An Observational, Multicenter Study of the Prevalence of Cerebrotendinous Xanthomatosis (CTX) in Patient Populations Diagnosed With Early-Onset Idiopathic Bilateral Cataracts
Conditions: Cerebrotendinous Xanthomatosis (CTX)
Sponsor: Travere Therapeutics, Inc.

 
 
RETROPHIN 
FINAL: 13 DECEMBER 2016 
PROPRIETARY AND CONFIDENTIAL 
 
 
 OBSERVATIONAL CLINICAL STUDY PROTOCOL 
An Observational, Multicenter Study of the Prevalence of Cerebrotendinous Xanthomatosis (CTX) in 
Patient Populations Diagnosed with Early-Onset Idiopathic Bilateral Cataracts 
Protocol Number:  018CTXX15001 
 
Original Version:  18 May 2015 
Amendment 1: 08 July 2015 
Amendment 2: 13 December 2016 
 
Sponsor: 
Retrophin, Inc. 
12255 El Camino Real, Suite 250 
San Diego, CA 92130 
USA 
Medical Monitor: 
Randall Marshall, MD 
Executive Medical Director 
Retrophin, Inc. 
141 Portland Street, 10th Floor 
Cambridge, MA 02142 
Tel: +1 617-477-0560 
Clinical Project Manager: 
Charlotte Brennand, MPH 
Associate Director, Clinical Operations 
Retrophin, Inc.  
141 Portland Street, 10th Floor 
Cambridge, MA 02142 
Tel:+1 617-500-7920  
 
This protocol was designed and will be conducted, recorded, and reported in accordance with the principles 
of GCP as stated in the ICH of Technical Requirements for Registration of Pharmaceuticals for Human Use 
and any applicable national and regional laws. 
I have read and agree to abide by the requirements of this protocol. 
Investigator Signature 
Date 
 
Investigator Name (please print or type) 

 
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1 
SYNOPSIS 
NAME OF COMPANY 
Retrophin, Inc. 
12255 El Camino Real, Suite 250 
San Diego, CA 92130 
USA 
NAME OF FINISHED PRODUCT 
Not Applicable 
NAME OF ACTIVE INGREDIENT 
Not Applicable 
TITLE:  
An Observational, Multicenter Study of the Prevalence of Cerebrotendinous Xanthomatosis (CTX) in Patient 
Populations Diagnosed with Early-Onset Idiopathic Bilateral Cataracts 
 
PROTOCOL NO.: 
018CTXX15001 
INVESTIGATOR STUDY SITES: 
This multi-center study will involve approximately 50 study sites in the United States.   
OBJECTIVES: 
Primary Objective: 
To calculate the prevalence of CTX in a patient population diagnosed between the ages of 2 and 21 years old 
(inclusive) with early-onset idiopathic bilateral cataracts 
Secondary Objective: 
To assess other manifestations of CTX within patients presenting with idiopathic bilateral cataracts 
METHODOLOGY: 
This is an observational, multicenter study to determine the prevalence of CTX in patient populations 
diagnosed with early-onset idiopathic bilateral cataracts.  Patients who are potentially eligible for study 
participation will be identified through a chart review of patients who were seen at each study site prior to that 
site’s initiation, or by entering care at the site while the site is participating in the trial. 
NUMBER OF PATIENTS: 
Approximately 500 patients will be enrolled in this study. 
 
INCLUSION/EXCLUSION CRITERIA: 
Inclusion Criteria: 
A patient must meet all of the following criteria to be eligible for this study. 
1. The patient and/or their parent/legal guardian is willing and able to provide signed informed 
consent and the patient, if <18 years of age, is willing to provide assent if deemed able to do so.  If 
the patient is ≥ 18 years of age but has diminished capacity to provide informed consent, their 
parent/legal guardian is willing and able to provide signed informed consent and the patient is 
willing to provide assent, if deemed able to do so. 
2. The patient has a diagnosis of idiopathic bilateral cataracts. 

 
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NAME OF COMPANY 
Retrophin, Inc. 
12255 El Camino Real, Suite 250 
San Diego, CA 92130 
USA 
NAME OF FINISHED PRODUCT 
Not Applicable 
NAME OF ACTIVE INGREDIENT 
Not Applicable 
3. The patient is between the ages of 2 to 21 years old (inclusive) at the time of diagnosis with 
idiopathic bilateral cataracts. 
Exclusion Criteria: 
A patient who meets any of the following criteria will be excluded from this study. 
1. The patient has a diagnosis of cataracts with known etiology other than CTX.  
2. The patient has a diagnosis of CTX. 
3. The patient has cataracts caused by cataractogenic treatments. 
4. The patient has taken or is currently taking cholic acid or chenodeoxycholic acid. 
5. The patient has received an investigational product in an interventional clinical trial in the past 30 
days. 
6. The patient and/or their parent/legal guardian, in the opinion of the Investigator, is unable to adhere 
to the requirements of the study. 
DOSE/ROUTE/REGIMEN (TEST ARTICLE): 
Not applicable – this is an observational study 
REFERENCE TREATMENT: 
Not applicable 
CRITERIA FOR EVALUATION: 
The plasma cholestanol levels and/or urine bile alcohol results (if urine sample is provided) will be used to 
determine whether genetic testing is indicated.  Genetic testing, if indicated, will be used to determine the 
prevalence of CTX. 
STATISTICAL METHODS: 
Power and Sample Size: 
Approximately 500 patients will be enrolled in the study.  Because this is an observational study, no power 
calculation has been performed.  The study size is considered to be appropriate to investigate the prevalence of 
CTX among patients diagnosed or treated for early-onset idiopathic bilateral cataracts.  
Analysis Sets: 
All study patients for whom results of cholestanol or urine bile alcohol testing (if urine sample is provided) are 
available will be included in the analysis dataset.  All study patients who undergo study procedures (i.e., a 
blood draw) will be included in the safety dataset. 
Demographics and Baseline Characteristics: 
Descriptive statistics will be used. 
Efficacy: 
There are no efficacy endpoints in this descriptive, observational study. 

 
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NAME OF COMPANY 
Retrophin, Inc. 
12255 El Camino Real, Suite 250 
San Diego, CA 92130 
USA 
NAME OF FINISHED PRODUCT 
Not Applicable 
NAME OF ACTIVE INGREDIENT 
Not Applicable 
 
Safety: 
Serious Adverse Events associated with study procedures (i.e., a blood draw) will be listed. 
CTX Testing: 
Plasma cholestanol levels, urine bile alcohol results (if urine sample is provided), and results of genetic testing 
for CTX will be summarized using descriptive statistics.    

 
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2 
TABLE OF CONTENTS 
1 
SYNOPSIS .................................................................................................................3 
2 
TABLE OF CONTENTS .........................................................................................6 
2.1 
List of Abbreviations ......................................................................................8 
3 
INTRODUCTION.....................................................................................................9 
3.1 
Summary of Potential Risks .........................................................................12 
3.2 
Summary of Potential Benefits .....................................................................12 
4 
STUDY OBJECTIVES ...........................................................................................13 
5 
INVESTIGATIONAL PLAN ................................................................................14 
5.1 
Endpoints ......................................................................................................14 
5.1.1 
Efficacy Endpoints ......................................................................14 
5.1.2 
Safety Endpoints .........................................................................14 
5.1.3 
Other Endpoints ..........................................................................14 
5.2 
Study Design .................................................................................................14 
5.2.1 
Site of Study Procedures .............................................................14 
5.2.2 
Completion of a Patient’s Participation in the Study and 
Overall Study Completion ..........................................................15 
5.2.2.1 
Completion of a Patient’s Participation in the 
Study ......................................................................15 
5.2.2.2 
Premature Patient Discontinuation from the 
Study ......................................................................15 
5.2.2.3 
Overall Study Completion .....................................15 
5.3 
Discussion of Study Design ..........................................................................15 
6 
PATIENT POPULATION AND SELECTION ...................................................16 
6.1 
Inclusion Criteria ..........................................................................................16 
6.2 
Exclusion Criteria .........................................................................................16 
7 
TREATMENTS.......................................................................................................17 
7.1 
Prior and Concomitant Medications and Therapeutic Procedures ................17 
7.2 
Method of Assigning Patients to Treatment .................................................17 
7.3 
Blinding and Randomization ........................................................................17 
7.4 
Treatment Compliance ..................................................................................17 
8 
STUDY ASSESSMENTS .......................................................................................18 
8.1 
Study Schedule of Events .............................................................................18 
8.2 
Demographic and Screening Assessments ...................................................18 
8.3 
Efficacy Assessments ...................................................................................18 
8.4 
Safety Assessments .......................................................................................18 
8.5 
CTX Testing (if necessary) ...........................................................................19 
9 
ADVERSE EVENT REPORTING .......................................................................20 
9.1 
Adverse Event ...............................................................................................20 
9.2 
Serious Adverse Event ..................................................................................20 
9.3 
Evaluation of Adverse Events/Serious Adverse Events ...............................21 
9.3.1 
Causality Assessment .................................................................21 
9.3.2 
Severity .......................................................................................22 
9.3.3 
Outcome ......................................................................................22 
9.3.4 
Action Taken Regarding the Investigational Product .................23 

 
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9.4 
Reporting Serious Study-Procedure-Related Adverse Events ......................23 
9.4.1 
Initial Reporting of Serious Study-Procedure-Related 
Adverse Events ...........................................................................23 
9.4.2 
Follow-Up of Serious Adverse Events .......................................24 
9.4.3 
Reporting to Regulatory Authorities, Investigators and 
IRB/IECs .....................................................................................24 
9.5 
Pregnancy Reporting.....................................................................................25 
10 
DATA COLLECTION, QUALITY ASSURANCE, AND MANAGEMENT ...26 
10.1 
Recording of Data .........................................................................................26 
10.2 
Data Quality Assurance ................................................................................26 
10.3 
Data Management .........................................................................................26 
11 
STATISTICAL METHODS AND PLANNED ANALYSES ..............................27 
11.1 
General Considerations .................................................................................27 
11.2 
Determination of Sample Size ......................................................................27 
11.3 
Analysis Sets .................................................................................................27 
11.4 
Demographics and Baseline Characteristics .................................................27 
11.5 
Patient Accountability...................................................................................27 
11.6 
Study Treatment Usage and Compliance......................................................27 
11.7 
CTX Testing Analyses ..................................................................................27 
11.8 
Safety Analyses.............................................................................................28 
11.8.1 
Physical Examination and Vital Signs ........................................28 
11.8.2 
Clinical Laboratory Tests............................................................28 
11.8.3 
Adverse Events ...........................................................................28 
11.8.4 
Other Safety Assessments ...........................................................28 
11.9 
Other Analyses ..............................................................................................28 
11.10 Other Statistical Issues ..................................................................................28 
11.10.1 
Significance Levels .....................................................................28 
11.10.2 
Missing or Invalid Data ..............................................................28 
11.11 Interim Analysis ............................................................................................28 
12 
SPECIAL REQUIREMENTS AND PROCEDURES .........................................29 
12.1 
Institutional and Ethics Review ....................................................................29 
12.2 
Data Monitoring Committee .........................................................................29 
12.3 
Changes to the Conduct of the Study or Protocol .........................................29 
12.4 
Investigator’s Responsibilities ......................................................................29 
12.4.1 
Patient Informed Consent ...........................................................29 
12.4.2 
Case Report Forms......................................................................30 
12.4.3 
Record Retention ........................................................................30 
12.4.4 
Monitoring ..................................................................................31 
12.4.5 
Study or Site Termination ...........................................................31 
12.4.6 
Investigational Product Control ..................................................32 
12.4.7 
Insurance .....................................................................................32 
12.4.8 
Disclosure of Data ......................................................................32 
12.4.9 
Clinical Study Report..................................................................32 
13 
REFERENCES ........................................................................................................33 
14 
APPENDIX ..............................................................................................................35 

 
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2.1 
List of Abbreviations 
AE 
Adverse Event 
CDCA 
Chenodeoxycholic Acid 
CTX 
Cerebrotendinous Xanthomatosis 
eCRF 
Electronic Case Report Forms 
EDC 
Electronic Data Capture 
FDA 
The United States Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
SOPs 
Standard Operating Procedures 
US 
United States 
WHO 
World Health Organization 

 
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3 
INTRODUCTION 
Genetic basis of cerebrotendinous xanthomatosis 
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease caused by 
mutations in the cytochrome P450 CYP27A1 gene that result in production of a defective sterol 
27-hydroxylase enzyme.  Physiologically, the CYP27 enzyme is present in mitochondria and 
involved in bile acid synthesis.  If normal, it functions by introducing a hydroxyl group in the 
C27 position, as the first step in shortening the steroid side chain of 7-hydroxylated 
intermediates or other substrates such as cholesterol.  In CTX patients, reduced bile acid 
synthesis causes decreased inhibition of cholesterol 7-hydroxylase activity and increased 
formation of 7-hydroxy-4-cholesten-3-one, which accumulates and leads to production of 
cholestanol and abnormal 25-hydroxylated bile alcohols. 
The upregulation of both cholesterol and cholestanol synthesis leads to an accumulation of 
cholesterol in cholestanol-containing xanthomas in a variety of body tissues over time.  This is 
the chief pathophysiologic mechanism responsible for many of the symptoms associated with 
CTX.[1] 
Verrips et al [2] reported on genotypes and genotype/phenotype correlation in 58 CTX patients 
they studied and 67 patients reported in published literature (total of 125 patients from 
74 unrelated families).  Among these patients there were 37 different mutations in the CYP27A1 
gene: 16 were missense mutations; 3 were deletions; 1 was an insertion; 8 were splice site 
mutations; 6 were nonsense mutations; and 3 mutations were in the last nucleotides of exons.  
Fifteen of the 37 mutations (41%) were located in the region of exons 6-8 of the CYP27A1 gene.  
Striking phenotypic heterogeneity was observed, even within families.  A genotype-phenotype 
correlation analysis was done for 79 homozygous patients from 45 families harboring 
23 different mutations, but no genotype-phenotype correlation could be established.  The authors 
concluded that a given mutation may result in the same or different CTX phenotypes, and that 
mutations at different sites of the CYP27A1 gene may likewise result in the same or different 
phenotypes. 
Symptoms of cerebrotendinous xanthomatosis 
CTX is typically a highly progressive disease, with case reports of symptoms that first appear at 
any time from birth through adulthood and then worsen over time.  There are a wide variety of 
clinical symptoms and considerable morbidity in CTX patients, with disabling effects in many 
body systems and a high burden of illness.  The most common manifestations reported are gait 

 
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disturbance, cataracts, decreased intelligence, dementia, impaired reflexes, pyramidal and 
cerebellar signs, dysarthria, epilepsy, neuropathy, ataxia, muscle atrophy, foot deformities, 
chronic diarrhea, and xanthomas, particularly of the Achilles tendon.  Psychiatric, nervous 
system, and musculoskeletal manifestations predominate.[3, 4]  The natural history of CTX has 
not been thoroughly studied, but case reports for several hundred patients have been published.  
Based on these case reports and the published review articles about CTX, the symptoms that 
occur earliest in children with CTX are chronic diarrhea, developmental delay, behavioral 
disorders, seizures, and cataracts.   
Prevalence of cerebrotendinous xanthomatosis 
Published articles generally state that the actual prevalence of CTX is unknown, with many 
patients thought to be unidentified; but the prevalence is widely assumed to be rare.  Three 
publications have presented attempts to estimate the prevalence of CTX in specific ethnic 
groups. 
Berginer and Abeliovich [5] noted that there had been 6 individuals from 3 Jewish families of 
Moroccan origin diagnosed with CTX over a 5-year period in the Beer-Sheba region of Israel.  
Because approximately 70,000 Jews of Moroccan origin lived in this region, the authors reported 
a CTX frequency of 6/70,000 for this community.  Whether this represents a good estimate of 
prevalence for this ethnic group generally or how it compares to prevalence in other ethnic 
groups is not known. 
Lorincz et al [6] used a genetic analysis of a CTX patient with German-English ancestry with 
consanguineous parents (second cousins) and her family members to estimate the prevalence of 
CTX.  Molecular genetic analysis was performed using DNA extracted from peripheral blood 
leukocytes of the patient, her family members, and 115 white volunteer controls of European 
ancestry.  The CYP27A1 exon from each sample was amplified by polymerase chain reaction.  
Sequencing of the amplified DNA resulted in the identification of a single homozygous 
substitution of thymidine for cytosine at complementary DNA position 1384 for the patient.  
Sequence analysis of DNA from both parents showed that they were both heterozygous, 
cytosine/ thymidine, at the same position.  Unexpectedly, one control patient who was 
heterozygous for the same mutation at position 1384 was identified.  Haplotype analysis of DNA 
from the heterozygous control patient was not performed, but there was no known familial 
relationship to the patient.  The observed frequency of the mutation calculated for the control 
group was 8.7 x 10-3.  The prevalence of CTX due to this one homozygous mutation was 

 
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estimated at 1.9 per 100,000.  The overall prevalence of CTX due to all known mutations was 
estimated to be “several-fold” higher, approximately 3 to 5 per 100,000.   
Pilo-de-la-Fuente et al [7] reported on data for all patients diagnosed with CTX between 1992 
and 2008 at any of the main reference centers for genetic diagnosis of CTX in Spain.  CTX 
diagnosis was based on clinical features and mutational analysis with one exception, a patient 
diagnosed in 1992 for whom DNA was not available.  Twenty-five CTX patients, from 
19 families were identified.  The authors estimated a minimum prevalence of 1/1,800,000 
individuals in Spain.   
Diagnosis of cerebrotendinous xanthomatosis 
Suspicion of CTX is typically based on clinical symptoms, most often including chronic diarrhea 
with infantile onset, bilateral cataracts in children, and the appearance of xanthomas on the 
Achilles tendons, extensor tendons of the elbows and hands or patellar tendons, often by the third 
decade of life.[8]  Biochemical abnormalities that indicate likely CTX are elevated bile and 
plasma cholestanol levels, increased ratio of serum cholestanol/cholesterol, increased urinary 
excretion of bile alcohol glucuronides and diminished biliary concentrations of 
chenodeoxycholic acid (CDCA).[9, 10]  In clinical practice, elevated plasma cholestanol and 
urine bile alcohol are used as tests for probable CTX, with the diagnosis confirmed by a finding 
of mutation in the CY 27A1 gene on chromosome 2q35-qter.[8, 11] 
Treatment of cerebrotendinous xanthomatosis 
CDCA has long been considered to be the standard of care for the condition.  CDCA treatment is 
effective in preventing adverse clinical manifestations of the disease from occurring or 
progressing if the treatment is administered early enough.[12]  Though the extent of published 
evidence is limited, available clinical studies and case reports suggest that the ability of CDCA 
treatment to reverse existing adverse clinical manifestations is mixed, with some manifestations 
being at least partially reversed and others stabilizing.  Initiation of CDCA treatment as early as 
possible is universally recommended by experts, before irreversible damage has occurred.[13]  
There are also published reports of cholic acid being used instead of CDCA.[14, 15, 27] 
Recently, cholic acid has been approved for the treatment of bile acid synthesis disorders, 
including CTX [27]. 
Other treatments that have been reported to be combined with CDCA treatment in clinical 
practice are: Vitamin D, Vitamin E, anti-seizure medications, L-dopa-carbidopa, anti-psychotic 
medications, anxiolytics, anti-depressants and statins.[16-23]  In a small number of reported 

 
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cases, statins were given without CDCA.[22, 24]  Apheresis treatment has also reported in a 
small number of cases, in combination with CDCA or alone.[7, 25, 26] 
Because idiopathic bilateral cataracts occur at an early age in many children with CTX, 
biomarker testing of these children  presents an opportunity for diagnosing children with CTX.  
Since initiation of treatment as early as possible may prevent or reverse the development of 
debilitating symptoms of CTX, the opportunity to use contact with health care providers in 
connection with pediatric cataract evaluation and treatment is a promising avenue for disease 
detection and prevention.[12] 
3.1 
Summary of Potential Risks 
This is an observational study with no drugs or treatments that could have associated risks.  
Drawing blood for diagnostic testing by venipuncture is an invasive procedure that may 
occasionally be associated with adverse events such as pain, bleeding, syncope, ecchymosis or 
infection.  
3.2 
Summary of Potential Benefits 
Patients in this study will not experience personal benefits from study participation in this non-
treatment, prevalence study.  However, patients with CTX who are identified through 
participation in the study may seek medical care for CTX as a result of the diagnosis made 
during study participation.  Study participants who test positive for CTX will be informed of the 
diagnosis by the Investigator and advised to seek appropriate medical evaluation and care. 

 
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4 
STUDY OBJECTIVES 
The primary objective of this study is to calculate the prevalence of CTX in a patient population 
diagnosed between the ages of 2 and 21 years old (inclusive) with early-onset idiopathic bilateral 
cataracts. 
The secondary objective of this study is to assess other manifestations of CTX within patients 
presenting with idiopathic bilateral cataracts. 

 
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5 
INVESTIGATIONAL PLAN 
5.1 
Endpoints 
5.1.1 
Efficacy Endpoints 
This study has no treatments and no efficacy endpoints. 
5.1.2 
Safety Endpoints 
Only serious adverse events (SAEs) associated with study procedures (i.e., a blood draw) will be 
recorded. 
5.1.3 
Other Endpoints 
CTX testing will be done using plasma cholestanol and urine bile alcohol levels (if urine sample 
is provided) for all study participants.  Genetic testing for mutations associated with CTX will be 
done for all study participants with elevated plasma cholestanol levels or positive urine bile 
alcohol results (if urine sample is provided).  Genetic testing will be performed at a Clinical 
Laboratory Improvement Amendment (CLIA) certified laboratory. The results of testing for 
plasma cholestanol and urine bile alcohol (if urine sample is provided), and genetic testing (when 
indicated) will be reported to the Investigator at each clinical site.  The results of plasma total 
cholesterol (fasting or nonfasting, if > 190 mg/dL) may also be reported to the Investigator.  
Samples will be retained only for the duration of testing of plasma cholestanol, urine bile alcohol 
(if urine sample is provided), plasma total cholesterol (if applicable) and genetic testing (when 
indicated).  Samples will not be used for future, presently unidentified research.   
5.2 
Study Design 
This is an observational, multicenter study to determine the prevalence of CTX in patient 
populations diagnosed or treated for early-onset idiopathic bilateral cataracts, identified through 
a chart review of patients who were seen at each study site prior to that site’s initiation or by 
entering care at the site while the site is participating in the trial.  
5.2.1 
Site of Study Procedures 
Study procedures may be completed at investigational sites, either during a visit for the clinical 
study, or in conjunction with other scheduled visits separate from the clinical study.  
Alternatively, study procedures may be completed during a visit at an alternate location (such as 
but not limited to a home, daycare or workplace) provided by personnel from a home health care 
company licensed and authorized to perform these procedures. 

 
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5.2.2 
Completion of a Patient’s Participation in the Study and Overall Study 
Completion 
5.2.2.1 
Completion of a Patient’s Participation in the Study 
Participation in the study is limited to one or more study visit(s) for collection of study data, 
including a blood draw and urine sample (if provided).  These procedures will typically be 
completed in a single visit, but additional visits are permitted if a blood sample is not obtained or 
a replacement blood sample is required for any reason.  The blood draw and urine sample (if 
provided) may be collected in conjunction with other scheduled treatments separate from the 
clinical study.  The length of a patient’s participation will be from the time the informed consent 
form is signed until results of the CTX testing have been obtained and reported to the patient.  
Study participation for patients who have normal test results for plasma cholestanol and urine 
bile alcohol (if urine sample is provided) will be complete after reporting of these test results to 
the patient.  Study participation for patients who require genetic testing will be complete after 
reporting of these test results to the patient.  The Investigator will contact the patient to share the 
results of the plasma cholestanol, urine bile alcohol, plasma total cholesterol (if applicable) and 
genetic testing for example, via a follow-up phone call.  For those participants who require 
genetic testing, the Investigator will provide a referral for appropriate follow-up care, if clinically 
indicated, to the patient or patient’s parent or guardian.  Genetic counseling will not be provided 
per the study.   
5.2.2.2 
Premature Patient Discontinuation from the Study 
Patients are free to withdraw consent and/or discontinue participation in the study at any time, 
without prejudice to further treatment.  A patient’s participation in the study may also be 
discontinued at any time at the discretion of the Investigator or Sponsor. 
5.2.2.3 
Overall Study Completion 
The study will be considered to be complete when CTX testing, including cholestanol, urine bile 
alcohol (if urine sample is provided) and genetic testing (if indicated), has been completed and 
recorded for all patients, and patients have been informed of the testing results. 
5.3 
Discussion of Study Design 
This is an observational, multicenter study to determine the prevalence of CTX in patient 
populations diagnosed or treated for early-onset idiopathic bilateral cataracts.  The number of 
patients to be enrolled in this study is considered appropriate for such a study.  Because this is an 
observational study, no power calculation has been performed. 

 
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6 
PATIENT POPULATION AND SELECTION 
6.1 
Inclusion Criteria 
A patient must meet all of the following criteria to be eligible for this study. 
1. The patient and/or their parent/legal guardian is willing and able to provide signed 
informed consent and the patient, if <18 years of age, is willing to provide assent if 
deemed able to do so.  If the patient is ≥18 years of age but has diminished capacity to 
provide informed consent, their parent/legal guardian is willing and able to provide 
signed informed consent and the patient is willing to provide assent, if deemed able to do 
so. 
2. The patient has a diagnosis of idiopathic bilateral cataracts. 
3. The patient is between the ages of 2 to 21 years old (inclusive) at the time of diagnosis 
with idiopathic bilateral cataracts. 
 
6.2 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study. 
1. The patient has a diagnosis of cataracts with known etiology other than CTX.  
2. The patient has a diagnosis of CTX 
3. The patient has cataracts caused by cataractogenic treatments. 
4. The patient has taken or is currently taking cholic acid or chenodeoxycholic acid. 
5. The patient has received an investigational product in an interventional clinical trial in the 
past 30 days.   
6. The patient and/or their parent/legal guardian, in the opinion of the Investigator, is unable 
to adhere to the requirements of the study. 
 

 
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7 
TREATMENTS 
No treatments will be administered during this observational study. 
7.1 
Prior and Concomitant Medications and Therapeutic Procedures 
Concomitant medications and therapies the patient has taken in the week prior to enrollment will 
be recorded during the study visit(s).  Patients will be excluded from enrollment in the study if 
they have taken or are currently taking cholic acid or chenodeoxycholic acid or if they have 
received an investigational product in an interventional clinical trial within 30 days before 
enrollment.  Patients excluded for receiving an investigational product may later be included in 
the study after the 30-day period has passed. 
7.2 
Method of Assigning Patients to Treatment 
Not applicable. 
7.3 
Blinding and Randomization 
Not applicable. 
7.4 
Treatment Compliance 
Not applicable. 

 
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8 
STUDY ASSESSMENTS 
8.1 
Study Schedule of Events 
The study schedule of events appears in Appendix. 
Study participants will attend a clinic visit or receive a visit at an alternate location (such as but 
not limited to home, daycare or workplace) during which the following procedures will be 
performed: 
 Confirmation of study eligibility 
 Informed consent 
 Targeted medical history  
 Collection of demographic data and concomitant medications and therapies 
 Collection of blood and urine (if urine sample is provided) for testing 
The blood draw and urine sample (if provided) may be collected in conjunction with other 
scheduled treatments separate from the clinical study.   
These procedures will be completed in a single visit, but additional visits are permitted if a blood 
sample is not obtained or a replacement blood sample is required for any reason. 
Written informed consent must be obtained prior to any protocol-required procedure.  Remote 
consenting of subjects by authorized study personnel, using telephone, mail, fax or other 
communication means, is permitted.  
8.2 
Demographic and Screening Assessments 
Demographic data will be collected at the study visit.  No physical examination will be 
performed as part of the study. 
A targeted medical history will be collected for all patients enrolled in the study.  It includes any 
history of or current manifestation of signs and symptoms commonly associated with CTX.  
8.3 
Efficacy Assessments 
Not applicable. 
8.4 
Safety Assessments 
Any SAEs associated with study procedures (i.e., blood draw) will be recorded.  

 
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8.5 
CTX Testing (if necessary) 
Blood and urine (if urine sample is provided) will be collected during the study for testing of the 
plasma cholestanol and urine bile alcohol levels.   The following is applicable: 
 If the plasma cholestanol level is < 0.4 mg/dL (4 µg/mL) and urine bile alcohol is 
negative (if urine sample is provided) then no further testing is required.  
 If the plasma cholestanol level is > 0.4 mg/dL (4 µg/mL) or urine bile alcohol is positive 
(if urine sample is provided), this will prompt genetic testing.  
o If a patient is diagnosed with CTX, photographic documentation of cataracts, if 
available, will be obtained from the patient’s clinical records for the study data 
files.   
 The Investigator may be notified if the plasma total cholesterol level (fasting or 
nonfasting) is > 190 mg/dL.  These results are provided for medically informative 
purposes only. 
 

 
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9 
ADVERSE EVENT REPORTING 
9.1 
Adverse Event 
For the purpose of this protocol, the following definitions and reporting requirements will apply: 
An adverse event (AE) is any untoward medical occurrence associated with the performance of a 
study procedure in a clinical investigation patient. 
AEs may include: 
 Symptoms described by the patient 
 Clinically significant changes in the patient’s physical exam or other signs observed 
by the Investigator or medical staff 
Definition of a Procedure-related AE: 
A procedure-related AE is an AE occurring during a clinical study that is considered by the 
Investigator or the Medical Monitor (or designee) to be related to a research procedure (i.e., 
related to the fact that a patient is undergoing a procedure in the study).  For example, a 
procedure-related AE may be an untoward event related to a medical procedure required by the 
protocol (i.e.,a blood draw, in the case of this study). 
Only serious procedure-related adverse events will be recorded.   
9.2 
Serious Adverse Event  
A serious adverse event (SAE) is an AE that results in any of the following: 
 Death:  The patient died as the result of the event. 
 Is life-threatening:  An AE that places the patient, in the view of the Investigator or 
Sponsor, at immediate risk of death from the AE as it occurred, i.e., does not include an 
AE that had it occurred in a more severe form, might have caused death. 
 Requires in-patient hospitalization or prolongation of an existing hospitalization   
 Persistent or significant disability/incapacity:  An AE that results in a substantial 
disruption of a person’s ability to conduct normal life functions. 
 Congenital anomaly/birth defect:  A congenital anomaly/birth defect that occurs in the 
offspring of a patient exposed to the study procedure. 

 
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 Other Medically Important Serious Medical events:  An AE that may not result in death, 
be life-threatening, or require hospitalization may be considered an SAE when, based 
upon appropriate medical judgment, the event may jeopardize the patient or patient may 
require medical or surgical intervention to prevent one of the outcomes listed above. 
9.3 
Evaluation of Adverse Events/Serious Adverse Events 
SAEs will be assessed by the Investigator.  Only SAEs determined by the Investigator to be 
possibly related or related to study procedures will be recorded.  Any study-procedure-related or 
possibly-related SAEs ongoing after the Screening/Baseline visit will be followed until 
resolution.   
9.3.1 
Causality Assessment 
For each SAE the Investigator must determine whether, based on available evidence, there is a 
reasonable possibility that the study procedure caused the event.  Causal relationship will be 
classified according to the following criteria: 
 Not Related:  There is no suspicion of a causal relationship between the procedure 
and the AE. 
 Unlikely Related:  There is no evidence for a causal relationship between the 
procedure and the AE; however, such a relationship cannot be ruled out. 
 Possibly Related:  There is some evidence supporting the possibility of a causal 
relationship between the procedure and the AE. 
 Related: There is strong evidence that there is a causal relationship between the 
procedure and the AE. 
 
A causality assessment must be provided for each SAE recorded even if there is only limited 
information at the time. 
Upon receipt of follow-up information, the Investigator may change his/her assessment of 
causality and amend the SAE report accordingly. 

 
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9.3.2 
Severity  
Severity indicates the intensity of the event and should not be confused with seriousness (i.e., 
Section 9.2), which is an event outcome applied for the purpose of event classification and 
regulatory reporting. 
Severity Grading 
The Investigator will assess the severity of all study-procedure-related SAEs as Mild, Moderate, 
or Severe, based on the following definitions.  
Definitions: 
 Mild:  A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention.  The event does not generally interfere with usual activities of 
daily living. 
 Moderate:  A type of AE that is usually alleviated with additional specific therapeutic 
intervention.  The event interferes with usual activities of daily living, causing 
discomfort, but poses no significant or permanent risk of harm to the research participant. 
 Severe:  A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
 
9.3.3 
Outcome 
Outcome describes the status of the SAE. 
The Investigator will provide information regarding the patient outcome of each SAE that is 
judged to be possibly related or related to a study procedure. 
Definitions for possible results of an SAE outcome: 
 Recovered/Resolved:  the event has improved or recuperated 
 Recovering/Resolving:  the event is improving 
 Not Recovered/Not Resolved:  the event has not improved or recuperated 
 Recovered/Resolved with sequelae:  the patient recuperated but retained pathological 
conditions resulting from the prior disease or injury 

 
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 Fatal:  termination of life as a result of an adverse event; there should be only one AE 
marked with this outcome 
 Unknown:  not known, not observed, not recorded or refused 
 
9.3.4 
Action Taken Regarding the Investigational Product 
Not applicable. 
9.4 
Reporting Serious Study-Procedure-Related Adverse Events  
9.4.1 
Initial Reporting of Serious Study-Procedure-Related Adverse Events 
Study-procedure-related or possibly related SAEs should be recorded using appropriate medical 
terminology.  When recording, it is preferable to provide a diagnosis.  In the absence of a 
diagnosis, each sign and symptom should be captured as a unique SAE.  Sufficient information 
should be sought to assist the Investigator both in determining the diagnosis and in making a 
causality assessment.   
The necessity and time requirements for reporting of study-procedure-related or possibly related 
SAEs to the Sponsor or its designee and/or regulatory agencies are as follows: 
 All SAEs related or possibly related to study procedures must be reported to the 
Sponsor or designee within 24 hours of the Investigator’s first knowledge of the 
event.    
 A completed Clinical Study SAE Report Form containing a detailed written 
description of the event along with available supporting documents (e.g., discharge 
summary, autopsy report, diagnostic test results, etc.) should be provided by fax or 
e-mail to the following address:   
 
Safety Reporting 
ProPharma 
E-mail:  clinicalsafety@propharmagroup.com 
 
 

 
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 Additional information that is not available at the time the initial SAE Report Form 
was completed, must be promptly reviewed and provided to the Sponsor within 48 
hours of receipt.  Full supporting documentation should be solicited by the 
investigative site even if the SAE occurred at another institution.  Such 
documentation may include copies of relevant patient/hospital records, discharge 
summaries, laboratory/test results or autopsy reports. 
 If, at any time after the patient has completed participation in the study (as defined in 
Section 5.2.2.1), the Investigator or study staff becomes aware of an SAE that they 
suspect is related to the study procedures (see Section 9.3.1), then the event and any 
known details must be reported promptly to the Sponsor or its designee, following the 
reporting instructions in Section 9.4.3. 
 
9.4.2 
Follow-Up of Serious Adverse Events 
All SAEs related or possibly related to study procedures will be followed until resolution, the 
condition stabilizes, or the Investigator and Sponsor agree that follow up is no longer necessary.   
Rules for SAE follow up apply to all patients, to the extent allowed by the patient’s consent.  The 
Investigator will ensure that follow up includes further investigations consistent with appropriate 
medical management to understand the nature and/or causality of the SAE.  The 
Sponsor/designee, or regulatory authorities may also request additional information regarding an 
SAE at any time. 
All follow-up information must be promptly reviewed by the Investigator and provided to the 
Sponsor within the specified timelines.  Additional procedure-related SAEs may be identified 
during the review of follow-up information and should be processed in accordance with 
requirements defined throughout Section 10. 
9.4.3 
Reporting to Regulatory Authorities, Investigators and IRB/IECs 
The Sponsor will ensure that processes are in place for provision of study-procedure-related or 
possibly related SAE reports to Investigators and institutional review boards (IRBs)/institutional 
ethics committees (IECs) as required, within the specified timelines.   
The Sponsor or its designee will submit study procedure-related or possibly related SAE reports 
to the Investigator as required.  In the US, Investigators will report study procedure-related or 
possibly related SAEs to their IRB in accordance with applicable standard operating procedures 

 
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and/or local reporting requirements.   
Investigators must forward copies of the IRB notification to the Sponsor or its designee, when 
applicable. 
9.5 
Pregnancy Reporting 
Not applicable. 

 
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10 
DATA COLLECTION, QUALITY ASSURANCE, AND MANAGEMENT 
10.1 
Recording of Data 
Copies of pertinent records in connection with the study, including all source documents, will be 
made available to the Sponsor or its designee on request with due precaution towards protecting 
the privacy of the patient. 
The Sponsor may elect to have data entered by the clinical site directly into an electronic system 
using electronic case report forms, eCRFs. 
Data will be entered by the site into the eCRFs in the electronic data capture (EDC) system that 
is 21 Part 11 compliant.  Unless explicitly directed, blank data fields are not acceptable.  Any 
erroneous entries made in the eCRFs must be corrected.  Changes made to the data after initial 
entry into the eCRF will be captured via an electronic audit trail, and include the reason for 
change.  Incomplete entries or entries needing additional explanation will be highlighted or 
queried to the Investigator for clarification. 
Adverse events may be coded with the latest version of the medical dictionary for regulatory 
activities (MedDRA) available at study initiation.  Similarly, prior and concomitant medications 
and concomitant therapies may be coded using the latest version of World Health Organization 
(WHO) drug available at study initiation.  If used, the versions employed at study start will be 
maintained throughout the project. 
10.2 
Data Quality Assurance 
Study monitors will perform source document verification according to the clinical monitoring 
plan to ensure there are no inconsistencies between the eCRFs and source documents.  
Discrepancies will be resolved in accordance with the principles of Good Clinical Practice 
(GCP).    
10.3 
Data Management 
Data management will be coordinated by Retrophin or its designated representative in 
accordance with the study data management plan.   

 
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11 
STATISTICAL METHODS AND PLANNED ANALYSES 
11.1 
General Considerations 
This is an observational, non-interventional study.   
11.2 
Determination of Sample Size 
Approximately 500 patients will be enrolled in the study.  Because this is an observational, non-
interventional study, no power calculation has been performed.  The study size is considered to 
be appropriate to investigate the prevalence of CTX among patients diagnosed or treated for 
early-onset idiopathic bilateral cataracts. 
11.3 
Analysis Sets 
All study patients for whom data are available will be included in the analysis dataset.  All study 
patients who undergo invasive study procedures (i.e., a blood draw) will be included in the safety 
dataset. 
11.4 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics (age/age categories, sex, race, ethnicity, and baseline 
characteristics) will be analyzed using the safety analysis set.  Summary statistics (n, mean, 
median, standard deviation, minimum, and maximum) will be reported.  Information collected 
from the targeted medical history will be summarized in the same fashion as the other baseline 
characteristics.   
11.5 
Patient Accountability 
Not applicable. 
11.6 
Study Treatment Usage and Compliance 
Not applicable. 
11.7 
CTX Testing Analyses 
Results of CTX testing (plasma cholestanol level, urine bile alcohol results (if urine sample is 
provided), and genetic testing) will be summarized.  Summary statistics (n, mean, median, 
standard deviation, minimum, and maximum) will be calculated for quantitative data.  Frequency 
counts will be compiled and rates of positive and negative tests will be calculated for 
classification of qualitative data.  

 
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11.8 
Safety Analyses 
Any SAEs related or possibly related to study procedures (i.e., a blood draw) will be listed. 
11.8.1 
Physical Examination and Vital Signs 
Not applicable. 
11.8.2 
Clinical Laboratory Tests 
No safety clinical laboratory tests will be conducted. 
11.8.3 
Adverse Events 
Only SAEs related or possibly related to invasive study procedures (i.e. a blood draw) will be 
recorded. 
11.8.4 
Other Safety Assessments 
Not applicable. 
11.9 
Other Analyses 
Not applicable. 
11.10 
Other Statistical Issues 
Deviations from the statistical plan, along with the reasons for the deviations, will be described 
in protocol amendments, the complete statistical plan, the clinical study report, or any 
combination of these, as appropriate. 
11.10.1 
Significance Levels 
Not applicable. 
11.10.2 
Missing or Invalid Data 
Missing data will remain missing and no imputation of missing data will be done.  Data points 
that appear to be invalid will be queried for correction or confirmation by the clinical site. 
11.11 
Interim Analysis 
No interim analysis is planned. 

 
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12 
SPECIAL REQUIREMENTS AND PROCEDURES 
This protocol was designed and will be conducted, recorded, and reported in compliance with the 
International Conference on Harmonisation (ICH)/GCP guideline.  These requirements are stated 
in the ICH Guideline Topic E6 entitled “Guideline for Good Clinical Practice.” 
12.1 
Institutional and Ethics Review 
This protocol, informed consent form, participant information sheet, and any proposed 
advertising material will be submitted to an appropriate ethics committee, applicable regulatory 
authorities, and host institution(s) for written approval (where applicable).  These documents will 
also be submitted to and approved by the above parties for all substantial amendments to the 
original approved documents (where applicable).  Documentation of any applicable approval(s) 
and the approved consent form must be received by the Sponsor or its designee prior to 
enrollment of patients. 
12.2 
Data Monitoring Committee 
There will be no data monitoring committee (DMC) for this study. 
12.3 
Changes to the Conduct of the Study or Protocol 
Any changes in the study protocol, such as changes in the study design, objectives or endpoints, 
inclusion and exclusion criteria, and/or procedures (except to eliminate an immediate hazard) 
will be implemented only after the mutual agreement of the Investigator and the Sponsor or its 
designee.  All protocol changes must be documented in protocol amendment(s).  Protocol 
amendment(s) must be signed by the Investigator and approved by the Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) prior to implementation.  Any changes in 
study conduct that result from a pending amendment will be considered protocol deviations until 
IRB or IEC approval is granted.  Documentation of IRB or IEC approval must be returned to the 
Sponsor or its designee. 
12.4 
Investigator’s Responsibilities 
Refer to the Study Operation Manual for further details regarding the Investigator’s 
responsibilities as outlined in the sections below. 
12.4.1 
Patient Informed Consent 
Investigators must adhere to GCP, which includes ethical principles that have their origin in the 
Declaration of Helsinki, when developing the patient informed consent form and when obtaining 
consent from the patient.  Written informed consent is required prior to enrollment in the study.  

 
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It is the responsibility of the Investigator to document the consent process within the source 
documents and obtain consent using an IRB or IEC approved consent form.  Remote consenting 
of subjects by authorized study personnel, using telephone, mail, fax or other communication 
means, is permitted. 
The patient and/or their parent/legal guardian must be willing and able to provide signed 
informed consent and the patient, if <18 years of age, is willing to provide assent if deemed able 
to do so.  If the patient is ≥ 18 years of age but has diminished capacity to provide informed 
consent, their parent/legal guardian must be willing and able to provide signed informed consent 
and the patient is willing to provide assent, if deemed able to do so. 
Confidenality will be maintained during the study.  Data and information collected during this 
study, including information on patients’ race and ethnicity, are required by government 
regulatory authorities and may be published but will not include any personal identity.  The study 
will use unique study identifiers to maintain confidentiality.  Any study-related records that 
identify patients will be kept confidential, and to the extent permitted by applicable laws and/or 
regulations will not be made publicbly available.  Any results that are published from this study 
will not include a patient’s personal identity.   
12.4.2 
Case Report Forms 
Copies of pertinent records in connection with the study, including all source documents, will be 
made available to the Sponsor or its designee on request with due precaution towards protecting 
the privacy of the patient. 
Data will be entered by the site into the eCRFs in the EDC system.  Unless explicitly directed, 
blank data fields are not acceptable.  Any erroneous entries made in the eCRFs must be 
corrected.  Changes made to the data after initial entry into the eCRF will be captured via an 
electronic audit trail, and include the reason for change.  Incomplete entries or entries needing 
additional explanation will be highlighted or queried to the Investigator for clarification. 
12.4.3 
Record Retention 
The Investigator is responsible for oversight and maintenance of the study records and patient 
source documents.  These records must be readily available for audit or inspection. 
The Investigator must retain study records for at least 2 years after completion of the clinical 
study.  However, these documents should be retained for a longer period, if required by other 
applicable requirements (e.g., applicable local regulatory requirement) or by an agreement with 

 
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the Sponsor or its designee.  The Investigator will contact the Sponsor or its designee prior to any 
record destruction. 
Patient records or other source data must be kept for the maximum period of time mandated by 
the hospital, institution, or private practice, but not less than 15 years. 
If off-site archiving is used, all records must be retrieved and made available for review at the 
time of an audit or regulatory authority inspection. 
12.4.4 
Monitoring 
A representative of the Sponsor or its designee will remotely interface with and may visit the 
Investigator periodically for the purpose of monitoring the progress of this study in accordance 
with the protocol, GCP, and local regulations.  A monitor, auditor, IRB and or/other regulatory 
authority, such as the The United States Food and Drug Administration (FDA), would have 
access to study-related medical documents for the purposes of the study.   Non-compliance with 
the protocol, GCP, and local regulations will be documented and corrective actions implemented, 
as necessary.  It is the responsibility of the Investigator to be present or available for consultation 
during remote or on-site monitoring visits.  In order to complete remote or on-site monitoring 
visits, all data pertaining to a patient’s participation in this clinical investigation must be made 
available to the monitor. 
At any time prior to, during, or after completion of the clinical study, an audit may be performed 
by the Sponsor or its designee or a representative of a national regulatory agency may choose to 
inspect a study site; this includes FDA. The FDA may inspect all records related to the study.  
Investigators must notify the Sponsor or its designee upon notification of inspection by a 
representative of a national regulatory agency.  A Sponsor or designee representative will be 
available to assist in the preparation for study site inspections.  All pertinent study data must be 
made available for verification, audit, or inspection purposes. 
12.4.5 
Study or Site Termination 
If the Sponsor or its designee, the Investigator, or regulatory authorities discover any conditions 
during the study that indicate that the study or study site should be terminated, this action may be 
taken after appropriate consultation between the Sponsor or its designee and the Investigator.  
The Sponsor or its designee has the right to terminate the participation of either an individual site 
or the study at any time, for any reason which may include the following: 
 The incidence and severity of AEs in this or other studies indicates a potential health 
hazard to patients. 

 
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 Patient enrollment is unsatisfactory. 
 Data recording is inaccurate or incomplete. 
 Investigator(s) do(es) not adhere to the protocol or applicable regulatory guidelines in 
conducting this study. 
 Submission of knowingly false information from the study site to the Sponsor or its 
designee, or regulatory authorities. 
In the event that the study is terminated early, the Sponsor or its designee will provide specific 
guidance to investigational sites regarding the end-of-study procedures. 
12.4.6 
Investigational Product Control 
Not applicable. 
12.4.7 
Insurance 
The Sponsor will maintain a liability insurance policy covering all clinical studies under its 
sponsorship, and that policy will comply with local laws and requirements.  The Sponsor or its 
designee will provide a certificate of insurance to any IRB/IEC or regional Health Authority that 
may require such a document.  Note that this Sponsor insurance coverage does not relieve the 
Investigator, the Institution, and their collaborators from each maintaining their own liability 
insurance policy for their clinical research activity. 
12.4.8 
Disclosure of Data 
All details related to the disclosure and publication of study data will be addressed in the 
Investigator’s study contract. 
12.4.9 
Clinical Study Report 
The Sponsor or the Sponsor’s designee is responsible for preparing a clinical study report.  The 
final report is signed by the Sponsor.  Study results will be provided to the Investigators. 
 

 
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13 
REFERENCES 
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Federico, A. and M.T. Dotti, Cerebrotendinous xanthomatosis: clinical manifestations, 
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Berginer, V.M., et al., Psychiatric disorders in patients with cerebrotendinous 
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three siblings and literature review. Chang Gung Med J, 2002. 25(5): p. 334-40. 
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Martini, G., et al., Long-term bone density evaluation in cerebrotendinous 
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Page 35 
Clinical Protocol Number 018CTXX15001 
 
 
 
RETROPHIN 
FINAL: 13 DECEMBER 2016 
PROPRIETARY AND CONFIDENTIAL 
 
 
14 
APPENDIX 
Table 1.  
Schedule of Events 
 
Screening/ 
Enrollment 
CTX Testing 
(if Necessary) 
Confirm Study Eligibility 
X 
 
Obtain Informed Consent 
X 
 
Demographics  
X 
 
Targeted Medical History1 
X 
 
Concomitant Medications/Therapies2 
X 
 
Blood draw for Plasma Cholestanol testing and 
Genetic testing3 
X 
 
Urine collection for Bile Alcohol testing (if urine 
sample is provided) 4 
X 
 
Serious Adverse Events related to procedures 
X 
 
Genetic Testing for CTX5 
 
X 
Photographic Documentation of Cataracts6 
 
X 
 Follow-Up  Notification of Results 
X7 
X8 
Study Discontinuation  
X7 
X8 
 
1 History of or current manifestations of signs and symptoms commonly associated with CTX 
2 Concomitant medications and therapies during the week prior to enrollment will be collected.   
3 Blood draw may be collected in conjunction with other scheduled treatments during medical care that is separate 
from the clinical study 
4 Urine sample (if provided) may be collected in conjunction with other scheduled treatments during medical care 
that is separate from the clinical study 
5 Will be completed if patient plasma cholestanol level is 0.4mg/dL (4µg/mL) or urine bile alcohol is positive (if 
urine sample is provided) 
6 If available, collected for patients who have been diagnosed with CTX. 
7 For those participants with normal results for plasma cholestanol < 0.4 mg/dL (4 µg/mL) and urine bile alcohol is 
negative (if urine sample is provided), participation ends after tests results have been communicated to the patient 
and study discontinuation page is completed. 
8 For those participants who require genetic testing, participation ends after reporting of test results to the patient, 
and study discontinuation page is completed.