Conditions: Safety and Tolerability
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 25
Healthy volunteers: yes

Brief summary:
The goal of this clinical trial was to learn about a single dose of fenretinide in healthy volunteers, in both a fasted and fed state. The main questions to answer were:

* How well is a single dose of fenretinide tolerated? AND
* How is a single dose of fenretinide metabolized in healthy volunteers?

Participants will be asked to:

* Remain confined in a clinical research unit for 5 days after dosing.
* Provide blood samples for intense PK sampling and safety labs.
* Fast for 10 hours prior to administration of study drug (fasted cohorts).
* Consume a high fat meal prior to administration of study drug (fed cohort).
* Return to the clinic for a single follow-up visit for safety assessments.

The study will compare active fenretinide to placebo to see if fenretinide is more or less tolerable than placebo.

Detailed description:
This study is a randomized, double-blind, placebo-controlled single ascending dose study. There are 3 planned dose-level cohorts (Cohorts 1-3). Each dose-level cohort will consist of 8 subjects (6 active + 2 placebo), who will be treated under fasted conditions. The subjects in the highest tolerated dose-level cohort (determined by the Safety Review Committee) will also be administered ISLA101 or placebo under fed conditions, in a cross-over manner (Cohort 4).

Proposed doses are 300, 600, and 900 mg/m\^2 (equivalent to 8.1, 16.2, and 24.3 mg/kg). Each subject will be allocated to 1 dose level only.

The study will include a 5-day stay in the clinical research unit followed by a final safety follow-up visit at Day 8, where subjects will be under fasted conditions when they are dosed on Study Day 1.

For cohort 4, the study will again include a 5-day stay in the clinical research unit followed by a final safety follow-up visit at Day 17, where subjects will be under fed conditions when they are dosed on Study Day 10.

Arms:
arm 1: Single oral dose of fenretinide, 300 mg/m\^2 under fasted conditions (Phase 1) arm 2: Single oral dose of fenretinide, 600 mg/m\^2 under fasted conditions (Phase 1)

Once all groups finish Phase 1, return to complete Phase 2 with a single oral dose of fenretinide, 600 mg/m\^2 under fed conditions per recommendation from the independent Safety Review Committee. arm 3: Single oral dose of fenretinide, 900 mg/m\^2 under fasted conditions (Phase 1) arm 4: Single oral dose of placebo capsules under fasted conditions (Phase 1)

Once all groups finish Phase 1, return to complete Phase 2 with a single oral dose of placebo capsules under fed conditions per recommendation from the independent Safety Review Committee.

Interventions: intervention 1: Fenretinide intervention 2: Placebo
Intervention descriptions: intervention 1: Ascending single doses of oral fenretinide intervention 2: Single oral dose of matching placebo capsules

Protocol document:
Prot_000.pdf: 
A Phase 1a, randomized, double-blind placebo-controlled study to evaluate safety and 
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NCT06181760 
Protocol Amendment #1 dated 18October2023 


CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1a, randomized, double-blind placebo-controlled study to evaluate 
safety and tolerability and to characterize the pharmacokinetic profile of 
single ascending doses of fenretinide oral capsules in healthy adult 
volunteers
Study Number:
ISLA101-P01-CT001
Study Phase:
Phase 1a
Product Name:
ISLA101 (fenretinide oral capsules)
IND Number:
142758
Indication:
Prophylaxis of dengue fever
Sponsor:
Island Pharmaceuticals Ltd
Suite 201, 697 Burke Road, Camberwell
Victoria 3124, Australia
Sponsor Contact:
David Foster, PhD, JD
dfoster@islandpharmaceuticals.com
Date
Original Protocol
31 March 2023
Amendment 1
18 October 2023
Confidentiality Statement
The information included in this document is the proprietary property of Island Pharmaceuticals Ltd. 
(Island). No part of this document may be reproduced or transmitted in any form without written 
permission from Island, except as required by local laws.


ISLA101 (fenretinide oral capsules) 
 
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Clinical Trial Protocol: ISLA101-P01-CT001 
 
Page 2  
 
 
SYNOPSIS 
Sponsor 
Island Pharmaceuticals, Ltd 
Study Title 
A Phase 1a, randomized, double-blind placebo-controlled study to evaluate safety 
and tolerability and to characterize the pharmacokinetic profile of single ascending 
doses of fenretinide oral capsules in healthy adult volunteers. 
Protocol Number 
ISLA101-P01-CT001 
IND Number 
142758 
Indication 
Prophylaxis of dengue fever 
Sites 
One study center located in Australia. A contract research organization will oversee 
operational aspects of this study on behalf of Island Pharmaceuticals, the sponsor of 
the study. 
Phase of Development 
Phase 1a 
Study Type 
Interventional 
Objectives 
The primary objective is to:  
x 
Evaluate the safety and tolerability of single ascending doses (SAD) of 
ISLA101 in healthy adult volunteers (fasted). 
The secondary objective is to: 
x 
Characterize the pharmacokinetic (PK) profile (fasted) of fenretinide after 
administration of SAD of ISLA101 in healthy adult volunteers (fasted). 
The exploratory objective is to: 
x 
Assess the PK profile of fenretinide in healthy adult volunteers under fed 
conditions. 
Endpoints 
The primary endpoints are: 
x 
Vital signs, clinical laboratory tests, changes from baseline in physical 
examinations, adverse events (AEs), and treatment emergent adverse events 
(TEAEs). 
The secondary endpoints are: 
x 
Single dose PK parameters for fenretinide in plasma: Cmax, Tmax, AUClast, 
AUCinf, T1/2, and others as relevant. 
The exploratory endpoints are: 
x 
Single dose PK parameters for fenretinide in plasma under fed conditions: 
Cmax, Tmax, AUClast, AUCinf, T1/2, and others as relevant.  
Study Design and 
Treatment 
This study is a randomized, double-blind, placebo-controlled SAD study. There are 
3 planned dose-level cohorts (Cohorts 1-3). Each dose-level cohort will consist of 8 
subjects (6 active + 2 placebo), who will be treated under fasted conditions. The 
subjects in the highest tolerated dose-level cohort will also be administered 
ISLA101 under fed conditions, in a cross-over manner (Cohort 4). Proposed doses 
are 300, 600, and 900 mg/m2 (equivalent to 8.1, 16.2, and 24.3 mg/kg). Each subject 
will be allocated to 1 dose level only.  
The study will include a 5-day stay in the clinical research unit followed by a final 
safety follow-up visit at Day 8.  
An independent Safety Review Committee (SRC) will review available safety data 
up to 96-hours post-dose for subjects enrolled in each dose-level cohort.  After 
safety review, the dose level may be escalated to the next planned or lower than 


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planned dose level, de-escalated to an intermediate dose level, or repeated at the 
same dose, if needed. 
The first 3 dose-level cohorts will be treated under fasting conditions. A single dose 
of study drug will be administered on the morning of Day 1, after an overnight fast 
of approximately 10 hours, followed by an additional 4-hour fast after dosing. Study 
drug will be taken with up to 8 oz/240 ml of water. Water will be allowed ad libitum 
except the interval from 1 hour before to 1 hour after dosing. 
Following review of the safety data of the highest tolerated dose level, the subjects 
enrolled in this dose-level cohort will be recalled to evaluate the PK of ISLA101 
dosed under fed conditions (Cohort 4; 8 subjects). These data will support a planned 
Phase 2 study.  Subjects will be informed and will be provided a consent form prior 
to the participation in the food effect cohort (Cohort 4) of the study.   
Subjects in Cohort 4 will be dosed after a meal. They will fast overnight for at least 
10 hours and will then consume a high-fat, high-calorie meal prior to administration 
of study drug, as outlined in the FDA’s Guidance for Industry- Assessing the Effects 
of Food and Drugs in INDs and NDAs – Clinical Pharmacology Considerations. 
The study drug should be administered approximately 30 minutes after start of the 
high-fat meal. No food consumption will be permitted for at least 4 hours post-dose. 
Water will be allowed ad libitum except the interval from 1 hour before to 1 hour 
after dose. 
Study Population 
Approximately 24 healthy male and female volunteers who are 18–65 years of age 
(inclusive). 
Inclusion Criteria 
Subjects must meet the following criteria to be enrolled in the study: 
1. Healthy male or female volunteers not of childbearing potential, who are 
18 years to 65 years of age (inclusive) at the time of signing the informed 
consent form (ICF). 
2. Females not of childbearing potential, as defined in the following criteria:  
a. History of hysterectomy.  
b. Post-menopausal.  
i. Natural post-menopausal females with at least 12 months 
from natural spontaneous amenorrhea and a serum follicle-
stimulating hormone (FSH) concentration ≥ 40 IU/L.  
ii. Post-surgical females must have undergone bilateral 
oophorectomy at least 6 weeks prior to study. 
3. Male subjects with female partners of childbearing potential must agree to 
practice abstinence or use a combination of 2 of the following acceptable birth 
control methods during the study and for at least 90 days after dosing:  
a. Partners have an intrauterine device (IUD) without hormones in 
place for at least 3 months. 
b. Barrier method (condom or diaphragm) for at least 14 days prior to 
screening and 90 days after dosing with study drug. 
c. Partners using stable hormonal contraceptive for at least 3 months 
prior to screening and for 90 days after dosing with study drug.  
d. History of vasectomy at least 3 months prior to signing the ICF.  
4. Must be able to understand and provide signed informed consent for study 
participation.  
5. Willing and able to comply with all scheduled visits, treatment plan, laboratory 
tests, and other study procedures. 


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6. Body mass index (BMI) 18.0 to 32.0 kg/m2 (inclusive), and a body weight ≥ 50 
kg. 
7. Normal renal function, defined as estimated glomerular filtration rate (eGFR) ≥ 
70 mL/min/1.73 m2 at screening and Day -1.  
8. Clinical laboratory values should be within the laboratory's stated normal range. 
If not within this range, they must be without clinical significance, as 
determined by the Investigator. 
9. No history of clinically relevant medical disorders, as determined by the 
Investigator. 
Exclusion Criteria 
A subject will be excluded from the study if he or she meets any of the following 
criteria: 
1. Known or suspected pregnancy (confirmed via a positive serum human 
chorionic gonadotropin [hCG] pregnancy test at screening), planned pregnancy 
during the study period, nursing, or lactation.  
2. Women of childbearing potential or men who intend to father a child or donate 
sperm during the study period and for 3 months after study drug administration. 
3. Known allergy to fenretinide or any of the components of ISLA101. 
4. Evidence or history of clinically significant medical conditions, such as 
hematological, renal, endocrine (e.g., polycystic ovarian syndrome or other 
anovulatory states), immunologic, pulmonary, metabolic, gastrointestinal (e.g., 
Crohn's disease, acute or chronic pancreatitis, and others) and surgery (except 
for simple appendectomy or repair of a hernia), which all can influence the 
absorption of study drug; cardiovascular, hepatic, psychiatric, neurologic, or 
allergic disease (including drug allergies, but excluding untreated, 
asymptomatic, seasonal allergies at the time of dosing), or any other illness that 
the Investigator considers exclusionary or that could interfere with the 
interpretation of the study results.  
5. History of severe infectious disease or recurrent infections. 
6. Aspartate transaminase (AST), alanine aminotransferase (ALT), or total 
bilirubin above the 1.5 x upper limit of normal (ULN) at screening and Day -1.  
7. Clinically significant electrocardiogram (ECG) abnormalities or vital sign 
abnormalities at screening and Day -1, long QT syndrome, or a history of 
cardiac disease.  
8. Abnormal diet that may affect absorption, distribution, metabolism, or excretion 
of drugs, for example, lacking standard nutrients (e.g, cleansing diet 2 weeks 
before or during the study). 
9. Positive result for hepatitis B, hepatitis C, or human immunodeficiency virus 
(HIV) at screening. 
10. History of positive test for tuberculosis (TB) at screening. 
11. A subject who has donated 1 unit of blood of over 500 mL within 56 days prior 
to the study drug administration, or donated plasma within 14 days prior to 
study drug administration. 
12. Use of systemic antibiotics within 30 days prior to dosing. 
13. Any use of drugs that inhibit or induce CYP enzymes within 30 days prior to 
administration of study drug and for the duration of study participation. 
14. Use of any tobacco products, e-cigarettes, and/or nicotine replacement products 
in the 3 months preceding screening.  
15. Any food allergy, intolerance, or restriction that, in the opinion of the 
Investigator, could contraindicate the subject’s participation in this study. 


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16. Recent history of (within the past 12 months), or strong potential for, alcohol or 
substance abuse. Alcohol abuse will be defined as > 14 drinks per week (1 drink 
= 10g of ethanol). 
17. History of drug or alcohol abuse within 5 years before screening or positive 
result of UDS (e.g, amphetamines, benzodiazepines, cannabinoids, cocaine, 
hallucinogens, opiates) or alcohol breath test at screening. 
18. Exposure to any investigational agent or used an invasive investigational 
medical device within 30 days or within a period less than 5 drug half-lives 
prior to study entry (whichever is longer). 
19. Study site employees, Sponsor’s employees, or immediate family members of a 
study site or Sponsor employee. 
20. Previously enrolled in this study.  
21. Vaccination within 14 days from screening or plans to get a vaccine within 30 
days after dosing. 
22. Acute infection (such as influenza) or relevant lesion at the time of Screening or 
Day -1. Subjects can be rescreened once they have recovered.  
23. Criteria at the discretion of the Investigator: 
a. Chronic medical condition that impacts subject safety. 
b. Clinically significant abnormal physical examination or vital signs 
at screening. 
c. Condition believed to interfere with the subject’s ability to provide 
informed consent or comply with study instructions, or that might 
confound the interpretation of the study results or put the subject at 
undue risk. 
d. History or evidence of a clinically significant disorder, condition, or 
disease that that is believed to significantly impair pain perception 
(e.g., history of stroke, history of neuropathy), would pose a risk to 
subject safety or interfere with evaluation, procedures, or study 
completion. 
Duration of 
Treatment 
The study participation will last for a total duration of approximately 6 weeks, 
including screening, confinement, and a follow-up period.  
 
The screening period may last up to 28 days. The confinement period will be 
approximately 5 days. The follow-up period is up to 3 days.  
 
The follow-up period after highest tolerated dose cohort will serve as the washout 
period for the food effect cohort.  
 
For the food effect cohort, an additional confinement period of approximately 5 
days will be required, followed by a follow-up period of up to 3 days.  
Study Drug, Dose, 
and Mode of 
Administration 
Dosing will begin with a dose level of 300 mg/m2 of fenretinide administered via 
oral capsules. The decision to advance to the next cohorts (600 mg/m2 and 
900 mg/m2) will be based on safety and tolerability data reviewed by the SRC.  
Number of Subjects 
Approximately 24 subjects will be enrolled in total. Subjects who withdraw or are 
removed from the study, except for safety reasons, may be replaced at the discretion 
of the Sponsor. 


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Island Pharmaceuticals Ltd. 
Clinical Trial Protocol: ISLA101-P01-CT001 
 
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Safety and 
Tolerability 
Evaluation 
This study will assess the safety and tolerability of the chosen doses of ISLA101 
(fenretinide oral capsules) as assessed by AEs, TEAEs, vital signs, physical 
examinations, and clinical laboratory tests.  
As clinical studies from IND38892 and from the published literature showed ocular 
toxicity upon treatment with fenretinide (eye irritation, dryness of eyes, nyctalopia), 
an ophthalmologist will be available to evaluate all significant ocular complaints. 
Discontinuation from the study will be at the discretion of the ophthalmologist.  
Due to teratogenic risks, all initial reports of pregnancy in female subjects or 
partners of male subjects must be reported to the Sponsor by the site personnel 
within 72 hours of their knowledge of the event. 
The safety and tolerability data will be reviewed by an independent SRC before 
proceeding to the next dose cohort. 
Dose-limiting Adverse 
Events 
The incidence and nature of any AEs, dose-limiting AE, SAEs, vital sign changes, 
ECG changes, and laboratory abnormalities will be assessed on an ongoing basis 
by the Investigator. 
Dose-limiting AEs are defined as clinically significant AEs or abnormal laboratory 
values that are Grade 3 or 4, based on toxicity grading scales as specified in FDA’s 
Guidance for Industry and Investigators – Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
The following signs of drug toxicity will be deemed to be of special interest: 
x sustained respiratory depression that results in oxygen saturation below 92% 
x  seizure 
x protracted nausea and vomiting 
x any AE deemed by the Investigator to be dose-limiting or Grade 3 and above 
x signs of drug-induced liver injury based on the following criteria from FDA 
guidance (Drug-Induced Liver Injury: Premarketing Clinical Evaluation): ALT 
or AST > 8 x ULN 
x ALT or AST > 3 x ULN and (total bilirubin > 2 x ULN or international 
normalized ratio > 1.5)  
x ALT or AST > 3 x ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%) 
Escalation from one dose level to the next will occur following the safety review 
by the SRC. If blinded study drug demonstrates an acceptable safety profile in the 
previous cohort, enrollment of the next higher dose cohort may begin. 
In the case of dose-limiting AE, dose reduction or repeat of the cohort with the 
previously tested dose may occur. 
Dose Escalation 
Criteria 
The decision to enroll the sequential cohort at the next dose level will be based on 
the safety data from previous dose cohorts. Dose escalation will depend on the 
emergence of dose-limiting AEs and review of the safety data. Progression to the 
next higher dose will only occur if the previous dose level was deemed to be safe 
and well tolerated by the SRC. Safety data sets to be reviewed by the SRC for dose 
escalation determination will include all available data up to 96 hours post-dosing 
for subjects enrolled into each dose-level cohort.  A minimum of 7 subjects’ data 
will be evaluated to make dose escalation decisions. 
 


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Clinical Trial Protocol: ISLA101-P01-CT001 
 
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Doses will be flexible during the study to allow for reductions in the planned 
escalation based on safety. When it is not appropriate to escalate the dose, then a 
previous dose, or an intermediate dose may be given following discussion between 
the Investigator and Sponsor. 
Stopping Criteria for 
the Study 
Further enrollment and study drug administration will be stopped if any of the 
following events occur: 
x A single SAE regardless of organ system if it is possibly, probably, or 
definitely related to the study drug; 
x Grade 3 or higher AEs and laboratory abnormalities determined to be possibly, 
probably, or definitely related to study drug should result in prompt 
discontinuation of study treatment; 
x Death of any subject considered related to study drug unless the SRC 
determines it is unrelated to study drug; 
x An anaphylactic reaction to study drug in any subject; 
x A potentially life-threatening AE or SAE, unless the SRC determines it is 
unrelated to study drug; 
x A pattern of significant symptoms, physical findings, or laboratory 
abnormalities that, although individually minor, collectively may represent a 
safety concern in the opinion of the Investigator or the medical monitor and are 
judged by the SRC to be at least possibly related to study drug; or 
x Sponsor’s decision to terminate the study for any reason. 
The human research ethics committee (HREC),), the FDA and local regulatory 
agencies as required will be notified if the study hold criteria are met. 
Pharmacokinetic 
Evaluation 
Blood samples will be collected at the pre-determined time points pre- and post-
dosing to characterize the PK profile of plasma fenretinide and its metabolites  
N-(4-methoxyphenyl) retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl) 
retinamide (oxo-HPR) and to capture appropriate PK parameters. PK samples will 
be analyzed and evaluated after completion of all cohorts. The PK sampling time 
points will be: pre-dose and 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12,24, 36, 48 ,72 
and 96 hours post-dose. 
Statistical Methods 
A statistical analysis plan (SAP) describing all statistical analyses will be provided 
as a separate document prior to data base lock. 
 
Sample Size Considerations: 
The study is considered to be exploratory with a sample size of 8 subjects per 
cohort (2 placebo + 6 active); this is considered sufficient to evaluate the safety 
profile and provide sufficient PK information for future development of the 
compound. 
 
General Statistical Methodology: 
Demographic data will be summarized using descriptive statistics. Descriptive 
statistics will be used to provide an overview of the safety results. For categorical 
parameters, the number and percentage of subjects will be presented. For 
continuous parameters, descriptive statistics will include n (number of subjects), 
mean, standard deviation, median, minimum, and maximum. No imputations will 
be made for missing data.  
 


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Clinical Trial Protocol: ISLA101-P01-CT001 
 
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Analysis Populations 
Two analysis populations will be used to summarize the results from this study: 
x 
Safety Population: All subjects who receive at least 1 dose of study drug.   
x 
PK Population: All subjects in the safety population who have a pre-dose 
PK sample, and at least 1 post-dose analyzable PK sample. 
 
Subjects disposition will be summarized and will include all subjects who have 
received one dose of study drug in the safety population, subjects in the PK 
population, and number and percent of subjects who complete or prematurely 
discontinue the study, along with reason for discontinuation.  Baseline demographic 
data will be summarized for all subjects who were randomized in this study and 
took at least 1 dose of study drug. 
 
Safety Analysis 
Safety will be assessed by the evaluation of AEs, TEAEs, laboratory test results, 
vital sign measurements, physical examination findings, and tolerability assessment. 
Safety variables will be tabulated and presented for all subjects in the Safety 
Population by dose. The AEs will be summarized and presented by dose and visit 
and overall. Change from screening in clinical laboratory parameters and vital sign 
parameters will be summarized by visit and overall. Shifts from baseline in 
continuous laboratory assessments will be tabulated.  
 
PK Analyses  
Pharmacokinetic and statistical analysis will be done using validated software (eg, 
Phoenix® WinNonlin® version 8.0 or higher).  
Pharmacokinetic parameters will be derived following noncompartmental analysis 
based on concentration-time data for fenretinide and its metabolites N-(4-
methoxyphenyl)retinamide (MPR) and  4-oxo-N-(4-
hydroxyphenyl)retinamide (oxo-HPR). On the day of dosing, the following 
parameters will be derived: Cmax, AUClast, AUCinf, Tmax, T½, Cl/F, and V/F. Other 
parameters will be estimated as applicable.  
Dose proportionality for key exposure parameters for fenretinide (Cmax, AUClast, and 
AUCinf) will be calculated based on the dose-normalized parameters. Descriptive 
statistics (n, mean, SD, geometric mean, %CV, median, minimum, and maximum) 
will be used to summarize the calculated PK parameters by dose level. For Tmax and 
T1/2, only n, median, minimum, and maximum will be presented. 
Analyses of variance (ANOVA) will be performed on ln-transformed PK 
parameters AUClast, AUCinf, and Cmax to evaluate fenretinide food effect for the 
recalled cohort. The ANOVA will include a calculation of least-squares means 
(LSMs), the differences between adjusted means, and the standard error associated 
with these differences. Ratios of means will be calculated using the LSM for 
ln-transformed AUClast, AUCinf, and Cmax. The 90% confidence interval (CI) for the 
difference between fed and fasted conditions will be calculated for the parameters 
AUClast, AUCinf, and Cmax using ln-transformed concentration data. The CIs will be 
expressed as a percentage relative to the LSM. 


SCHEDULE OF ASSESSMENTS 
Table 1 
 
Study Procedures and Assessments to Dose Under Fasted (Cohorts 1-3) and Fed Condition (Cohort 4) 
 
Study Procedure 
 
Cohorts 1-3 
Cohort 4 
Study 
Period 
Screening 
Clinic 
Check-
in 
Treatment Period 
Follow-
up/ET 
Clinic 
Check-
in 
Treatment Period 
Follow-
up/ET 
Study 
Day 
-28 to -2 
-1 
1 
2 
3 
4 
5 
8 
99 
10 
11 
12 
13 
14 
17 
Visit 
Window 
(days) 
N/A 
Inpatient 
+/-1 
+/-3 
Inpatient 
+/-1 
Informed Consent 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height and weight 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Medical History 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Vital Signs1 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead 
electrocardiogram 
(ECG)2 
 
X 
X 
X 
 
 
 
 
 
X 
X 
 
 
 
 
 
Full Physical Exam 
 
X 
X 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
Hep B, Hep C, HIV 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety laboratory tests 
(chemistry, 
hematology, 
coagulation, urinalysis) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test3 
 
X 
X 
 
 
 
 
 
X 
X 
 
 
 
 
 
X 
FSH4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine screen for drugs 
of abuse5 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Alcohol breath test 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Admission 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 


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Clinical Trial Protocol: ISLA101-P01-CT001 
 
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Study drug 
administration 
 
 
 
X 
 
 
 
 
 
 
X6 
 
 
 
 
 
High-fat, high-calorie 
breakfast 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
PK blood samples7 
 
 
 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
Adverse events8 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medication review 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discharge 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
ECG = electrocardiogram; ET = early termination; FSH = follicle-stimulating hormone; Hep = hepatitis; HIV =human immunodeficiency virus; PK = pharmacokinetic(s);  
1 
Vital signs include blood pressure, pulse, respiration and temperature.  
2 
12-lead ECG will be performed in triplicate at screening, and on Day -1 (check-in) to confirm eligibility, and on Day 1 at 5 hours (±15-minute) post dose. A single ECG will be performed on Day 
9 (check-in) and on Day 10 at 5 hours (±15-minute) post dose.  
3 
A serum pregnancy test will be performed at screening and urine pregnancy test will be performed at check-in and at follow-up for all female subjects. 
4 
For all female subjects to confirm or refute postmenopausal status. 
5 
A nicotine urine or breath  test may be utilized for tobacco use testing at site discretion. 
6 
Study drug will be administered approximately 30 minutes after start of a high-fat, high-calorie meal; 100% meal consumption is preferred.  
7 
PK sampling to assess the PK of fenretinide will be performed at the time points as specified in Table 2. 
8 
Monitoring for serious adverse events begins when the informed consent form is signed; and treatment-emergent adverse events begins after the first dose is 
administered. 
9 
Study day is relative to study drug administration for the subjects in Cohort 3. 
 
 


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Table 2 
Study Schedule and Sampling Time Points for Pharmacokinetic Analysis 
 
 
 
Time Relative to Dose (hours)a 
-1 0.5 0.75 1 1.5 2 
3 
4 
5 
6 
8 10 12 24 36 48 72 96 
Assessment Window (minutes)b 
+/-2 
+/-5 
+/-15 
+/-30 
Study Day 
Cohorts 1-3 
1 
X 
X 
X 
X 
X 
X X X X X X 
X 
X 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Cohort 4 
10 
X 
X 
X 
X 
X 
X X X X X X 
X 
X 
 
 
 
 
 
11 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
a: Time from dose begins when first capsule is consumed 
 
b: Vital signs should be assessed prior to PK samples taken


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Table of Contents 
CLINICAL STUDY PROTOCOL ............................................................................................1 
SYNOPSIS .................................................................................................................................2 
SCHEDULE OF ASSESSMENTS ............................................................................................9 
TABLE OF CONTENTS .........................................................................................................12 
OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...................................................16 
1 
INTRODUCTION .................................................................................................18 
1.1 
Background ......................................................................................................18 
1.2 
Fenretinide .......................................................................................................18 
1.2.1 
Clinical Experience ..............................................................................19 
1.2.1.1 
Teratogenicity ....................................................................................20 
1.3 
ISLA101 ...........................................................................................................20 
1.4 
Risk and Benefits .............................................................................................21 
2 
STUDY OBJECTIVES ..........................................................................................22 
2.1 
Primary Objective and Endpoints ....................................................................22 
2.1.1 
Primary Objective ................................................................................22 
2.1.2 
Primary Endpoints ...............................................................................22 
2.2 
Secondary Objective and Endpoints ................................................................22 
2.2.1 
Secondary Objective ............................................................................22 
2.2.2 
Secondary Endpoints ...........................................................................22 
2.3 
Exploratory Objective and Endpoints ..............................................................22 
2.3.1 
Exploratory Objective ..........................................................................22 
2.3.2 
Exploratory Endpoints .........................................................................22 
3 
INVESTIGATIONAL PLAN ................................................................................23 
3.1 
Overall Study Design .......................................................................................23 
3.2 
Rationale for Study Design ..............................................................................24 
3.2.1 
Dose Rationale for SAD ......................................................................24 
3.3 
Dose and Dosing Regimen...............................................................................25 
3.4 
Study Duration and Dates ................................................................................26 
3.5 
End of Study ....................................................................................................26 
3.6 
Study Oversight ...............................................................................................26 
3.6.1 
Safety Review Committee ...................................................................26 
4 
STUDY POPULATION SELECTION AND WITHDRAWAL ...........................28 
4.1 
Study Population ..............................................................................................28 
4.2 
Inclusion Criteria .............................................................................................28 
4.3 
Exclusion Criteria ............................................................................................29 
4.4 
Discontinuation of Treatment and Withdrawal of Subjects .............................30 


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4.4.1 
Documenting Subject Withdrawal .......................................................31 
4.5 
Subject Replacement ........................................................................................31 
5 
STUDY TREATMENT .........................................................................................32 
5.1 
Description of Treatment .................................................................................32 
5.1.1 
Study Drug ...........................................................................................32 
5.1.2 
Drug Administration ............................................................................32 
5.2 
Dose Modification ...........................................................................................33 
5.3 
Stopping/Halting Rules ....................................................................................34 
5.4 
Packaging and Labeling ...................................................................................35 
5.5 
Supply, Storage, Dispensing ............................................................................35 
5.5.1 
Supply ..................................................................................................35 
5.5.2 
Storage .................................................................................................35 
5.5.3 
Dispensing Study Drug ........................................................................35 
5.6 
Accountability, Retention, and Return.............................................................35 
6 
ALLOCATION, DOSING AND STUDY DRUG ADMINISTRATION .............37 
6.1 
Randomization Procedures ..............................................................................37 
6.2 
Blinding............................................................................................................37 
7 
PERMITTED THERAPIES AND CONTRAINDICATIONS ..............................38 
7.1 
Prohibited Therapies ........................................................................................38 
7.2 
Permitted Therapies .........................................................................................38 
7.3 
Lifestyle Restrictions .......................................................................................38 
7.3.1 
Dietary Restrictions .............................................................................38 
7.3.2 
Tobacco Restrictions ............................................................................39 
7.3.3 
Exercise Restrictions ............................................................................39 
7.4 
Treatment Compliance .....................................................................................39 
8 
STUDY PROCEDURES .......................................................................................40 
8.1 
Study Assessments by Visit .............................................................................40 
8.1.1 
Screening (Days-28 to Day -2) ............................................................40 
8.1.2 
Check-in (Day-1) .................................................................................41 
8.1.3 
Treatment/Confinement Period Procedures .........................................42 
8.1.3.1 
Days 1 through 3 ................................................................................42 
8.1.3.2 
Day 4 and 5 ........................................ Error! Bookmark not defined. 
8.1.4 
Early Termination/Safety Follow-up Visit ..........................................42 
8.1.5 
Unscheduled Assessments ...................................................................42 
8.2 
Safety Assessments ..........................................................................................43 
8.2.1 
Vital Signs ............................................................................................43 
8.2.2 
Physical Examination...........................................................................43 
8.2.3 
Clinical Laboratory Assessments .........................................................43 
8.2.4 
Pregnancy .............................................................................................44 


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8.3 
Pharmacokinetic Assessments .........................................................................44 
9 
ADVERSE EVENTS .............................................................................................46 
9.1.1 
Definition of an Adverse Event ...........................................................46 
9.1.1.1 
Reporting Adverse Events .................................................................46 
9.1.2 
Treatment-Emergent Adverse Events ..................................................46 
9.1.3 
Serious Adverse Events .......................................................................47 
9.1.3.1 
Definition ...........................................................................................47 
9.1.3.2 
Reporting Serious Adverse Events ....................................................47 
9.1.4 
Dose-limiting Adverse Events .............................................................48 
9.1.5 
Adverse Events of Special Interest ......................................................48 
9.1.6 
Severity ................................................................................................49 
9.1.7 
Relationship .........................................................................................49 
9.1.8 
Outcome ...............................................................................................50 
9.1.9 
Expectedness ........................................................................................50 
10 
PLANNED STATISTICAL METHODS ..............................................................51 
10.1 
General Considerations ....................................................................................51 
10.2 
Determination of Sample Size .........................................................................51 
10.3 
Analysis Populations ........................................................................................51 
10.4 
Disposition and Demographics ........................................................................51 
10.5 
Safety Analysis ................................................................................................52 
10.6 
PK Analysis .....................................................................................................52 
11 
QUALITY CONTROL AND ASSURANCE .......................................................54 
12 
REGULATORY AND ETHICAL CONSIDERATIONS .....................................55 
12.1 
Institutional Review Board or Independent Ethics Committee Approval .......55 
12.2 
Ethical Conduct of the Study ...........................................................................55 
12.3 
Subject Information and Consent.....................................................................55 
12.4 
Subject Confidentiality ....................................................................................56 
13 
ADMINSTRATIVE CONSIDERATIONS ...........................................................57 
13.1 
Clinical Study Research Agreement ................................................................57 
13.2 
Clinical Study Registration and Disclosure ..... Error! Bookmark not defined. 
13.3 
Case Report Forms and Study Records ...........................................................57 
13.4 
Protocol Violations/Deviations ........................................................................57 
13.5 
Access to Source Documentation ....................................................................58 
13.6 
Data Generation and Analysis .........................................................................58 
13.7 
Retention of Data .............................................................................................59 
13.8 
Study and Site Closure .....................................................................................59 
13.9 
Financial Disclosure.........................................................................................60 
13.10 
Conflict of Interest ...........................................................................................60 
13.11 
Publication and Disclosure Policy ...................................................................60 


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14 
REFERENCE LIST ...............................................................................................61 
15 
APPENDICES .......................................................................................................62 
 
 
 
LIST OF TABLES 
 
Table 1 
 Study Procedures and Assessments to Dose Under Fasted (Cohorts 1-
3) and Fed Condition (Cohort 4) ..................................................................9 
Table 2 
Study Schedule and Sampling Time Points for Pharmacokinetic 
Analysis......................................................................................................11 
Table 3 
Summary of Fenretinide NOAEL Data and PK Exposures to be Used 
to Determine Starting Dose and Exposure Caps in the ISLA101 Study....25 
Table 4 
Proposed Single Ascending Dose Escalation ............................................25 
 
 
LIST OF FIGURES 
Figure 1 
Structure and Chemical Properties of Fenretinide .....................................32 
 
LIST OF APPENDICES 
Appendix 1 
Sponsor Signatures.....................................................................................62 
Appendix 2 
Investigator’s Signature .............................................................................63 
 


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 ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate transaminase 
AUC 
Area under curve for pharmacokinetic concentration vs time profile 
AUCinf 
Area under curve from time 0 extrapolated to infinity 
AUClast 
Area under curve from time 0 to the last measured concentration 
BID 
Twice daily 
BMI 
Body mass index 
CI 
Confidence interval 
Cmax  
Maximum observed concentration 
CrCl 
Creatinine clearance 
CRF 
Case report form 
CRO 
Contract research organization 
CRU 
Clinical research unit 
CSR 
Clinical study report  
DENV 
Dengue virus 
ECG 
Electrocardiogram 
eGFR 
Estimated glomerular filtration rate 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
hCG 
Human chorionic gonadotropin 
HED 
Human equivalent dose 
HREC 
Human research ethics committee 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation  
IND 
Investigational New Drug application 
INR 
International Normalized Ratio 
IUD 
Intrauterine device 
J&J 
Johnson & Johnson Pharmaceutical Research & Development, LLC 
LSM 
Least-squares means 
MPR 
N-(4-methoxyphenyl) retinamide 
NCI 
National Cancer Institute 
NDA 
New Drug Application 
NOAEL 
No-observed-adverse-effect level 
OTC 
Over-the-counter 
PD 
Pharmacodynamics  
PK 
Pharmacokinetics 
QTC 
QT interval corrected for heart rate 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SRC 
Safety Review Committee 
SUSAR 
Suspected unexpected serious adverse reaction 
T1/2 
Terminal elimination half-life 
TB 
Tuberculosis 
Tmax 
Time to achieve maximum concentration 


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TEAE 
Treatment-emergent adverse event 
UDS 
Urine drug screen  
ULN 
Upper limit of normal 
US 
United States 
 


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1 
INTRODUCTION 
1.1 
Background 
An estimated 3.9 billion people in more than 125 countries are at risk of dengue fever, with 
approximately 390 million infections occurring annually. These infections lead about 
500,000 persons to require hospitalization due to dengue each year, and about 20,000 deaths 
occur due to severe dengue every year (WHO, 2018). Dengue is a mosquito-borne infection 
caused by the dengue virus (DENV) and is found in tropical and sub-tropical climates 
worldwide, mostly in urban and semi-urban areas. The severe form of the disease is a leading 
cause of serious illness and death in some Asian and Latin American countries (WHO, 2021). 
Endemic areas include some United States (US) territories and freely associated states. 
In 2021, 63 dengue cases were reported in the US and 435 cases were reported in US 
territories (CDC, 2021; CDC, 2022). Importantly, there is no specific treatment for dengue 
infection.  
Dengue prevention and control is based on vector control measures, which require sustained 
community involvement and usually are not highly effective in preventing disease 
transmission. The first dengue vaccine, Dengvaxia® (CYD-TDV), developed by Sanofi 
Pasteur, was licensed in 2015 and has now been approved in about 20 countries, including 
the US (Food and Drug Administration [FDA]-approved in 2019) (FDA, 2020; WHO, 2021). 
The vaccine was considered a major breakthrough in the prevention of DENV infection; 
however, results of a retrospective analysis showed that trial subjects who were seronegative 
at time of first vaccination had a higher risk of more severe dengue and hospitalizations from 
dengue compared with unvaccinated subjects. In addition, the vaccine is not licensed for 
people younger than 9 years and older than 16 years of age. Thus, the use of Dengvaxia is 
restricted to children (9 to 16 years) living in endemic areas who have previously had at least 
1 documented DENV infection (WHO, 2018; WHO, 2021; CDC, 2022). 
Recently, a new dengue vaccine, QDENGA®, was approved for use regardless of prior 
exposure and without the need for pre-vaccination testing. Approval was based on results 
across 19 Phase 1, 2, and 3 trials with more than 28,000 children and adults, including 
4.5 years of follow-up data showing sustained efficacy and no important safety risks. This 
vaccine is approved for use in Brazil, Indonesia, and in Europe, and was granted priority 
review for its Biologics License Application by the FDA (Takeda, 2023).  
In view of the current situation, there is an unmet medical need for therapies focusing on the 
prophylaxis of dengue infection, aiming to minimize viral transmission in endemic areas. To 
answer to this need, Island Pharmaceuticals Ltd (also referred to as the Sponsor) is 
developing the ISLA101 product, an immediate-release oral capsule of fenretinide (100 mg), 
for the prophylaxis of dengue fever.  
1.2 
Fenretinide  
Fenretinide (4-[hydroxyphenyl]retinamide; also known as 4-HPR) is an analog of 
all-trans-retinoic acid, first synthesized in the 1960s as an alternative to naturally occurring 
retinoids to treat skin diseases. Since then, nonclinical and clinical studies have demonstrated 
that this drug has lower toxicity when compared to other retinoids and exhibits cytotoxic 


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activity in a variety of cancer types (Cooper et al., 2017). According to the FDA’s Approved 
Drug Products with Therapeutic Equivalence Evaluations (also known as the “Orange 
Book”), there are currently no marketed or discontinued drug products in the US that include 
fenretinide as the active ingredient. 
Fenretinide has been used to treat cancer patients for decades with a favorable safety profile. 
To strategically support the development of ISLA101 for the prophylaxis of dengue fever, 
the Sponsor obtained the right of reference to Investigational New Drug application (IND) 
38892, which focused on fenretinide for the treatment of cancer, psoriasis, and acne. 
IND 38892 was initially sponsored by Johnson & Johnson Pharmaceutical Research & 
Development, LLC (J&J), and later by the National Cancer Institute (NCI) and was 
withdrawn in 2003 due to non-satisfactory efficacy data. The Sponsor developed a 
formulation very similar to the previous formulation, to facilitate bridging and reliance on 
safety information from IND 38892. 
While tumor responses have been minimal, the established safety profile makes fenretinide a 
desirable candidate for drug repurposing. In a high-throughput screen to identify compounds 
that inhibit the binding of the DENV NS5 to host nuclear import proteins, IMP-α and 
IMP-β1, fenretinide was identified. Using a lethal mouse model of DENV, it was 
demonstrated that fenretinide is effective in protecting against DENV1-4 infections, possibly 
by targeting NS5 (Fraser et al., 2014). In a second study that targeted the identification of 
anti-DENV compounds, the screening of a library of bioactive lipids and modulators of lipid 
metabolism also identified fenretinide as an inhibitor of DENV replication in vitro and within 
an in vivo mouse model, through an unknown mechanism (Carocci et al., 2015). These 
studies unveiled the potential of fenretinide as an anti-dengue therapy.  
1.2.1 
Clinical Experience 
To date, there are no studies in humans that evaluate the efficacy of fenretinide to prevent 
DENV infection. However, the safety profile of fenretinide has been thoroughly described in 
5 clinical pharmacology studies conducted under IND 38892, to which Island has right of 
reference, and in clinical studies from the published literature. 
Clinical studies conducted under IND 38892 and the published literature characterize 
fenretinide as well-tolerated and did not identify major safety concerns. A total of 
3487 healthy subjects (3273 from the literature and 214 from IND 38892, including 
approximately 150 pediatric subjects) have been exposed to fenretinide. Of the subjects 
exposed, 3188 healthy subjects (2974 from the literature and 214 from IND 38892) were 
treated with the oral capsule formulation provided by the NCI or J&J, which was the subject 
of IND 38892. Despite the high number of exposed subjects, at doses up to 4000 mg/m2/day, 
the most common adverse events (AEs) reported for all subjects treated with oral fenretinide 
were mild and included headache, diarrhea, nausea, skin irritation, and nyctalopia. No deaths 
or serious adverse events (SAEs) were reported in studies with fenretinide administered 
orally. 


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1.2.1.1 
Teratogenicity 
Oral retinoids, such as isotretinoin (13-cis retinoic acid), are known to produce teratogenic 
effects in animals and in humans, therefore representing a clinical concern when used to treat 
female patients of childbearing potential. Isotretinoin is approved in the US for the treatment 
of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older, 
although due to its teratogenicity, isotretinoin is marketed only under a special restricted 
distribution program (FDA, 2021). 
Fenretinide is a retinoid, and teratogenicity risks are a concern, even though the teratogenic 
effects of fenretinide have been shown to be milder at higher doses when compared with 
other retinoids such as isotretinoin. In reproductive and developmental toxicity studies 
conducted under IND 38892, the most biologically significant events in the offspring of rats 
involved ocular toxicity and delayed ossification of skull bones (doses up to 800 mg/kg, 
HED = 4774.2 mg/m2). In rabbits, a low incidence of tail, cleft/palate, and limb 
malformations were observed in the offspring from mid- and high-dosage groups (doses up 
to 800 mg/kg, HED = 9548.4 mg/m2). 
Clinical studies in healthy volunteers from IND 38892 were conducted in males, to avoid the 
risk of teratogenic effects. In studies in patients with ichthyosis, psoriasis, multiple basal cell 
carcinoma, and treatment-resistant acne, 16 females and 79 males were exposed to 600 and 
800 mg daily doses of fenretinide (370 and 493.3 mg/m2 for 60 kg humans) for up to 
16 weeks (mean length of therapy was 66.57 days for all patients). No pregnancy cases were 
reported. Fenretinide has also been tested in clinical research for decades without significant 
teratogenic events being reported. In over 30 clinical studies in the published literature, 
approximately 2560 female subjects were exposed to fenretinide at doses ranging from 61.7 
to 4000 mg/m2/day for up to 5 years; no teratogenicity issues were reported in these studies.  
1.3 
ISLA101 
ISLA101 is an oral capsule formulation of fenretinide. Island plans to submit a New Drug 
Application (NDA) for ISLA101 for the prophylaxis of dengue fever via the 505(b)(2) 
regulatory pathway. To support the ISLA101 NDA, Island intends to rely on clinical and 
nonclinical studies from IND 38892 and from the published literature, in addition to Sponsor-
conducted studies.  
The current Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics (PK) of 
single ascending doses of fenretinide after administration of ISLA101 (at doses of 300, 600, 
and 900 mg/m2) in healthy subjects. This study will also assess the dose proportionality of 
systemic exposure of ISLA101 and food effect as an exploratory objective. To safeguard 
against the possible risk of teratogenicity, the study will evaluate male subjects and female 
subjects who are not of childbearing potential.  Contraception requirements compliant with 
local regulations and clinical practices are included as part of the inclusion criteria for the 
study. 


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1.4 
Risk and Benefits 
The well-tolerated safety profile of fenretinide in clinical studies conducted under IND 38892 
and in published literature, as evidenced by the absence of SAEs and low incidence of mild 
AEs, supports the safety of ISLA101. The healthy subjects who enroll in this study are not 
expected to derive direct benefit from study participation. The safety, tolerability, and PK 
data obtained in this study, however, are expected to support the development of a 
prophylactic for the treatment of dengue fever, thereby addressing an unmet medical need. 
Previous nonclinical and clinical data indicate that retinoids have teratogenic potential, 
although the teratogenic effects of fenretinide have been shown to be milder compared to 
other retinoids. To promote subject safety, this study will only evaluate male subjects and 
female subjects of nonchildbearing potential. Female subjects will be excluded if they are 
pregnant or lactating, taking hormonal contraceptives (due to potential drug-drug interactions 
with fenretinide), or are less than 12 months postmenopausal or have had less than 6 weeks 
elapse following bilateral oophorectomy. As a safety measure, pregnancy testing will be 
conducted frequently during the study. Male subjects with female partners must agree to use 
appropriate contraceptive measures during the study, in keeping with the special restricted 
distribution program for isotretinoin (FDA, 2021), and in compliance with local regulations 
and clinical practice. If subject or partner pregnancy occurs, study drug will be discontinued, 
and the pregnancy will be promptly reported to the Sponsor for appropriate follow-up. 
Collectively, these safeguards and monitoring processes will promote subject safety, and the 
potential benefit of developing a therapy for the prophylaxis of dengue fever is thought to 
outweigh a potential teratogenic risk. 
Overall, there is no potential benefit to healthy subjects, while the risks appear to be minimal 
based on the available safety data, study inclusion criteria, and study monitoring procedures. 


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2 
STUDY OBJECTIVES 
2.1 
Primary Objective and Endpoints 
2.1.1 
Primary Objective 
The primary objective is to:  
x Evaluate the safety and tolerability of single ascending doses of ISLA101 in healthy 
adult volunteers (fasted). 
2.1.2 
Primary Endpoints 
The primary endpoints are: 
x Vital signs, clinical laboratory tests, changes from baseline in physical examinations, 
AEs, and treatment-emergent adverse events (TEAEs). 
2.2 
Secondary Objective and Endpoints 
2.2.1 
Secondary Objective 
The secondary objective is to: 
x Characterize the PK profile (fasted) of fenretinide after administration of single 
ascending doses of ISLA101 in healthy adult volunteers. 
2.2.2 
Secondary Endpoints 
The secondary endpoints are: 
x Single dose PK parameters for fenretinide in plasma: Cmax, Tmax, AUClast, AUCinf, 
T1/2, and others as relevant.  
2.3 
Exploratory Objective and Endpoints 
2.3.1 
Exploratory Objective 
The exploratory study objective is to: 
x Assess the PK profile of fenretinide in healthy adult volunteers under fed conditions. 
2.3.2 
Exploratory Endpoints 
The exploratory endpoints are: 
x Single dose PK parameters for fenretinide in plasma under fed conditions: Cmax, Tmax, 
AUClast, AUCinf, T1/2, and others as relevant.  


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3 
INVESTIGATIONAL PLAN 
3.1 
Overall Study Design 
The study is a randomized, double-blind, placebo-controlled single ascending dose (SAD) 
study of ISLA101 (fenretinide oral capsules) to evaluate safety, tolerability, and 
pharmacokinetics in healthy human subjects. The study will consist of up to 4 cohorts that 
will evaluate dose levels of 300 mg/m2 (fasted), 600 mg/m2 (fasted), and 900 mg/m2 (fasted). 
The highest tolerated dose level cohort will then be evaluated in a fed condition (in a cross-
over manner).  Eight subjects will be enrolled per dose cohort, with 6 subjects receiving 
active drug and 2 subjects receiving placebo treatment in a blinded manner. Each subject will 
be allocated to 1 dose level only.  
After completing screening activities, eligible subjects will enter the clinical research unit 
(CRU) on Day -1 for 5 days. Subjects will receive a single dose of study drug in the morning 
of Day 1 after an overnight fast of approximately 10 hours, followed by additional 4 hours 
fast after dose for PK sampling. Cohorts 1 through 3 will receive 300 mg/m2, 600 mg/m2, and 
900 mg/m2, respectively, under fasted conditions. After the safety review by the independent 
safety review committee (SRC), the dose level can be escalated to the planned or lower than 
planned dose level or de-escalated to an intermediate dose level. Decisions to proceed to the 
next cohort will be made by the Investigator, SRC, and Sponsor based on the safety data 
from previous cohort(s).  
Safety data will be reviewed to identify the cohort that received the highest dose level under 
fasted condition. The subjects in this cohort will be recalled to evaluate the PK of ISLA101 
under fed conditions (8 subjects; Cohort 4). In Cohort 4, subjects will fast for approximately 
10 hours overnight and will consume a high-fat, high-calorie meal approximately 30 minutes 
prior to administration of study drug. No food consumption will be permitted for at least 
4 hours post-dose.  
For all cohorts, study drug will be taken with up to 240 mL of water. In fasted cohorts, water 
will be allowed ad libitum except the interval from 1 hour before to 1 hour after the dose. In 
the fed cohort, water will be allowed ad libitum except the interval from 1 hour before to 
1 hour after dose. 
Subjects will be discharged from the clinic on Day 5. At the discretion of the Investigator or 
designee, the confinement time can be extended to ensure the safety of each subject. Subjects 
will have up to 3 days of follow up. For Cohort 4 (the food effect cohort), the confinement 
and follow-up visit will be repeated. Subjects who are dosed but withdrawn prior to study 
completion will participate in an Early Termination visit and may be replaced if needed to 
obtain sufficient information as possible based on the timing.  
In all cohorts, safety will be assessed via vital signs, clinical laboratory tests, physical 
examinations, AEs, and TEAEs. Pharmacokinetic data will be collected and analyzed at the 
end of the study but will not be used for dose escalation decisions. A description of study 
assessments is provided in Table 1. 


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3.2 
Rationale for Study Design  
A randomized, double-blind study in healthy subjects is considered appropriate to evaluate 
the safety, tolerability, and PK of ISLA101. Single ascending doses of ISLA or placebo will 
be administered under fasting conditions, and safety and tolerability data will be evaluated in 
each cohort to guide doses administered to future cohorts. The highest tolerated dose will 
also be administered under fed conditions to assess any potential food effect (in a crossover 
manner). A rationale for dose selection is provided in Section 3.2.1. 
3.2.1 
Dose Rationale for SAD 
The starting dose of 300 mg/m2 was selected based on the safety profile of fenretinide, which 
was extensively studied in multiple animal species in IND 38892: 
• Single-dose oral toxicity studies (Good Laboratory Practice [GLP]):  
◦ Dogs: doses up to 3000 mg/kg (human equivalent dose [HED] = 61666.7 mg/m2); the 
maximum determinable non-lethal dosage was > 1350 mg/kg (HED = 27750 mg/m2); 
observed clinical signs included emesis (> 2000 mg/kg), black tarry stool 
(2000 mg/kg), and loose stool (1350 mg/kg). 
◦ Rats: dose of 5000 mg/kg (HED = 29838.7 mg/m2); the median lethal dose was 
> 5000 mg/kg; clinical signs included diarrhea, unkempt appearance, yellow stool, 
hunched posture; no mortality was observed. 
◦ Mice: dose of 7000 mg/kg (HED = 21056.9 mg/m2); no clinical signs or mortality 
were observed. 
These studies provided safety margins for the 300 mg/m2 ISLA101 starting dose ranging 
from 70.2- to 99.5-fold. 
• Repeat-dose oral toxicity studies (GLP): 
◦ Dogs: doses up to 800 mg/kg/day (HED = 16444.4 mg/m2). The 
no-observed-adverse-effect levels (NOAEL) from these studies were 90 mg/kg 
(HED = 1850 mg/m2) for a 12-month study, 600 mg/kg (HED = 12333.3 mg/m2) for a 
20-day study, and 800 mg/kg (HED = 16444.4 mg/m2) for a 3-month study.  
◦ Rats: doses up to 800 mg/kg/day (HED = 4774.2 mg/m2). The NOAEL from these 
studies was 800 mg/kg (HED = 4774.2 mg/m2) for a 3-month study and 70 mg/kg 
(HED = 417 mg/m2) for a 12-month study. 
Although ISLA101 is not intended for chronic use, studies for up to 3 months in 
IND 38892 provide safety margins for a ISLA101 starting dose of 300 mg/m2 ranging 
from 15.9- to 54.8-fold. 
Therefore, in this study, a starting dose of 300 mg/m2 is believed to be safe for 
administration to healthy subjects. 


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The starting dose and systemic safety of ISLA101 for the SAD study will be based on the 
rationale that the highest exposure in humans in the SAD study will not exceed the 
exposure levels derived in the nonclinical studies. Human equivalent doses of the 
NOAEL of selected studies with related exposure caps are shown in Table 3. 
Table 3 
Summary of Fenretinide NOAEL Data and PK Exposures to be Used 
to Determine Starting Dose and Exposure Caps in the ISLA101 Study 
Species 
 
Duration 
(weeks) 
NOAEL 
(mg/kg/day) 
 
Through 
Concentrations 
(ng/mL; mean ± 
SD) 
Cmax (ng/mL; 
mean ± SD) 
Human Equivalent 
Dose* (mg/m2) 
Dogs (Study 
1084) 
12 
800  
1383 ± 908 (male); 
819 ± 294 (female) 
2299 ± 1456 
16444.4 
Rats (Study 
1077) 
12 
800  
183 ± 83 (male); 
186 ± 82 (female) 
NA 
4774.2 
* Assumes a 60 kg human. 
NA = not available; NOAEL = no-observed-adverse-effect level; SD = standard deviation 
The doses in this study were chosen based on the dose-response relationships described in 
nonclinical mouse models of dengue fever, and on the correlation between nonclinical and 
clinical exposures to fenretinide. In vivo, an oral fenretinide at 20 mg/kg 
(HED = 60.2 mg/m2) given at the time of infection and BID for 5 days protected 70% of 
mice from death (Fraser et al., 2014). At 180 mg/kg (HED = 541.5 mg/m2), given 24 hours 
prior to 10 days post-infection, there was a significant reduction in mice peak viremia 
(Carocci et al., 2015). In vitro and ex vivo, concentrations from 5 to 10 μM exhibited highly 
specific and potent anti-dengue virus activity, with an average EC50 of 1.6 μM and EC90 of 
2 μM (Fraser et al., 2014; Carocci et al., 2015). In humans, plasma concentrations produced 
by doses near 300 mg/m2 ranged from 0.87 to 2.8 μM, and by doses near 600 mg/m2, from 
2.1 to 5.2 μM. The doses selected for inclusion in this study are therefore expected to be 
therapeutically relevant for the treatment of dengue fever. 
3.3 
Dose and Dosing Regimen 
The starting dose for the SAD study is 300 mg/m2. The proposed dose escalation paradigm 
for SAD is shown in Table 4. Briefly, the doses to be tested are 300 mg/m2 (fasted), 
600 mg/m2 (fasted), and 900 mg/m2 (fasted). The highest tolerated dose level cohort will then 
be evaluated in a fed condition. Subjects will initially receive a dose of 300 mg/m2, and the 
decision to advance to the next cohort will be based on safety and tolerability data. 
Table 4 
Proposed Single Ascending Dose Escalation 
Cohort 1 
Cohort 2 
Cohort 3 
300 mg/m2 
600 mg/m2 
900 mg/m2 
 
Actual doses may be decreased from the planned doses based on emerging safety and 
tolerability data, as recommended by the independent SRC and agreed by the Investigator 


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and Sponsor. The initiation of the next cohort with a higher dose level will be decided during 
the interim safety review by the SRC. The recommendation of the SRC will be documented 
in a memo that will be filed in the Trial Master File (TMF). The SRC memo will serve as a 
source document for the clinical study report (CSR) and all supporting information can be 
presented to the human research ethics committee (HREC) if required. A description of the 
SRC is provided in Section 3.6.1. 
If an acceptable safety profile is demonstrated in the previous cohort, enrollment of the next 
higher dose cohort may begin. For dose progression to occur, a minimum number of 7 
subjects per cohort must have data from at least 96 hours after dosing, to ensure availability 
of placebo data. 
Additional cohorts may be added as needed to test lower or repeat doses. Any changes to the 
dosing will made following discussions between the Sponsor and Investigator. The number 
of added cohorts will not exceed four. If the decision to enroll additional cohorts is made, an 
amendment will be submitted describing the safety and PK data from the portion of the study 
conducted to date. Enrollment of any additional cohorts will be initiated following HREC 
review and approval. The timing of vital sign assessment and PK sampling may be modified 
by SRC based on the emerging data after SAD dosing. 
The incidence and nature of any AEs, dose-limiting AEs, SAEs, vital sign changes, and 
laboratory abnormalities will be assessed on an ongoing basis by SRC. Depending on the 
severity of these and/or other AEs or the occurrence of more than 1 AE in the same subject, 
the subject(s) may be unblinded if it is deemed necessary for the treatment of AEs.  
3.4 
Study Duration and Dates 
The study will involve participation for a total of approximately 6 weeks. This includes up to 
28 days for screening and approximately 5 days of confinement,and up to 3 days of follow-
up after discharge from the clinic. For subjects in Cohort 4 (the food effect cohort), there will 
be an additional up to 5 days of confinement, and up to 3 days of follow-up. 
3.5 
End of Study 
The clinical study is considered completed when the last subject’s final study visit has been 
completed. 
3.6 
Study Oversight 
The study will be overseen by the Sponsor or an appropriate designee. 
3.6.1 
Safety Review Committee 
An SRC will be comprised of, but not limited to, the Investigator, Medical Monitor, and an 
independent clinical representative. Other members of the SRC will be added on an as need 
basis, such as a PK scientist. The SRC will be responsible for reviewing data and deciding 
on: 
• The continued safety of the study subjects. 


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• The continued validity of the trial. 
• The continued scientific merit of the trial. 
• Recommended dose for next cohort, as applicable. 
The SRC will facilitate management and identification of potential safety concerns, will 
review safety data, and will determine if dosing of each cohort should continue, if dose 
escalation should continue following completion of each cohort, or if dose de-escalation or 
repeating a dose level should be performed. 


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4 
STUDY POPULATION SELECTION AND WITHDRAWAL 
4.1 
Study Population 
This study will enroll up to 24 healthy, male and female subjects who are 18 to 65 years old 
at the time of consent. Subjects who withdraw or are removed from the study, except for 
safety reasons, may be replaced at the discretion of the Sponsor. 
4.2 
Inclusion Criteria 
Subjects must meet the following criteria to be enrolled in the study: 
1. Healthy male and female volunteers not of childbearing potential who are 18 years to 65 
years of age (inclusive) at the time of signing the informed consent form (ICF). 
2. Females not of childbearing potential as defined in the following criteria: 
a. History of hysterectomy. 
b. Post-menopausal: 
i. Natural post-menopausal females with at least 12 months from natural 
spontaneous amenorrhea and a serum follicle-stimulating hormone (FSH) 
concentration ≥ 40 IU/L. 
ii. Post-surgical females must have undergone bilateral oophorectomy at least 
6 weeks prior to study. 
3. Male subjects with female partners of childbearing potential must agree to practice 
abstinence or use a combination of 2 of the following acceptable birth control methods 
during the study and for at least 90 days after dosing: 
a. Partners with an intrauterine device (IUD) without hormones in place for at least 
3 months. 
b. Barrier method (condom or diaphragm) for at least 14 days prior to screening and for 
90 days after dosing with study drug. 
c. Partners using stable hormonal contraceptive for at least 3 months prior to the study 
and for 90 days after dosing with study drug. 
d. History of vasectomy at least 3 months prior to signing the ICF. 
4. Must be able to understand and provide signed informed consent for study participation. 
5. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and 
other study procedures. 
6. Females must have a negative serum hCG pregnancy test at screening. 
7. Body mass index (BMI) ≥ 18.0 to 32.0 kg/m2 (inclusive) and a body weight ≥ 50 kg. 
8. Normal renal function, defined as estimated glomerular filtration rate (eGFR) ≥ 70 
mL/min/1.73 m2 at screening and Day -1. 


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9. Clinical laboratory values should be within the laboratory’s stated normal range. If not 
within this range, they must be without clinical significance, as determined by the 
Investigator. 
10. No history of clinically relevant medical disorders. 
4.3 
Exclusion Criteria 
A subject will be excluded from the study if he or she meets any of the following criteria: 
1. Known or suspected pregnancy (confirmed via a positive serum hCG pregnancy test at 
screening), planned pregnancy during the study period, nursing, or lactation. 
2. Women of childbearing potential or men who intend to father a child or donate sperm 
during the study period, and for 3 months after dosage of study drug. 
3. Known allergy to fenretinide or any of the components of ISLA101. 
4. Evidence or history of clinically significant medical conditions, such as hematological, 
renal, endocrine (e.g., polycystic ovarian syndrome PCOS or other anovulatory states), 
immunologic, pulmonary, metabolic, gastrointestinal (e.g., Crohn’s disease, acute or 
chronic pancreatitis, and others), and surgery (except for simple appendectomy or repair 
of a hernia), which all can influence the absorption of study drug; cardiovascular, hepatic, 
psychiatric, neurologic, or allergic disease (including drug allergies but excluding 
untreated, asymptomatic, seasonal allergies at the time of dosing), or any other illness 
that the Investigator considers exclusionary or that could interfere with the interpretation 
of the study results.  
5. History of severe infectious disease or recurrent infections. 
6. Aspartate transaminase (AST), alanine aminotransferase (ALT), or total bilirubin above 
the 1.5 x upper limit of normal (ULN) at screening and Day -1.  
7. Clinically significant electrocardiogram (ECG) abnormalities or vital sign abnormalities 
at screening and Day -1, long QT syndrome, or a history of cardiac disease. 
8. Abnormal diet that may affect absorption, distribution, metabolism, or excretion of drugs, 
for example, lacking standard nutrients (e.g., cleansing diet 2 weeks before or during the 
study). 
9. Positive result for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at 
screening. 
10. History of positive tuberculosis (TB) test at screening. 
11. Has donated 1 unit of blood of over 500 mL within 56 days prior to the study drug 
administration, or donated plasma within 14 days of study drug administration. 
12. Use of antibiotics within 30 days prior to dosing. 
13. Use of drugs that inhibit or induce CYP enzymes within 30 days prior to administration 
of study drug and for the duration of study participation. 
14. Use of tobacco products, e-cigarettes, and/or nicotine replacement products in the 
3 months before screening.  


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15. Any food allergy, intolerance, or restriction that, in the opinion of the Investigator, could 
contraindicate the subject’s participation in this study. 
16. Recent history of (within the past 12 months), or strong potential for, alcohol or 
substance abuse. Alcohol abuse will be defined as > 14 drinks per week (1 drink = 10g of 
ethanol). 
17. History of drug or alcohol abuse within 5 years before screening or positive result of 
UDS (e.g., amphetamines, benzodiazepines, cannabinoids, cocaine, hallucinogens, 
opiates) at screening, or alcohol breath test at screening or Day -1. 
18. Exposure to any investigational agent or used an invasive investigational medical device 
within 30 days or within a period less than 5 drug half-lives prior to study entry 
(whichever is longer). 
19. Study site employees, Sponsor’s employees, or immediate family members of a study site 
or Sponsor employee. 
20. Previously enrolled in this study.  
21. Vaccination within less than 14 days from screening or plans to get a vaccine within 30 
days after dosing. 
22. Have an acute infection (such as influenza) or relevant lesion at the time of screening or 
admission. Subjects can be rescreened once they have recovered.  
23. Criteria at the discretion of the Investigator: 
a. Chronic medical condition that impacts subject safety. 
b. Clinically significant abnormal physical examination or vital signs at screening. 
c. Condition believed by Investigator to interfere with the subject’s ability to provide 
informed consent or comply with study instructions, or that might confound the 
interpretation of the study results or put the subject at undue risk. 
d. History or evidence of a clinically significant disorder, condition, or disease that that 
is believed by Investigator to significantly impair pain perception (e.g., history of 
stroke, history of neuropathy), would pose a risk to subject safety or interfere with 
evaluation, procedures, or study completion. 
4.4 
Discontinuation of Treatment and Withdrawal of Subjects 
Subjects are free to withdraw from the study at any time for any reason. Subjects who 
withdraw from the study early will be asked to complete the Early Termination procedures, 
as described in Table 1. 
In addition, subjects are required to be withdrawn from the study by the Principal 
Investigator or sub-Investigator for the following reasons: 
• Any unacceptable or intolerable AEs  
• Difficulties in blood collection 
• Non-compliance with study restrictions 


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• Study terminated by Sponsor 
• Personal decision by the subject 
• A subject who vomits immediately after study drug administration or up through 6 hours 
after administration or within 2 x Tmax (once the Tmax is known) after dosing.  
The CSR will include reasons for subject withdrawals as well as additional details relevant to 
the subject withdrawal. Withdrawn subjects can be replaced if timing permits unless the 
withdrawal happened due to safety reasons related to the drug. 
4.4.1 
Documenting Subject Withdrawal  
If a subject prematurely withdraws from the study, either at her/his request or at the 
Investigator’s discretion, the Investigator will record the reason for withdrawal on the 
relevant case report form (CRF) page. Subjects prematurely discontinuing the study, 
regardless of cause, should have all Early Termination study assessments performed. 
It is important to obtain follow-up data for any subject withdrawn because of an AE,or 
abnormal laboratory test, vital sign measurement, or physical examination. In any case, every 
effort must be made to undertake safety follow-up procedures. 
4.5 
Subject Replacement 
Subjects who withdraw or are removed from the study, except for safety reasons, may be 
replaced at the discretion of the Sponsor. 


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5 
STUDY TREATMENT 
The CRU’s Standard Operating Procedures will be followed with respect to the preparation, 
proper labeling, storage, and dispensing of investigational study drugs. A summary of 
appropriate procedures is provided below; additional instructions specific to the preparation 
of ISLA101 will be provided in the ISLA101 Pharmacy Manual. 
5.1 
Description of Treatment 
5.1.1 
Study Drug 
Fenretinide (N-[4-Hydroxyphenyl] retinamide) is a yellow to orange crystalline powder with 
molecular weight of 523.32 g/mol. The chemical name and structure of fenretinide are shown 
in Figure 1. 
Figure 1 
Structure and Chemical Properties of Fenretinide 
 
Subjects will be randomly assigned to receive either ISLA101 (Fenritinide) or placebo. The 
ISLA101 and placebo capsules will be indistinguishable from each other in size, shape, and 
smell. ISLA101 will be administered at doses of 300 mg/m2 (fasted), 600 mg/m2 (fasted), and 
900 mg/m2 (fasted).  The highest tolerated dose level cohort will then be evaluated in a fed 
condition. Administration of placebo will be aligned with administration of ISLA101. 
5.1.2 
Drug Administration 
In each cohort, a single dose of study drug will be administered to each subject. Study drug 
will be taken with up to 8 oz/240 mL of water. 


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ISLA101 or placebo will be administered orally. The dose will be calculated according to the 
subject’s body surface area (BSA) using the calculation (Mosteller formula): 
BSA (m2) = the square root (ξሻof ([Height (cm) x weight (kg)]/3600)  
For example: Subject: 150 cm, weighing 68 kg 
m2= ξ [150*68]/3600 = 10200/3600 
m2= ξ 2.83 
m2= 1.68 
600mg/m2/d = 600 * 1.68 = 1009 mg/day 
1009 mg/day /100mg capsule = 10 capsules per day 
The number of capsules will be rounded up if the daily dose is equal to or greater than daily 
dose = XX51, e.g., 1051 = 11 capsules. 
For subjects participating in the fasted cohorts (Cohorts 1 through 3), subjects will receive 
study drug following an overnight fast of approximately 10 hours. Subjects will continue to 
fast for no less than 4 hours after study drug administration. Water will be allowed ad libitum 
except 1 hour before and 1 hour after dosing. 
Subjects in the food effect cohort (Cohort 4) will fast overnight for at least 10 hours and will 
receive a high-fat, high-calorie meal, approximately 30 minutes prior to administration of 
study drug. No food consumption will be permitted for at least 4 hours post-dose. Water will 
be allowed ad libitum except the interval from 1 hour before dosing to 1 hour after dosing. 
Prior to dosing, subjects will be reminded of the study restrictions: 
x Do not speak while trying to swallow capsule(s). 
x All capsules need to be consumed within 5 minutes of the start of consumption. 
x Report any AEs to the study staff. 
x Request an escort to the restroom, if needed, during the first hour after receiving study 
drug. 
5.2 
Dose Modification 
The decision to enroll the sequential cohort at the next dose level will be based on the safety 
data from previous dose cohorts. Dose escalation will depend on the emergence of 
dose-limiting AEs and review of the safety data. Progression to the next higher dose will only 
occur if the previous dose level was deemed to be well tolerated by the SRC. Safety data sets 
to be reviewed by the SRC for dose escalation determination will include all available data 
up to 96 hours post-dosing for subjects enrolled into each dose-level cohort.  A minimum of 
7 subjects’ data will be evaluated to make dose escalation decisions. Decisions to proceed to 
the next cohort will be based upon the recommendation of the SRC and agreed upon with the 
Investigator and Sponsor. 


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Doses will be flexible during the study to allow for reductions in the planned escalation 
based on safety. When it is not appropriate to escalate the dose, then the same dose, a 
previous dose, or an intermediate dose may be given following discussion between the 
Investigator and Sponsor. 
5.3 
Stopping/Halting Rules 
Further enrollment and study drug administration will be stopped if any of the following 
events occur: 
• A single SAE regardless of organ system if it is possibly, probably, or definitely related 
to the study drug. 
• Grade 3 or higher AEs and laboratory abnormalities determined to be possibly, probably, 
or definitely related to study drug. 
• Death of any subject considered related to study drug unless the SRC determines it is 
unrelated to study drug. 
• An anaphylactic reaction to study drug in any subject. 
• A potentially life-threatening AE or SAE, unless the SRC determines it is unrelated to 
study drug.  
• A pattern of significant symptoms, physical findings, or laboratory abnormalities that, 
although individually minor, collectively may represent a safety concern in the opinion of 
the Investigator or the medical monitor and are judged by the SRC to be at least possibly 
related to study drug. 
• Sponsor’s decision to terminate the study for any reason. 
Dose-limiting AEs that will halt further enrollment into the affected cohort and study drug 
administration within the cohort are described in Section 9.1.4. Additionally, if any AEs of 
special interest (see Section 9.1.5) occur that meet the following criteria, they will be 
considered dose-limiting: 
x Any two ≥ Grade 2 AE of special interest, unless they are clearly and incontrovertibly 
due to extraneous causes. 
x Any one ≥ Grade 3 AE of special interest, unless the event is clearly and 
incontrovertibly due to extraneous causes. 
x Any SAE of special interest, unless the event is clearly and incontrovertibly due to 
extraneous causes. 
The HREC and the FDA will be notified if the study hold criteria are met.  


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5.4 
Packaging and Labeling 
• ISLA101 oral capsules and matching placebo capsules will be prepared, labeled, supplied 
to the clinical site in bulk bottles, and stored as described in Section 5.5, until dispensing 
by the pharmacist. For each bottle, the following information will be provided on the 
label, as well as any information required by local regulations: Protocol Number  
• Storage Requirements   
• Directions for Use  
• Contents (i.e., 50 capsules per bottle) 
• Investigational New Drug Statement 
• Lot Number  
• Manufactured by and Date  
• Sponsor  
• Expiry Date   
5.5 
Supply, Storage, Dispensing 
5.5.1 
Supply 
ISLA101 capsules, 100 mg (50 count) are packaged in high-density polyethylene bottles with 
polypropylene seal. Study drug (ISLA101 and placebo) will be supplied by the Sponsor’s 
designated manufacturer in accordance with current Good Manufacturing Practices (GMP). 
5.5.2 
Storage 
ISLA101capsules and placebo should be stored as indicated on the label (59-86°F [15-30°C]) 
in a secure, limited-access area in tight containers and protected from light.  
The study drug will be stored in a safe and locked place with restricted, controlled access. 
The temperature of the storage units will be monitored daily with a validated temperature 
monitoring device(s) and documented. Any temperature excursion (i.e., temperature outside 
the defined range of storage) must be reported to the Sponsor within 24 hours of knowledge 
of the excursion.  
5.5.3 
Dispensing Study Drug 
Complete instructions regarding the preparation of study drug for dispensing can be found in 
the ISLA101 Pharmacy Manual. The pharmacy staff will prepare the ISLA101 and placebo 
tablets for dispensing. Once prepared by the pharmacy team, the study drug will be kept in a 
limited access area under appropriate environmental conditions. The study drug is to be used 
exclusively in the clinical study according to the instructions of this protocol. 
 
5.6 
Accountability, Retention, and Return 
The site Investigator or his/her designee is responsible for receipt of the study drug at the 
study site. The Sponsor has ultimate responsibility for product accountability. The 


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Investigator is responsible for and will maintain logs of study drug receipt, storage, 
reconstitution, accountability by subject, and study drug remaining before final disposition. 
The Investigator may delegate, in writing, this responsibility to another individual, but the 
Investigator is ultimately responsible for the study drug and its proper storage upon receipt at 
the study site until it is transferred back to the Sponsor or designee or is destroyed, as 
directed by the Sponsor. 
All unused study drug provided by the Sponsor will be retained and returned to the Sponsor 
or their designee at the completion of the study for reconciliation and destruction. The 
Investigator must provide an explanation for any missing capsules. 
The pharmacist will maintain an accurate record of all study drug supplies received and dates 
of receipt. The dispensing and return of study drug will be documented on a Pharmacist’s 
Dispensing Log that will be maintained for each subject. At the completion of the study, the 
clinical study monitor must be able to verify and reconcile that all subjects received the 
correct study drug assignment (according to the randomization schedule), proper dose of 
study drug, and that the individual subject study medication bottles were properly labeled. 


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6 
ALLOCATION, DOSING AND STUDY DRUG 
ADMINISTRATION 
6.1 
Randomization Procedures 
Subjects will be randomly assigned to a cohort per the clinical research unit’s standard 
randomization, participation, and blinding protocol. Within each cohort, 8 subjects will be 
assigned in a 3:1 ratio to receive ISLA101 (6 subjects) or placebo (2 subjects).  Subjects 
participating in Cohort 4, the food effect cohort, will maintain the same treatment assignment 
from their fasted cohort. 
6.2 
Blinding 
This will be a double-blind study. The study drug, including both ISLA101 oral capsule and 
matching placebo, will be dispensed using a method that ensures site staff and subjects 
remain blinded to the study drug being administered. 
If a reportable safety issue is detected during the review of unblinded safety data, notification 
will be sent to designated clinical research unit staff consisting of the unblinded pharmacy 
team and the designated regulatory compliance specialist for submission to the HREC, per 
local reporting requirements. 


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7 
PERMITTED THERAPIES AND CONTRAINDICATIONS 
For this protocol, a prescription medication is defined as a medication that can be prescribed 
only by a properly authorized/licensed clinician. Medications to be reported in the CRF are 
concomitant prescription medications, OTC medications, and non-prescription medications 
including dietary and herbal supplements.  
All medications, taken by subjects 14 days before screening and during the study (starting 
with the signing of the ICF) will be recorded on the Prior and Concomitant Medication 
section of CRF. Any additions, deletions, or changes in the dose of these medications will 
also be entered in the CRF.  
7.1 
Prohibited Therapies 
Subjects should not take prescription medications that may, in the opinion of the Investigator, 
impact the status of the subject as healthy within 28 days prior to study drug administration 
and throughout the study. Subjects will refrain from using OTC medications, vitamin 
supplements, or herbal preparations from 7 days prior to study drug administration and 
throughout the study; paracetamol, however, is permitted for pain relief. Subjects should not 
use antibiotics or drugs that inhibit or induce CYP enzymes within 30 days prior to 
administration of study drug and throughout the study. 
Subjects should not receive a vaccine within 14 days of screening or plan to get a vaccine 
during the study or within 14 days after discontinuation of the study. Subjects should not 
receive live or attenuated vaccines for 30 days prior to dosing and throughout the study.  
7.2 
Permitted Therapies 
Paracetamol (up to 2 g per day) is permitted for pain relief. Medication use will be controlled 
by the Investigator or designee during the time of sample collection or during the washout 
period between drug administrations. 
The Investigator may prescribe appropriate medication to treat AEs. The Sponsor and 
Investigator will confer to determine whether it is appropriate to continue such a subject in 
the study. 
7.3 
Lifestyle Restrictions 
7.3.1 
Dietary Restrictions 
Restrictions related to fasting and consumption of water in the day of study drug 
administration are described in Section 5.1.2.  
Subjects should not consume grapefruit, pomegranate, star fruit, or Seville oranges (or juices 
or products containing these fruits) for 7 days prior to dosing throughout the study. Subjects 
should not use St. John’s wort within 28 days prior to dosing and for the duration of the 
study. 


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Subjects should abstain from food containing poppy seeds within 48 hours prior to clinic 
check-in. Subjects should not consume food or beverages containing caffeine, xanthine 
derivatives or xanthine-related compounds, or energy drinks within 24 hours prior to clinic 
check-in. 
Subjects should abstain from consumption of alcohol-based products from 24 hours prior 
clinic check-in until after the last study assessments are performed at the Follow-up/Early 
Termination Visit. 
7.3.2 
Tobacco Restrictions 
Subjects should not use tobacco products for 3 months prior to the screening visit and during 
the study. 
7.3.3 
Exercise Restrictions 
Subjects should abstain from strenuous exercise for 48 hours prior to Day -1 and throughout 
the study. 
Vigorous activity will be prohibited at all times during the confinement. Subjects will be 
escorted by clinical staff to the restrooms or to other restricted areas of the clinic during the 
1 hour after study drug administration. Any deviation to these restrictions should be 
recorded.  
7.4 
Treatment Compliance 
Study drug must be used exclusively in the clinical study according to the instructions of this 
protocol. Study drug will be administered in the clinic under the supervision of site staff. Any 
deviations from planned dosing will be recorded. 


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8 
STUDY PROCEDURES 
All study procedures will be performed according to the Schedule of Assessments (Table 1). 
All visits are planned to be conducted at the clinic. 
The following is a guideline for the order of assessments when more than 1 of the following 
assessments is required at a particular timepoint: 
x Obtain vital signs, including temperature as applicable 
x Perform 12-lead ECG 
x Perform physical examination 
x Collect blood for safety laboratory tests 
x Collect blood for PK analysis 
When applicable, the blood draw for PK analysis should be given priority of timing such that 
it is drawn as close to the scheduled time as possible. 
8.1 
Study Assessments by Visit 
For subjects who participate in Cohort 4 (the food effect cohort), the assessments described 
on Days -1, 1, 2, 3, 4, 5, and 8 will generally be repeated on Days 9, 10, 11, 12, 13, 14, and 
17, respectively, unless noted otherwise in the Schedule of Assessments (Table 1). 
8.1.1 
Screening (Days-28 to Day -2) 
Prior to any study procedure, the subject will read and sign an ICF. All subjects will receive a 
copy of the signed ICF. The informed consent process will be noted in the subject’s medical 
record. 
Within approximately 28 days of the study drug administration, the screening visit should be 
completed. All subjects will be evaluated for adherence with study inclusion/exclusion 
criteria. A complete medical history evaluation, including surgical history and demographic 
data (age, gender, ethnicity, and race) will be completed for each subject. A complete history 
of all medications taken within 4 weeks of this visit will be obtained. Subjects will be 
instructed about permitted therapies and study restrictions (see Section 7). 
A full physical examination will be performed. Vital signs will be measured (blood pressure, 
pulse, respirations). Temperature will be measured. Clinical significance will be noted for 
any abnormal findings. A serum pregnancy test will be done on all female subjects. Follicle-
stimulating hormone (FSH) will be measured to confirm postmenopausal status. A urine drug 
screen will be done on all screening subjects. A breath alcohol test will be administered. 
Body mass index (BMI) will be determined from height and weight (shoes off) 
measurements. BMI can be calculated using pounds and inches, or kilograms and 
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• BMI = [Weight in Pounds/ (Height in Inches x Height in Inches)] x 703  
• BMI = Weight in Kilograms/ (Height in centimeters x Height in centimeters) 
For any out-of-normal range values, clinical significance will be noted. The clinical 
laboratory tests include: 
• Serum Chemistry: alanine transaminase, albumin, alkaline phosphatase, aspartate 
transaminase, blood urea nitrogen, calcium, carbon dioxide, chloride, creatinine, glucose, 
inorganic phosphorus, magnesium, potassium, sodium, total bilirubin, total protein, uric 
acid. 
• Hematology: differential white blood cell count, hematocrit, hemoglobin, platelet count, 
red blood cell count, international normalized ratio (INR).  
• Serology: hepatitis B surface antigen, hepatitis C antibody titer, HIV.  
• Serum Pregnancy Test: hCG will be conducted for all female subjects. 
• FSH will be tested for all female subjects to confirm or refute postmenopausal status. 
• Urinalysis: bilirubin, blood, clarity, color, glucose, ketones, leukocyte esterase, nitrite, 
pH, protein, specific gravity. A microscopic test on the urine sample will be done where 
indicated. 
• Urine Drug Screen: Methamphetamine, morphine, cocaine, tetrahydrocannabinol, 
phencyclindine, benzodiazepines, barbiturates, methadone, tricyclic antidepressants, 
amphetamine, urine cotinine or breath CO test for use of tobacco, MDMA metabolite 
(ecstasy) and opiates. 
• Alcohol breath test. 
• Coagulation: prothrombin time. 
8.1.2 
Check-in (Day-1) 
Subjects will enter the facility the day before study drug administration for each study period. 
All subjects will be domiciled and under medical supervision in the CRU. All subjects will 
be confined to the clinical unit for the entire treatment period, up to Day 5.  
A pregnancy test (females), alcohol breath test, and urine cotinine or breath CO test will be 
performed at each study period check-in. Results must be negative to continue in the study. 
Any untoward changes in medical history of the subject since the screening visit will be 
documented and added to the medical history. For female subjects, start and stop date of last 
menstrual period will be collected. Untoward changes in medical history since dosing will be 
recorded as AEs. Subjects will be asked about any medications taken since the screening visit 
or previous study period and adherence to restrictions. Vital signs (in a semi-recumbent 
position) and temperature will be measured. A full physical exam will be performed. Blood 
and urine will be collected for safety laboratory testing (chemistry, hematology, coagulation, 
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The clinical laboratory tests for check-in are the same as at screening. 
The Investigator will review this information and determine continuing eligibility of the 
subject prior to each study drug administration. 
A supervised fast of at least 10 hours will start after the evening meal. The subjects will have 
free access to drinking water until at least one hour before dosing and one hour after dosing.  
8.1.3 
Treatment/Confinement Period Procedures 
8.1.3.1 
Days 1 through 5 
On Day 1 of the confinement period, each subject will be randomized to receive study drug 
or placebo, at a dose determined by the part and cohort into which the subject is enrolled. 
The next cohort will only be dosed after completing the safety review of the previous cohort 
as per the schedule of assessments.  
ISLA101 will be administered on Day 1 as described in Section 5.1.2. Meals and snacks will 
be provided at standard times throughout the confinement period in accordance with the 
site’s usual procedures. 
Vital signs, temperature, clinical laboratory testing and physical examinations will be 
performed.  
Monitoring for TEAEs will begin as soon as the subject is dosed and continue for the last 
Follow-up Visit after the final dose of the study drug. Blood draws for PK sampling to assess 
the PK of ISLA101 will be performed.  
The safety laboratory parameters for the confinement days (Day 1 to Day 5) are the same as 
at screening. 
8.1.4 
Early Termination/Safety Follow-up Visit 
At follow up or at early withdrawal from any cohort, subjects will complete the Follow-
up/ET visit. Vital signs and temperature will be measured, and clinical laboratory tests will 
be performed. A physical exam will be performed, and clinically significant abnormalities 
will be reviewed by the Investigator. For females, urine pregnancy test will be performed. A 
review of AEs and concomitant medications will be performed.  
8.1.5 
Unscheduled Assessments 
If a subject reports any AE(s) that present cause for concern during the study, they may be 
asked to complete further assessments. Any other procedures necessary to monitor the AE 
may be performed at the Investigator’s discretion.  


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8.2
Safety Assessments
This study is designed to assess the safety of ISLA101. Safety will be determined by 
evaluating physical examination findings, vital signs, clinical laboratory parameters, AEs,
and TEAEs. Scheduled safety assessments will be performed at the time points shown in
Table 1. If deemed necessary, additional safety measurements will be performed at the 
discretion of the Investigator, or Sponsor representative.
Adverse events will be assessed as described in Section 9.
8.2.1
Vital Signs
Vital signs will consist of respiratory rate, heart rate, and semi-recumbent blood pressure.
Subjects should be resting in a semi-recumbent position for at least 3 minutes prior to and 
during vital signs measurement. When the time of vital signs measurement coincides with a 
blood draw, the vital signs will be taken before the scheduled blood draw where possible 
while ensuring the blood draw is within the window specified in the protocol. Additional 
vital signs may be performed at other times if deemed necessary.
If temperature measurement is oral, subjects should not eat or drink hot or cold foods or 
beverages within 15 minutes of oral temperature measures. On dosing days, temperature will 
be taken prior to dosing.  
8.2.2
Physical Examination
A complete physical examination includes evaluation of the following: General Appearance, 
Head, Ears, Eyes, Nose, Mouth, Throat, Neck (including thyroid and lymph nodes),
Cardiovascular, Respiratory, Gastrointestinal, Renal, Neurological, Musculoskeletal, Skin, 
and Other. Symptom-directed physical examinations may also be performed at any time.
As clinical studies from IND38892 and from the published literature showed ocular toxicity 
following treatment with fenretinide (eye irritation, dryness of eyes, nyctalopia), an 
ophthalmologist will be available to evaluate all significant ocular complaints.
8.2.3
Clinical Laboratory Assessments
Standard clinical laboratory profiles for serum chemistry, hematology, and urinalysis will be 
evaluated. Specific laboratory tests to be performed at each study visit are described in 
Section 8.1.
All clinically significant laboratory abnormalities beginning with Day 1 must be recorded as 
an AE in the subject’s source documents and on the appropriate CRF. A clinically significant 
laboratory abnormality that has been verified by retesting will be followed until the 
abnormality returns to an acceptable level or a satisfactory explanation has been obtained.
Tests for hepatitis B surface antigen, hepatitis C virus antibodies, and HIV will be completed 
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A UDS, an alcohol breath test, and a urine cotinine test or breath CO test will be performed 
at screening.  An alcohol breath test and urine cotinine or breath CO test will be performed at 
Day -1.  
8.2.4 
Pregnancy 
An FSH test will be performed at screening for all female subjects to confirm or refute 
postmenopausal status. A serum pregnancy test will be performed for all females at 
screening. Urine pregnancy tests will be performed at check-in and at follow-up for all 
females. 
Due to teratogenic risks, all initial reports of pregnancy in female subjects or partners of male 
subjects must be reported to the Sponsor by the site personnel within 72 hours of their 
knowledge of the event. 
If a female subject is suspected or known to become pregnant during the study, she should be 
discontinued from the study. If a female subject, or if a female partner of a male subject, 
becomes pregnant while enrolled in the study, information regarding the pregnancy should be 
submitted to the Sponsor or designee within 72 hours of the treating physician’s/research 
personnel’s awareness of the pregnancy. Every effort should be made to follow the 
pregnancy until completion or until pregnancy termination and, if applicable, the health of 
the child for 1 year post-birth.  
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(ie, spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in 
an aborted fetus, stillbirth, or neonatal death]), the Investigator should follow the procedures 
for reporting SAEs described in Section 9.1.3. 
8.2.5 
Electrocardiogram 
A 12-lead ECG will be performed at the screening visit, Day -1, and Day 1 for subjects in 
Cohorts 1-3, and again at the clinic check-in (Day 9) and Day 10 for subjects in the fed 
cohort (Cohort 4). 
8.3 
Pharmacokinetic Assessments 
Blood samples will be collected to characterize the fasted and fed PK profiles of ISLA101, as 
described in Table 2. 
Blood samples will be taken by fresh venipuncture or indwelling catheter; IV cannula may be 
utilized on days requiring intensive sampling.  
The following is a listing of the PK plasma sampling times relative to the time of study drug 
administration, defined as the time at which the first capsule is consumed: 


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• At pre-dose (approximately 1 hour before study drug administration) and at 0.5, 0.75, 1, 
1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after dosing. 
The total amount of blood sampled from a subject will be up to approximately 185 mL 
during the study. This will include 72 mL (18 total blood draws × 4 mL per blood draw) for 
PK assessments; approximately 25 mL for screening evaluations and 12.5 mL each for other 
laboratory evaluations (Days -1, 1, 2, 3, and 8); and approximately 25 mL for 2 repeat lab 
assessments (approximately 12.5 mL each), if needed. For subjects in Cohort 4 (the food 
effect cohort), additional 160 mL of blood will be collected, including samples for PK 
assessment, laboratory evaluation (Day 9, 10, 11, 12, and 17) and repeat lab assessments. 
Plasma samples will be collected and processed as per the instructions developed by the 
bioanalytical laboratory and aliquoted into at least 2 separate tubes. The plasma samples 
(split into 2 different aliquots) from each subject will be shipped in 2 separate shipments to 
the selected bioanalytical laboratory for analysis. The second shipment will be sent after 
receipt in good condition of the first shipment. The address of the selected bioanalytical 
laboratory will be supplied to the clinical research organization for shipment of the samples. 


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9 
ADVERSE EVENTS 
The incidence and nature of any AEs, dose-limiting AEs, SAEs, vital sign changes, and 
laboratory abnormalities will be assessed on an ongoing basis by the SRC. 
9.1.1 
Definition of an Adverse Event 
An AE is the development of an undesirable medical condition or the deterioration of a 
pre-existing medical condition, regardless of whether it is considered casually related to the 
study treatment. 
The term also covers laboratory findings or results of other diagnostic procedures which are 
considered clinically relevant. Vital signs or laboratory abnormalities that show shifts from 
baseline which the Investigator considers clinically significant must be reported as AEs if 
they are symptomatic, require either corrective treatment or consultation, and/or lead to study 
drug discontinuation.  
Surgical procedures themselves are not AEs; they are therapeutic measures for conditions 
that require surgery. The condition for which surgery is required may be an AE, if it occurs 
or is detected during the study period. Planned surgical measures and the condition(s) leading 
to these measures are not AEs, if the condition(s) was known before the subject signed the 
ICF. In these instances, the condition should be reported as medical history. 
9.1.1.1 
Reporting Adverse Events 
All AEs, whether or not they are considered by the Investigator to be related to the study 
drug, must be recorded in the subject’s source documents and in the electronic CRF. For each 
AE, the reported term, onset and end dates, severity, consequences on study drug intake 
(action taken), relationship to study drug, treatment provided, outcome, and information on 
seriousness of the event will be recorded.  
The severity of the AE, relationship of the AE to study drug, and the outcome of the AE will 
be assessed by the Investigator. 
Subjects will be monitored throughout the study for adverse reactions to the study drug 
and/or procedures. The subjects will be instructed to inform the study staff of any AEs that 
may occur at any time during the study. Observation of AEs extends from the time of ICF 
signing until the subject has left the study. Any AEs presenting within 30 days after the last 
scheduled visit will be followed up with a phone call or a visit until an outcome has been 
determined. After that time point, the need for additional follow-up of ongoing AEs or SAEs 
will be discussed between the Investigator and Sponsor. 
9.1.2 
Treatment-Emergent Adverse Events 
A TEAE is defined as any event that was not present prior to the initiation of study treatment, 
or any event already present which worsens either in intensity or frequency following 
exposure to study treatment.  


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9.1.3 
Serious Adverse Events 
9.1.3.1 
Definition 
A SAE is an AE occurring during any study phase that fulfils one or more of the following: 
• Results in death. 
• Is immediately life-threatening. 
• Requires hospitalization or prolongation of existing hospitalization. 
• Results in persistent or significant disability/incapacity. 
• Results in a congenital anomaly/birth defect. 
• Is a medically important event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above. 
In this context, “life-threatening” means that the subject is at immediate risk of death at the 
time of the SAE; it does not refer to an event that hypothetically might have caused death if it 
was more severe. “Hospitalization” is defined as inpatient care that covers more than 
one calendar day. “Persistent or significant disability or incapacity” means that there is a 
substantial disruption of a person’s ability to carry out normal life functions, compared to the 
person’s ability prior to the study. Medical judgment should be exercised in deciding whether 
AEs may be considered serious because they jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above. The list of 
critical terms (1998 adaptation of World Health Organization Adverse Reaction Terminology 
Critical Terms List) should be used as guidance for AEs that may be considered serious 
because they are medically important.  
9.1.3.2 
Reporting Serious Adverse Events 
All SAEs, whether or not they are deemed drug-related or expected, must be reported to the 
Sponsor immediately (or within 72 hours) of becoming aware of the event. The Investigator 
must inform the site monitor, and if required by local regulations or procedures, the 
Investigator should report these events to the HREC and/or national regulatory authority. The 
Investigator must report all SAEs on the eCRF regardless of relationship to study drug. If the 
site experiences a temporary disruption of the eCRF system, a back-up paper SAE report 
form will be available for site staff to complete.  
Any SAEs should be submitted to CRO’s Pharmacovigilance & Safety Services to the email 
listed below. CRO’s Pharmacovigilance & Safety Services should be supplied with the name 
of the Investigator and the name, title, and contact information (email and telephone) of 
person submitting the report. 
safety@beyonddrugdev.com is the safety reporting email address for the CRO overseeing 
this study. 


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Site staff must enter the SAE information into the eCRF system as soon as the system 
becomes available. Should a back-up SAE form be used, the original SAE form should be 
kept at the study site. 
Any additional follow-up including medically relevant follow-up information must be 
reported within the same timelines. 
The SAE reports should include a detailed written report including all available data allowing 
the event to be documented and using only anonymized copies (with only the subject 
identification code: treatment number and initials) from hospitalization reports and additional 
examination(s). The Investigator should also report all elements concerning the follow-up of 
the SAE.  
When reporting a death, the Investigator should supply any additional requested information 
such as autopsy reports (if available) and final medical reports. 
The back-up SAE report form and the instructions on completion will be provided to the 
sites. The “Instructions for Completing the SAE Form” document provides detailed guidance 
on the reporting of SAEs, and AEs initially reported as non-serious which become serious. 
The Sponsor will ensure compliance with all regulatory reporting requirements and notify the 
authorities, ethics committees, and Investigators as appropriate. All safety reporting 
responsibilities, timelines, and procedures will be described in detail in the Safety 
Management Plan. 
9.1.4 
Dose-limiting Adverse Events 
Dose-limiting AEs are defined as clinically significant AEs or abnormal laboratory values that are Grade 3 or 4 
in severity, based on toxicity grading scales as specified in FDA’s Guidance for Industry and 
Investigators – Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials. 
 
9.1.5 
Adverse Events of Special Interest 
The following signs of drug toxicity will be deemed to be of special interest and may be 
dose-limiting: 
x Sustained respiratory depression that results in oxygen saturation below 92%. 
x Seizure 
x Protracted (> 1 hour) nausea and vomiting. 
x Any AE deemed by the Investigator to be dose-limiting or ≥ Grade 3 in intensity. 
x Clinical investigations indicating signs of drug-induced liver injury based on the 
following criteria from FDA guidance: 


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o Alanine aminotransferase (ALT) or aspartate transaminase (AST) > 8 x the 
upper limit of normal (ULN). 
o ALT or AST > 5 x ULN for more than 2 weeks.  
o ALT or AST > 3 x ULN and (total bilirubin > 2 x ULN or international 
normalized ratio > 1.5).  
o ALT or AST > 3 x ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(> 5%). 
x Any clinically significant findings of blood chemistry and hematology. 
Depending on the severity of these and/or other AEs or the occurrence of more than 1 AE in 
the same subject, the subject(s) may be unblinded if it is deemed necessary for the treatment 
of AEs.   
9.1.6 
Severity 
The severity (intensity) of each AE must be assessed according to the following 
classification: 
x Mild: does not interfere with routine activities. 
x Moderate: interferes with routine activities. 
x Severe: subject is unable to perform routine activities. 
9.1.7 
Relationship 
The relationship of any AE to the study drug must be assessed, according to the following 
rating, by the clinician who examines and evaluates the subject based on temporal 
relationship and clinical judgment:  
x Definitely: 
The AE is clearly related to the study drug. 
x Probably: 
The AE is likely related to the study drug. 
x Possibly: 
The AE may be related to study drug. 
x Unlikely: 
The AE is doubtfully related to study drug. 
x Unrelated: 
The AE is clearly not related to the study drug. 


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9.1.8 
Outcome 
The outcome of each AE may be classified as resolved (spontaneously or with treatment) or 
unresolved. 
Any subject who experiences an AE (whether serious or non-serious) or has a clinically 
significant abnormal laboratory test values will be evaluated by the Investigator or a 
monitoring physician and will be treated and/or followed up until the symptoms or values 
return to normal, or acceptable levels, as judged by the Investigator. Where appropriate, 
medical tests and/or examination) will be performed to document resolution of events. 
9.1.9 
Expectedness 
An unexpected adverse reaction is any untoward and unintended response that is related to 
the administration of the study drug at any dose that is not consistent with the applicable 
product information (as described in the Investigator’s Brochure for ISLA101). 
All suspected unexpected serious adverse reactions (SUSARs) will be the subject of 
expedited reporting. The Sponsor and/or CRO shall ensure that all relevant information about 
a SUSAR that is fatal or life-threatening is reported to the relevant competent authorities and 
HREC within 7 days after the Sponsor becomes aware of the event. Relevant follow-up 
information will subsequently be communicated within an additional 8 days. All other 
SUSARs will be reported to the relevant competent authorities and HREC within 15 days 
after the Sponsor becomes aware of the event. All Investigators should follow SUSARs until 
the event is resolved or until, in the opinion of the Investigator, the event is stabilized or 
determined to be chronic. Suspected unexpected serious adverse reactions that occur after the 
subject has withdrawn from the clinical study must be reported by the Investigator to the 
Sponsor. 
 


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10 
PLANNED STATISTICAL METHODS 
10.1 
General Considerations 
A statistical analysis plan (SAP) describing all statistical analyses will be provided as a 
separate document prior to data lock-out. 
Descriptive statistics will be used to provide an overview of the safety results. For categorical 
parameters, the number and percentage of subjects will be presented. For continuous 
parameters, descriptive statistics will include n (number of subjects), mean, standard 
deviation, median, minimum, and maximum. No imputations will be made for missing data. 
A brief outline of planned statistical analyses is presented below. 
10.2 
Determination of Sample Size 
No formal sample size calculation was performed. The study is considered exploratory with a 
sample size of 8 subjects per cohort (2 placebo + 6 active). This cohort size and 
active/placebo ratio are considered standard to evaluate safety profile and to provide 
sufficient PK information for future development of the compound. 
10.3 
Analysis Populations 
In fasted and fed cohorts, 2 analysis populations will be used to summarize the results from 
this study: 
Safety Population: All subjects who receive at least 1 dose of study drug (active and 
placebo). Safety analyses will be based on the safety population.  
PK Population: All subjects in the Safety Population who have a pre-dose PK sample and at 
least 1 post-dose analyzable PK sample. 
Subjects who received planned doses of ISLA101 will be included in the PK evaluation and 
statistical comparisons, based on availability of sufficient PK profiles. Actual treatments will 
be used for all analyses. 
All subjects who receive at least one dose of the study drug (placebo or active) will be 
included in the safety analyses. 
10.4 
Disposition and Demographics 
Subject disposition will be summarized and will include all subjects who have received one 
dose of study drug in the safety population, subjects in the PK population, and number and 
percent of subjects who complete or prematurely discontinue from the study along with 
reason for discontinuation. Demographic data will be summarized using descriptive statistics 
for all subjects who were randomized in this study and took at least 1 dose of study drug. 


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10.5 
Safety Analysis 
All safety data from the study will be listed by subject, dose, and cohort. Changes in safety 
assessments from screening to post-dose measurements will be assessed using summary 
statistics (mean, minimum, maximum, standard deviation, and corresponding sample size [N] 
for continuous variables, and frequency of category shifts from screening to post-study for 
discrete variables) for each part/cohort. Additionally, summary statistics for vital signs 
(blood pressure, pulse, pulse oximetry, and respiratory rate) and oral temperature will be 
reported.  
Adverse events will be coded using the toxicity grading scale tables as specified in Guidance 
for Industry and Investigators – Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials and Medical Dictionary for 
Regulatory Activities terminology. The AEs will be summarized by dose and visit and 
overall. The AEs will be tabulated and summarized by body system, preferred term, severity, 
frequency, and relationship to study drug. A listing of SAEs will be provided.  
Change from screening in clinical laboratory parameters and vital sign parameters will be 
summarized by visit and overall. Shift tables for key safety parameters including clinical lab 
investigations will be presented. Frequency descriptors for the safety analyses will be 
reported as needed. 
10.6 
PK Analysis 
Descriptive statistics for PK concentrations and parameters will consist of number of subjects 
(n), arithmetic mean, standard deviation (SD), geometric mean, geometric coefficient of 
variation (%), median, minimum, and maximum. For Tmax and T1/2, only n, median, 
minimum, and maximum will be presented. 
This study will perform PK analysis using validated software, such as Phoenix® 
WinNonlin® version 8.0 or higher. Pharmacokinetic parameters will be calculated through 
noncompartmental analysis of fenretinide and its metabolites MPR and oxo-HPR, including 
Cmax, AUClast, AUCinf, Tmax, T½, Cl/F, and V/F on the day of dosing. Other relevant 
parameters will also be estimated.  
Dose proportionality for fenretinide exposure parameters (Cmax, AUClast, and AUCinf) will be 
assessed statistically based on the natural log (ln)-transformed PK parameters. 
Proportionality analysis will be done using a Power Model defined as: 
ln (PK parameter) = α + β • ln (Dose) + ε 
where α is the intercept, β is the slope, and ε is the error term. A linear model with 
ln-transformed dose as a continuous effect will be fitted. A point estimate and a 90% CI will 
be derived for the slope (β), measure of the proportionality between the dose and the PK 
parameter. Evidence of dose proportionality for each PK parameter evaluated will be 
assessed by the 90% CI of each slope. 


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Appropriate dose-normalized PK parameters will also be assessed graphically for dose 
proportionality. 
An ANOVA will be conducted on ln-transformed PK parameters, including AUClast, AUCinf, 
and Cmax to evaluate the effect of food on fenretinide in the recalled cohort (Cohort 4 vs 
Cohort 3). The study will calculate the differences between adjusted means and the standard 
error associated with these differences. The ratio of means will be calculated using the LSM 
for ln-transformed AUClast, AUCinf, and Cmax values. The 90% confidence interval (CI) for 
the difference between the fed and fasted conditions will be calculated for AUClast, AUCinf, 
and Cmax using ln-transformed concentration data. The CI will be expressed as a percentage 
relative to the LSM. 
 


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11 
QUALITY CONTROL AND ASSURANCE 
Each clinical site will be responsible for internal quality management of study conduct, data 
and biological specimen collection, documentation, and completion based on their internal 
processes. 
Quality control procedures will be implemented beginning with the data entry system and 
data quality control checks that will be run on the database to generate queries to the site(s) 
where applicable. Any missing data or data anomalies will be communicated to the site(s) for 
clarification/resolution. 
Following written Standard Operating Procedures and the Clinical Monitoring Plan, the 
monitors will verify that the clinical trial is conducted, that data are generated, documented 
(recorded), and reported, and that biological specimens are collected in compliance with the 
protocol, International Council for Harmonisation (ICH) Good Clinical Practice (GCP), and 
applicable regulatory requirements (e.g., Good Laboratory Practices and GMP).  
The investigational site will provide direct access to all study-related locations, source 
data/documents, and reports for the purpose of monitoring and auditing by the Sponsor and 
inspection by local and regulatory authorities. 


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12 
REGULATORY AND ETHICAL CONSIDERATIONS 
12.1 
Institutional Review Board or Independent Ethics Committee 
Approval 
The protocol, ICF, Investigator’s Brochure, and other relevant documents 
(eg, advertisements) must be submitted to an HREC by the Investigator and be reviewed and 
approved by the HREC before the study is initiated. 
Any amendments to the protocol will require HREC approval before implementation of 
changes made to the study design. 
The Investigator will provide written summaries of the status of the study to the HREC 
annually or more frequently in accordance with the requirements, policies, and procedures 
established by the HREC. The Investigator will also notify the HREC of SAEs or other 
significant safety findings as required by HREC procedures. 
12.2 
Ethical Conduct of the Study 
This study will be conducted in accordance with the protocol and with the following: 
• current Declaration of Helsinki (Ethical Principles for Medical Research Involving 
Human Subjects) National Health and Medical Research Council National Statement on 
Ethical Conduct in Human Research 2007 (updated 2018). 
• International Council for Harmonisation (ICH) Integrated Addendum to E6(R1): 
Guideline for Good Clinical Practice (GCP) ICH E6(R2), annotated with comments by 
the Australian Therapeutic Goods Administration (2018). 
• Applicable laws and regulations. 
12.3 
Subject Information and Consent 
Consent forms that describe the study drug, study procedures, and risks will be given to each 
potential subject and the nature and purpose of the study shall be fully explained. Written 
documentation of informed consent must be obtained from each subject prior to any study 
procedures being performed. 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate 
in the study and continues throughout the individual’s study participation. Consent forms will 
be approved by the HREC, and the subject will be asked to read and review the document. 
Consent forms must be in a language fully comprehensible to the prospective subject. The 
Investigator (or designee as per local regulation) will explain the research study to the subject 
and answer any questions that may arise. A verbal explanation will be provided in terms 
suited to the subject’s comprehension of the purposes, procedures, and potential risks of the 
study and of their rights as research subjects.  
Subjects will have the opportunity to carefully review the written ICF and ask questions prior 
to signing. The subjects should have the opportunity to discuss the study with their family or 


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surrogates or think about it prior to agreeing to participate. Subjects must be informed that 
participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the subject for their 
records.  
The informed consent process will be conducted and documented in the subject’s medical 
records (including the date), as required by the ICH Integrated Addendum to ICH E6(R1): 
Guideline for GCP E6(R2), as adopted by the Australian Therapeutic Goods Administration 
(TGA), and the NHMRC National Statement on Ethical Conduct in Human Research.. 
Electronic media may be used to replace paper-based informed consent processes (electronic 
informed consent), utilizing electronic signatures. An electronic informed consent may be 
used to provide the same information that is contained within the written informed consent 
document, evaluate the subject’s comprehension of the information presented, and document 
the consent of the subject. The rights and welfare of the subjects will be protected by 
emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
The informed consent form should be updated or amended whenever new important 
information that may be relevant to the subject becomes available. Modifications must be 
approved by the Sponsor and by the HREC before being implemented.  
12.4 
Subject Confidentiality 
Subject confidentiality and privacy are strictly held in trust by the participating Investigators, 
their staff, and the Sponsor. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to subjects. 
Therefore, the study protocol, documentation, data, and all other information generated will 
be held in strict confidence. No information concerning the study, or the data will be released 
to any unauthorized third party without prior written approval of the Sponsor.  
The study monitor, other authorized representatives of the Sponsor, representatives of the 
HREC, or regulatory agencies may inspect all documents and records required to be 
maintained by the Investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the subjects in this study. The clinical study site will 
permit access to such records. 
The study subject’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as is dictated by the reviewing HREC, institutional 
policies, regulatory authorities, or Sponsor requirements. 
Subject research data for purposes of statistical analysis and scientific reporting will be 
transmitted to and stored in the IBM Clinical Development database. A subject’s contact or 
identifying information will not be included.  


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13 
ADMINSTRATIVE CONSIDERATIONS 
13.1 
Clinical Study Research Agreement 
Agreements will be initiated between the Sponsor, Investigator(s), applicable CROs, and any 
other relevant parties involved in conducting the study to delineate key responsibilities. 
The Sponsor is obligated to conduct the study in accordance with strict ethical principles. 
The Sponsor agrees to provide the Investigator with sufficient material and support to permit 
the Investigator to conduct the study according to the study protocol. 
The Investigator is obligated to read the protocol carefully, fully understand the study 
requirements, and to conduct the study in accordance with the protocol. Investigators should 
ensure that all persons who are delegated study-related responsibilities are adequately 
qualified and informed about the protocol, the study drug, and their specific duties within the 
context of the study. Investigators are responsible for providing the Sponsor with 
documentation of the qualifications, GCP training, and research experience for themselves 
and their staff as required by the Sponsor and the relevant governing authorities. 
13.2 
Case Report Forms and Study Records 
The Investigator agrees to maintain accurate eCRFs and source documentation as part of the 
case histories for all subjects who sign an ICF. CRFs are considered confidential documents 
and should be handled and stored accordingly. The Sponsor or its designee will provide the 
necessary training on the use of the specific eCRF used during the study to ensure that the 
study information is captured accurately and appropriately. 
To ensure data accuracy, eCRF data for individual subject visits should be completed as soon 
as possible after the visit. All requested information must be entered in the eCRF according 
to the completion guidelines provided by the Sponsor or its designee. The eCRFs must be 
signed by the Investigator or a sub-Investigator. These signatures serve to attest that the 
information contained in the eCRF is accurate and true.  
Information recorded in the eCRF should be supported by corresponding source 
documentation. Data reported on the eCRF that are transcribed from source documents must 
be consistent with the source documents, or the discrepancies must be explained. 
13.3 
Protocol Violations/Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol and associated 
documents. The noncompliance may be on the part of the subject, the Investigator, or the 
study site staff. As a result of deviations, corrective actions are to be developed by the site 
and implemented promptly.  
No deviation from the protocol or investigational plan will be made except to protect the life 
or physical well-being of a subject in an emergency situation. Except in such emergencies, 
prior approval of the Sponsor, and the regulatory authorities or the HREC, is required before 
deviating from the protocol. All protocol deviations that occur during the study will be 


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documented in the eCRF and reported to the Sponsor and to the HREC if applicable, 
according to regulations. The site Investigator is responsible for knowing and adhering to the 
reviewing HREC requirements. Further details about the documentation, evaluation, and 
follow-up of protocol deviations will be detailed in this study’s Clinical Monitoring Plan. 
13.4 
Access to Source Documentation 
Source documents provide evidence for the subject’s experience in the study and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s site. A 
definition of what constitutes source data will be found in the Clinical Monitoring Plan. 
Source documents are original documents, data, and records from which the subject’s eCRF 
data are obtained. These include, but are not limited to, hospital records, clinical and office 
charts, laboratory and pharmacy records, paper diaries, electronic diaries, video recordings, 
microfiches, radiographs, angiograms, study medication accountability logs, and 
correspondence. Case report form entries may be considered source data if the eCRF is the 
repository of the original recording (i.e., there is no other written or electronic record of 
data). In this case, a source document agreement should indicate which eCRFs are considered 
source documents for the study. The Investigator may also need to request previous medical 
records or transfer records to obtain source documents.  
Monitors, auditors, and other authorized representatives of the Sponsor, the HREC, and 
health authorities may be granted access to source documentation as appropriate an in 
accordance with all applicable laws. Specifically, the study site, facilities, all data (including 
source data), and documentation will be made available for audit by quality assurance 
auditors and for HREC or regulatory authorities according to GCP guidelines. The 
Investigator agrees to cooperate with any audits and to supply the auditor with eCRFs or 
other files necessary to conduct the audit. Any findings will be strictly confidential. 
If a regulatory authority informs the Investigator that it intends to conduct an inspection, the 
Investigator shall notify the Sponsor immediately.  
13.5 
Data Generation and Analysis 
Clinical data (including AEs and concomitant medications) and clinical laboratory data will 
be entered into an EDC system that complies with regional and national regulatory standards. 
The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. 
The Investigator, or designated representative, will be trained on the EDC prior to receiving 
access. Each user will have a unique password to enter or review data. According to the ICH 
GCP, the monitoring team must check the eCRF entries against the source documents, except 
for the pre-identified source data directly recorded in the eCRF. A source data location list 
will be prepared and updated during the study. This list will be filed in both the trial master 
file and the Investigator study file. 
Additional information related to eCRF completion is provided in Section 13.2. 


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13.6 
Retention of Data 
The Investigator must maintain confidentiality for all study documentation and take measures 
to prevent accidental or premature destruction of these documents.  
All primary data that are a result of the original observations and activities of the study that 
are necessary for the reconstruction and evaluation of any study report will be retained in a 
secure archive at the study site for a period of not less than15 years after the last approval of 
a marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 15 years have lapsed since the 
formal discontinuation of the clinical development of the study drug. 
The site will maintain a Clinical Study Document Binder, which will be maintained at the 
study site. In this binder, there will be tabbed sections for study documents including the 
following: study personnel identification and signature list, subject screening records, subject 
roster (names omitted), protocol and amendments or administrative changes, study staff 
Curricula Vitae, HREC documentation, an approved sample ICF, drug accountability 
records, correspondence, site monitoring reports, blank Data Documentation form, lab 
accreditations, and normal values. The site must keep this binder current and available for 
review or audit by the Sponsor, HREC and/or regulatory authority.  
13.7 
Study and Site Closure 
The Sponsor reserves the right to terminate the study but intends to only exercise this right 
for valid scientific or administrative reasons or reasons related to the protection of subjects. 
Possible reasons for the study termination include, but are not limited to: 
• The discovery of an unexpected, significant, or unacceptable risk to subjects enrolled in 
the study. 
• A decision on the part of the Sponsor to suspend or discontinue the development of the 
study drug. 
• A request by a relevant regulatory agency. 
Written notification, documenting the reason for study suspension or termination, will be 
provided by the Sponsor to study subjects, Investigators, and regulatory authorities. If the 
study is prematurely terminated or suspended, the Sponsor, or designee, will inform the 
Investigator and will provide the reason(s) for the termination or suspension. The 
Investigator will then promptly inform the subjects and the HREC. Subjects will be 
contacted, as applicable, and will be informed of changes to the study visit schedule 
including a possible “end of study visit.” 
If the study is put on hold, the study may resume once any relevant concerns about safety, 
protocol compliance, and data quality are addressed, and the resolution satisfies the Sponsor, 
HREC, and relevant regulatory authorities. 


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13.8 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate 
financial information to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. Details of financial disclosure responsibilities 
will be provided in a separate agreement between the Investigator and the Sponsor. 
13.9 
Conflict of Interest 
The independence of this study from any actual or perceived influence is critical. Therefore, 
any actual conflict of interest for persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this study will be disclosed and managed. Furthermore, persons 
who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this study. The 
study leadership has established policies and procedures for all study group members to 
disclose all conflicts of interest and will establish a mechanism for the management of all 
reported dualities of interest. 
13.10 
Publication and Disclosure Policy 
The designated CRO will be responsible for conducting the statistical analysis and for 
preparing a CSR. The Sponsor must provide a summary of study results to the Investigator. 
The Sponsor may publish the results at the end of the study in an international journal on 
behalf of the study group, including the Investigator site.  
The communication or publication of all or part of the results of this study, including 
ancillary studies, will be only permitted after receiving written agreement from the Sponsor. 
Any manuscript or presentation should be submitted to the Sponsor at least 30 days before 
submission for review and approval. In addition, if requested by the Sponsor, any 
presentation or submission for publication shall be delayed for a limited time, to allow for 
filing of a patent application or other measures that the Sponsor deems appropriate to 
establish and preserve its proprietary rights. The Sponsor has the right at any time to publish 
the results of the study. 


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14 
REFERENCE LIST 
 
Carocci M, Hinshaw SM, Rodgers MA, et al. The bioactive lipid 4-hydroxyphenyl 
retinamide inhibits flavivirus replication. Antimicrob Agents Chemother. 2015;59(1):85-95. 
 
CDC. Dengue: Statistics and Maps. https://www.cdc.gov/dengue/statisticsmaps/2021.html. 
2021. 
 
CDC. CDC Reminds Clinical Laboratories and Healthcare Infection Preventionists of their 
Role in the Search and Containment of Vancomycin-Resistant Staphylococcus aureus 
(VRSA). 2022. 
 
Cooper JP, Reynolds CP, Cho H, Kang MH. Clinical development of fenretinide as an 
antineoplastic drug: Pharmacology perspectives. Exp Biol Med (Maywood). 
2017;242(11):1178-1184. 
 
FDA. Dengvaxia. https://www.fda.gov/vaccines-blood-biologics/dengvaxia. 2020. 
 
FDA. iPLEDGE REMS. Prescriber Guide. https://ipledgeprogram.com/#Main/Resources 
2021. 
 
Fraser JE, Watanabe S, Wang C, et al. A nuclear transport inhibitor that modulates the 
unfolded protein response and provides in vivo protection against lethal dengue virus 
infection. J Infect Dis. 2014;210(11):1780-1791. 
 
Takeda. QDENGA information. Dengue tetravalent vaccine (live, attenuated). Available 
online at https://www.takeda.com/search?query=qdenga. 2023. 
 
WHO. Dengue vaccines: WHO position paper. World Health Organization. 
https://www.who.int/immunization/policy/position_papers/who_pp_dengue_2018_summary.
pdf. 2018. 
 
WHO. Dengue and severe dengue. World Health Organization. https://www.who.int/news-
room/fact-sheets/detail/dengue-and-severe-dengue. 2021. 
 
 


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15
APPENDICES
Appendix 1
Sponsor Signatures
Study Title:
A Phase 1a, randomized, double-blind placebo-controlled study to 
evaluate safety and tolerability and to characterize the pharmacokinetic 
profile of single ascending doses of fenretinide oral capsules in healthy 
adult volunteers
Study Number:
ISLA101-P01-CT001
Final Date:
18 October 2023 Ver 2.0
This clinical study protocol was subject to critical review and has been approved by the 
Sponsor. The following personnel contributed to writing and/or approving this protocol:
Signed:
Date:
David C. Foster, PhD, JD
Chief Executive Officer
Island Pharmaceuticals Ltd
20 November 2023


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Appendix 2 
Investigator’s Signature 
Study Title: 
A Phase 1a, randomized, double-blind placebo-controlled study to 
evaluate safety and tolerability and to characterize the pharmacokinetic 
profile of single ascending doses of fenretinide oral capsules in healthy 
adult volunteers 
Study Number: 
ISLA101-P01-CT001 
Final Date: 
18 October 2023 Ver 2.0 
I have read the protocol described above. I agree to comply with all applicable regulations 
and to conduct the study as described in the protocol.  
 
 
 
Signed: 
 
 
Date:  
 
Dr Chrisopher Argent 
Principal Investigator 
Scientia Clinical Research Pty Ltd 
 
 

SAP_001.pdf: 
A Phase 1a, randomized, double-blind placebo-controlled study to evaluate safety and 
tolerability and to characterize the pharmacokinetic proﬁle of single ascending doses of 
fenretinide oral capsules in healthy adult volunteers 
NCT06181760 
SAP dated 07December2023 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Confidential 
Statistical Analysis Plan 
Sponsor: Island Pharmaceuticals Ltd 
Protocol Number: ISLA101-P01-CT001 
A Phase 1a, Randomized, Double-blind Placebo-controlled Study to 
Evaluate Safety and Tolerability and to Characterize the 
Pharmacokinetic Profile of Single Ascending Doses of Fenretinide 
Oral Capsules in Healthy Adult Volunteers 
Version: 
Final Version 1.0 
Date: 
2023-12-07 


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Version and Date: Version 1.0, 2023-12-07 
Page 2 of 37 
Confidential 
 
 
Statistical Analysis Plan 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
Signature Page 
 
 
 
 
 
 
Author: 
 
Name: Ella Liu 
Title: Senior Biostatistician 
Company: Resolutum Global 
 
 
 
 
 
 
 
 
Approved by: 
 
Name: Teresa M. Byrne 
Title: VP, Clinical Development 
Company: Island Pharmaceuticals Ltd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
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Confidential 
 
 
 
 
Statistical Analysis Plan 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
Table of Contents 
1. 
INTRODUCTION ...................................................................................................................... 5 
1.1 
Rationale .................................................................................................................................. 5 
2. 
SUMMARY OF THE PROTOCOL ........................................................................................... 5 
2.1 
Study Objectives ...................................................................................................................... 5 
2.1.1 
Primary Objective ..................................................................................................................... 5 
2.1.2 
Secondary Objectives .............................................................................................................. 5 
2.1.3 
Exploratory Objective ............................................................................................................... 5 
2.2 
Study Endpoints ....................................................................................................................... 6 
2.2.1 
Primary Endpoints .................................................................................................................... 6 
2.2.2 
Secondary Endpoints ............................................................................................................... 6 
2.2.3 
Exploratory Endpoints .............................................................................................................. 6 
2.3 
Study Design ............................................................................................................................ 6 
2.4 
Sample Size Determination ...................................................................................................... 7 
2.5 
Schedule of Assessments ........................................................................................................ 7 
3. 
ANALYSIS POPULATIONS .................................................................................................. 10 
3.1 
Safety Population ................................................................................................................... 10 
3.2 
Pharmacokinetic (PK) Population ........................................................................................... 10 
3.3 
Analysis of Subgroups ........................................................................................................... 10 
4. 
STUDY MEASURES .............................................................................................................. 10 
4.1 
Safety Measures .................................................................................................................... 10 
4.1.1 
Exposure to Study Drug ......................................................................................................... 10 
4.1.2 
Adverse Events ...................................................................................................................... 11 
4.1.3 
Laboratory Evaluations ........................................................................................................... 11 
4.1.4 
Vital Signs Evaluations ........................................................................................................... 13 
4.1.5 
12-lead ECG Evaluations ....................................................................................................... 13 
4.1.6 
Physical Examination ............................................................................................................. 13 
4.2 
Pharmacokinetic Concentrations ............................................................................................ 14 
4.3 
Pharmacokinetic Parameters ................................................................................................. 15 
4.4 
Baseline Characteristics and Other Measures ....................................................................... 16 
4.4.1 
Subject Disposition ................................................................................................................. 16 
4.4.2 
Protocol Deviations and Eligibility........................................................................................... 16 
4.4.3 
Demographics ........................................................................................................................ 17 
4.4.4 
Baseline Subject Characteristics ............................................................................................ 17 
4.4.5 
Medical and surgical History .................................................................................................. 17 
4.4.6 
Prior and Concomitant Medications ....................................................................................... 18 
4.4.7 
Assignment to Treatment ....................................................................................................... 18 
5. 
STATISTICAL METHODOLOGY .......................................................................................... 18 
5.1 
General Statistical Methods ................................................................................................... 18 
5.1.1 
Software ................................................................................................................................. 18 
5.1.2 
Definitions .............................................................................................................................. 18 
5.1.3 
Default Descriptive Statistics and Data Presentation Rules ................................................... 19 
5.1.4 
Date and Time Display Conventions ...................................................................................... 19 
5.1.5 
General Display Conventions ................................................................................................. 20 
5.2 
Hypotheses and Decision Rules ............................................................................................ 21 
5.3 
Multiple Comparisons and Adjustments for Multiplicity .......................................................... 21 
5.4 
Covariates .............................................................................................................................. 21 
5.5 
Multi-Centre Data ................................................................................................................... 21 
5.6 
Handling of Missing Data ....................................................................................................... 21 
5.6.1 
Efficacy Endpoints .................................................................................................................. 21 
5.6.2 
Safety Endpoints .................................................................................................................... 21 
5.7 
Windowing Conventions ......................................................................................................... 22 
5.8 
Interim Analyses ..................................................................................................................... 22 


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Confidential 
 
 
 
 
Statistical Analysis Plan 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
5.9 
Clinical Data Interchange Standards Consortium (CDISC) Specifications ............................. 22 
6. 
STATISTICAL ANALYSES ................................................................................................... 22 
6.1 
Subject Disposition and Analysis Sets ................................................................................... 23 
6.2 
Protocol Deviations and Eligibility........................................................................................... 23 
6.3 
Demographic .......................................................................................................................... 23 
6.4 
Baseline Subject Characteristics ............................................................................................ 23 
6.5 
Medical and Surgical History .................................................................................................. 23 
6.6 
Prior and Concomitant Medication ......................................................................................... 24 
6.7 
Efficacy Analyses ................................................................................................................... 24 
6.8 
Safety Analyses ..................................................................................................................... 24 
6.8.1 
Exposure to Study Drug ......................................................................................................... 24 
6.8.2 
Adverse Events ...................................................................................................................... 24 
6.8.3 
Laboratory Parameters ........................................................................................................... 26 
6.8.4 
Vital Signs .............................................................................................................................. 26 
6.8.5 
12-lead ECG Evaluations ....................................................................................................... 26 
6.8.6 
Physical Examination ............................................................................................................. 27 
6.9 
Pharmacokinetic Analyses ..................................................................................................... 27 
6.9.1 
Plasma Concentrations .......................................................................................................... 27 
6.9.2 
Pharmacokinetic Parameters ................................................................................................. 27 
7. 
CHANGES TO THE PLANNED ANALYSES ........................................................................ 28 
7.1 
Changes to the Analyses Described in the Study Protocol and Protocol Amendments ......... 28 
7.2 
Changes from the Statistical Analysis Plan Version x.x to Version x.x .................................. 28 
8. 
REFERENCES ....................................................................................................................... 29 
9. 
ATTACHMENTS AND APPENDICES ................................................................................... 30 
Appendix 1 
Dose Proportionality Analysis SAS® Code ................................................................. 30 
Appendix 2 
Food Effect Analysis SAS® Code ............................................................................... 31 
ATTACHMENT 1 
LIST OF TABLES, LISTINGS AND FIGURES ..................................................... 32 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
1. 
Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the methodology that will be followed 
in the analysis of the data that were collected for the Island Pharmaceuticals Ltd, ISLA101-P01-CT001 
study. 
This SAP is based on assessments and methods described in the study Protocol Amendment Version 
1, dated 18 October 2023. The SAP contains a complete and detailed specification of the statistical 
analyses that will be performed. 
All analyses described in this document will be conducted in accordance with Resolutum Global’s 
standard operating procedures (SOPs). 
 
1.1 
Rationale 
An estimated 3.9 billion people in more than 125 countries are at risk of dengue fever, with 
approximately 390 million infections occurring annually. These infections lead about 500,000 persons 
to require hospitalization due to dengue each year, and about 20,000 deaths occur due to severe 
dengue every year (WHO, 2018). Dengue is a mosquito-borne infection caused by the dengue virus 
(DENV) and is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban 
areas. The severe form of the disease is a leading cause of serious illness and death in some Asian 
and Latin American countries (WHO, 2021). Importantly, there is no specific treatment for dengue 
infection. 
Dengue prevention and control is based on vector control measures, which require sustained 
community involvement and usually are not highly effective in preventing disease transmission. In view 
of the current situation, there is an unmet medical need for therapies focusing on the prophylaxis of 
dengue infection, aiming to minimize viral transmission in endemic areas. To answer to this need, Island 
Pharmaceuticals Ltd is developing the ISLA101 product, an immediate-release oral capsule of 
fenretinide (100 mg), for the prophylaxis of dengue fever. ISLA101 is an oral capsule formulation of 
fenretinide. Island plans to submit a New Drug Application (NDA) for ISLA101 for the prophylaxis of 
dengue fever via the 505(b)(2) regulatory pathway. 
This study is a randomized, double-blind, placebo-controlled single ascending dose (SAD) study in 
healthy subjects and is considered appropriate to evaluate the safety, tolerability, and PK of ISLA101. 
Single ascending doses of ISLA or placebo will be administered under fasting conditions, and safety 
and tolerability data will be evaluated in each cohort to guide doses administered to future cohorts. The 
highest tolerated dose will also be administered under fed conditions to assess any potential food effect 
(in a crossover manner). 
 
2. 
Summary of the Protocol 
2.1 
Study Objectives 
2.1.1 
Primary Objective 
The primary objective of the study is to evaluate the safety and tolerability of single ascending doses 
(SAD) of ISLA101 in healthy adult volunteers (fasted). 
 
2.1.2 
Secondary Objectives 
The secondary objective of the study is to characterize the pharmacokinetic (PK) profile (fasted) of 
fenretinide and its metabolites after administration of SAD of ISLA101 in healthy adult volunteers 
(fasted). 
 
2.1.3 
Exploratory Objective 
The exploratory objective of the study is to assess the PK profile of fenretinide and its metabolites in 
healthy adult volunteers under fed conditions. 


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Confidential 
 
 
 
 
Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
2.2 
Study Endpoints 
2.2.1 
Primary Endpoints 
The primary endpoints are: 
• 
Vital Signs, clinical laboratory tests, changes from baseline in physical examinations, adverse 
events (AEs) and treatment-emergent adverse events (TEAEs). 
 
2.2.2 
Secondary Endpoints 
The secondary endpoints are: 
• 
Single dose PK parameters for fenretinide and its metabolites in plasma: Maximum plasma 
concentration (Cmax), Time to Cmax (tmax), Area under the curve from time 0 to infinity (AUCinf), 
Area under the curve to the last concentration (AUClast), Terminal half-life (T½) and others as 
relevant. 
 
2.2.3 
Exploratory Endpoints 
The exploratory endpoints are: 
• 
Single dose PK parameters for fenretinide and its metabolites in plasma under fed conditions: 
Maximum plasma concentration (Cmax), Time to Cmax (tmax), Area under the curve from time 0 to 
infinity (AUCinf), Area under the curve to the last concentration (AUClast), Terminal half-life (T½) 
and others as relevant. 
 
2.3 
Study Design 
The study is a randomized, double-blind, placebo-controlled single ascending dose (SAD) study of 
ISLA101 (fenretinide oral capsules) to evaluate safety, tolerability, and pharmacokinetics in healthy 
human subjects. The study will consist of up to 4 cohorts that will evaluate dose levels of 300 mg/m2 
(fasted), 600 mg/m2 (fasted), and 900 mg/m2 (fasted). The highest tolerated dose level cohort will then 
be evaluated in a fed condition (in a crossover manner). Eight subjects will be enrolled per dose cohort, 
with 6 subjects receiving active drug and 2 subjects receiving placebo treatment in a blinded manner. 
Each subject will be allocated to 1 dose level only. 
After completing screening activities, eligible subjects will enter the clinical research unit (CRU) on Day 
-1 for 5 days. Subjects will receive a single dose of study drug in the morning of Day 1 after an overnight 
fast of approximately 10 hours, followed by additional 4 hours fast after dose for PK sampling. Cohorts 
1 through 3 will receive 300 mg/m2, 600 mg/m2, and 900 mg/m2, respectively, under fasted conditions. 
After the safety review by the independent safety review committee (SRC), the dose level can be 
escalated to the planned or lower than planned dose level or de-escalated to an intermediate dose 
level. Decisions to proceed to the next cohort will be made by the Investigator, SRC, and Sponsor based 
on the safety data from previous cohort(s). 
Safety data will be reviewed to identify the cohort that received the highest dose level under fasted 
condition. The subjects in this cohort will be recalled to evaluate the PK of ISLA101 under fed conditions 
(8 subjects; Cohort 4). In Cohort 4, subjects will fast for approximately 10 hours overnight and will 
consume a high-fat, high-calorie meal approximately 30 minutes prior to administration of study drug. 
No food consumption will be permitted for at least 4 hours post-dose. 
For all cohorts, study drug will be taken with up to 240 mL of water. In fasted cohorts, water will be 
allowed ad libitum except the interval from 1 hour before to 1 hour after the dose. In the fed cohort, 
water will be allowed ad libitum except the interval from 10 minutes before to 1 hour after dose. 
Subjects will be discharged from the clinic on Day 5. At the discretion of the Investigator or designee, 
the confinement time can be extended to ensure the safety of each subject. Subjects will have up to 3 
days of follow up. For Cohort 4 (the food effect cohort), the confinement and follow-up visit will be 
repeated. Subjects who are dosed but withdrawn prior to study completion will participate in an Early 
Termination visit and may be replaced if needed to obtain sufficient information as possible based on 
the timing. 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
In all cohorts, safety will be assessed via vital signs, clinical laboratory tests, physical examinations, 
AEs, and TEAEs. Pharmacokinetic data will be collected and analyzed at the end of the study but will 
not be used for dose escalation decisions. 
 
2.4 
Sample Size Determination 
No formal sample size calculation was performed. The study is considered exploratory with a sample 
size of 8 subjects per cohort (2 placebo + 6 active). This cohort size and active/placebo ratio are 
considered standard to evaluate safety profile and to provide sufficient PK information for future 
development of the compound. 
 
2.5 
Schedule of Assessments 
Table 1 presents the schedule of study events. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 1 
Study Procedures and Assessment to Dose Under Fasted (Cohort 1-3) and Fed Condition (Cohort 4) 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
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 Protocol Number: ISLA101-P01-CT001 
 
 
 
 
 


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Statistical Analysis Plan 
 
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 Protocol Number: ISLA101-P01-CT001 
 
 
3. 
Analysis Populations 
Two (2) different analysis populations will be defined: 
• 
Safety Population 
• 
Pharmacokinetic (PK) Population 
The criteria for exclusion from each analysis set will be described in the following sections. 
 
3.1 
Safety Population 
This Safety Population will include all subjects who received at least 1 dose of study drug (active and 
placebo). 
The following is reason for exclusion from the Safety Population: 
• 
Subjects did not receive at least one dose of study drug. 
The Safety Population will be used for all baseline characteristics, disposition and safety analyses and 
will be based on actual treatment received if different from randomized treatment. 
 
3.2 
Pharmacokinetic (PK) Population 
The Pharmacokinetic (PK) Population will consist of all subjects in the safety population who received 
at least one dose of ISLA101 and have a pre-dose PK sample and at least 1 post-dose analyzable PK 
sample (quantifiable Plasma concentration). 
The following are reasons for exclusion from the PK Population: 
• 
Subjects did not receive at least one dose of the ISLA101. 
• 
Subjects did not have at least one quantifiable plasma fenretinide concentration. 
Subjects will be analyzed according to the treatment they actually receive if this differs from that to 
which the subject was randomized. Adverse events (e.g., vomiting within 2 hours of dose), protocol 
deviations or dosing or sampling issues which may potentially impact PK will be assessed on a subject- 
by-subject basis. 
Subjects with sufficient PK concentrations of fenretinide to allow determination of at least 1 PK 
parameter from (Cmax or AUC) will be included in the PK parameters evaluations. 
 
3.3 
Analysis of Subgroups 
No subgroup analyses are planned for this study. 
 
4. 
Study Measures 
This section describes the measures that were collected and/or derived during the study at the time 
points specified in the Schedule of Assessments (Section 2.5). 
 
4.1 
Safety Measures 
The safety endpoints described in this section will be analyzed according to the analysis methods 
described in Section 6.8. 
 
4.1.1 
Exposure to Study Drug 
Study drug administration information, including treatment administered (Yes/No), the date/time of last 
meal, high fat meal taken before dosing (Yes/No), the date/time of high meal consumed, the date/time 
 
 
 


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 Protocol Number: ISLA101-P01-CT001 
 
 
of the first capsule consumed, the dosage, the capsule administration quantity, the completion of all 
administered (Yes/No), the subject fasting for at least 4 hours post-study drug administration (Yes/No) 
and the calculated body surface area (BSA), will be reported on the ‘Study Drug Administration’ eCRF. 
 
4.1.2 
Adverse Events 
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing 
medical condition, regardless of whether it is considered casually related to the study treatment. 
Adverse events data will be collected and recorded on the ‘Adverse Events’ eCRF from the time that 
informed consent was given and throughout the duration of the study. 
Missing and partial AE dates will be handled according to the rules specified in Sections 5.1.4 and 5.6.2. 
 
4.1.2.1 
Adverse Event Definitions 
Treatment-emergent AEs (TEAEs) are defined as AEs occurring or worsening after the first 
administration of the study drug. If only partial information is available, the rules specified in Section 
5.6.2 will be applied to determine treatment emergence. 
Treatment-related AEs are defined as AEs where the relationship to study drug was reported as 
‘Possibly’, ‘Probably” or ‘Definitely” Related or where the relationship is missing. 
Serious AEs (SAEs) are defined as AEs where the events are reported as serious. 
Severe AEs are defined as AEs where the event severity rating is reported as ‘Severe’. 
Adverse events leading to study drug discontinuation are defined as AEs where the action taken with 
study drug is reported as ‘Drug Withdrawn’. 
Adverse events leading to study discontinuation are defined as AEs where ‘Other’ action taken is 
reported as ‘Withdrawn from study’. 
 
4.1.2.2 
Coding of Adverse Event Terms 
Adverse event terms (Investigator terms) will be coded to a lowest level term (LLT), preferred term (PT), 
high level term (HLT), high level group term (HLGT) and a system organ class (SOC) according to the 
Medical Dictionary for Regulatory Activities (MedDRA) dictionary, Version 26.1 or later, depending on 
the latest version available during the study. 
 
4.1.3 
Laboratory Evaluations 
Laboratory evaluations will be performed in accordance with the Schedule of Study Assessments 
(Section 2.5). Blood and urine samples will be collected and analyzed by a local laboratory and the 
results of urinalysis will be reported on the ‘Dipstick Urinalysis and Microscopy’ eCRF and the result of 
hematology, coagulation, chemistry and microscopy will be provided in electronic format from the 
analyzing laboratory. 
If the results for a specific laboratory test are not required by the study protocol (for example, only one 
subject has data for a specific test that was performed in error) or for urine microscopy tests that were 
only required in the presence of abnormal urinalysis results, the results will not be included in the 
summary tables, but the data will be listed. 
The test panels and parameters presented in Table 2 will be collected and analyzed. 
Parameter names will be based on the Clinical Data Interchange Standards Consortium (CDISC) Study 
Data Tabulation Model (SDTM) Controlled Terminology terms. The mapping of the reported parameter 
names to the standardized names will be presented in the SDTM specifications. Parameters will be 
sorted alphabetically. 
 
 
 
 
 


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Statistical Analysis Plan 
 
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 Protocol Number: ISLA101-P01-CT001 
 
 
If the results for a parameter were reported in different units, the results (including the actual 
measurement and the normal range limits) will be converted to the Système International (S.I.) unit for 
the specific parameter and the standardized results/units will be reported. The specific conversion rules 
will be documented in the SDTM specifications. 
Quantitative laboratory measurements reported as ‘< X’, i.e., below the lower limit of quantification 
(BLQ), or ‘> X’, i.e., above the upper limit of quantification (ULQ), will be converted to X for the purpose 
of quantitative summaries, but will be presented as recorded, i.e., as ‘<X’ or ‘>X’ in the listing. Any 
conversion rules that are applied will be highlighted in the footnotes of the affected tables and listings. 
Where applicable, parameter names in the outputs will be comprised of the test name and the 
standardized unit of measure (if applicable), for example, ‘Albumin (g/L)’. If a specific test is qualitative 
or unitless, the parameter name will be the test name only. 
For all parameters where a normal range limit value was reported, the normal range will be derived 
based on the available lower and upper limit values and any reported mathematical symbols. If both a 
lower and upper limit value is available, the normal range will be presented as ‘(Lower, Upper)’. If the 
event that only one of the limit values exist, ‘N/A’ will be used to replace the ‘missing’ limit value (for 
example, ‘(N/A, Upper)’), unless a direction has been specified, in which case the normal range will be 
displayed as ‘(< or > Limit)’. 
Quantitative parameter results will be classified as being ‘Low’ or ‘High’ depending on whether the result 
is below or above the normal range limits provided by the analyzing laboratory. 
Baseline and change from baseline values will be derived for each parameter (as appropriate) in 
accordance with the methods defined in Section 5.1.2. 
Table 2   Laboratory Assessments 
 
Hematology: 
Clinical Chemistry: 
Urinalysis (dipstick) 
Platelet count 
ALT (Alanine aminotransferase) 
Specific gravity 
Red blood cell count (RBC) 
Albumin 
pH 
Hemoglobin 
ALP (Alkaline phosphatase) 
Clarity 
Hematocrit 
AST (Aspartate aminotransferase) 
Color 
White Blood Cell (WBC) 
count 
Blood urea nitrogen (BUN) 
Calcium 
Glucose 
Protein 
with Differential: 
Carbon dioxide (CO2) 
Blood 
Basophils (% and Absolute) 
Chloride 
Leukocytes Esterase 
Eosinophils (% and Absolute) 
Creatinine 
Bilirubin 
Lymphocytes (% and 
Absolute) 
Monocytes (% and Absolute) 
Neutrophils (% and Absolute) 
Glucose 
Inorganic phosphorus 
Magnesium 
Potassium 
Ketones 
Nitrites 
Microscopy (if applicable) 
Urinary sediment 
Sodium 
WBC (White blood cells) 
Total bilirubin 
RBC (Red blood cells) 
Total Protein 
Casts 
Coagulation 
Uric acid 
Crystals 
Prothrombin time (PT) 
Epithelial cells 
International normalized ratio 
(INR) 
Bacteria 
 
 
 
 


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 Protocol Number: ISLA101-P01-CT001 
 
4.1.4 
Vital Signs Evaluations 
Vital signs will be performed according to the schedule of assessment (Section 2.5). 
The following parameters will be assessed, and measurements and findings will be reported on the 
‘Vital Signs’ eCRF: 
• 
Systolic blood pressure (SBP) (mmHg). 
• 
Diastolic blood pressure (DBP) (mmHg). 
• 
Pulse rate (beats/min). 
• 
Respiratory Rate (breaths/min) 
• 
Temperature (°C) 
• 
Height (cm) (Screening only) 
• 
Body Weight (kg) (Screening only) 
• 
Body Mass Index (kg/m2) (Screening only) 
• 
Body Surface Area (BSA) (m2) 
Baseline and change from baseline values will be derived for each parameter (as appropriate) in 
accordance with the methods defined in Section 5.1.2 
 
4.1.5 
12-lead ECG Evaluations 
Triplicate and single 12-lead ECG recordings will be performed according to the schedule of 
assessments (Section 2.5). 
The following parameters will be assessed, and measurements and findings will be reported on the ’12- 
lead Electrocardiogram’ eCRF: 
• 
Heart Rate (beats/min) 
• 
RR Interval (msec) 
• 
QTcF Interval (msec). 
• 
PR Interval (msec). 
• 
QRS Duration (msec). 
• 
Overall Assessment (‘Normal’, ‘Abnormal Not Clinically Significant [NCS]’ or ‘Abnormal 
Clinically Significant [CS]’). 
Baseline and change from baseline values will be derived for each parameter (as appropriate) in 
accordance with the methods defined in Section 5.1.2. 
 
4.1.6 
Physical Examination 
Complete physical examinations will be performed in accordance with the schedule of assessments 
(Section 2.5). 
The following body systems will be assessed as part of the physical examination findings and clinical 
significance as assessed by the investigator (‘Normal’, ‘Abnormal NCS’, ‘Abnormal CS’ including 
specification of any abnormalities observed) will be recorded on the ‘Physical Examination’ eCRF: 
• 
General appearance 
• 
Head, ears, eyes, nose, and throat 
 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
• 
Neck and thyroid 
• 
Lymph nodes 
• 
Cardiovascular system 
• 
Respiratory System 
• 
Gastrointestinal system 
• 
Renal system 
• 
Neurological system 
• 
Musculoskeletal system 
• 
Skin 
• 
Other 
 
4.2 
Pharmacokinetic Concentrations 
Plasma PK samples will be collected at the time points specified in the schedule of assessments 
(Section 2.5) and Table 3. The PK samples from pre-dose to 96 hours post dose will be considered. 
The actual sample collection dates and times will be reported on the ‘PK Blood Sample Collection’ 
eCRF. 
Table 3   Study Schedule and Sampling Time Points for Pharmacokinetic Analysis 
The actual elapsed time (hours) from the reference study drug administration will be calculated as the 
difference between the actual date time of the sample collection at the nominal time point and the date 
time of the study drug administration for the specific period. 
The time deviation at each time point (minutes), defined as the difference between the nominal 
(planned) and actual collection times will be calculated as the difference between the nominal collection 
time point value (i.e., 2 hours post-dose will be 2 hours). 
For pre-dose visit, the actual elapsed time from the reference study drug administration and the time 
deviation will be presented as ‘- ‘. 
Deviations from the collection time points will be used to identify out of window samples that may be 
excluded from the PK analysis (and PK parameter derivation) if deemed to have a major impact on the 
overall analysis. 
 
 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
The plasma concentrations of fenretinide and its metabolites N-(4-methoxyphenyl) retinamide (MPR) 
and 4-oxo-N-(4-hydroxyphenyl) retinamide (oxo-HPR) will be determined using a validated analytical 
procedure. Specifics about the analytical method will be provided in the bioanalysis report. 
Concentrations data will be provided electronically by the analyzing laboratory. 
Concentrations that are below limit of quantification (BLQ) prior to the first measurable concentration 
will be set to zero for all calculation and analyses. BLQ concentrations observed after the first 
measurable concentration will be treated as missing. In addition to statistical descriptors, number of 
BLQ concentrations will be presented in the summary for each treatment and time point. 
 
4.3 
Pharmacokinetic Parameters 
The PK parameters described in this section will be derived based on the plasma concentration-time 
profiles of fenretinide, MPR and oxo-HPR as observed after the study drug administrations on Day 1 
for Cohort 1-3 and Day 10 for Cohort 4 if the data permits using actual timepoints for PK samples. The 
parameters will be calculated separately for each cohort based on concentrations collected during the 
specific period. 
The PK concentrations will be processed using standard noncompartmental analytical procedures to 
derive the required parameters. The software used for the analysis will be Phoenix™ WinNonlin® v8.4.0 
or greater (Certara, Princeton NJ, USA). Extravascular plasma model with linear up log down 
trapezoidal rule will be utilized. 
The PK parameters described in Table 4 will be derived for the analytes (fenretinide, MPR and oxo- 
HPR) provided that the required concentration data are available. Supporting PK parameters (used to 
derive or assess the validity of λz and associated parameters) which include Adjusted R2, number of 
points for estimation of λz or Kel , %AUCextrap and span (ratio of time interval to estimate λz to t1/2) will only 
be listed and not included in the summary tables. %AUCextrap < 20% will be used to validate AUCinf and 
parameters derived from AUCinf. 
 
Table 4   Plasma PK Parameters 
 
Parameter 
Definition 
Cmax 
Maximum concentration which is directly determined from the plasma 
concentration-time profiles. 
Tmax 
Time to maximum observed plasma concentration. If the same Cmax 
concentration occurs at different time points, Tmax is assigned to the first 
occurrence of Cmax. 
AUCinf 
The area under the plasma concentration-time curve from time 0 (time of 
dosing) extrapolated to infinity. AUCinf is calculated as the sum of AUClast plus 
the ratio of the last measurable plasma concentration (Clast) to the elimination 
rate constant (λz), calculated by ‘the linear up and log down’ method. 
AUClast 
Area under the drug concentration-time curve, from time 0 (time of dosing) to 
the last measurable concentration. 
AUC0-24 
The area under the plasma concentration-time curve, from time 0 (time of 
dosing) to 24 hours, calculated by ‘the linear up and log down’ method. 
λz or kel 
Apparent terminal elimination rate constant calculated by linear regression of 
the terminal linear portion of the log concentration vs. time curve. 
T1/2 
Apparent plasma terminal half-life calculated as ln (2)/λz. 
CL/F 
Apparent total plasma clearance, using the following formula: 
Dose/AUCinf (Parent compound only). 
 
 
 


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 Protocol Number: ISLA101-P01-CT001 
 
 
Parameter 
Definition 
Vz/F 
Apparent volume of distribution, using the formula: 
CL/F/λz (Parent compound only). 
DN_Cmax 
Dose-normalised Cmax will be calculated by dividing Cmax by the total 
administered dose in mg (Cmax/Dose). 
DN_AUCinf 
Dose-normalised AUC0-inf will be calculated by dividing AUCinf by the total 
administered dose in mg (AUCinf /Dose). 
DN_AUClast 
Dose-normalised AUC0-last will be calculated by dividing AUClast by the total 
administered dose in mg (AUClast/Dose). 
Adjusted R2 (*) 
R-squared adjusted. 
No. of Points (*) 
Number of points for determination of λz. 
Span(*) 
Span = (λz upper – λz lower)/ t1/2 (h). 
AUC%extrap(*) 
The percentage of the AUC that has been extrapolated beyond the last 
observed data point, using the following formula, calculated by ‘the linear up 
and log down’ method 
Values for λz, t½, AUCinf, CL/F and Vz/F will not be reported for cases that do not exhibit an acceptable terminal log-linear phase 
in the concentration versus time profile. Additional pharmacokinetic parameters may be determined where appropriate. 
(*) Derived to determine t1/2, results will only be listed. 
λz and T1/2, will only be included in the summary statistics if the following criteria are met: 
• 
A minimum of 3 measurable concentration-time points is available during log-linear portion of the 
terminal elimination phase (excluding Cmax), i.e., No. of Points is ≥ 3. 
• 
Adjusted R2 > 0.80. 
AUCinf , CL/F and Vz/F will only be included in the summary statistics if the following criterion is met: 
• 
%AUCextrap < 20%. 
• 
Span ≥ 2 
 
4.4 
Baseline Characteristics and Other Measures 
4.4.1 
Subject Disposition 
Subject disposition data will be collected on the ‘End of Study Participation’ eCRF when a subject 
completed or early terminated the study. 
The following data will also be presented in the disposition listing: 
• 
Date of informed consent (‘Informed Consent’ eCRF), 
• 
Date/time of the first study drug administrations (‘Study Drug Administration’ eCRF.) 
The number of subjects included in the analysis sets defined in Section 3 will be summarized and 
presented as part of the subject disposition data. 
 
4.4.2 
Protocol Deviations and Eligibility 
Protocol deviations will be reported on the ‘Protocol Deviation’ eCRF. 
Protocol deviations will be grouped by deviation grade (minor/major), deviation term, assessment type, 
and a description of the deviation will also be noted. 
Eligibility will be reported on the ‘Eligibility Confirmation’ eCRF. 
 
 
 


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Statistical Analysis Plan 
 
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The eligibility of all subjects for entry into the study will be assessed at Screening and Day -1 (For 
Cohort 1-3)/Day 9 (for Cohort 4). A subject should have met all the inclusion, and none of the exclusion 
criteria before entry into the study. 
 
4.4.3 
Demographics 
Demographic information provides data about the subjects and is necessary to determine whether the 
individuals in the study are a representative sample of the target population. 
The following demographic data will be collected on the ‘Demography’ eCRF at Screening. 
• 
Year of birth 
• 
Age (Years) 
• 
Sex (‘Male’, ‘Female’) 
• 
Childbearing Potential (Yes/No) -If yes, the menopausal status 
• 
Ethnicity (‘Hispanic or Latino’, ‘Not Hispanic or Latino’, ‘Not Reported’, ‘Unknown’) 
• 
Race: 
o 
‘White’ 
o 
‘Black or African American’ 
o 
‘Asian’ 
o 
‘American Indian or Alaska Native’ 
o 
‘Native Hawaiian or Other Pacific Islander’ 
o 
‘Other’ 
o 
‘Not Reported’ 
o 
‘Unknown’ 
4.4.4 
Baseline Subject Characteristics 
Baseline subject characteristics include characteristics that subjects presented with prior to the 
administration of study drug. 
The following subject characteristics will be collected on the ‘Vital Signs’ eCRF at Screening (for 
Cohort1-3) and on Day 9 (for Cohort 4): 
• 
Height (cm) 
• 
Body Weight (kg) 
• 
Body Mass Index (BMI) (kg/m2) 
The following other baseline data will also be collected: 
• 
Alcohol Breath Test (‘Alcohol Breath Test’ eCRF) 
• 
Pregnancy Test (‘Pregnancy Test’ eCRF) 
• 
Serology – hepatitis B surface antigen, hepatitis C antibody titer, and HIV (‘Serology’ eCRF) 
• 
Urine Drug Screen (‘Urine Drug Test’ eCRF) 
 
4.4.5 
Medical and surgical History 
Medical history is information about conditions that a subject might have suffered from prior to the 
administration of study drug, or conditions that were ongoing at the time of the administration of study 
drug. 
Medical and surgical history data will be collected on the ‘Medical and Surgical History’ eCRF. 
 
 
 
 
 


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4.4.5.1 
Coding of Medical History Terms 
Medical and surgical history terms (Investigator terms) will be coded to a lowest level term (LLT), 
preferred term (PT), high level term (HLT), high level group term (HLGT) and a system organ class 
(SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA) dictionary, Version 26 or 
later, depending on the latest version available during the study. 
 
4.4.6 
Prior and Concomitant Medications 
Prior and concomitant medications/vaccinations data will be collected throughout the study on the ‘Prior 
and Concomitant Medications’ eCRF. 
Missing and partial concomitant medications dates will be handled according to the rules specified in 
Sections 5.1.4 and 5.6.2. 
 
4.4.6.1 
Medication Definitions 
Prior medications are defined as any medication where the use was stopped prior to the first 
administration of study drug. 
Concomitant medications are defined as any medication (other than the study drug) that was used at 
least once after the first administration of study drug. Medications stopping on the same day as the first 
study drug administration will be considered as concomitant medications. 
 
4.4.6.2 
Coding of Medication Terms 
Prior and concomitant medication terms will be coded to an anatomical therapeutic chemical (ATC) 
class term (Level 2) and a preferred medication name based on the active drug substance using the 
World Health Organization-Drug Dictionary (WHO-DD), Version Global C3, Sep 2023. 
 
4.4.7 
Assignment to Treatment 
Subjects will be randomized to a treatment and the randomization number will be reported on the 
‘Randomization’ eCRF. The randomization information collected on the ‘Randomization’ eCRF will be 
listed. 
 
5. 
Statistical Methodology 
5.1 
General Statistical Methods 
5.1.1 
Software 
All analysis data sets and outputs will be produced by the Biostatistics Department of Resolutum Global 
using the SAS® Version 9.4 (SAS Institute, Cary, North Carolina, USA) or higher. 
The pharmacokinetic concentrations will be processed using standard noncompartmental analytical 
procedures to derive the required parameters. The software used for the analysis will be Phoenix™ 
WinNonlin® v8.4.0 or greater (Certara, Princeton NJ, USA). 
 
5.1.2 
Definitions 
The following definitions will be used: 
• 
Date of the First Study Drug Administration: The date of the first study drug administration is 
defined as the earliest date on which study drug was administered as reported on the ‘Study 
Drug Administration’ eCRF. 
• 
Baseline: The baseline value is defined as the last available valid assessment collected prior 
to the first study drug administration. Repeat and unscheduled assessments will be included in 
 
 
 


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the derivation of the baseline values. Results including, but not limited to, ‘Not done’, ‘Not 
applicable’, ‘Unknown’ will not be included in the baseline derivations. 
Baseline calculation for the ECG parameters will be based on the mean value of the triplicate 
ECG reading at baseline visit for Cohort 1-3. 
• 
Change from Baseline: The change from baseline value is defined as the difference between 
the result collected/derived at a post-baseline visit and the baseline value (for that specific 
period for changes from the baseline values). 
The change from baseline value at each post-baseline visit will be calculated for all continuous 
parameters using the following formula: 
Change from Baseline Value = Result at Post-Baseline Visit – Baseline Value 
The change from baseline value will only be calculated if the specific post-baseline result and 
the baseline value for the parameter are both available and will be treated as missing otherwise. 
In the data listings, the change values will be set to ‘-’ (not applicable) for pre-baseline 
assessments. 
• 
Study Day: The study day of an event is defined as the relative day of the event starting with 
the date of the first study drug administration (reference date) as Day 1 (there will be no Day 
0). 
The study day of events occurring before the study drug administration will be calculated as: 
Study Day = (Date of Event - Date of Study Drug Administration) 
For events occurring on or after Day 1, study day will be calculated as: 
Study Day = (Date of Event - Date of Study Drug Administration) + 1 
Study days will only be calculated for events with complete dates and will be undefined 
otherwise. 
 
5.1.3 
Default Descriptive Statistics and Data Presentation Rules 
Unless otherwise stated, summary statistics including the number of subjects, mean, standard 
deviation, median, minimum, and maximum, will be presented for all continuous variables. Minimum 
and maximum values will be presented to the same decimal precision as the raw values, the mean and 
median values to one more and the standard deviation values to two more than the raw values. Derived 
values (including descriptive statistics) will be presented to a maximum of 4 significant decimals. 
For categorical variables, per category, the absolute counts (n) and percentages (%) of subjects with 
data, and if appropriate, the number of subjects with missing data, will be presented. Unless specifically 
stated otherwise, denominator for all percentage calculations will be the number of subjects in the 
specific treatment group and analysis set. All percentages will be presented to one decimal place except 
for 100%. Where a count is zero, the percentage will not be shown (e.g., 0 (0.0%) will be displayed as 
0). 
If required, results will be rounded using the SAS® function ROUND. Values will be rounded after all 
calculations have been performed. 
 
5.1.4 
Date and Time Display Conventions 
The following display conventions will be applied in all outputs where dates and/or times are displayed: 
• 
Date only: YYYY-MM-DD 
• 
Date and time: YYYY-MM-DD HH:MM 
If only partial information is available, unknown components of the date or time will not be presented, 
for example if only the year is known, ‘2016’. Times will be reported using a 24-hour clock. 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
5.1.5 
General Display Conventions 
All data collected during the study (data originating from the eCRFs or electronic transfers), except for 
screen failure data, will be presented in the data listings. Event-based listings will be sorted by cohort, 
treatment group, subject number and event start and end dates. Assessment-based listings will be 
sorted by cohort, treatment group, subject number, parameter name (alphabetically unless specifically 
stated otherwise), visit and time point (if applicable). 
Fields that are missing because they are not applicable for the subject/time point (for example change 
from baseline results at the baseline visit) will be presented as “-”, unless otherwise specified. Missing 
data points will be presented as blank fields in the data listings. 
All summary tables will be presented by the treatment group. Assessment-based tables will be sorted 
alphabetically by parameter (unless specifically stated otherwise) and chronologically by visits/time 
point within parameter. Only values collected at scheduled study visits/time points will be presented in 
summary tables. Event-based tables will be ordered as specified in Section 6. 
Treatment groups will be presented based on increasing dose levels of ISLA101 followed by a pooled 
Placebo groups and an All-Subjects group (only for the baseline tables). 
Tables 5,6, and 7 present the treatment group, and visit labels that will be used in the tables, listings, 
and figures (TLFs). 
Table 5   Study Treatments – Tables and Figures 
 
Cohort: Actual Treatment 
Treatment Label 
Cohort 1: ISLA101 300 mg Fasted 
ISLA101 300 mg Fasted 
Cohort 2: ISLA101 600 mg Fasted 
ISLA101 600 mg Fasted 
Cohort 3: ISLA101 900 mg Fasted 
ISLA101 900 mg Fasted 
Cohort 4: ISLA101 TBD* mg Fed 
ISLA101 TBD* mg Fed 
Cohort x/4: ISLA101 TBD* mg 
ISLA101 TBD* mg Fasted/Fed 
Cohort 1-3: Placebo 
Pooled Placebo 
Cohort 4: Placebo (Fasted) 
Placebo (Fasted) 
Cohort 4: Placebo (Fed) 
Placebo (Fed) 
Cohort 1-3 
All Subjects 
*One of the Cohort 1 to 3 Subjects (the highest tolerated dose-level cohort) will return 
for additional dose to determine the effect of food. Subjects participating in Cohort 4, the 
food effect cohort, will maintain the same treatment assignment from their fasted cohort. 
Table 6   Study Treatments – Listings 
 
Cohort: Actual Treatment 
Treatment Label 
Cohort 1: ISLA101 300 mg Fasted 
Cohort 1: ISLA101 300 mg Fasted 
Cohort 1: Placebo 
Cohort 1: Placebo Fasted 
Cohort 2: ISLA101 600 mg Fasted 
Cohort 2: ISLA101 600 mg Fasted 
Cohort 2: Placebo 
Cohort 2: Placebo Fasted 
Cohort 3: ISLA101 900 mg Fasted 
Cohort 3: ISLA101 900 mg Fasted 
Cohort 3: Placebo 
Cohort 3: Placebo Fasted 
Cohort 4: ISLA101 TBD* mg Fed 
Cohort 4: ISLA101 TBD* mg Fed 
Cohort 4: Placebo 
Cohort 4: Placebo Fed 
*One of the Cohort 1 to 3 Subjects (the highest tolerated dose-level cohort) will return for additional 
dose to determine the effect of food. 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
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 Protocol Number: ISLA101-P01-CT001 
 
 
Table 7 
Study Visits 
 
Actual Visit 
Summary Table Treatment Label 
By-subject Listing 
Treatment Label 
Screening 
Screening 
Day -1 – Clinic Check-In 
Baseline 
Day -1 
Day 9 -Clinic Check-In 
Day 9 
Day 1 
Day 1 
Day 1 
Day 10 
Day 10 
Day 2 
Day 2 
Day 2 
Day 11 
Day 11 
Day 3 
Day 3 
Day 3 
Day 12 
Day 12 
Day 4 
Day 4 
Day 4 
Day 13 
Day 13 
Day 5 - Discharge 
Day 5 
Day 5 
Day 14 - Discharge 
Day 14 
Day 8 – Follow Up/ET 
Follow-up 
Day 8 – Follow UP 
Day 17 – Follow Up/ET 
Day 17 – Follow Up 
Unscheduled 
Unscheduled 
Early Termination* 
*If early termination occurred, the visit labels “Day 8 – Follow Up” and “Day 17 – Follow Up” will be 
marked as “Early Termination”. 
 
5.2 
Hypotheses and Decision Rules 
Not applicable for this study. 
 
5.3 
Multiple Comparisons and Adjustments for Multiplicity 
Not applicable for this study. 
 
5.4 
Covariates 
Not applicable for this study. 
 
5.5 
Multi-Centre Data 
Not applicable for this study. 
 
5.6 
Handling of Missing Data 
5.6.1 
Efficacy Endpoints 
Not applicable for this study. 
 
5.6.2 
Safety Endpoints 
Missing start dates/times will be imputed to one minute after the study drug administration. 
Partial start dates will be imputed to the last day of the month/year considering that the start date should 
not be after the stop date/time. Missing start times will be imputed to ‘23:59’. If the imputation results in 
the start date/time being after the stop date/time, the start date/time will be set to the stop/date time. 
 
 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
The imputation method will only be used to determine treatment emergence and to determine the time 
of the event relative to the first administration of study drug. If no clear determination can be made, the 
event will be deemed to have started at the same time as the study drug, i.e., the event will be analyzed 
as being treatment emergent. 
Stop dates/times will not be imputed if the AE is ongoing. 
A worst-case approach will be followed in the event of missing severity or causality data. If the severity 
is missing, ‘Severe’ will be imputed. If causality data are missing, ‘Definitely Related’ will be imputed. 
Missing/partial concomitant medication dates will be handled in a similar fashion as described for the 
adverse event dates. 
 
5.7 
Windowing Conventions 
Not applicable. 
 
5.8 
Interim Analyses 
No interim analyses are planned for this study. 
 
5.9 
Clinical Data Interchange Standards Consortium (CDISC) 
Specifications 
The study data will be converted into CDISC-compliant datasets based on the Study Data Tabulation 
Model Implementation Guide (SDTMIG) Version 3.3 and the Analysis Data Model Implementation 
Guide (ADaMIG) Version 1.1. 
The SDTM data package will be based on raw data (clinical database and external data) and will include 
SAS® datasets and transport files (.XPT format) for each required SDTM domain, as well as the SDTM 
Case Report Tabulation Data Definition Specifications (CRT-DD) (define.xml Version 2.1) that 
describes the origin of the data and all the derivations and imputations that were applied, and includes 
an SDTM-annotated CRF and the Study Data Reviewer’s Guide (SDRG). 
The ADaM datasets will be based on the SDTM datasets and will be used for the analysis. The ADaM 
data package will include SAS® datasets and transport files (.XPT format) for each analysis dataset, as 
well as the ADaM CRT-DD (define.xml Version 2.1) and the Analysis Data Reviewer’s Guide (ADRG). 
The SDTM and ADaM data packages will be validated using Pinnacle 21 Community (531 Plymouth 
Road, Suite 508, Plymouth Meeting, PA 19462) and the validation reports will be included with the 
respective data packages. 
All data conversions will be performed using SAS® Version 9.4 or higher (SAS Institute, Cary, North 
Carolina, USA) with program code prepared specifically for the study. 
The output SAS® programs will generate rich-text-formatted (RTF) output with the “.RTF” extension 
using the SAS® Output Delivery System (ODS). Each output display will show the name of the SAS® 
program which was used to produce it. 
 
6. 
Statistical Analyses 
The baseline cohort 1 to 4 results will be presented in the same outputs. Furthermore, the results from 
the highest tolerated dose-level cohort (fasted results) in one of Cohort 1 to Cohort 3 will be presented 
with the results of Cohort 4 (fed results) (where appropriate). 
Summary tables and analyses will be based on the specified analysis population in each section. Data 
listings will be based on the Safety Population unless specifically stated otherwise. 
 
 
 
 
 


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Statistical Analysis Plan 
 
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 Protocol Number: ISLA101-P01-CT001 
 
 
6.1 
Subject Disposition and Analysis Sets 
Summary tables will be based on the Safety Population. 
The number and percentage of randomized subjects, subjects completing or discontinuing from the 
study as well as the primary reason for discontinuation will be presented by treatment group and for all 
subjects overall in the subject disposition table. The denominator for the reason for discontinuation from 
the study percentage calculations will be the number of subjects that discontinued from the study. 
All subject disposition information (as described in Section 4.4.1) will be listed together with the date 
that the subjects provided informed consent and the date/time of the first study drug administration in 
the subject disposition listing. 
The number of subjects included in the analysis populations defined in Section 3 will be summarized 
along with the reasons for exclusion from any analysis population by treatment group and for all subjects 
overall using frequencies and percentages. 
In addition, the inclusion/exclusion of each subject into/from each of the defined analysis set will be 
listed. 
The randomization information (where applicable) including the randomized treatment group will be 
listed. 
 
6.2 
Protocol Deviations and Eligibility 
Summary tables will be based on the Safety Population. 
The number and percentage of subjects with at least one protocol deviation, at least one major protocol 
deviation, and at least one minor protocol deviation, as well as the number and percentage of subjects 
with a deviation in each of the deviation categories will be presented by treatment groups in the protocol 
deviation table. Subjects will be counted once per category, but all deviations will be counted. 
All protocol deviation information and all eligibility data will be listed. 
 
6.3 
Demographic 
Summary tables will be based on the Safety Population. 
Demographic data (as described in Section 4.4.3) will be summarized and presented by treatment group 
and for all subjects overall in the demography table. The homogeneity between treatments will be 
assessed based on the descriptive statistics only. 
All collected and derived demographic data will be listed. 
 
6.4 
Baseline Subject Characteristics 
Summary tables will be based on the Safety Population. 
Baseline subject characteristics data (as described in Section 4.4.4) will be summarized and presented 
by treatment groups and for all subjects overall in the baseline characteristics table. 
The vital sign parameters will be listed as part of the vital signs listing. 
The listings of alcohol breath test results, serology test results, pregnancy test results and urine drug 
test results will include all available results (collected at scheduled and unscheduled visits) in the clinical 
database. 
 
6.5 
Medical and Surgical History 
Summary tables will be based on the Safety Population. 
 
 
 
 


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Statistical Analysis Plan 
 
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 Protocol Number: ISLA101-P01-CT001 
 
 
Medical and surgical history conditions will be summarized by SOC and by PT within SOC by treatment 
group and for all subjects overall. Within each category, the number of subjects who experienced a 
condition (frequency and percentage) and the actual number of events (frequency only) will be 
presented by treatment group and for all subjects overall. Subjects who experienced the same condition 
on more than one occasion (based on the specific category) will only be counted once in each relevant 
category (SOC and PT), but all conditions will be included in the event frequencies. System organ class 
terms will be sorted alphabetically, and preferred terms will be sorted alphabetically within SOCs in the 
table. 
In addition to the coded terms, the number of subjects with at least one medical and surgical history 
condition and the total number of events will be presented. 
All information that was collected as well as the coded MedDRA terms will be included in the listing. 
Partial dates will not be imputed. 
 
6.6 
Prior and Concomitant Medication 
Summary of concomitant medication table will be based on the Safety Population. 
Concomitant mediations will be summarized by WHO-DD ATC Level 2 term and preferred medication 
name. Within each ATC term and preferred name, the number of subjects who used the medication 
(frequency and percentage) will be presented. Subjects who used the same medication on multiple 
occasions will only be counted once. ATC terms and preferred names with ATC term will be sorted 
alphabetically. 
In addition to the summaries by the WHO-DD terms, the number of subjects who used at least one 
concomitant medication during the study will be presented. 
All information as well as the WHO-DD terms, will be included in the relevant prior and concomitant 
medication listings. Furthermore, the relative medication starts, and end days (relative to the first study 
drug administration) will be presented where complete medication start and end dates are available. 
 
6.7 
Efficacy Analyses 
Not applicable for this study. 
 
6.8 
Safety Analyses 
Statistical methods for the safety analyses will be descriptive in nature and no formal statistical 
comparisons will be made. Endpoints will be summarized by the treatment group based on the methods 
described in Section 5.1. 
Safety endpoints will be analyzed based on the Safety Population according to the actual treatment 
received. 
All listings will be presented by treatment group. 
 
6.8.1 
Exposure to Study Drug 
All collected study drug administration data (as described in section 4.1.1) will be listed. 
 
6.8.2 
Adverse Events 
All tables will present the number of subjects who experienced an AE (count and percentage) and the 
actual number of AEs (count only) within each specific category by treatment group. Subjects who 
experienced multiple AEs will only be counted once in each relevant category (high-level summary, 
SOC, PT, severity rating or relationship to study drug category), but all events will be included in the 
event counts. Percentages will be based on the number of subjects in the Safety Population. Tables 
will only include treatment-emergent events. 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
The overall summary of TEAEs table will present the total number of subjects who experienced a TEAE 
and the total number of TEAEs in each of the following categories: 
• 
At least one TEAE. 
• 
At least one serious TEAE. 
• 
At least one severe TEAE. 
• 
At least one treatment-related TEAE. 
• 
At least one TEAE leading to study discontinuation. 
• 
At least one TEAE leading to study drug discontinuation. 
The incidence of TEAEs table will include the number and percentage of subjects who experienced at 
least one TEAE and the corresponding number of events, and furthermore summarize the TEAE data 
by SOC and preferred term (PT) within SOCs. SOC/PT terms will be sorted alphabetically. 
The incidence of serious TEAE table will include the number and percentage of subjects who 
experienced at least one serious TEAE and the corresponding number of events, and furthermore 
summarize the serious TEAE data by SOC and preferred term within SOCs. SOC/PT terms will be 
sorted alphabetically. 
The incidence of treatment-related TEAEs table will include the number and percentage of subjects 
who experienced at least one treatment-related TEAE and the corresponding number of events, and 
furthermore summarize the treatment-related TEAE data by SOC and PT within SOCs. SOC/PT terms 
will be sorted alphabetically. 
The incidence of TEAEs by severity rating table will include the number and percentage of subjects who 
experienced at least one TEAE, at least one TEAE within each severity rating (‘Mild’, ‘Moderate’, 
‘Severe’) and the corresponding number of events for each severity rating. In addition, the TEAE data 
will be summarized by SOC, PT within SOCs, and severity rating within SOC and PT. SOC/PT terms 
will be sorted alphabetically, and severity ratings will be sorted in increasing order of severity (Mild to 
Severe) within SOCs and PTs in the table. 
The incidence of TEAEs by relationship to study drug (causality) table will include the number and 
percentage of subjects who experienced at least one TEAE, at least one TEAE within each relationship 
to study drug category (‘Unrelated’, ‘Unlikely’, ‘Possibly’, ‘Probably’, Definitely’) and the corresponding 
number of events for each category. In addition, the TEAE data will be summarized by SOC, PT within 
SOCs, and relationship category within SOC and PT. SOC/PT terms will be sorted alphabetically, and 
relationship category will be sorted from the least to the strongest relationship to study drug (Unrelated 
to Definitely) within SOCs and PTs in the table. 
The incidence of TEAEs leading to study drug discontinuation will include the number of subjects who 
experienced at least one TEAE that lead to study drug discontinuation and the corresponding number 
of events, and furthermore summarize the TEAE data by SOC and preferred term within SOCs. SOC/PT 
terms will be sorted alphabetically. 
The incidence of TEAEs leading to study discontinuation will include the number of subjects who 
experienced at least one TEAE that lead to study discontinuation and the corresponding number of 
events, and furthermore summarize the TEAE data by SOC and preferred term within SOCs. SOC/PT 
terms will be sorted alphabetically. 
The listing of AEs will include all AE data in the clinical database. The listing will present all the 
information (fields) collected on the ‘Adverse Event’ eCRF, as well as the SOC and preferred terms 
obtained from the MedDRA dictionary. In addition, the AE start and end days (relative to the first study 
drug administration) and a flag indicating whether the AE was treatment emergent will be presented. 
Non-TEAEs will not be assigned to any treatment. If the AE was ongoing at the end of the study, 
 
 
 
 
 


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Statistical Analysis Plan 
 
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‘Ongoing’ will be presented under the ‘End Date Time/Study Day’ heading. Partial dates/times will be 
presented as described in Section 5.1.4. 
The subsets of SAEs, treatment-related AEs, AEs leading to the discontinuation of study drug will be 
listed separately and will include all the information presented in the main AE listing. 
 
6.8.3 
Laboratory Parameters 
The laboratory parameters described in Section 4.1.3 will be summarized and listed. 
The summary tables of hematology, coagulation and biochemistry results will present summary 
statistics for each laboratory parameter within the specific test panel by treatment group. For each 
parameter, summaries will be presented for the baseline and each scheduled post-baseline visit. In 
addition, summaries will be presented for the change from baseline values at each scheduled post- 
baseline visit. Refer to Section 4.1.3 for the handling of character results. 
The summary of hematology, coagulation, and biochemistry shift tables will present summaries for the 
shifts in the result classifications (‘Normal’, ’Low’, ‘High’) from the baseline to each of the scheduled 
post-baseline visit for each parameter with a defined reference range, within the specific test panel. 
The listings of hematology, coagulation and biochemistry data will include all laboratory data (collected 
at scheduled and unscheduled visits) in the clinical database. The listings will present all the information 
(fields) that is available in the laboratory dataset. In addition, the observation that was used as the 
baseline records (values) for each parameter will be flagged, the change from baseline value and the 
derived result classification (based on the normal ranges where applicable) at each post-baseline visit 
will be presented. 
The summary of urinalysis table will present the number and percentage of subjects for each or the 
result classifications (Normal, Abnormal NCS and Abnormal CS) for the baseline, each scheduled post- 
baseline per parameter. 
The listing of urinalysis (including microscopy) data will include all laboratory data (collected at 
scheduled and unscheduled visits) in the clinical database. The listings will present all the information 
(fields) that is available in the laboratory dataset. In addition, the observation that was used as the 
baseline record (value) for each parameter will be flagged. 
The FSH parameters will be listed as part of the pregnancy listing. 
 
6.8.4 
Vital Signs 
The vital signs parameters described in Section 4.1.4 will be summarized and listed. 
The summary tables of vital signs results will present summary statistics for results at the baseline and 
each scheduled post-baseline visit for each parameter by treatment group. In addition, summaries will 
be presented for the change from baseline values (baselines) at each scheduled post-baseline visit. 
The listings of vital signs results will include all data (collected at scheduled and unscheduled visits) in 
the clinical database. The observations that were used as the baseline records for each parameter will 
be flagged and the change from baseline values at each post-baseline visit will be presented. Height, 
weight, derived BMI and BSA will be listed only. 
 
6.8.5 
12-lead ECG Evaluations 
The 12-lead ECG parameters described in Section 4.1.5 will be summarized and listed. 
The summary of ECG results tables will present summary statistics for results at the baseline and each 
scheduled post-baseline visit for each parameter by treatment group. In addition, summaries will be 
presented for the change from baseline values at each scheduled post-baseline visit. 
 
 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
The summary of ECG overall assessment table will present summaries for the baseline and each 
scheduled post-baseline visit for the overall result (Normal, Abnormal not clinically significant and 
Abnormal clinically significant). 
If multiple tracings are conducted as part of one assessment, the mean of the three tracings per 
parameter and the worst clinical interpretation per timepoint will be summarized for each subject. All 
values will be listed including the mean value per parameter and the worst clinical interpretation. 
Changes from baseline will be calculated based on the mean values of the triplicates where appropriate. 
The listings of ECG results will include all data (collected at scheduled and unscheduled visits) in the 
clinical database. The observations that were used as the baseline records for each parameter will be 
flagged and the change from baseline values at each post-baseline visit will be presented. 
 
6.8.6 
Physical Examination 
The physical examination assessment data described in Section 4.1.6 will be listed. 
 
6.9 
Pharmacokinetic Analyses 
6.9.1 
Plasma Concentrations 
The analysis of the PK concentration data will be based on the PK population. The PK analysis will be 
conducted separately for fenretinide and its metabolism (MPR and oxo-HPR) based on the available 
concentrations data (data permitting). Results will be presented by treatment group and study visit/ time 
point. 
The plasma concentrations data for Fenretinide, MPR and oxo-HPR will be summarized by treatment 
group and nominal collection time points using the statistics described in Section 5.1.3. Below the lower 
limit of quantification (BLQ) concentration that occurred prior to the first quantifiable concentration will 
be set to 0 and treated as missing otherwise, for the calculation of summary statistics. The number of 
BLQ concentrations per treatment group per time point will be included in the summary of 
concentrations. Zero values will be excluded from the calculation of the geometric statistics. Missing 
values will be omitted from the calculation of descriptive statistics. 
For Cohort 1 to 3, figures of the individual plasma concentrations vs. actual time profiles (all subjects 
within a treatment group on the same plot) will be presented on a linear and a log-linear scale for 3 
analytes (Fenretinide, MPR and oxo-HPR). For the food effect cohort (Cohort 4 and one of the Cohort 
1 to 3), the individual fasting and fed (fasted and fed results for all subjects in separate plots, and plots 
showing each subject’s fasting and fed results in the same plot) plasma concentrations vs. actual time 
profiles will be presented on linear and log-linear scales. BLQ concentrations that occurred prior to the 
first quantifiable concentration will be set to 0 and treated as missing otherwise in the linear plots. BLQ 
concentrations will be set to missing in the log-linear plots. 
Mean concentration with error bars for standard deviations vs. nominal time curves will be presented 
on a linear and log-linear scale for 3 analytes (Fenretinide, MPR and oxo-HPR). All treatment groups 
will be presented on the same plot. Standard deviation bars will also be presented. 
All plasma concentration data will be listed, and the listing will include the calculated elapsed time since 
the study drug administration in the specific period and the time deviations between the actual and 
planned sample collection times. 
 
6.9.2 
Pharmacokinetic Parameters 
The calculated plasma PK parameters described in Section 4.3 will be summarized by treatment group 
using the statistics described in Section 5.1.3. For Tmax and T1/2, only n, median, minimum, and 
maximum will be presented. The summary tables will be based on the PK population. The food effect 
analysis will be analyzed separately based on the food effect cohorts. 
 
 
 
 


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Statistical Analysis Plan 
 
Sponsor: Island Pharmaceuticals Ltd 
 Protocol Number: ISLA101-P01-CT001 
 
 
The dose proportionality of fenretinide will be evaluated across Cohort 1 to Cohort 3 under fasted 
condition based on the AUCinf, AUClast and Cmax values, using a power model and a graphical evaluation 
of the results. 
 
The power model will be used to estimate the slope parameters and the 90% confidence interval (CI) 
for the slope. The power model is a linear regression model constructed with the natural log transformed 
dose as the independent variable and the natural log-transformed PK parameter as the dependent 
variable. The resulting estimated slope (β) is a measure of dose proportionality, i.e., the relationship is 
dose proportional when β=1. Associated 90% confidence intervals (CIs) will be presented. Refer to 
Appendix 1 for the SAS® code that will be used for the analysis. Scatter plots with the power model 
regression line will be prepared with the natural log-transformed PK parameter results as the values on 
the y-axis, and the natural log-transformed dose level as the values on the x-axis. The plot will also 
include the mean parameters values and standard error bars. 
 
The food effect analysis of fenretinide (for cohort 1 to Cohort 3, the highest tolerated dose level cohort 
will then be evaluated in a fed condition) will be conducted to evaluate the effect of food on fenretinide 
based on the parameters AUCinf, AUClast and Cmax. The natural log-transformed parameters will be 
analyzed separately using a mixed effect model (data permitting) with the food effect (with and without 
food) as fixed effect and subjects as a random effect. The geometric means (exponentiated least- 
squares means) for each food effect and the geometric mean ratio (exponentiated difference between 
the fed cohort least-square mean as test and the fasted cohort least-squares mean as reference) and 
the associated 90% confidence interval (CI) will be presented. The geometric mean rations and the 
associated confidence intervals will be expressed as percentages. Refer to Appendix 2 for the SAS® 
code that will be used for the food effect analysis. 
 
The parameters AUCinf, AUClast, and Cmax on fenretinide will also be presented graphically by means of 
box and whisker plots. The results for all treatment groups will be presented on the same plot. The 
dose-normalized results for each parameter will also be plotted separately. 
All parameter results will be listed based on the PK population and any results that may have been 
excluded from the summary tables will be flagged. 
 
7. 
Changes to the Planned Analyses 
7.1 
Changes to the Analyses Described in the Study Protocol and Protocol 
Amendments 
Not applicable. 
 
7.2 
Changes from the Statistical Analysis Plan Version x.x to Version x.x 
Not applicable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8. 
References 
• 
WHO. Dengue vaccines: WHO position paper. World Health Organization. 
https://www.who.int/immunization/policy/position_papers/who_pp_dengue_2018_summary.pd 
f. 2018. 
• 
WHO. Dengue and severe dengue. World Health Organization. 
https://www.who.int/newsroom/fact-sheets/detail/dengue-and-severe-dengue. 2021. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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9. 
Attachments and Appendices 
Appendix 1 Dose Proportionality Analysis SAS® Code 
The following SAS® code will be used for the dose proportionality analysis of fenretinide for the 
comparison: 
ODS Output estimates=estimates; 
ODS Output diffs=diffs; 
PROC MIXED DATA = pk; 
BY param; 
MODEL log_aval = log_dose / ddfm = kr; 
ESTIMATE 'ESTIMATED SLOPE' log_dose 1/cl alpha=0.1; 
ESTIMATE 'INTERCEPT' INTERCEPT 1/cl alpha=0.1; 
run; 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendix 2 Food Effect Analysis SAS® Code 
The following SAS® code will be used for the food effect analysis: 
ODS Output lsmeans=lsmeans; 
ODS Output diffs=diffs; 
PROC MIXED DATA = pk; 
BY param; 
CLASS subjid trt; 
MODEL log_aval = trt / ddfm = kr; 
RANDOM subjid / subject =subjid type=un; 
LSMEANS trt/pdiff=control(‘Fasted’) CL ALPHA=0.1; 
RUN; 
 
If the unstructured covariance structure results in invalid (i.e., not non-negative definite) results use 
TYPE=FA0(2) and then TYPE=CSH. If the model still produces invalid results or does not converge 
use the default covariance structure. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ATTACHMENT 1 
LIST OF TABLES, LISTINGS AND FIGURES 
Tables 
 
Table 14.1.1.1 Summary of Analysis Population (Safety Population) 
Table 14.1.2.1 Summary of Subject Disposition (Safety Population) 
Table 14.1.3.1 Summary of Protocol Deviations (Safety Population) 
Table 14.1.3.2 Summary of Protocol Deviations - Fasted and Fed Cohorts (Safety Population) 
Table 14.1.4.1 Summary of Demography (Safety Population) 
Table 14.1.5.1 Summary of Subject Baseline Characteristics (Safety Population) 
Table 14.1.6.1 Summary of Medical and Surgical History (Safety Population) 
Table 14.1.7.1 Summary of concomitant Medication (Safety Population) 
Table 14.1.7.2 Summary of concomitant Medication – Fasted and Fed Cohorts (Safety Population) 
Table 14.2.1.1 Summary of Plasma Pharmacokinetic Concentrations (Pharmacokinetic Population) 
Table 14.2.1.2 Summary of Plasma Pharmacokinetic Concentrations – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Table 14.2.2.1 Summary of Plasma Pharmacokinetic Parameters (Pharmacokinetic Population) 
Table 14.2.2.2 Summary of Plasma Pharmacokinetic Parameters – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Table 14.2.3 Analysis of Dose Proportionality of Plasma Pharmacokinetic Parameters of Fenretinide (Pharmacokinetic Population) 
Table 14.2.4 Analysis of Food Effect on Plasma Pharmacokinetic Parameters of Fenretinide (Pharmacokinetic Population) 
Table 14.3.1.1.1 Overall Summary of Adverse Events (Safety Population) 
Table 14.3.1.1.2 Overall Summary of Adverse Events – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.1.2.1 Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.2.2 Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety 
Population) 
Table 14.3.1.3.1 Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.3.2 Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety 
Population) 
Table 14.3.1.4.1 Summary of Treatment-Related Adverse Events by System Organ Class and Preferred Term (Safety Population) 


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Table 14.3.1.4.2 Summary of Treatment-Related Adverse Events by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.1.5.1 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Severity Rating (Safety Population) 
Table 14.3.1.5.2 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Severity Rating – Fasted and Fed Cohorts 
(Safety Population) 
Table 14.3.1.6.1 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Relationship to Study Drug (Safety 
Population) 
Table 14.3.1.6.2 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Relationship to Study Drug – Fasted and Fed 
Cohorts (Safety Population) 
Table 14.3.1.7.1 Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term (Safety 
Population) 
Table 14.3.1.7.2 Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term – Fasted 
and Fed Cohorts (Safety Population) 
Table 14.3.1.8.1 Part A SAD: Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and Preferred 
Term (Safety Population) 
Table 14.3.1.8.2 Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and Preferred Term – 
Fasted and Fed Cohorts (Safety Population) 
Listing 14.3.2.1. Serious Adverse Events (Safety Population) 
Listing 14.3.2.2 Adverse Events Leading to Study Discontinuation (Safety Population) 
Listing 14.3.2.3 Adverse Events Leading to Study Drug Discontinuation (Safety Population) 
Table 14.3.4.1.1.1 Summary of Hematology Results (Safety Population) 
Table 14.3.4.1.1.2 Summary of Hematology Results – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.4.1.2.1 Summary of Shifts from Baseline in Hematology Laboratory Range Indicator Categories (Safety Population) 
Table 14.3.4.1.2.2 Summary of Shifts from Baseline in Hematology Laboratory Range Indicator Categories – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.4.2.1.1 Summary of Biochemistry Results (Safety Population) 
Table 14.3.4.2.1.2 Summary of Biochemistry Results – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.4.2.2.1 Summary of Shifts from Baseline in Biochemistry Laboratory Range Indicator Categories (Safety Population) 
Table 14.3.4.2.2.2 Summary of Shifts from Baseline in Biochemistry Laboratory Range Indicator Categories – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.4.3.1.1 Summary of Coagulation Results (Safety Population) 
Table 14.3.4.3.1.2 Summary of coagulation Results – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.4.3.2.1 Summary of Shifts from Baseline in Coagulation Laboratory Range Indicator Categories (Safety Population) 


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Table 14.3.4.3.2.2 Summary of Shifts from Baseline in Coagulation Laboratory Range Indicator Categories – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.4.4.1.1 Summary of Dipstick Urinalysis Results (Safety Population) 
Table 14.3.4.4.1.2 Summary of Dipstick Urinalysis Results – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.5.1 Summary of Vital Signs Results (Safety Population) 
Table 14.3.5.2 Summary of Vital Signs Results – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.6.1.1 Summary of 12-Lead ECG Results (Safety Population) 
Table 14.3.6.1.2 Summary of 12-Lead ECG Results – Fasted and Fed Cohorts (Safety Population) 
Table 14.3.6.2.1 Summary of 12-Lead ECG Overall Assessment (Safety Population) 
Table 14.3.6.2.2 Summary of 12-Lead ECG Overall Assessment - Fasted and Fed Cohorts (Safety Population) 


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Listings 
 
Listing 16.2.1.1 Analysis Sets (Safety Population) 
Listing 16.2.1.2 Subject Disposition (Safety Population) 
Listing 16.2.2.1 Protocol Deviations (Safety Population) 
Listing 16.2.2.2 Subject Eligibility (Safety Population) 
Listing 16.2.3 Randomization (Safety Population) 
Listing 16.2.4.1 Demography (Safety Population) 
Listing 16.2.4.2 Medical and Surgical History (Safety Population) 
Listing 16.2.4.3 Alcohol Breath Test Results (Safety Population) 
Listing 16.2.4.4 Urine Drug Test Results (Safety Population) 
Listing 16.2.4.5 Pregnancy Test Results (Safety Population) 
Listing 16.2.4.6 Serology Results (Safety Population) 
Listing 16.2.4.7.1 Prior Medications (Safety Population) 
Listing 16.2.4.7.2 Concomitant Medications (Safety Population) 
Listing 16.2.5.1 Study Drug Administration (Safety Population) 
Listing 16.2.6.1 Plasma Pharmacokinetic Concentrations (Pharmacokinetic Population) 
Listing 16.2.6.2 Plasma Pharmacokinetic Parameters (Pharmacokinetic Population) 
Listing 16.2.7.1 Adverse Events (Safety Population) 
Listing 16.2.7.2 Treatment-Related Adverse Events (Safety Population) 
Listing 16.2.8.1 Hematology Results (Safety Population) 
Listing 16.2.8.2 Biochemistry Results (Safety Population) 
Listing 16.2.8.3 Coagulation Results (Safety Population) 
Listing 16.2.8.4 Urinalysis Results Including Microscopy (Safety Population) 
Listing 16.2.9.1 Vital Signs Results (Safety Population) 
Listing 16.2.9.2.1 12-Lead ECG Results (Safety Population) 
Listing 16.2.9.2.2 12-Lead ECG Overall Assessment (Safety Population) 


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Listing 16.2.9.3 Physical Examination Findings (Safety Population) 


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Figures 
 
Figure 14.2.1.1.1 Individual Plasma PK Concentrations over Time (Linear) (Pharmacokinetic Population) 
Figure 14.2.1.1.2 Individual Plasma PK Concentrations over Time (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.1.1.3 Individual Plasma PK Concentrations over Time by Subject (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.1.2.1 Individual Plasma PK Concentrations over Time (Log-Linear) (Pharmacokinetic Population) 
Figure 14.2.1.2.2 Individual Plasma PK Concentrations over Time (Log-Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.1.2.3 Individual Plasma PK Concentrations over Time by Subject (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.2.1.1 Mean Plasma PK Concentrations over Time (Linear) (Pharmacokinetic Population) 
Figure 14.2.2.1.2 Mean Plasma PK Concentrations over Time (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.2.2.1 Mean Plasma PK Concentrations over Time (Log-Linear) (Pharmacokinetic Population) 
Figure 14.2.2.2.2 Mean Plasma PK Concentrations over Time (Log-Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.3.1.1 Box Plots of Plasma PK Parameters – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.4.1.1 Box-Whisker Plots of Dose-Normalized Plasma PK Parameters (Pharmacokinetic Population) 
Figure 14.2.4.1.2 Box-Whisker Plots of Dose-Normalized Plasma PK Parameters – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Figure 14.2.5.1 Scatterplots of Natural Log-Transformed Plasma PK Parameters (Pharmacokinetic Analysis Set) 


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Attachment 1 of the Statistical Analysis Plan 
 
Tables, Listings, and Figures 
 
 
 
Sponsor: Island Pharmaceuticals Ltd 
 
 
 
Protocol Number: ISLA101-P01-CT001 
 
 
 
A Phase 1a, randomized, double-blind placebo-controlled study to 
evaluate safety and tolerability and to characterize the 
pharmacokinetic profile of single ascending doses of fenretinide 
oral capsules in healthy adult volunteers. 
 
 
 
 
 
 
 
 
 
 
 
 
Version: 
Final Version 1.0 
Date: 
2023-12-07 
 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
List of Tables, Listings and Figures 
1 
General Statistical Methods ..................................................................................................... 5 
Table 14.1.1.1 Summary of Analysis Population (Safety Population) ............................................................ 6 
Table 14.1.2.1 Summary of Subject Disposition (Safety Population) ............................................................. 7 
Table 14.1.3.1 Summary of Protocol Deviations (Safety Population) ............................................................. 8 
Table 14.1.3.2 Summary of Protocol Deviations - Fasted and Fed Cohorts (Safety Population) ................... 9 
Table 14.1.4.1 Summary of Demography (Safety Population) ..................................................................... 10 
Table 14.1.5.1 Summary of Subject Baseline Characteristics (Safety Population) ...................................... 11 
Table 14.1.6.1 Summary of Medical and Surgical History (Safety Population) ............................................ 12 
Table 14.1.7.1 Summary of concomitant Medication (Safety Population) .................................................... 13 
Table 14.1.7.2 Summary of concomitant Medication – Fasted and Fed Cohorts (Safety Population) .......... 14 
Table 14.2.1.1 Summary of Plasma Pharmacokinetic Concentrations (Pharmacokinetic Population) ......... 15 
Table 14.2.1.2 Summary of Plasma Pharmacokinetic Concentrations – Fasted and Fed Cohorts 
(Pharmacokinetic Population) ................................................................................................ 16 
Table 14.2.2.1 Summary of Plasma Pharmacokinetic Parameters (Pharmacokinetic Population) ............... 17 
Table 14.2.2.2 Summary of Plasma Pharmacokinetic Parameters – Fasted and Fed Cohorts 
(Pharmacokinetic Population) ................................................................................................ 18 
Table 14.2.3 Analysis of Dose Proportionality of Plasma Pharmacokinetic Parameters of Fenretinide 
(Pharmacokinetic Population) ................................................................................................ 19 
Table 14.2.4 Analysis of Food Effect on Plasma Pharmacokinetic Parameters of Fenretinide 
(Pharmacokinetic Population) ................................................................................................ 20 
Table 14.3.1.1.1 Overall Summary of Adverse Events (Safety Population) ................................................. 21 
Table 14.3.1.1.2 Overall Summary of Adverse Events – Fasted and Fed Cohorts (Safety Population) ....... 22 
Table 14.3.1.2.1 Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term (Safety Population) ....................................................................................................... 23 
Table 14.3.1.2.2 Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term – Fasted and Fed Cohorts (Safety Population) ............................................................ 24 
Table 14.3.1.3.1 Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term (Safety Population) ....................................................................................... 25 
Table 14.3.1.3.2 Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term – Fasted and Fed Cohorts (Safety Population) ............................................ 26 
Table 14.3.1.4.1 Summary of Treatment-Related Adverse Events by System Organ Class and Preferred 
Term (Safety Population) ....................................................................................................... 27 
Table 14.3.1.4.2 Summary of Treatment-Related Adverse Events by System Organ Class and Preferred 
Term – Fasted and Fed Cohorts (Safety Population) ............................................................ 28 
Table 14.3.1.5.1 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Severity Rating (Safety Population) ...................................................................... 29 
Table 14.3.1.5.2 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Severity Rating – Fasted and Fed Cohorts (Safety Population) ............................ 30 
Table 14.3.1.6.1 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Relationship to Study Drug (Safety Population) .................................................... 31 
Table 14.3.1.6.2 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred 
Term and Relationship to Study Drug – Fasted and Fed Cohorts (Safety Population) .......... 32 
Table 14.3.1.7.1 Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by 
System Organ Class and Preferred Term (Safety Population) ............................................. 33 
Table 14.3.1.7.2 Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by 
System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety Population) ... 34 
Table 14.3.1.8.1 Part A SAD: Summary of Treatment-Emergent Adverse Events Leading to Study Drug 
Discontinuation by System Organ Class and Preferred Term (Safety Population) ................ 35 
Table 14.3.1.8.2 Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation 
by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety Population) 
36 
 


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Listing 14.3.2.1. Serious Adverse Events (Safety Population) ..................................................................... 37 
Listing 14.3.2.2 Adverse Events Leading to Study Discontinuation (Safety Population) .............................. 38 
Listing 14.3.2.3 Adverse Events Leading to Study Drug Discontinuation (Safety Population) ...................... 39 
Table 14.3.4.1.1.1 Summary of Hematology Results (Safety Population) .................................................... 40 
Table 14.3.4.1.1.2 Summary of Hematology Results – Fasted and Fed Cohorts (Safety Population) ......... 41 
Table 14.3.4.1.2.1 Summary of Shifts from Baseline in Hematology Laboratory Range Indicator Categories 
(Safety Population) ................................................................................................................. 42 
Table 14.3.4.1.2.2 Summary of Shifts from Baseline in Hematology Laboratory Range Indicator Categories 
– Fasted and Fed Cohorts (Safety Population) ...................................................................... 43 
Table 14.3.4.2.1.1 Summary of Biochemistry Results (Safety Population) .................................................. 44 
Table 14.3.4.2.1.2 Summary of Biochemistry Results – Fasted and Fed Cohorts (Safety Population) ........ 45 
Table 14.3.4.2.2.1 Summary of Shifts from Baseline in Biochemistry Laboratory Range Indicator 
Categories (Safety Population) .............................................................................................. 46 
Table 14.3.4.2.2.2 Summary of Shifts from Baseline in Biochemistry Laboratory Range Indicator 
Categories – Fasted and Fed Cohorts (Safety Population) .................................................... 47 
Table 14.3.4.3.1.1 Summary of Coagulation Results (Safety Population) .................................................... 48 
Table 14.3.4.3.1.2 Summary of coagulation Results – Fasted and Fed Cohorts (Safety Population) .......... 49 
Table 14.3.4.3.2.1 Summary of Shifts from Baseline in Coagulation Laboratory Range Indicator Categories 
(Safety Population) ................................................................................................................. 50 
Table 14.3.4.3.2.2 Summary of Shifts from Baseline in Coagulation Laboratory Range Indicator Categories 
– Fasted and Fed Cohorts (Safety Population) ...................................................................... 51 
Table 14.3.4.4.1.1 Summary of Dipstick Urinalysis Results (Safety Population) .......................................... 52 
Table 14.3.4.4.1.2 Summary of Dipstick Urinalysis Results – Fasted and Fed Cohorts (Safety Population) 
53 
Table 14.3.5.1 Summary of Vital Signs Results (Safety Population) ............................................................ 54 
Table 14.3.5.2 Summary of Vital Signs Results – Fasted and Fed Cohorts (Safety Population) ................. 56 
Table 14.3.6.1.1 Summary of 12-Lead ECG Results (Safety Population) .................................................... 57 
Table 14.3.6.1.2 Summary of 12-Lead ECG Results – Fasted and Fed Cohorts (Safety Population).......... 58 
Table 14.3.6.2.1 Summary of 12-Lead ECG Overall Assessment (Safety Population) ................................ 59 
Table 14.3.6.2.2 Summary of 12-Lead ECG Overall Assessment - Fasted and Fed Cohorts (Safety 
Population) ............................................................................................................................. 60 
Listing 16.2.1.1 Analysis Sets (Safety Population) ....................................................................................... 61 
Listing 16.2.1.2 Subject Disposition (Safety Population) .............................................................................. 62 
Listing 16.2.2.1 Protocol Deviations (Safety Population).............................................................................. 63 
Listing 16.2.2.2 Subject Eligibility (Safety Population) .................................................................................. 64 
Listing 16.2.3 Randomization (Safety Population) ....................................................................................... 65 
Listing 16.2.4.1 Demography (Safety Population) ........................................................................................ 66 
Listing 16.2.4.2 Medical and Surgical History (Safety Population) ............................................................... 67 
Listing 16.2.4.3 Alcohol Breath Test Results (Safety Population) ................................................................ 68 
Listing 16.2.4.4 Urine Drug Test Results (Safety Population) ...................................................................... 69 
Listing 16.2.4.5 Pregnancy Test Results (Safety Population) ...................................................................... 70 
Listing 16.2.4.6 Serology Results (Safety Population) ................................................................................. 71 
Listing 16.2.4.7.1 Prior Medications (Safety Population) .............................................................................. 72 
Listing 16.2.4.7.2 Concomitant Medications (Safety Population) ................................................................. 73 
Listing 16.2.5.1 Study Drug Administration (Safety Population) ................................................................... 74 
Listing 16.2.6.1 Plasma Pharmacokinetic Concentrations (Pharmacokinetic Population) ............................ 75 
Listing 16.2.6.2 Plasma Pharmacokinetic Parameters (Pharmacokinetic Population) ................................. 76 
Listing 16.2.7.1 Adverse Events (Safety Population) ................................................................................... 77 
Listing 16.2.7.2 Treatment-Related Adverse Events (Safety Population) ..................................................... 78 
Listing 16.2.8.1 Hematology Results (Safety Population) ............................................................................ 79 
Listing 16.2.8.2 Biochemistry Results (Safety Population)  .......................................................................... 80  


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Listing 16.2.8.3 Coagulation Results (Safety Population) ............................................................................ 81 
Listing 16.2.8.4 Urinalysis Results Including Microscopy (Safety Population) .............................................. 82 
Listing 16.2.9.1 Vital Signs Results (Safety Population)............................................................................... 83 
Listing 16.2.9.2.1 12-Lead ECG Results (Safety Population) ....................................................................... 84 
Listing 16.2.9.2.2 12-Lead ECG Overall Assessment (Safety Population) ................................................... 85 
Listing 16.2.9.3 Physical Examination Findings (Safety Population) ............................................................ 86 
Figure 14.2.1 1.1 Individual Plasma PK Concentrations over Time (Linear) (Pharmacokinetic Population) 87 
Figure 14.2.1.1.2 Individual Plasma PK Concentrations over Time (Linear) – Fasted and Fed Cohorts 
(Pharmacokinetic Population) ................................................................................................ 88 
Figure 14.2.1.1.3 Individual Plasma PK Concentrations over Time by Subject (Linear) – Fasted and Fed 
Cohorts (Pharmacokinetic Population) .................................................................................. 89 
Figure 14.2.1.2.1 Individual Plasma PK Concentrations over Time (Log-Linear) (Pharmacokinetic 
Population) ............................................................................................................................. 90 
Figure 14.2.1.2.2 Individual Plasma PK Concentrations over Time (Log-Linear) – Fasted and Fed Cohorts 
(Pharmacokinetic Population) ................................................................................................ 91 
Figure 14.2.1.2.3 Individual Plasma PK Concentrations over Time by Subject (Linear) – Fasted and Fed 
Cohorts (Pharmacokinetic Population) ................................................................................... 92 
Figure 14.2.2.1.1 Mean Plasma PK Concentrations over Time (Linear) (Pharmacokinetic Population) ....... 93 
Figure 14.2.2.1.2 Mean Plasma PK Concentrations over Time (Linear) – Fasted and Fed Cohorts 
(Pharmacokinetic Population) ................................................................................................ 94 
Figure 14.2.2.2.1 Mean Plasma PK Concentrations over Time (Log-Linear) (Pharmacokinetic Population) 
95 
Figure 14.2.2.2.2 Mean Plasma PK Concentrations over Time (Log-Linear) – Fasted and Fed Cohorts 
(Pharmacokinetic Population) ................................................................................................ 96 
Figure 14.2.3.1.1 Box Plots of Plasma PK Parameters – Fasted and Fed Cohorts (Pharmacokinetic 
Population) ............................................................................................................................. 97 
Figure 14.2.4.1.1 Box-Whisker Plots of Dose-Normalized Plasma PK Parameters (Pharmacokinetic 
Population) ............................................................................................................................. 98 
Figure 14.2.4.1.2 Box-Whisker Plots of Dose-Normalized Plasma PK Parameters – Fasted and Fed 
Cohorts (Pharmacokinetic Population) .................................................................................. 99 
Figure 14.2.5.1 Scatterplots of Natural Log-Transformed Plasma PK Parameters (Pharmacokinetic 
Analysis Set) ........................................................................................................................ 100 


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Tables, Listings and Figures Shells 
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1 General Statistical Methods 
 
Courier New will be used as font for all output produced in SAS®. The font size for all output will be 
8p. 
Results presented in table columns will be positioned as follows: 
• 
Alphanumeric values will be left aligned. 
• 
Integer numbers (e.g., counts) will be right aligned. 
• 
Numbers containing fractional portions will be decimal aligned. 
In all titles and analysis population names, coordinating conjunctions (and, or), articles (a, an, the) or 
prepositions will not be capitalized. All other words will be capitalized as well as the first and last words 
of the title or name. 
The footnotes must make provision for the name of the SAS® program used to produce the output and 
the date and time that the output was created. 
Words followed by a designator will be capitalized, for example, Day 1, Subject 3046, Day 10 etc. 
Page numbers will be indicated as “Page x of y” at the bottom of each page. 
Individual subject listings will be produced for all raw data and a selection of the derived data. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
 
 
Table 14.1.1.1 Summary of Analysis Population (Safety Population) 
ISLA101 
300 mg Fasted 
ISLA101 
600 mg Fasted 
ISLA101 
900 mg Fasted/Fed 
Pooled Placebo 
All Subjects 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
Safety Population 
Number of Subjects Included 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Number of Subjects Excluded 
Reasons for Exclusion 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reasons for Exclusion 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Pharmacokinetic Population 
Number of Subjects Included 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Number of Subjects Excluded 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Reasons for Exclusion 
Reasons for Exclusion 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
The Safety Population will include all subjects who received at least one dose of the study drug (ISLA101 or Placebo). 
The Pharmacokinetic Population will consist of all subjects in the safety population who have a pre-dose PK sample and at least one post dose 
analyzable PK sample and at least 1 post-dose analyzable PK sample (quantifiable Plasma concentration). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Percentage (%) of subjects (n) for the reason for exclusion categories are calculated based on the number of subjects that were excluded 
from the specific analysis population. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: 
 
In the final analysis, the group “ISLA101 900 mg Fasted/Fed” will be replaced by the highest tolerated dose-level cohort. For the “Pooled 
Placebo” group, the placebo fasted and Fed subjects will be counted once only. Therefore, the number of subjects (N) in Pooled Placebo basically 
should be 6. 


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Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
 
 
Table 14.1.2.1 Summary of Subject Disposition (Safety Population) 
 
ISLA101 
300 mg Fasted 
 
ISLA101 
600 mg Fasted 
 
ISLA101 
900 mg Fasted/Fed Pooled Placebo 
All Subjects 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
(N=xx) 
n (%) 
Number of Subjects who Completed the Study 
Number of Subjects who did not Complete the Study 
xx 
xx 
(xx%) 
(xx%) 
xx 
xx 
(xx%) 
(xx%) 
xx 
xx 
(xx%) 
(xx%) 
xx 
xx 
(xx%) 
(xx%) 
xx 
xx 
(xx%) 
(xx%) 
Primary Reason for Early Study Discontinuation 
Adverse Event 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Withdrawal of Consent 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Physician Decision 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Pregnancy 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Protocol Deviation 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Lost to Follow-up 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Sponsor Request 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Other 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Percentages (%) of subjects (n) for the reason of early study termination categories are based on the number of subjects who early terminated 
the study. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: 
In the final analysis, the group “ISLA101 900 mg Fasted/Fed” will be replaced by the highest tolerated dose-level cohort. For the “Pooled 
Placebo” group, the placebo fasted and Fed subjects will be counted once only. Therefore, the number of subjects (N) in Pooled Placebo basically 
should be 6. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 8 of 100 
Confidential 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
 
Protocol Number: ISLA101-P01-CT001 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.1.3.1 Summary of Protocol Deviations (Safety Population) 
ISLA101 
ISLA101 
300 mg Fasted 
600 mg Fasted 
ISLA101 
900 mg Fasted 
Pooled Placebo 
(N=xx) 
(N=xx) 
n (%) E 
n (%) E 
(N=xx) 
n (%) E 
(N=xx) 
n (%) E 
At least one Protocol deviation 
xx 
xx 
xx 
xx 
At least one Major Protocol deviation 
xx 
xx 
xx 
xx 
At least one Minor Protocol deviation 
xx 
xx 
xx 
xx 
Major Protocol Deviation 
 
 
 
 
 
 
 
 
 
 
Minor Protocol Deviation 
Missed Procedure/Assessment 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Procedures/Assessments Outside Protocol Window 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Order of Procedure/Assessments 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Etc. 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Subjects who experienced multiple deviations within a category are counted only once in the specific category (n), however each instance of the 
deviation is counted (E). 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
The “ Pooled Placebo” group means the placebo fasted subjects. Therefore, the number of subjects (N) in Pooled Placebo basically should be 6. 
Missed Procedure/Assessment 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Procedures/Assessments Outside Protocol Window 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Order of Procedure/Assessments 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Missed Visit 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Eligibility 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Incorrect Randomization 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Informed Consent Error 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Study Drug Administration Error 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Incomplete Documentation 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Other 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 


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Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.1.3.2 Summary of Protocol Deviations - Fasted and Fed Cohorts (Safety Population) 
 
ISLA101 
xxx mg Fasted 
(N=xx) 
ISLA101 
xxx mg Fed 
Placebo (Fasted) 
(N=xx) 
(N=xx) 
Placebo (Fed) 
(N=xx) 
n (%) E 
n (%) E 
n (%) E 
n (%) E 
At least one Protocol deviation 
xx 
xx 
xx 
xx 
At least one Major Protocol deviation 
xx 
xx 
xx 
xx 
At least one Minor Protocol deviation 
xx 
xx 
xx 
xx 
Major Protocol Deviation 
Missed Procedure/Assessment 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Procedures/Assessments Outside Protocol Window 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Order of Procedure/Assessments 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Missed Visit 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Eligibility 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Incorrect Randomization 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Informed Consent Error 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Study Drug Administration Error 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Incomplete Documentation 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Other 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Minor Protocol Deviation 
Missed Procedure/Assessment 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Procedures/Assessments Outside Protocol Window 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Order of Procedure/Assessments 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Etc. 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Subjects who experienced multiple deviations within a category are counted only once in the specific category (n), however each instance of the 
deviation is counted (E). 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Version and Date: Final Version 1.0, 2023-12-07 
Page 10 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.1.4.1 Summary of Demography (Safety Population) 
 
ISLA101 
300 mg Fasted 
ISLA101 
600 mg Fasted 
900 
ISLA101 
mg Fasted/Fed Pooled Placebo 
All Subjects 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
Statistic 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Age (Years) 
n 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Minimum 
xx 
xx 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
xx 
xx 
Sex 
n 
xx 
xx 
xx 
xx 
xx 
Male 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Female 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Childbearing Potential 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Ethnicity 
n 
xx 
xx 
xx 
xx 
xx 
Hispanic or Latino 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Not Hispanic or Latino 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Race 
n 
xx 
xx 
xx 
xx 
xx 
White 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Black or African American 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Asian 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
American Indian or Alaskan Native 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Native Hawaiian or Other Pacific Islander 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Other 
n (%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
SD: Standard deviation. 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Percentages (%) of subjects (n) of childbearing potential are based on the number of female subjects. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
In the final analysis, the group “ISLA101 900 mg Fasted/Fed” will be replaced by the highest tolerated dose-level cohort. For the “Pooled 
Placebo” group, the placebo fasted and Fed subjects will be counted once only. Therefore, the number of subjects (N) in Pooled Placebo basically 
should be 6. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 11 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.1.5.1 Summary of Subject Baseline Characteristics (Safety Population) 
 
Statistic 
ISLA101 
300 mg Fasted 
(N=xx) 
ISLA101 
600 mg Fasted 
(N=xx) 
ISLA101 
900 mg Fasted/Fed 
(N=xx) 
Pooled Placebo 
(N=xx) 
All Subjects 
(N=xx) 
Height (cm) at Screening 
n 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
xx 
xx 
Weight (kg) at Screening 
n 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
xx 
xx 
Body Mass Index (kg/m2) at Screening 
n 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
xx 
xx 
Body Surface Area (m2) at Screening 
n 
xx 
xx 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Minimum 
xx 
xx 
xx 
xx 
xx 
Maximum 
xx 
xx 
xx 
xx 
xx 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.1.6.1 Summary of Medical and Surgical History (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted/Fed 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
All Subjects 
(N=xx) 
n (%) E 
Number of Subjects With at Least One Medical History 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
System Organ Class 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Term 4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Medical history terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: 
In the final analysis, the group “ISLA101 900 mg Fasted/Fed” will be replaced by the highest tolerated dose-level cohort. 


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Version and Date: Final Version 1.0, 2023-12-07 
Page 13 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
 
 
Table 14.1.7.1 Summary of concomitant Medication (Safety Population) 
ISLA101 
300 mg Fasted 
ISLA101 
600 mg Fasted 
ISLA101 
900 mg Fasted 
Pooled Placebo 
ATC Class Level 2 
Preferred Name 
(N=xx) 
n (%) E 
(N=xx) 
n (%) E 
(N=xx) 
n (%) E 
(N=xx) 
n (%) E 
Number of Subjects With at Least One Concomitant Medication 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
ATC Class Level 2 Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
ATC Class Level 2 Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
ATC: Anatomical Therapeutic Chemical. 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Subjects who used the same medication on multiple occasions are counted only once in the specific category (n), however each instance of the 
medication is counted (E). 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of 
study drug. 
Medication terms were coded using the World Health Organization – Drug Dictionary (WHO-DD) Version Global C3, September 2023. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
Sort preferred names alphabetically. 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 14 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.1.7.2 Summary of concomitant Medication – Fasted and Fed Cohorts (Safety Population) 
 
ATC Class Level 2 
Preferred Name 
ISLA101 
XXX mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
XXX mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Number of Subjects With at Least One Concomitant Medication 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
ATC Class Level 2 Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
ATC Class Level 2 Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Preferred Name 4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
ATC: Anatomical Therapeutic Chemical. 
 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Subjects who used the same medication on multiple occasions are counted only once in the specific category (n), however each instance of the 
medication is counted (E). 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of 
study drug. 
 
Medication terms were coded using the World Health Organization – Drug Dictionary (WHO-DD) Version Global C3, September 2023. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
Sort preferred names alphabetically. 
In the final analysis, the dosage for the food effect cohorts will be replaced by the highest tolerated dose-level cohort from Cohort 1 to 3. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
Table 14.2.1.1 Summary of Plasma Pharmacokinetic Concentrations (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Statistics 
Treatment Group 
Geometric 
Geometric 
Time Point (hours) 
n 
n BLQ 
Mean 
SD 
CV (%) 
Median 
Minimum 
Maximum 
Mean 
CV (%) 
ISLA101 300 mg Fasted (N=x) 
Pre-dose 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
0.5 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
0.75 hour 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
1 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
1.5 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
2 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
3 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
4 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
5 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
6 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
8 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
10 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
12 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
24 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
36 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
Etc. 
BLQ: Below the LLOQ; CV: Coefficient of Variation; LLOQ: Lower Limit of Quantification; 
n BLQ: Number of BLQ Concentrations; SD: Standard Deviation. 
BLQ concentrations observed prior to the first measurable concentration were set to zero for the calculation of the summary statistics and 
other BLQ concentrations were treated as missing. Zero concentrations were set to missing for the calculation of the geometric statistics. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: 
Repeat for analyte = MPR and oxo-HPR 
The treatment group will be displayed as the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted and ISLA101 900 mg Fasted. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.2.1.2 Summary of Plasma Pharmacokinetic Concentrations – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Treatment Group 
 
 
Statistics 
 
 
 
Geometric 
 
 
 
Geometric 
Time Point (hours) 
n 
n BLQ 
Mean 
SD 
CV (%) 
Median 
Minimum 
Maximum 
Mean 
CV (%) 
 
ISLA101 XXX mg Fasted (N=x) 
Pre-dose 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
0.5 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
0.75 hour 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
1 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
1.5 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
2 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
3 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
4 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
5 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
6 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
8 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
10 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
12 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
24 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
36 hours 
X 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
Etc. 
BLQ: Below the LLOQ; CV: Coefficient of Variation; LLOQ: Lower Limit of Quantification; 
n BLQ: Number of BLQ Concentrations; SD: Standard Deviation. 
BLQ concentrations observed prior to the first measurable concentration were set to zero for the calculation of the summary statistics and 
other BLQ concentrations were treated as missing. Zero concentrations were set to missing for the calculation of the geometric statistics. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: 
Repeat for analyte = MPR and oxo-HPR 
The treatment group will be displayed as the following: ISLA101 XXX mg Fasted, and ISLA101 XXX mg Fed. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.2.2.1 Summary of Plasma Pharmacokinetic Parameters (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Treatment Group 
 
 
Statistics 
 
 
 
Geometric 
 
 
 
Geometric 
Time Point (hours) 
n 
Mean 
SD 
CV (%) 
Median 
Minimum 
Maximum 
Mean 
CV (%) 
 
ISLA101 300 mg Fasted (N=x) 
Cmax (ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
Tmax (h) 
X 
- 
- 
- 
XXXX.XXX 
XXXX 
XXXX 
- 
- 
AUClast (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
AUC0-24 (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
AUCinf (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
λz (1/h) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
t1/2 (h) 
X 
- 
- 
- 
XXXX.XXX 
XXXX 
XXXX 
- 
- 
CL/F (L/h) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
Vz/F (L) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
DN_Cmax (ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
DN_AUCinf (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
DN_AUClast (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
… 
DN: Dose normalized; AUC: Area Under the Curve; CV: Coefficient of Variation; -: Not Applicable; SD: Standard Deviation. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
The treatment group will be displayed as the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fed, and ISLA101 900 mg. 
Repeat for analyte = MPR and oxo-HPR 
The treatment group will be displayed as the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted and ISLA101 900 mg Fasted. 
Results for λz, t1/2, will only be included in the summary statistics if the following criteria are met: 
• 
A minimum of 3 measurable concentrations-time points is available during log-linear portion of the terminal elimination phase (excluding 
Cmax), i.e., No. of Points is ≥ 3. 
• 
Adjusted R2 > 0.80. 
AUCinf, CL/F and Vz/F will only be included in the summary statistics if the following criterion is met: 
• 
%AUCextrap < 20%. 
• 
Span >=2 
Cz/F and Vz/F will be displayed for the parent compound only. 


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Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.2.2.2 Summary of Plasma Pharmacokinetic Parameters – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Treatment Group 
 
 
Statistics 
 
 
 
Geometric 
 
 
 
Geometric 
Time Point (hours) 
n 
Mean 
SD 
CV (%) 
Median 
Minimum 
Maximum 
Mean 
CV (%) 
 
ISLA101 xx mg Fasted (N=x) 
Cmax (ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
Tmax (h) 
X 
- 
- 
- 
XXXX.XXX 
XXXX 
XXXX 
- 
- 
AUClast (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
AUC0-24 (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
AUCinf (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
λz (1/h) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
t1/2 (h) 
X 
- 
- 
- 
XXXX.XXX 
XXXX 
XXXX 
- 
- 
CL/F (L/h) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
Vz/F (L) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
DN_Cmax (ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
DN_AUCinf (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
DN_AUClast (h*ng/ml) 
X 
XXX.XXX 
XXX.XXXX 
XX.X 
XXXX.XXX 
XXXX 
XXXX 
XXX.XXX 
XX.X 
… 
DN: Dose normalized; AUC: Area Under the Curve; CV: Coefficient of Variation; -: Not Applicable; SD: Standard Deviation. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
The treatment group will be displayed as the following: ISLA101 XXX mg Fasted, and ISLA101 XXX mg Fed. 
Repeat for analyte = MPR and oxo-HPR 
Repeat for the treatment groups: ISLA101 xxx mg Fed. 
Results for λz, t1/2, will only be included in the summary statistics if the following criteria are met: 
• 
A minimum of 3 measurable concentrations-time points is available during log-linear portion of the terminal elimination phase (excluding 
Cmax), i.e., No. of Points is ≥ 3. 
• 
Adjusted R2 > 0.80. 
AUCinf, CL/F and Vz/F will only be included in the summary statistics if the following criterion is met: 
• 
%AUCextrap < 20%. 
• 
Span >=2 
Cz/F and Vz/F will be displayed for the parent compound only. 


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Tables, Listings and Figures Shells 
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Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.2.3 Analysis of Dose Proportionality of Plasma Pharmacokinetic Parameters of Fenretinide (Pharmacokinetic Population) 
 
  
 
Power Model 
 
 
Parameter (Unit) 
n 
Model Coefficient 
 
Estimates (SE) 
90% Confidence Interval 
 
Cmax (ng/mL) 
xx 
Slope (β) 
Intercept (α) 
xx.x (xx.xx) 
xx.x (xx.xx) 
(xx.x, xx.x) 
(xx.x, xx.x) 
AUCinf (h*ng/ml) 
xx 
Slope (β) 
Intercept (α) 
xx.x (xx.xx) 
xx.x (xx.xx) 
(xx.x, xx.x) 
(xx.x, xx.x) 
AUClast (h*ng/ml) 
xx 
Slope (β) 
Intercept (α) 
xx.x (xx.xx) 
xx.x (xx.xx) 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
AUC: Area Under the Curve; SE: Standard Error. 
A power model was used to assess dose proportionality: Natural log-transformed (PK Parameter Result) = α + β * Natural Log-transformed(Dose). 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming note: 
Include cohort 1 to 3 (fasted cohorts)in this analysis only. 


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Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.2.4 Analysis of Food Effect on Plasma Pharmacokinetic Parameters of Fenretinide (Pharmacokinetic Population) 
 
90% CI for the Ratio 
 
(Fed : Fasted) 
 
Geometric Least 
Ratio of Geometric 
Least Squares Means 
Parameter (Unit) 
Treatment 
n 
Squares Means 
(Fed : Fasted) 
Lower 
Upper 
AUCinf (h*ng/mL) 
ISLA101 xxx mg (Fed) 
xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
ISLA101 xxx mg (Fasted) 
xx 
xx.xx 
AUClast (h*ng/mL) 
ISLA101 xxx mg (Fed) 
xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
ISLA101 xxx mg (Fasted) 
xx 
xx.xx 
Cmax (ng/mL) 
ISLA101 xxx mg (Fed) 
xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
ISLA101 xxx mg (Fasted) 
xx 
xx.xx 
 
AUC: Area Under the Curve 
An analysis of variance model with fasting status as fixed effect was fitted to the natural log-transformed pharmacokinetic parameters. 
The geometric least squares mean and geometric mean ratios and confidence intervals were derived by back transforming the point estimates and 
confidence intervals from the model. 
The point estimates and the associated confidence intervals are expressed as percentages. 
If will be concluded that there is a food effect on the rate and extent of absorption of ISLA101 if the point estimates for the AUCinf, AUClast and 
Cmax ratios lie outside of the range of 80 to 125%. 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.1.1 Overall Summary of Adverse Events (Safety Population) 
 
ISLA101 
300 mg Fasted 
(N=xx) 
ISLA101 
600 mg Fasted 
(N=xx) 
ISLA101 
900 mg Fasted 
(N=xx) 
Pooled Placebo 
(N=xx) 
n (%) E 
n (%) E 
n (%) E 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at Least One Serious TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at Least One Severe TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at Least One Treatment-Related TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at least one TEAE leading to study discontinuation. 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at least one TEAE leading to study drug discontinuation. 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Severe adverse events are defined as adverse events where the event severity is reported as ‘Severe’. 
Treatment-related adverse events are defined as adverse events where the relationship to study drug is reported as ‘Possibly’, ‘Probably” or 
‘Definitely” Related or where the relationship is missing. 
Adverse events leading to study drug discontinuation are defined as AEs where action taken is reported as ‘Drug Withdrawn’. 
Adverse events leading to study discontinuation are defined as AEs where ‘Other’ action taken is reported as ‘Withdrawn from study’. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentages (%) are calculated based on the number of subjects in the analysis set (N). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis set (N). 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer Note: 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.1.2 Overall Summary of Adverse Events – Fasted and Fed Cohorts (Safety Population) 
 
ISLA101 
xxx mg Fasted 
(N=xx) 
ISLA101 
xxx mg Fed 
(N=xx) 
Placebo (Fasted) 
(N=xx) 
Placebo (Fed) 
(N=xx) 
n (%) E 
n (%) E 
n (%) E 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at Least One Serious TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at Least One Severe TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at Least One Treatment-Related TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at least one TEAE leading to study discontinuation. 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Subjects with at least one TEAE leading to study drug 
discontinuation. 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Severe adverse events are defined as adverse events where the event severity is reported as ‘Severe’. 
Treatment-related adverse events are defined as adverse events where the relationship to study drug is reported as ‘Possibly’, ‘Probably” or 
‘Definitely” Related or where the relationship is missing. 
Adverse events leading to study drug discontinuation are defined as AEs where action taken is reported as ‘Drug Withdrawn’. 
Adverse events leading to study discontinuation are defined as AEs where ‘Other’ action taken is reported as ‘Withdrawn from study’. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentages (%) are calculated based on the number of subjects in the analysis population (N). 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.2.1 Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
Table 14.3.1.2.2 Summary of Treatment-Emergent Adverse Events by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety 
Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
xxx mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
xxx mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.3.1 Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One Serious TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis 
population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.3.2 Summary of Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety 
Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
xxx mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
xxx mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Subjects with at Least One Serious TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis 
population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.4.1 Summary of Treatment-Related Adverse Events by System Organ Class and Preferred Term (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One Treatment-Related AE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events. 
Treatment-related adverse events are defined as adverse events where the relationship to study drug is reported as ‘Possibly’, ‘Probably” or 
‘Definitely” Related or where the relationship is missing. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wrap onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.4.2 Summary of Treatment-Related Adverse Events by System Organ Class and Preferred Term – Fasted and Fed Cohorts (Safety 
Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
xxx mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
xxx mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Subjects with at Least One Treatment-Related AE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events. 
Treatment-related adverse events are defined as adverse events where the relationship to study drug is reported as ‘Possibly’, ‘Probably” or 
‘Definitely” Related or where the relationship is missing. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.5.1 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Severity Rating 
(Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Mild 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Moderate 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Severe 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Mild 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Moderate 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Severe 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Mild 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Moderate 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Severe 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 
For this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.5.2 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Severity Rating – Fasted and Fed Cohorts 
(Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
xxx mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
xxx mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Mild 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Moderate 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Severe 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Mild 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Moderate 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Severe 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Mild 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Moderate 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Severe 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
n: Number of subjects, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.6.1 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Relationship to Study Drug 
(Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
Relationship to Study Drug 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unrelated 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unlikely 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Possibly 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Probably 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Definitely 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unrelated 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unlikely 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Possibly 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Probably 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Definitely 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unrelated 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unlikely 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Possibly 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Probably 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Definitely 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. For 
this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.6.2 Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and Relationship to Study Drug – Fasted and 
Fed Cohorts (Safety Population) 
 
ISLA101 
ISLA101
System Organ Class (SOC) 
Preferred Term (PT) 
xxx mg Fasted 
xxx mg Fed 
Placebo (Fasted) 
(N=xx) 
(N=xx) 
(N=xx) 
Placebo (Fed) 
(N=xx) 
Relationship to Study Drug 
n (%) E 
n (%) E
n (%) E 
n (%) E 
Subjects with at Least One TEAE 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unrelated 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Possibly Related 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Related 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx 
xx 
(xx%) 
(xx%) 
xx 
xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unrelated 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Possibly Related 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Related 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx 
xx 
(xx%) 
(xx%) 
xx 
xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Unrelated 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Possibly Related 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Related 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.7.1 Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by System Organ Class and 
Preferred Term (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE Leading to Study 
Discontinuation 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Adverse events leading to study discontinuation are defined as AEs where ‘Other’ action taken is reported as ‘Withdrawn from study’. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis 
population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. For 
this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.7.2 Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by System Organ Class and 
Preferred Term – Fasted and Fed Cohorts (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
xxx mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
xxx mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE Leading to Study 
Discontinuation 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Adverse events leading to study discontinuation are defined as AEs where ‘Other’ action taken is reported as ‘Withdrawn from study’. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis 
population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.8.1 Part A SAD: Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and 
Preferred Term (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
300 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
600 mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
900 mg Fasted 
(N=xx) 
n (%) E 
Pooled Placebo 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE Leading to Study Drug 
Discontinuation 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Adverse events leading to study drug discontinuation are defined as AEs where action taken is reported as ‘Drug Withdrawn’. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). 
Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘ (Continued)’ appended to the term. For 
this “Pooled Placebo” group, only the placebo subjects under the fasted condition will be included. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.1.8.2 Summary of Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and 
Preferred Term – Fasted and Fed Cohorts (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
ISLA101 
xxx mg Fasted 
(N=xx) 
n (%) E 
ISLA101 
xxx mg Fed 
(N=xx) 
n (%) E 
Placebo (Fasted) 
(N=xx) 
n (%) E 
Placebo (Fed) 
(N=xx) 
n (%) E 
Subjects with at Least One TEAE Leading to Study 
Drug Discontinuation 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
System Organ Class 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 1 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 2 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 3 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
Preferred Term 4 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
xx (xx%) xx 
 
n: Number of subjects, E: Number of adverse events, TEAE: Treatment-emergent adverse event. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Adverse events leading to study drug discontinuation are defined as AEs where action taken is reported as ‘Drug Withdrawn’. 
Subjects who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the 
event is counted (E). Percentage (%) of subjects (n) in each category are calculated based on the number of subjects in the analysis 
population (N). 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Results will be sorted by alphabetically. 
If PT terms within a SOC wraps onto a second page, the SOC term will be repeated on the second page with ‘(Continued)’ appended to the term. 


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HH:MM/ XX 
Resolved 
Resolving 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 14.3.2.1. Serious Adverse Events (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Subject Number: xxx-xxx 
 
System Organ Class 
End Date 
(SOC)/ Preferred Term 
Start Date 
Time/ 
Signs of 
Relationship 
Other 
AE 
(PT)/ 
Time/ Study 
Study Day/ 
SAE/ 
Drug 
to Study 
Action 
Action 
No. Verbatim Term 
Day/ TEAE 
Ongoing 
AESI/DL_AE 
Toxicity 
Outcome 
Severity 
Drug 
Taken 
Taken 
 
XXXXXXXXXXXXXXXXXXX/ 
1 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM/ XX/ 
Yes 
YYYY-MM-DD 
Yes/Yes/Yes 
Xxxxx 
Recovered/ 
Mild 
Probably 
Unknown 
None 
None 
XXXXXXXXXXXXXXXXXXX/ 
2 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM / XX/ 
Yes 
YYYY-MM-DD 
HH:MM/ 
Ongoing 
Yes/No/No 
- 
Recovering/ 
Severe 
Definitely 
Dose 
not 
Changed 
None 
 
 
AE No.: Adverse Event Number, SAE: Serious adverse event, TEAE: Treatment-emergent adverse event, -: Not Applicable. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Only serious adverse events are presented. 
Study days are calculated relative to the date of the treatment group first study drug administration. 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all AEs that a subject experienced and repeat for all treatment groups. 
Add code list for Other Action Taken if results cannot be fitted onto a single page. 


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HH:MM/ XX 
Resolved 
Resolving 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 14.3.2.2 Adverse Events Leading to Study Discontinuation (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Subject Number: xxx-xxx 
 
System Organ Class 
End Date 
(SOC)/ Preferred Term 
Start Date 
Time/ 
Signs of 
Relationship 
Other 
AE 
(PT)/ 
Time/ Study 
Study Day/ 
SAE/ 
Drug 
to Study 
Action 
Action 
No. Verbatim Term 
Day/ TEAE 
Ongoing 
AESI/DL_AE 
Toxicity 
Outcome 
Severity 
Drug 
Taken 
Taken 
 
XXXXXXXXXXXXXXXXXXX/ 
1 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM/ XX/ 
Yes 
YYYY-MM-DD 
Yes/Yes/Yes 
Xxxxx 
Recovered/ 
Mild 
Probably 
Unknown 
None 
None 
XXXXXXXXXXXXXXXXXXX/ 
2 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM / XX/ 
Yes 
YYYY-MM-DD 
HH:MM/ 
Ongoing 
No/No/No 
- 
Recovering/ 
Severe 
Definitely 
Dose 
not 
Changed 
None 
 
 
AE No.: Adverse Event Number, SAE: Serious adverse event, TEAE: Treatment-emergent adverse event, -: Not Applicable. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Adverse events leading to study discontinuation are defined as AEs where ‘Other’ action taken is reported as ‘Withdrawn from study’. 
Study days are calculated relative to the date of the treatment group first study drug administration. 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all AEs that a subject experienced and repeat for all treatment groups. 
Add code list for Other Action Taken if results cannot be fitted onto a single page. 


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Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 14.3.2.3 Adverse Events Leading to Study Drug Discontinuation (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Subject Number: xxx-xxx 
 
AE 
No. 
System Organ Class (SOC)/ 
Preferred Term (PT)/ 
Verbatim Term 
Start Date 
Time/ Study 
Day/ TEAE 
End Date/ 
Study Day/ 
Ongoing 
Outcome 
SAE 
Severity 
Relationship 
to Study Drug 
Action 
Taken 
Other 
Action 
Taken 
1 
XXXXXXXXXXXXXXXXXXX/ 
YYYY-MM-DD 
YYYY-MM-DD/ 
Recovered/ 
Yes 
Grade 1 
Unrelated 
- 
Withdrawn
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
HH:MM/ XX/ 
Yes 
XX 
Resolved 
(Mild) 
from 
Study 
2 
XXXXXXXXXXXXXXXXXXX/ 
YYYY-MM-DD 
YYYY-MM-DD/ 
Recovering/ 
No 
Grade 3 
Related 
None/ 
Withdrawn
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
HH:MM / XX/ 
Yes 
Ongoing 
Resolving 
(Severe) 
Dose not 
Changed 
from 
Study 
AE No.: Adverse Event Number, SAE: Serious adverse event, TEAE: Treatment-emergent adverse event, -: Not Applicable. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Adverse events leading to study drug discontinuation are defined as AEs where action taken is reported as ‘Drug Withdrawn’. 
Study days are calculated relative to the date of the treatment group first study drug administration. 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all AEs that a subject experienced and repeat for all treatment groups. 
Add code list for Other Action Taken if results cannot be fitted onto a single page. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.1.1.1 Summary of Hematology Results (Safety Population) 
Parameter (Unit) 
 
Treatment Group 
Visit 
Actual Values 
Change from Baseline[1] 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 300 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
ISLA101 600 mg Fasted (N=xx) 
 
 
ISLA101 900 mg Fasted (N=xx) 
 
 
Pooled Placebo (N=xx) 
 
 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 
Start each new parameter on a new page. 
Baseline[1] 
…. 
xx 
xx 
xx.xx 
xx.xx 
xx.xxx 
xx.xxx 
xx.xx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
- 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
…. 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.1.1.2 Summary of Hematology Results – Fasted and Fed Cohorts (Safety Population) 
Parameter (Unit) 
 
Treatment Group 
Visit 
Actual Values 
Change from Baseline[1] 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo (Fasted) (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo (Fed) (N=xx)_ 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer Note: 
Start each new parameter on a new page. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 42 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.1.2.1 Summary of Shifts from Baseline in Hematology Laboratory Range Indicator Categories (Safety Population) 
Parameter (Unit) 
 
Baseline[1] Range Indicator 
 
Treatment Group 
Post-Baseline Visit 
ISLA101 300 mg Fasted (N=xx) 
Post-Baseline 
Range Indicator 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Range Indicators (result classifications) are based on the laboratory defined normal ranges for the specific parameter. 
Percentage (%) are based on the number of participants (n) in the analysis population (N) with assessments available at baseline and the 
relevant post-baseline visit. Only parameters with a defined reference range are included in the table. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
Start each new parameter on a new page. 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 
Day 1 
Low 
Normal 
High 
Total 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
Day 2 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
…< repeat for Day 3,4,5 and follow up visit> 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
ISLA101 600 mg Fasted (N=xx) 
Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
……< repeat for Day 3,4,5 and follow up visit> 
ISLA101 900 mg Fasted (N=xx) 
Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Pooled Placebo (N=xx) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
…Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 43 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.1.2.2 Summary of Shifts from Baseline in Hematology Laboratory Range Indicator Categories – Fasted and Fed Cohorts (Safety 
Population) 
Parameter (Unit) 
 
Baseline[1] Range Indicator 
Treatment Group 
Post-Baseline Visit 
 
ISLA101 xx mg Fasted (N=xx) 
Day 1 
Post-Baseline 
Range Indicator 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Total 
n (%) 
 
 
 
Day 2 
 
 
…< repeat for Day 3,4,5 and follow up visit> 
… 
ISLA101 xx mg Fed (N=xx) 
Day 1 
 
 
……< repeat for Day 3,4,5 and follow up visit> 
Placebo (Fasted) (N=xx) 
Day 1 
 
 
Placebo (Fed) (N=xx) 
…Day 1 
……< repeat for Day 3,4,5 and follow up visit> 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Range Indicators (result classifications) are based on the laboratory defined normal ranges for the specific parameter. 
Percentage (%) are based on the number of participants (n) in the analysis set (N) with assessments available at baseline and the relevant 
post-baseline visit. Only parameters with a defined reference range are included in the table. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: Start each new parameter on a new page. 
Low 
Normal 
High 
Total 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 44 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.2.1.1 Summary of Biochemistry Results (Safety Population) 
Parameter (Unit):xxx 
 
Treatment Group 
Visit 
Actual Values 
Change from Baseline[1] 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 300 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
ISLA101 600 mg Fasted (N=xx) 
 
 
ISLA101 900 mg Fasted (N=xx) 
 
 
Pooled Placebo (N=xx) 
 
 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programming note: 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 
Baseline[1] 
…. 
xx 
xx 
xx.xx 
xx.xx 
xx.xxx 
xx.xxx 
xx.xx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
- 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
…. 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 45 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.2.1.2 Summary of Biochemistry Results – Fasted and Fed Cohorts (Safety Population) 
Parameter (Unit): 
 
Treatment Group 
Visit 
Actual Values 
Change from Baseline[1] 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo (Fasted) (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo (Fed) (N=xx)_ 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Start each new parameter on a new page. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 46 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.2.2.1 Summary of Shifts from Baseline in Biochemistry Laboratory Range Indicator Categories (Safety Population) 
Parameter (Unit) 
 
Baseline[1] Range Indicator 
 
Treatment Group 
Post-Baseline Visit 
ISLA101 300 mg Fasted (N=xx) 
Post-Baseline 
Range Indicator 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Range Indicators (result classifications) are based on the laboratory defined normal ranges for the specific parameter. 
Percentage (%) are based on the number of participants (n) in the analysis population (N) with assessments available at baseline and the 
relevant post-baseline visit. Only parameters with a defined reference range are included in the table. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
Start each new parameter on a new page. 
Day 1 
Low 
Normal 
High 
Total 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
Day 2 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
…< repeat for Day 3,4,5 and follow up visit> 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
ISLA101 600 mg Fasted (N=xx) 
Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
……< repeat for Day 3,4,5 and follow up visit> 
ISLA101 900 mg Fasted (N=xx) 
Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Pooled Placebo (N=xx) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
…Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 47 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.2.2.2 Summary of Shifts from Baseline in Biochemistry Laboratory Range Indicator Categories – Fasted and Fed Cohorts (Safety 
Population) 
Parameter (Unit) 
 
Baseline[1] Range Indicator 
Treatment Group 
Post-Baseline Visit 
 
ISLA101 xx mg Fasted (N=xx) 
Day 1 
Post-Baseline 
Range Indicator 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Total 
n (%) 
 
 
 
Day 2 
 
 
…< repeat for Day 3,4,5 and follow up visit> 
… 
ISLA101 xx mg Fed (N=xx) 
Day 1 
 
 
……< repeat for Day 3,4,5 and follow up visit> 
Placebo (Fasted) (N=xx) 
Day 1 
 
 
Placebo (Fed) (N=xx) 
…Day 1 
……< repeat for Day 3,4,5 and follow up visit> 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Range Indicators (result classifications) are based on the laboratory defined normal ranges for the specific parameter. 
Percentage (%) are based on the number of participants (n) in the analysis set (N) with assessments available at baseline and the relevant 
post-baseline visit. Only parameters with a defined reference range are included in the table. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: Start each new parameter on a new page. 
Low 
Normal 
High 
Total 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 48 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.3.1.1 Summary of Coagulation Results (Safety Population) 
Parameter (Unit):xxx 
 
Treatment Group 
Visit 
Actual Values 
Change from Baseline[1] 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 300 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
ISLA101 600 mg Fasted (N=xx) 
 
 
ISLA101 900 mg Fasted (N=xx) 
 
 
Pooled Placebo (N=xx) 
 
 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programming note: 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 
Baseline[1] 
…. 
xx 
xx 
xx.xx 
xx.xx 
xx.xxx 
xx.xxx 
xx.xx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
- 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
…. 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 49 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.3.1.2 Summary of coagulation Results – Fasted and Fed Cohorts (Safety Population) 
Parameter (Unit): 
 
Treatment Group 
Visit 
Actual Values 
Change from Baseline[1] 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo (Fasted) (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo (Fed) (N=xx)_ 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Start each new parameter on a new page. 


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Version and Date: Final Version 1.0, 2023-12-07 
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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.3.2.1 Summary of Shifts from Baseline in Coagulation Laboratory Range Indicator Categories (Safety Population) 
Parameter (Unit) 
 
Baseline[1] Range Indicator 
 
Treatment Group 
Post-Baseline Visit 
ISLA101 300 mg Fasted (N=xx) 
Post-Baseline 
Range Indicator 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Total 
n (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Range Indicators (result classifications) are based on the laboratory defined normal ranges for the specific parameter. 
Percentage (%) are based on the number of participants (n) in the analysis population (N) with assessments available at baseline and the 
relevant post-baseline visit. Only parameters with a defined reference range are included in the table. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer Note: 
Start each new parameter on a new page. 
Day 1 
Low 
Normal 
High 
Total 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
Day 2 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
…< repeat for Day 3,4,5 and follow up visit> 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
ISLA101 600 mg Fasted (N=xx) 
Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
……< repeat for Day 3,4,5 and follow up visit> 
ISLA101 900 mg Fasted (N=xx) 
Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Pooled Placebo (N=xx) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
…Day 1 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.3.2.2 Summary of Shifts from Baseline in Coagulation Laboratory Range Indicator Categories – Fasted and Fed Cohorts (Safety 
Population) 
Parameter (Unit) 
 
Baseline[1] Range Indicator 
Treatment Group 
Post-Baseline Visit 
 
ISLA101 xx mg Fasted (N=xx) 
Day 1 
Post-Baseline 
Range Indicator 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Total 
n (%) 
 
 
 
Day 2 
 
 
…< repeat for Day 3,4,5 and follow up visit> 
… 
ISLA101 xx mg Fed (N=xx) 
Day 1 
 
 
……< repeat for Day 3,4,5 and follow up visit> 
Placebo (Fasted) (N=xx) 
Day 1 
 
 
Placebo (Fed) (N=xx) 
…Day 1 
……< repeat for Day 3,4,5 and follow up visit> 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Range Indicators (result classifications) are based on the laboratory defined normal ranges for the specific parameter. 
Percentage (%) are based on the number of participants (n) in the analysis set (N) with assessments available at baseline and the relevant 
post-baseline visit. Only parameters with a defined reference range are included in the table. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: Start each new parameter on a new page. 
Low 
Normal 
High 
Total 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
xx 
xx 
xx 
xx 
(xx.x) 
(xx.x) 
(xx.x) 
(xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Total 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.4.1.1 Summary of Dipstick Urinalysis Results (Safety Population) 
Parameter (unit): 
Treatment Group 
 
 
 
Result Classification 
 
Visit 
Normal 
n 
n (%) 
Abnormal NCS 
n (%) 
Abnormal CS 
n (%) 
ISLA101 300 mg Fasted (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Day 1 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Day 2 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Day 3 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
<repeat for Day 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ISLA101 600 mg Fasted (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
<repeat for Day1,2,3 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ISLA101 900 mg Fasted (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…<repeat for Day1,2,3 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Pooled Placebo (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…<repeat for Day1,2,3 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
[1] The baseline value is defined as the last available valid, non-missing observation prior to the first study drug administration. 
CS: Clinically significant; NCS: Not clinically Significant. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programming Note: 
Start each new parameter on a new page. 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 


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Version and Date: Final Version 1.0, 2023-12-07 
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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.4.4.1.2 Summary of Dipstick Urinalysis Results – Fasted and Fed Cohorts (Safety Population) 
Parameter (unit): 
Treatment Group 
 
 
 
Result Classification 
 
Visit 
Normal 
n 
n (%) 
Abnormal NCS 
n (%) 
Abnormal CS 
n (%) 
ISLA101 xxx mg Fasted (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Day 1 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Day 2 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Day 3 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
<repeat for Day 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ISLA101 xxx mg Fed (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
<repeat for Day1,2,3 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Placebo (Fasted) (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…<repeat for Day1,2,3 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Placebo (Fed) (N=X) 
Baseline[1] 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…<repeat for Day1,2,3 4,5, follow-up visit> 
xx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
[1] The baseline value is defined as the last available valid, non-missing observation prior to the first study drug administration. 
CS: Clinically significant; NCS: Not clinically Significant. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programming Note: 
Start each new parameter on a new page. 


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Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
 
 
Table 14.3.5.1 Summary of Vital Signs Results (Safety Population) 
 
Parameter (Unit) 
 
Treatment Group 
Visit: Time Point 
 
 
Actual Values 
Change from Baseline[1] 
 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 300 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
ISLA101 600 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
…… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
ISLA101 900 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Pooled Placebo (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Programmer note: 
Start each new parameter on a new page. 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 
Present the results in the following order: 
• 
SBP. 
• 
DBP. 
• 
Pulse Rate. 
• 
Respiratory Rate. 
• 
Temperature. 
• 
BSA. 


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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.5.2 Summary of Vital Signs Results – Fasted and Fed Cohorts (Safety Population) 
 
Parameter (Unit) 
 
Treatment Group 
Visit: Time Point 
 
 
Actual Values 
Change from Baseline[1] 
 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 xx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 2 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 3 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 4 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Day 5 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Follow-up 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
ISLA101 xx mg Fed (N=xx) 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
….. 
Placebo (Fasted) (N=xx) 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Placebo (Fed) (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
… 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Version and Date: Final Version 1.0, 2023-12-07 
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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
 
 
Table 14.3.6.1.1 Summary of 12-Lead ECG Results (Safety Population) 
 
Parameter (Unit) 
 
Treatment Group 
Visit: Time Point 
 
 
Actual Values 
Change from Baseline[1] 
 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 300 mg Fasted (N=xx) 
Baseline[1] 
Day 1- 5 hours post dose 
xx 
xx 
xx.xx 
xx.xx 
xx.xxx 
xx.xxx 
xx.xx 
xx.xx 
xx.x 
xx.x 
xx.x 
xx.x 
- 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
ISLA101 600 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
ISLA101 900 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
Pooled Placebo (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to study drug administration in that period. 
Where triplicate measurements were taken, summaries were based on the mean of the triplicate measurements at each visit/time point. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Start each new parameter on a new page. 
Present the results in the following order: 
• 
Heart Rate. 
• 
RR Interval. 
• 
QTcF Interval. 
• 
PR Duration. 
 
• 
QRS Interval. 
 


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Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.6.1.2 Summary of 12-Lead ECG Results – Fasted and Fed Cohorts (Safety Population) 
 
Parameter (Unit) 
 
Treatment Group 
Visit: Time Point 
 
 
Actual Values 
Change from Baseline[1] 
 
 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
ISLA101 xx mg Fed (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo Fasted (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
Placebo Fed (N=xx) 
Baseline[1] 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
- 
Day 1- 5 hours post dose 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
xx 
xx.xx 
xx.xxx 
xx.xx 
xx.x 
xx.x 
 
SD: Standard deviation, - : Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to study drug administration in that period. 
Where triplicate measurements were taken, summaries were based on the mean of the triplicate measurements at each visit/time point. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
Table 14.3.6.2.1 Summary of 12-Lead ECG Overall Assessment (Safety Population) 
 
 
Treatment Group 
Visit: Time Point 
 
 
Normal 
n 
n (%) 
 
Overall Assessment 
Abnormal NCS 
n (%) 
 
 
Abnormal CS 
n (%) 
 
 
ISLA101 300 mg Fasted (N=xx) 
Baseline[1] 
Day 1- 5 hours post dose 
xx 
xx 
xx 
xx 
(xx.xx%) 
(xx.xx%) 
xx 
xx 
(xx.xx%) 
(xx.xx%) 
xx 
xx 
(xx.xx%) 
(xx.xx%) 
ISLA101 600 mg Fasted (N=xx) 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Baseline[1] 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Day 1- 5 hours post dose 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
ISLA101 900 mg Fasted (N=xx) 
Baseline[1] 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Day 1- 5 hours post dose 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Pooled Placebo (N=xx) 
Baseline[1] 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Day 1- 5 hours post dose 
… 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
CS: Clinically Significant, NCS: Not Clinically Significant 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Percentage (%) are based on the number of participants (n) with assessments available at the relevant post-baseline visit. 
Where triplicate measurements were taken, summaries were based on the worst overall interpretation of the triplicate measurements at each 
visit/time point. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
The treatment groups will be displayed for the following: ISLA101 300 mg Fasted, ISLA101 600 mg Fasted, ISLA101 900 mg Fasted, Pooled Placebo. 


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Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Table 14.3.6.2.2 Summary of 12-Lead ECG Overall Assessment - Fasted and Fed Cohorts (Safety Population) 
 
 
Treatment Group 
Visit: Time Point 
 
 
Normal 
n 
n (%) 
 
Overall Assessment 
Abnormal NCS 
n (%) 
 
 
Abnormal CS 
n (%) 
 
 
ISLA101 xxx mg Fasted (N=xx) 
Baseline[1] 
Day 1- 5 hours post dose 
xx 
xx 
xx 
xx 
(xx.xx%) 
(xx.xx%) 
xx 
xx 
(xx.xx%) 
(xx.xx%) 
xx 
xx 
(xx.xx%) 
(xx.xx%) 
ISLA101 xxx mg Fed (N=xx) 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Baseline[1] 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Day 1- 5 hours post dose 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Placebo Fasted (N=xx) 
Baseline[1] 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Day 1- 5 hours post dose 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Placebo Fed (N=xx) 
Baseline[1] 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
Day 1- 5 hours post dose 
… 
xx 
xx (xx.xx%) 
xx (xx.xx%) 
xx (xx.xx%) 
CS: Clinically Significant, NCS: Not Clinically Significant 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Percentage (%) are based on the number of participants (n) with assessments available at the relevant post-baseline visit. 
Where triplicate measurements were taken, summaries were based on the worst overall interpretation of the triplicate measurements at each 
visit/time point. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.1.1 Analysis Sets (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Analysis Set 
 
Included in 
Analysis Set 
Reason if Excluded from Analysis set 
 
xxx-xxx 
Safety Population 
Yes 
Pharmacokinetic Population 
Yes 
xxx-xxx 
Safety Population 
Pharmacokinetic Population 
Yes 
Yes 
… 
 
This Safety Population will include all subjects who received at least 1 dose of the study drug (ISLA101 or Placebo). 
The PK Population will consist of all subjects in the safety population who have a pre-dose PK sample and at least 1 post-dose analyzable PK 
sample and at least 1 post-dose analyzable PK sample (quantifiable Plasma concentration). 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.1.2 Subject Disposition (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
 
Subject 
Number 
Date of Informed Consent 
Date Time of First Study Drug 
Administration 
Subject Completed the Study / If No, 
Reason 
End of Study Date/ 
Study Day 
xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
HH:MM 
Yes 
YYYY-MM-DD/ 
XX 
xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
HH:MM 
No – AE No. 
YYYY-MM-DD/ 
XX 
xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
HH:MM 
No – PD No. 
YYYY-MM-DD/ 
XX 
xxx-xxx 
YYYY-MM-DD 
YYYY-MM-DD 
HH:MM 
Yes 
YYYY-MM-DD/ 
XX 
 
 
 
 
 
 
Study days are calculated relative to the date of the study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.2.1 Protocol Deviations (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Deviation 
Number 
Start Date 
of Deviation 
Deviation 
Category 
Deviation 
Type 
 
Assessment 
Type 
Deviation Description 
Reported to 
HREC/If Yes, 
Date 
Reason for Not 
Reported to HREC 
Missed 
Procedure/A 
XXXXXXXXXXXXXXXXXXXXXXXX 
xxx-xxx 
xx 
YYYY-MM-DD 
Minor 
ssessments 
12-lead ECG 
X 
No 
XXXXXXX 
Major 
XXXXXXXXXX 
XXXXXXXXXXX 
XXXXXXXXXXX 
Other 
Vital Sign 
Xxxx 
xxxx 
XXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXX 
X 
XXXXXXXXXXXXXXXXXXXXXXXX 
X 
XXXXXXXXXXXXXXXXXXXXXXXX 
X 
Yes/ YYYY-MM-DD 
NA 
No 
 
 
 
 
 
 
NA: Not Applicable; HREC: Human Research Ethics Committees. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.2.2 Subject Eligibility (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Visit 
Protocol Date/Version 
Eligibility Assessment 
Date 
Did the Subject Meet 
All Eligibility 
Criteria 
Category Failed 
(Inclusion/ 
Exclusion) 
Inclusion Criterion not 
met/ 
Exclusion Criterion met 
xxx-xxx 
Screening 
ISLA101-P01-CT001, 18- 
Sep-2023,V1.1 
YYYY-MM-DD 
No 
Inclusion and 
Exclusion 
Exclusion: xx, xx; 
Inclusion xx, xx 
Day -1 
YYYY-MM-DD 
Yes 
 
 
 
 
 
 
 
 
 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. List all screening failures at the beginning of the listing. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.3 Randomization (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
 
 
Subject Number 
Date of Randomization 
Replacement Subject 
Randomization Number/Replacement 
Randomization Number 
xxx-xxx 
YYYY-MM-DD HH:MM 
No 
xxxxxxxx 
xxx-xxx 
YYYY-MM-DD HH:MM 
Yes 
xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group, and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.1 Demography (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
 
Subject 
Number 
Year of 
Birth 
Age 
(Years) 
Sex 
Childbearing Potential, 
No – Specify 
Ethnicity 
Race 
xxx-xxx 
YYYY 
xx 
Female 
Yes 
Hispanic or Latino 
White 
xxx-xxx 
YYYY 
xx 
Male 
- 
Hispanic or Latino 
Other - XXXXXXXXXXXXX 
xxx-xxx 
YYYY 
xx 
Female 
No – Postmenopausal 
Not Hispanic or Latino 
Asian 
xxx-xxx 
YYYY 
xx 
Female 
No – Perimenopausal 
Not Hispanic or Latino 
Asian 
 
 
 
 
-: Not applicable. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.2 Medical and Surgical History (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject MH 
Number 
No. 
Subcategory 
System Organ Class/ 
Preferred Term/ 
Medical Name 
Start Date/ 
Study Day 
End Date / 
Study Day 
Ongoing 
XXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX/ 
YYYY-MM-DD/ 
xxx-xxx 1 
Surgery 
XXXXXXXXXXXXXXXXXXXXXX 
-XXX 
YYYY-MM 
No 
XXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX/ 
YYYY-MM-DD/ 
YYYY-MM-DD/ 
2 
Endocrine 
XXXXXXXXXXXXXXXXXXXXXX 
-XXX 
-XXX 
No 
XXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX/ 
YYYY-MM-DD/ 
3 
Other 
XXXXXXXXXXXXXXXXXXXXXX 
-XXX 
Yes 
 
MH = Medical History. 
Study days are calculated relative to the date of the first study drug administration. 
 
Medical history terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 
Sort terms by start and end date, then alphabetically within subject. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.3 Alcohol Breath Test Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
 
Subject Number 
Visit 
Assessment Date 
Alcohol Breath Test Results 
Specify Equivocal/Unevaluable 
xxx-xxx 
Screening 
Day -1 
YYYY-MM-DD 
YYYY-MM-DD 
Negative 
Equivocal/Unevaluable 
- 
xxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
-: Not applicable. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects/visits/drugs or test within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.4 Urine Drug Test Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Visit 
Sample 
Collected 
Date 
Test 
Urine Drug Test Results 
Drugs Tested Positive 
Specify 
Equivocal/Unevaluable 
xxx-xxx 
Screening 
YYYY-MM-DD 
Urine Drug 
Cotinine 
Positive 
Negative 
Amphetamines 
Barbiturates 
Benzodiazepines 
- 
- 
- 
Day -1 
YYYY-MM-DD 
Urine Drug 
Negative 
- 
- 
Cotinine 
Negative 
- 
- 
-: Not applicable. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects/visits/drugs or test within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.5 Pregnancy Test Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject Number 
Visit 
Sample 
Collection Date 
Specimen 
type 
Result 
Specify Equivocal/Unevaluable 
xxx-xxx 
Screening 
Day-1 
YYYY-MM-DD 
YYYY-MM-DD 
Urine 
Serum 
Negative 
Equivocal/Unevaluable 
- 
xxxxxxxxxxx 
 
 
 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.6 Serology Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject Number 
Visit 
Sample Collection Date 
Time 
Parameter 
Result 
xxx-xxx 
Screening 
YYYY-MM-DD HH: MM 
HBsAg 
Hepatitis C Virus 
HIV 1/2 
Negative 
Negative 
Negative 
 
 
 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.7.1 Prior Medications (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Subject Number: xxx-xxx 
 
CM 
No 
. 
WHO-DD ATC Class Level 2 Term/ 
WHO-DD Preferred Name/ 
Verbatim Term 
Indication 
Category 
Dose 
Unit 
Frequency 
Route 
Start Date/ 
Study Day 
End Date/ 
Study Day 
ZZZZZZZZZZZZZZZZZZZ/ 
XXXXXXXXXXXXXXXXXXX/ 
Medical 
History: MH 
YYYY-MM-DD/ 
YYYY-MM-DD/ 
1 
YYYYYYYYYYYYYYYYYYY 
XXXXXXX 
No. 
xx.x 
XXX 
XXXXXXXX 
XXXXXX 
XX 
XX 
ZZZZZZZZZZZZZZZZZZZ/ 
XXXXXXXXXXXXXXXXXXX/ 
Adverse 
Event: AE 
YYYY-MM-DD/ 
YYYY-MM-DD/ 
2 
YYYYYYYYYYYYYYYYYYY 
XXXXXX 
No. 
xx.x 
XXX 
XXXXXXXX 
XXXXXX 
XX 
XX 
CM No.: Medication Number. 
Prior medications are defined as any medication where the use was stopped prior to the first administration of study drug. 
Only prior medications are presented. 
Study days are calculated relative to the date of the first study drug administration. 
Medication terms were coded using the World Health Organisation – Drug Dictionary Version Global (WHO-DD) C3, September 2023. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.4.7.2 Concomitant Medications (Safety Population) 
 
Cohort 1: ISLA101 100 mg Fasted 
Subject Number: xxx-xxx 
 
CM 
No 
. 
WHO-DD ATC Class Level 2 Term/ 
WHO-DD Preferred Name/ 
Verbatim Term 
Indication 
Category 
Dose 
Unit 
Frequency 
Route 
Start Date/ 
Study Day 
End Date/ 
Study Day 
ZZZZZZZZZZZZZZZZZZZ/ 
XXXXXXXXXXXXXXXXXXX/ 
Medical 
History – 
YYYY-MM-DD/ 
YYYY-MM-DD/ 
1 
YYYYYYYYYYYYYYYYYYY 
Xxxxxx 
Headache 
xx.x 
XXX 
XXXXXXXX 
XXXXXX 
XX 
XX 
ZZZZZZZZZZZZZZZZZZZ/ 
XXXXXXXXXXXXXXXXXXX/ 
Adverse 
Event - 
YYYY-MM-DD/ 
YYYY-MM-DD/ 
2 
YYYYYYYYYYYYYYYYYYY 
xxxxxxx 
XXXXXXXXXXX 
xx.x 
XXX 
XXXXXXXX 
XXXXXX 
XX 
Ongoing 
CM No.: Medication Number. 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration 
of study drug. Medications stopping on the same day as the first study drug administration will be considered as concomitant medications. 
Only concomitant medications are presented. 
Study days are calculated relative to the date of the first study drug administration. 
 
Medication terms were coded using the World Health Organisation – Drug Dictionary Version Global (WHO-DD) C3, September 2023. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Version and Date: Final Version 1.0, 2023-12-07 
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Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.5.1 Study Drug Administration (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Take High Fat Meal 
How Many 
Fasting at Least 4 
Hours After Study 
Date Time of Last 
Before Dosing/ 
Date Time of 
Dispensed 
All Capsules 
Drug 
Meal (Before 
Date time of High 
First Capsule 
Capsules 
consumed/ If No, 
Administration/ If 
Subject Number 
Visit 
Fasting) 
Fat Meal consumed 
consumed/ Dose 
Administered 
Capsules consumed 
No, hours (Fasted) 
xxx-xxx 
Day 1 
YYYY-MM-DD HH:MM 
No 
YYYY-MM-DD 
HH:MM/ 300 mg/m2 
xx 
Yes 
No/ xx hrs 
xxx-xxx 
Day 1 
YYYY-MM-DD HH:MM 
Yes/ YYYY-MM-DD 
HH:MM 
YYYY-MM-DD 
HH:MM/ 300 mg/m2 
Xx 
No/ xx 
Yes 
xxx-xxx 
Day 1 
YYYY-MM-DD HH:MM 
No 
 
 
 
 
 
 
 
 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups. 


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Version and Date: Final Version 1.0, 2023-12-07 
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Tables, Listings and Figures Shells 
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Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.6.1 Plasma Pharmacokinetic Concentrations (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Cohort 1: ISLA101 300 mg Fasted 
 
 
 
 
Subject Number 
Time Point 
Sample Collection Date Time 
Elapsed Time Since Study 
Drug Administration 
(Hours) 
 
Time Deviation 
(Minutes) 
Concentration (ng/mL) 
 
xxx-xxx 
Pre-dose 
YYYY-MM-DD HH:MM 
- 
- 
BLQ 
0.5 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
0.75 hour 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
1 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
1.5 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
2 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
3 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
4 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
5 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
6 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
8 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
10 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
12 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
24 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
XX.XX 
36 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
48 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
72 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
96 hours 
YYYY-MM-DD HH:MM 
xx.xx 
xx 
xx.xx 
 
BLQ: Below the LLOQ; LLOQ: Lower Limit of Quantification; 
Elapsed Time Since Study Drug Administration is calculated as the difference between the Date Time of the sample collection and the Date Time 
of the study drug administration for the specific period. 
Time Deviation is calculated as the difference between the Elapsed Time Since Study Drug Administration and the nominal visit or time point in 
the specific period. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer Note: 
Repeat for all treatment groups. 
Repeat for the analyte = MPR and oxo-HPR 


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Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
 
Listing 16.2.6.2 Plasma Pharmacokinetic Parameters (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Cohort 1: ISLA101 300 mg Fasted 
 
 
Subject 
Number 
Cmax 
(ng/ml) 
DN_Cmax 
Tmax 
(ng/ml) 
(h) 
AUC0-24 
(h*ng/ml) 
AUClast 
(h*ng/ml) 
DN_AUClast 
(h*ng/ml) 
AUCinf 
(h*ng/ml) 
DN_AUCinf 
(h*ng/ml) 
CL/F 
(L/h) 
Vz/F 
(L) 
Adjusted 
R2 
No. of 
Points 
Span 
λz 
(1/h) 
t1/2 
(h) 
%AUCextrap 
(%) 
xx-xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx-xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx-xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx-xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx-xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
DN: Dose Normalized; AUC: Area Under the Curve. 
*Result excluded from the summaries and analyses. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmers note: 
Repeat for the analyte = MPR and oxo-HPR 


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HH:MM/ XX 
Resolved 
Resolving 
 
 
Tables, Listings and Figures Shells 
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Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.7.1 Adverse Events (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Subject Number: xxx-xxx 
 
System Organ Class 
End Date 
(SOC)/ Preferred Term 
Start Date 
Time/ 
Signs of 
Relationship 
Other 
AE 
(PT)/ 
Time/ Study 
Study Day/ 
SAE/ 
Drug 
to Study 
Action 
Action 
No. Verbatim Term 
Day/ TEAE 
Ongoing 
AESI/DL_AE 
Toxicity 
Outcome 
Severity 
Drug 
Taken 
Taken 
 
XXXXXXXXXXXXXXXXXXX/ 
1 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM/ XX/ 
Yes 
YYYY-MM-DD 
Yes/Yes/Yes 
Xxxxx 
Recovered/ 
Mild 
Probably 
Unknown 
None 
None 
XXXXXXXXXXXXXXXXXXX/ 
2 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM / XX/ 
Yes 
YYYY-MM-DD 
HH:MM/ 
Ongoing 
No/No/No 
- 
Recovering/ 
Severe 
Definitely 
Dose 
not 
Changed 
None 
 
 
AE No.: Adverse Event Number, SAE: Serious adverse event, TEAE: Treatment-emergent adverse event, AESI: Adverse event of special interest, 
DL: Dose-Limiting, -: Not Applicable. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Study days are calculated relative to the date of the treatment group first study drug administration. 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all AEs that a subject experienced and repeat for all treatment groups. 


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HH:MM/ XX 
Resolved 
Resolving 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Listing 16.2.7.2 Treatment-Related Adverse Events (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
Subject Number: xxx-xxx 
 
System Organ Class 
End Date 
(SOC)/ Preferred Term 
Start Date 
Time/ 
Signs of 
Relationship 
Other 
AE 
(PT)/ 
Time/ Study 
Study Day/ 
SAE/ 
Drug 
to Study 
Action 
Action 
No. Verbatim Term 
Day/ TEAE 
Ongoing 
AESI/DL_AE 
Toxicity 
Outcome 
Severity 
Drug 
Taken 
Taken 
 
XXXXXXXXXXXXXXXXXXX/ 
1 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM/ XX/ 
Yes 
YYYY-MM-DD 
Yes/Yes/Yes 
Xxxxx 
Recovered/ 
Mild 
Probably 
Unknown 
None 
None 
XXXXXXXXXXXXXXXXXXX/ 
2 
YYYYYYYYYYYYYYYYYYY/ 
ZZZZZZZZZZZZZZZZZZZ 
YYYY-MM-DD 
HH:MM / XX/ 
Yes 
YYYY-MM-DD 
HH:MM/ 
Ongoing 
No/No/No 
- 
Recovering/ 
Severe 
Definitely 
Dose 
not 
Changed 
None 
 
 
AE No.: Adverse Event Number, SAE: Serious adverse event, TEAE: Treatment-emergent adverse event, AESI: Adverse event of special interest, 
DL: Dose-Limiting, -: Not Applicable. 
Treatment-emergent adverse events are defined as adverse events that commenced or worsened on or after the first study drug administration. 
Study days are calculated relative to the date of the treatment group first study drug administration. 
Only treatment related AE will be presented. 
Adverse event terms were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 26.1. 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all AEs that a subject experienced and repeat for all treatment groups. 


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Protocol: ISLA101-P01-CT001 
Listing 16.2.8.1 Hematology Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Parameter 
(Unit) 
Visit 
Sample Collection 
Date Time 
Result 
Change from 
Baseline[1] 
Reference Range 
(Low, High) 
Reference Range 
Indicator 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day -1[1] 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Low 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 3 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 4 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Low 
… 
Day 5 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 8 – Follow Up 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day -1 [1] 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Early Termination 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
High 
 
-: Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Reference range indicators (result classifications) are based on the laboratory defined reference ranges for the specific parameter. 
 
Program Name: xxx.sas, Creation Date and Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Repeat for all treatment groups. Repeat for all parameters/subjects within a treatment group. 
Present ‘Early Termination’ or ‘Day 8 - Follow up’ or ‘Day 17 - Follow Up’ depending on whether the subjects complete the study or not. 


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Listing 16.2.8.2 Biochemistry Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Parameter 
(Unit) 
Visit 
Sample Collection 
Date Time 
Result 
Change from 
Baseline[1] 
Reference Range 
(Low, High) 
Reference Range 
Indicator 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day -1[1] 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Low 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 3 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 4 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Low 
… 
Day 5 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 8 – Follow Up 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day -1 [1] 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Early Termination 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
High 
 
-: Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Reference range indicators (result classifications) are based on the laboratory defined reference ranges for the specific parameter. 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all treatment groups. Repeat for all parameters/subjects within a treatment group. 
Present ‘Early Termination’ or ‘Day 8 - Follow up’ or ‘Day 17 - Follow Up’ depending on whether the subjects complete the study or not. 


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Listing 16.2.8.3 Coagulation Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Parameter 
(Unit) 
Visit 
Sample Collection 
Date Time 
Result 
Change from 
Baseline[1] 
Reference Range 
(Low, High) 
Reference Range 
Indicator 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day -1[1] 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Low 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 3 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 4 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Low 
… 
Day 5 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 8 - Follow Up 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day -1 [1] 
YYYY-MM-DD HH:MM 
XXX 
- 
(XXX, XXX) 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
Early Termination 
YYYY-MM-DD HH:MM 
XXX 
XXX 
(XXX, XXX) 
High 
 
-: Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Reference range indicators (result classifications) are based on the laboratory defined reference ranges for the specific parameter. 
 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programmer note: 
Repeat for all treatment groups. Repeat for all parameters/subjects within a treatment group. 
Present ‘Early Termination’ or ‘Day 8 - Follow up’ or ‘Day 17 - Follow Up’ depending on whether the subjects complete the study or not. 


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Listing 16.2.8.4 Urinalysis Results Including Microscopy (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Parameter (Unit) 
Visit 
Sample Collection Date Time 
Result 
Result Evaluation 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Day -1[1] 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
NCS 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
NCS 
Day 3 
YYYY-MM-DD HH:MM 
XXX 
CS 
Day 4 
YYYY-MM-DD HH:MM 
XXX 
Normal 
… 
Day 5 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Day 8 – Follow Up 
YYYY-MM-DD HH:MM 
XXX 
Normal 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Day -1 [1] 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
Normal 
Early Termination 
YYYY-MM-DD HH:MM 
XXX 
Normal 
 
-: Not applicable, CS: Clinically significant, NCS Not clinically significant. 
[1] The baseline value is defined as the last available valid assessment collected prior to first study drug administration. 
Clinical significance flags as reported by the Investigator. 
Programmer note: 
Repeat for all treatment groups. Repeat for all parameters/subjects within a treatment group. 
Present ‘Early Termination’ or ‘Day 8 - Follow up’ or ‘Day 17 - Follow Up’ depending on whether the subject complete the study or not. 


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Listing 16.2.9.1 Vital Signs Results (Safety Population) 
 
 Cohort 1: ISLA101 300 mg Fasted 
 
 
Subject 
Number 
Parameter 
(Unit) 
Visit 
Assessment Date Time 
Result 
Change from Baseline[1] 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
Day -1 [1] 
YYYY-MM-DD HH:MM 
XXX 
- 
Day 1 
YYYY-MM-DD HH:MM 
XXX 
XXX 
Day 2 
YYYY-MM-DD HH:MM 
XXX 
XXX 
Day 3 
YYYY-MM-DD HH:MM 
XXX 
XXX 
Day 4 
YYYY-MM-DD HH:MM 
XXX 
XXX 
Day 5 
YYYY-MM-DD HH:MM 
XXX 
XXX 
Day 8 - Follow Up 
YYYY-MM-DD HH:MM 
XXX 
XXX 
xxx-xxx 
XXXXXX (XX) 
Screening 
YYYY-MM-DD HH:MM 
XXX 
- 
Day -1 [1] 
YYYY-MM-DD HH:MM 
XXX 
- 
Early Termination 
YYYY-MM-DD HH:MM 
XXX 
XXX 
 
-: Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to the first study drug administration. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programmer note: 
Repeat for all treatment groups. Repeat for all parameters/subjects within a treatment group. 
Present ‘Early Termination’ or ‘Day 8 - Follow up’ or ‘Day 17 - Follow Up’ depending on whether the subjects complete the study or not. 
Present the results in the following order: 
SBP, DBP, Pulse Rate, Respiratory Rate, Temperature, Height, Body Weight, BMI, BSA. 


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Listing 16.2.9.2.1 12-Lead ECG Results (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Parameter (Unit) 
Visit 
Trace 
Reading 
Assessment Date Time 
Result 
Change from 
Baseline[1] 
xxx-xxx 
XXXXX 
Screening 
1 
YYYY-MM-DD HH:MM 
XXX 
- 
2 
YYYY-MM-DD HH:MM 
XXX 
- 
3 
Mean 
YYYY-MM-DD HH:MM 
XXX 
XXX.X 
- 
- 
Day -1 [1] 
1 
YYYY-MM-DD HH:MM 
XXX 
- 
2 
YYYY-MM-DD HH:MM 
XXX 
- 
3 
Mean 
YYYY-MM-DD HH:MM 
XXX 
XXX.X 
- 
- 
Day 1 – 5 hours Post Dose 
1 
YYYY-MM-DD HH:MM 
XXX 
2 
YYYY-MM-DD HH:MM 
XXX 
3 
Mean 
YYYY-MM-DD HH:MM 
XXX 
XXX.X 
XXX.X 
 
 
 
 
-: Not applicable. 
[1] The baseline value is defined as the last available valid assessment collected prior to the first study drug administration. 
Where triplicate measurements were taken, continuous results were based on the mean of the triplicate measurements and overall interpretation 
was based on the worst overall interpretation of the triplicate measurements at each visit/time point. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Present the results in the following order: 
• 
Heart Rate. 
• 
RR Interval. 
• 
PR Interval. 
• 
QRS Duration. 
• 
QTcF Interval. 


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Listing 16.2.9.2.2 12-Lead ECG Overall Assessment (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Visit 
Trace Reading 
Assessment Date Time 
Result 
Comments 
xxx-xxx 
Screening 
1 
YYYY-MM-DD HH:MM 
Normal 
2 
YYYY-MM-DD HH:MM 
Normal 
3 
Worst 
YYYY-MM-DD HH:MM 
Abnormal NCS 
Abnormal NCS 
XXXXXXXXXXX 
XXXXXXXXXXX 
Day -1 
1 
YYYY-MM-DD HH:MM 
Normal 
2 
YYYY-MM-DD HH:MM 
Normal 
3 
Worst 
YYYY-MM-DD HH:MM 
Normal 
Normal 
Day 1 – 5 Hours Post Dose 
1 
YYYY-MM-DD HH:MM 
Normal 
2 
YYYY-MM-DD HH:MM 
Normal 
3 
Worst 
YYYY-MM-DD HH:MM 
Normal 
Normal 
-: Not applicable, -: Not applicable, CS: Clinically Significant, NCS: Not Clinically Significant. 
[1] The baseline value is defined as the last available valid assessment collected prior to the first study drug administration. 
Where triplicate measurements were taken, continuous results were based on the mean of the triplicate measurements and overall interpretation 
was based on the worst overall interpretation of the triplicate measurements at each visit/time point. 
 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 


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Listing 16.2.9.3 Physical Examination Findings (Safety Population) 
 
Cohort 1: ISLA101 300 mg Fasted 
 
Subject 
Number 
Visit 
Assessment Date Time 
Body System 
Examination Status 
Abnormal Finding 
xxx-xxx 
Screening 
YYYY-MM-DD HH:MM 
General Appearance 
Abnormal NCS 
XXXXXXX 
Head, Ears, Eyes, Nose and Throat 
Neck and Thyroid 
Normal 
Normal 
Lymph Nodes 
Cardiovascular system 
Normal 
Normal 
Respiratory System 
Normal 
Gastrointestinal system 
Normal 
Renal system 
Normal 
Neurological system 
Musculoskeletal system 
Normal 
Normal 
Skin 
Other: XXXXXXXX 
Normal 
Normal 
Day -1 
YYYY-MM-DD HH:MM 
General appearance 
Normal 
 
-: Not applicable, CS: clinically Significant, NCS Not clinically Significant 
Program Name: xxx.sas, Creation Date Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programmer note: 
Repeat for all subjects within the treatment group and for all treatment groups and all time points. 
Present ‘Early Termination’ or ‘Day 8 - Follow up’ or ‘Day 17 - Follow Up’ depending on whether the subjects complete the study or not. 


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Protocol: ISLA101-P01-CT001 
Figure 14.2.1.1.1 Individual Plasma PK Concentrations over Time (Linear) (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Cohort 1: ISLA101 300 mg Fasted 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 88 of 100 
Confidential 
 
 
 
BLQ: Below the Lower Limit of Quantitation. 
BLQ concentrations observed prior to the first quantificationse concentration were set to zero and other BLQ concentrations were treated as 
missing. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• x-axis will represent the actual study time in hours. 
• Y-axis: Use the analyte name/unit as the axis label. Adjust tick marks based on the actual concentrations for the specific analyte across all 
the treatment groups to ensure that the y-axis range is the same across all plots. The y-axis should be presented on a linear scale. 
• Legend: Subject Number. 
• Present each subject with a different line type/color and present each treatment group in a separate plot. 
• Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 89 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.1.1.2 Individual Plasma PK Concentrations over Time (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Treatment: ISLA101 xxx mg Fasted (n=xx) 
 
BLQ: Below the Lower Limit of Quantitation. 
BLQ concentrations observed prior to the first quantificationse concentration were set to zero and other BLQ concentrations were treated as 
missing. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
Programming Note: 
The treatment group will be displayed as the following: ISLA101 XXX mg Fasted, and ISLA101 XXX mg Fed. 
• x-axis will represent the actual study time in hours. 
• Y-axis: Use the analyte name/unit as the axis label. Adjust tick marks based on the actual concentrations for the specific analyte across all 
the treatment groups to ensure that the y-axis range is the same across all plots. The y-axis should be presented on a linear scale. 
• Legend: Subject Number. 
• Present each subject with a different line type/color and present the Fasted and Fed Cohort in a separate plot. 
• Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 90 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.1.1.3 Individual Plasma PK Concentrations over Time by Subject (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Subject Number: XXX-XXX 
 
BLQ: Below the Lower Limit of Quantitation. 
BLQ concentrations observed prior to the first quantificationse concentration were set to zero and other BLQ concentrations were treated as 
missing. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• Present each subject in a separate plot and Repeat for the analyte = MPR and oxo-HPR. 
• x-axis will represent the actual study time in hours. 
• Y-axis: Use the analyte name/unit as the axis label. Adjust tick marks based on the actual concentrations for the specific analyte across all 
the treatment groups to ensure that the y-axis range is the same across all plots. The y-axis should be presented on a linear scale. 
• Legend: show the two treatment groups for the Food Effect cohort ‘ISLA101 XX mg Fasted’, and ‘ISLA101 XX Fed’. 
• Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 91 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.1.2.1 Individual Plasma PK Concentrations over Time (Log-Linear) (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Cohort 1: ISLA101 300 mg Fasted 
 
BLQ: Below the Lower Limit of Quantitation. 
BLQ concentrations were treated as missing. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• x-axis will represent the actual study time in hours. 
• Y-axis: Use the analyte name/unit as the axis label. Adjust tick marks based on the actual concentrations for the specific analyte across all 
the treatment groups to ensure that the y-axis range is the same across all plots. The y-axis should be presented on a log-linear scale. 
• Legend: Subject Number. 
• Present each subject with a different line type/color and present each treatment group in a separate plot. 
• Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 92 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.1.2.2 Individual Plasma PK Concentrations over Time (Log-Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Treatment: ISLA101 xxx mg Fasted (n=xx) 
 
BLQ: Below the Lower Limit of Quantitation. 
BLQ concentrations were treated as missing. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• x-axis will represent the actual study time in hours. 
• Y-axis: Use the analyte name/unit as the axis label. Adjust tick marks based on the actual concentrations for the specific analyte across all 
the treatment groups to ensure that the y-axis range is the same across all plots. The y-axis should be presented on a log-linear scale. 
• Legend: Subject Number. 
• Present each subject with a different line type/color and present the Food Effect Cohort in a separate plot. 
• Repeat for the analyte = MPR and oxo-HPR 
• The treatment group will be displayed as the following: ISLA101 XXX mg Fasted, and ISLA101 XXX mg Fed. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 93 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.1.2.3 Individual Plasma PK Concentrations over Time by Subject (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
Subject Number: XXX-XXX 
 
BLQ: Below the Lower Limit of Quantitation. 
BLQ concentrations were treated as missing. 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• Present each subject in a separate plot and Repeat for the analyte = MPR and oxo-HPR. 
• x-axis will represent the actual study time in hours. 
• Y-axis: Use the analyte name/unit as the axis label. Adjust tick marks based on the actual concentrations for the specific analyte across all 
the treatment groups to ensure that the y-axis range is the same across all plots. The y-axis should be presented on a log-linear scale. 
• Legend: show the two treatment groups for the Food Effect cohort ‘ISLA101 XX mg Fasted’, and ‘ISLA101 XX Fed’. 
• Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 94 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.2.1.1 Mean Plasma PK Concentrations over Time (Linear) (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD: Standard deviation 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
The x-axis will represent the scheduled study time in hours. 
The y-axis will represent the mean Plasma Concentrations (ng/mL). The y-axis will be on the linear scale. 
Legend: Show the treatment groups and the number of participants in each group. Present the legend in the top right corner of the plot unless the 
plots are overlapping with the legend (then move to best position on plot). Each treatment group will be presented as a distinct line type/color 
Repeat for the analyte = MPR and oxo-HPR. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 95 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.2.1.2 Mean Plasma PK Concentrations over Time (Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD: Standard deviation 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
The x-axis will represent the scheduled study time in hours. 
The y-axis will represent the mean Plasma Concentrations (ng/mL). The y-axis will be on the linear scale. 
Legend: Show the treatment groups: ISLA101 xx mg Fasted and ISLA101 xx mg Fed and the number of participants in each group. Present the legend in 
the top right corner of the plot unless the plots are overlapping with the legend (then move to best position on plot). Each treatment group will 
be presented as a distinct line type/color. 
Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 96 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.2.2.1 Mean Plasma PK Concentrations over Time (Log-Linear) (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD: Standard deviation 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
The x-axis will represent the scheduled study time in hours. 
The y-axis will represent the mean Plasma Concentrations (ng/mL). The y-axis will be on the log-linear scale. 
Legend: Show the treatment groups and the number of participants in each group. Present the legend in the top right corner of the plot unless the 
plots are overlapping with the legend (then move to best position on plot). Each treatment group will be presented as a distinct line type/color. 
Repeat for the analyte = MPR and oxo-HPR. 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 97 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.2.2.2 Mean Plasma PK Concentrations over Time (Log-Linear) – Fasted and Fed Cohorts (Pharmacokinetic Population) 
Analyte (Unit): Fenretinide (ng/ml) [LLOQ = x.xx ng/mL] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD: Standard deviation 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
 
 
Programming Note: 
The x-axis will represent the scheduled study time in hours. 
The y-axis will represent the mean Plasma Concentrations (ng/mL). The y-axis will be on the log-linear scale. 
Legend: Show the treatment groups: ISLA101 xx mg Fasted and ISLA101 xx mg Fed and the number of participants in each group. Present the legend in 
the top right corner of the plot unless the plots are overlapping with the legend (then move to best position on plot). Each treatment group will 
be presented as a distinct line type/color. 
Repeat for the analyte = MPR and oxo-HPR 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 98 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.3.1.1 Box Plots of Plasma PK Parameters – Fasted and Fed Cohorts (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) 
Parameter: Cmax (ng/ml) 
 
AUC: Area under the curve. 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• 
Present the treatment groups: ISLA101 XXX mg Fasted, and ISLA101 XXX mg Fed in the plot. 
• 
Y-axis: Use the parameter name/unit as the axis label. 
• 
X-axis: Add tick marks between the treatments (equally spaced) and use the treatment label and the number of subjects in the treatment 
arm as the label (i.e., ‘ISLA101 XXX mg Fasted (N=xx)’, ‘ISLA101 xxx mg Fed (N=xx)’). 
• 
Repeat for AUCinf and AUClast 
• 
for the analyte = Fenretinide (ng/ml) only 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 99 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.4.1.1 Box-Whisker Plots of Dose-Normalized Plasma PK Parameters (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) 
Parameter: DN_Cmax (ng/ml) 
 
AUC: Area under the curve.DN: Dose-Normalized 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• 
Present the treatment groups: ISLA101 300 mg Fasted, 600 mg Fasted and 900 mg Fasted in the plot showing the results for each 
treatment by increasing dose level. 
• 
Y-axis: Use the parameter name/unit as the axis label. 
• 
X-axis: Add tick marks between the treatments (equally spaced) and use the treatment label and the number of subjects in the treatment 
arm as the label (i.e., ‘ISLA101 300 mg Fasted (N=xx)’, ‘ISLA101 600 mg Fasted (N=xx)’ etc.). 
• 
for the analyte = Fenretinide (ng/ml) only 
• 
Repeat for AUCinf and AUClast 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 100 of 100 
Confidential 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.4.1.2 Box-Whisker Plots of Dose-Normalized Plasma PK Parameters – Fasted and Fed Cohorts (Pharmacokinetic Population) 
 
Analyte (Unit): Fenretinide (ng/ml) 
Parameter: DN_Cmax (ng/ml) 
 
AUC: Area under the curve. 
 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• 
Present the treatment groups: ISLA101 XXX mg Fasted, and ISLA101 XXX mg Fed in the plot. 
• 
Y-axis: Use the parameter name/unit as the axis label. 
• 
X-axis: Add tick marks between the treatments (equally spaced) and use the treatment label and the number of subjects in the treatment 
arm as the label (i.e., ‘ISLA101 XXX mg Fasted (N=xx)’, ‘ISLA101 xxx mg Fed (N=xx)’). 
• 
Repeat for DN_AUCinf and DN_AUClast 
• 
for the analyte = Fenretinide (ng/ml) only 


DocuSign Envelope ID: 64A712DB-30C2-4F8C-8FED-7E6FB171863A 
Version and Date: Final Version 1.0, 2023-12-07 
Page 101 of 100 
Confidential 
 
 
 
 
 
 
 
Tables, Listings and Figures Shells 
Sponsor: Island Pharmaceuticals, Ltd 
Protocol Number: ISLA101-P01-CT001 
 
 
Sponsor: Island Pharmaceuticals Ltd 
Protocol: ISLA101-P01-CT001 
Figure 14.2.5.1 Scatterplots of Natural Log-Transformed Plasma PK Parameters (Pharmacokinetic Analysis Set) 
 
Analyte (Unit): Fenretinide (ng/ml) 
Parameter: Cmax (ng/ml) 
 
 
 
1500 
 
 
 
 
 
 
1000 
 
 
 
 
 
 
500 
 
 
 
 
 
 
0 
0  10 
30 
100 
300 
Dose (mg) 
 
 
SD: Standard deviation. 
A power model was used to assess dose proportionality: Natural log-transformed(PK Parameter Result) = α + β * Natural Log-transformed(Dose). 
Program Name: xxx.sas, Creation Date/Time: YYYY-MM-DD HH:MM 
Page 1 of x 
Programming Note: 
• 
Present scatter plots of the natural log-transformed AUCinf, AUClast and Cmax values on the y-axis vs the natural log-transformed dose 
values on the x-axis. Use the actual numerical values for the x-axis and label the tick marks as described below. 
• 
Y-axis: Use the parameter name/unit as the axis label. 
• 
X-axis: The x-axis label should be ‘Dose ISLA101 (mg)’ and the tick marks should be: 
o 
‘300’, ‘600’, ‘900’. 
Include the power model regression line and 90% confidence limits. 
For the Analyte (Unit) = Fenretinide (ng/ml)only. 
Cmax (ng/mL) 


 
Certificate Of Completion 
 
 
Envelope Id: 64A712DB30C24F8C8FED7E6FB171863A 
Status: Completed 
Subject: Complete with DocuSign: Island_ISLA101-P01-CT001_SAP with mock shells_Final_Version_1.0_2023-12... 
Source Envelope: 
Document Pages: 137 
Signatures: 2 
Envelope Originator: 
Certificate Pages: 5 
Initials: 0 
Ella Liu 
AutoNav: Enabled 
EnvelopeId Stamping: Enabled 
Time Zone: (UTC+10:00) Canberra, Melbourne, Sydney 
ella.liu@rgcro.com 
IP Address: 27.131.74.15 
 
 
Status: Original 
12/7/2023 1:57:35 PM 
Holder: Ella Liu 
ella.liu@rgcro.com 
Location: DocuSign 
 
 
Ella Liu 
ella.liu@rgcro.com 
Security Level: Email, Account Authentication 
(Required) 
 
 
 
 
 
 
 
 
 
 
Electronic Record and Signature Disclosure: 
Not Offered via DocuSign 
 
Teresa M. Byrne 
tbyrne@islandpharmaceuticals.com 
Security Level: Email, Account Authentication 
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Electronic Record and Signature Disclosure: 
Accepted: 12/9/2023 6:42:59 AM 
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Company Name: Resolutum Global 
 
 
 
 
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Electronic Record and Signature Disclosure created on: 8/31/2023 10:25:47 AM 
Parties agreed to: Teresa M. Byrne 
 
 
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