0.006
       18 
-1.8844
-1.9932
0.0698
0.1088
0.185
0.589  |      |*     | 
0.017
       19 
-2.0951
-1.9932
0.0698
-0.1019
0.185
-0.552  |     *|      | 
0.014
       20 
-1.9182
-1.9932
0.0698
0.0750
0.185
0.406  |      |      | 
0.008
       21 
-1.8884
-1.9932
0.0698
0.1048
0.185
0.567  |      |*     | 
0.015
       22 
-1.9465
-1.9932
0.0698
0.0467
0.185
0.253  |      |      | 
0.003
       23 
-2.0413
-1.9932
0.0698
-0.0481
0.185
-0.261  |      |      | 
0.003
       24 
-2.1108
-1.9932
0.0698
-0.1176
0.185
-0.637  |     *|      | 
0.019
 Sum of Residuals 
0
 Sum of Squared Residuals 
0.81910
 Predicted Residual SS (PRESS) 1.06984


14:27 Thursday, February 8, 2018
77
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
77
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=lLambdaZ
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 0.39380
10.10 0.0008
 Denominator 
21 0.03900


14:27 Thursday, February 8, 2018
78
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
78
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lVz_F
 Number of Observations Read 24
 Number of Observations Used 24
Analysis of Variance
Source
DF Sum of
Squares
Mean
Square
F Value Pr > F
 Model 
2 0.08360 0.04180
0.26 0.7713
 Error 
21 3.33827 0.15897
 Corrected Total 23 3.42187
 Root MSE 
0.39870  R-Square 
0.0244
 Dependent Mean 6.86418  Adj R-Sq -0.0685
 Coeff Var 
5.80848    
Parameter Estimates
Variable
DF Parameter
Estimate
Standard
Error
t Value Pr > |t|
95%
Confidence
Limits
 Intercept 
1
6.81651
0.14096
48.36
<.0001
6.52336 7.10966
 GrpA 
1
0.01216
0.19935
0.06
0.9519 -0.40242 0.42674
 GrpB 
1
0.13084
0.19935
0.66
0.5187 -0.28374 0.54541


14:27 Thursday, February 8, 2018
79
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
14:27 Thursday, February 8, 2018
79
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
Dependent Variable: Value
NAME OF FORMER VARIABLE=lVz_F
Output Statistics
Obs
Dependent
Variable
Predicted
Value
Std Error
Mean Predict
Residual Std Error
Residual
Student
Residual
-2-1 0 1 2
Cook's
D
        1 
7.3691
6.8287
0.1410
0.5405
0.373
1.449  |      |**    | 
0.100
        2 
7.2227
6.8287
0.1410
0.3940
0.373
1.057  |      |**    | 
0.053
        3 
7.1371
6.8287
0.1410
0.3084
0.373
0.827  |      |*     | 
0.033
        4 
6.2291
6.8287
0.1410
-0.5996
0.373
-1.608  |   ***|      | 
0.123
        5 
6.7516
6.8287
0.1410
-0.0770
0.373
-0.207  |      |      | 
0.002
        6 
6.6126
6.8287
0.1410
-0.2161
0.373
-0.579  |     *|      | 
0.016
        7 
6.9255
6.8287
0.1410
0.0968
0.373
0.260  |      |      | 
0.003
        8 
6.3818
6.8287
0.1410
-0.4469
0.373
-1.198  |    **|      | 
0.068
        9 
7.5490
6.9474
0.1410
0.6016
0.373
1.613  |      |***   | 
0.124
       10 
7.0335
6.9474
0.1410
0.0862
0.373
0.231  |      |      | 
0.003
       11 
6.5155
6.9474
0.1410
-0.4318
0.373
-1.158  |    **|      | 
0.064
       12 
7.2216
6.9474
0.1410
0.2743
0.373
0.735  |      |*     | 
0.026
       13 
6.6930
6.9474
0.1410
-0.2543
0.373
-0.682  |     *|      | 
0.022
       14 
6.6517
6.9474
0.1410
-0.2957
0.373
-0.793  |     *|      | 
0.030
       15 
7.5628
6.9474
0.1410
0.6154
0.373
1.650  |      |***   | 
0.130
       16 
6.3517
6.9474
0.1410
-0.5956
0.373
-1.597  |   ***|      | 
0.121
       17 
6.7052
6.8165
0.1410
-0.1113
0.373
-0.298  |      |      | 
0.004
       18 
6.5566
6.8165
0.1410
-0.2600
0.373
-0.697  |     *|      | 
0.023
       19 
6.7883
6.8165
0.1410
-0.0282
0.373
-0.0756  |      |      | 
0.000
       20 
6.6470
6.8165
0.1410
-0.1695
0.373
-0.455  |      |      | 
0.010
       21 
7.0634
6.8165
0.1410
0.2469
0.373
0.662  |      |*     | 
0.021
       22 
6.4808
6.8165
0.1410
-0.3357
0.373
-0.900  |     *|      | 
0.039
       23 
7.4268
6.8165
0.1410
0.6103
0.373
1.636  |      |***   | 
0.128
       24 
6.8640
6.8165
0.1410
0.0475
0.373
0.127  |      |      | 
0.001
 Sum of Residuals 
0
 Sum of Squared Residuals 
3.33827
 Predicted Residual SS (PRESS) 4.36019


14:27 Thursday, February 8, 2018
80
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
14:27 Thursday, February 8, 2018
80
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
Regression Analysis of Group Child-Pugh Classification at Baseline
--------------------- SUMMARY REPORT ---------------------
The REG Procedure
Model: MODEL1
NAME OF FORMER VARIABLE=lVz_F
Test test_FunctionGroup Results for
Dependent Variable Value
Source
DF
Mean
Square
F Value Pr > F
 Numerator 
2 0.04180
0.26 0.7713
 Denominator 
21 0.15897


14:27 Thursday, February 8, 2018
81
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
NON-PARAMETRIC TEST OF FIXED EFFECT for Tmax parameter
--------------------- SUMMARY REPORT ---------------------
The NPAR1WAY Procedure
14:27 Thursday, February 8, 2018
81
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
NON-PARAMETRIC TEST OF FIXED EFFECT for Tmax parameter
--------------------- SUMMARY REPORT ---------------------
The NPAR1WAY Procedure
Wilcoxon Scores (Rank Sums) for Variable Value
Classified by Variable FunctionGroup
FunctionGroup
N
Sum of
Scores
Expected
Under H0
Std Dev
Under H0
Mean
Score
 2 
8
38.50
68.0 9.465728
4.81250
 3 
8
97.50
68.0 9.465728 12.18750
Average scores were used for ties.
Wilcoxon Two-Sample Test
 Statistic 
38.5000
   
 Normal Approximation 
 Z 
-3.0637
 One-Sided Pr <  Z 
0.0011
 Two-Sided Pr > |Z| 
0.0022
   
 t Approximation 
 One-Sided Pr <  Z 
0.0039
 Two-Sided Pr > |Z| 
0.0079
Z includes a continuity correction of 0.5.
Kruskal-Wallis Test
 Chi-Square 
9.7126
 DF 
1
 Pr > Chi-Square 
0.0018
Hodges-Lehmann Estimation
Location Shift (2 - 3)    -1.2500
Type
90%
Confidence
Limits
Interval
Midpoint
Asymptotic
Standard Error
 Asymptotic (Moses) -2.0000 -0.5333
-1.2667
0.4458
 Exact 
-2.0000 -0.7500
-1.3750


14:27 Thursday, February 8, 2018
82
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
NON-PARAMETRIC TEST OF FIXED EFFECT for Tmax parameter
--------------------- SUMMARY REPORT ---------------------
The NPAR1WAY Procedure
14:27 Thursday, February 8, 2018
82
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
NON-PARAMETRIC TEST OF FIXED EFFECT for Tmax parameter
--------------------- SUMMARY REPORT ---------------------
The NPAR1WAY Procedure
Wilcoxon Scores (Rank Sums) for Variable Value
Classified by Variable FunctionGroup
FunctionGroup
N
Sum of
Scores
Expected
Under H0
Std Dev
Under H0
Mean
Score
 1 
8
52.50
68.0 9.402127
6.56250
 3 
8
83.50
68.0 9.402127 10.43750
Average scores were used for ties.
Wilcoxon Two-Sample Test
 Statistic 
52.5000
   
 Normal Approximation 
 Z 
-1.5954
 One-Sided Pr <  Z 
0.0553
 Two-Sided Pr > |Z| 
0.1106
   
 t Approximation 
 One-Sided Pr <  Z 
0.0657
 Two-Sided Pr > |Z| 
0.1315
Z includes a continuity correction of 0.5.
Kruskal-Wallis Test
 Chi-Square 
2.7178
 DF 
1
 Pr > Chi-Square 
0.0992
Hodges-Lehmann Estimation
Location Shift (1 - 3)    -1.0000
Type
90%
Confidence
Limits
Interval
Midpoint
Asymptotic
Standard Error
 Asymptotic (Moses) -1.7500 0.0000
-0.8750
0.5320
 Exact 
-1.7500 0.0000
-0.8750


14:27 Thursday, February 8, 2018
83
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
NON-PARAMETRIC TEST OF FIXED EFFECT for Tmax parameter
--------------------- SUMMARY REPORT ---------------------
The NPAR1WAY Procedure
14:27 Thursday, February 8, 2018
83
--------------------- SUMMARY REPORT ---------------------
Algorithme Pharma
CUD-P9-453: Effect of Hepatic Impairment on Pharmacokinetics of Lasmiditan
NON-PARAMETRIC TEST OF FIXED EFFECT for Tmax parameter
--------------------- SUMMARY REPORT ---------------------
The NPAR1WAY Procedure
Wilcoxon Scores (Rank Sums) for Variable Value
Classified by Variable FunctionGroup
FunctionGroup
N
Sum of
Scores
Expected
Under H0
Std Dev
Under H0
Mean
Score
 1 
8
81.0
68.0 9.423375 10.1250
 2 
8
55.0
68.0 9.423375
6.8750
Average scores were used for ties.
Wilcoxon Two-Sample Test
 Statistic 
81.0000
   
 Normal Approximation 
 Z 
1.3265
 One-Sided Pr >  Z 
0.0923
 Two-Sided Pr > |Z| 
0.1847
   
 t Approximation 
 One-Sided Pr >  Z 
0.1023
 Two-Sided Pr > |Z| 
0.2045
Z includes a continuity correction of 0.5.
Kruskal-Wallis Test
 Chi-Square 
1.9032
 DF 
1
 Pr > Chi-Square 
0.1677
Hodges-Lehmann Estimation
Location Shift (1 - 2)    0.5000
Type
90%
Confidence
Limits
Interval
Midpoint
Asymptotic
Standard Error
 Asymptotic (Moses) -0.2500 1.2500
0.5000
0.4560
 Exact 
0.0000 1.2500
0.6250